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    "primaryId" : "PMID:1",
    "title" : "Formate assay in body fluids: application in methanol poisoning.",
    "datePublished" : "1975-06-01T00:00:00.000-05:00",
    "citation" : "Makar AB, etal., Biochem Med. 1975 Jun;13(2):117-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-05-08T17:22:52.000-05:00",
    "volume" : "13",
    "pages" : "117-26",
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      "firstName" : "A B",
      "lastName" : "Makar",
      "authorRank" : 1,
      "name" : "Makar AB",
      "referenceId" : "RGD:A457905"
    }, {
      "firstName" : "K E",
      "lastName" : "McMartin",
      "authorRank" : 2,
      "name" : "McMartin KE",
      "referenceId" : "RGD:A457906"
    }, {
      "firstName" : "M",
      "lastName" : "Palese",
      "authorRank" : 3,
      "name" : "Palese M",
      "referenceId" : "RGD:A48035"
    }, {
      "firstName" : "T R",
      "lastName" : "Tephly",
      "authorRank" : 4,
      "name" : "Tephly TR",
      "referenceId" : "RGD:A436763"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13542090"
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  }, {
    "primaryId" : "PMID:10",
    "title" : "Digitoxin metabolism by rat liver microsomes.",
    "datePublished" : "1975-10-01T00:00:00.000-05:00",
    "citation" : "Schmoldt A, etal., Biochem Pharmacol 1975 Sep 1;24(17):1639-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:56.000-05:00",
    "volume" : "24",
    "pages" : "1639-41",
    "issueName" : "17",
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      "referenceType" : "JOURNAL ARTICLE",
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    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Schmoldt",
      "authorRank" : 1,
      "name" : "Schmoldt A",
      "referenceId" : "RGD:A6281"
    }, {
      "firstName" : "HF",
      "lastName" : "Benthe",
      "authorRank" : 2,
      "name" : "Benthe HF",
      "referenceId" : "RGD:A6282"
    }, {
      "firstName" : "G",
      "lastName" : "Haberland",
      "authorRank" : 3,
      "name" : "Haberland G",
      "referenceId" : "RGD:A6283"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68877"
    } ]
  }, {
    "primaryId" : "PMID:100",
    "title" : "Bovine mannosidosis--a model lysosomal storage disease.",
    "datePublished" : "1975-08-01T00:00:00.000-05:00",
    "citation" : "Jolly RD, etal., Birth Defects Orig Artic Ser 1975;11(6):273-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-08-26T09:38:54.000-05:00",
    "volume" : "11",
    "pages" : "273-8",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
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    "authors" : [ {
      "firstName" : "RD",
      "lastName" : "Jolly",
      "authorRank" : 1,
      "name" : "Jolly RD",
      "referenceId" : "RGD:A45750"
    }, {
      "firstName" : "KG",
      "lastName" : "Thompson",
      "authorRank" : 2,
      "name" : "Thompson KG",
      "referenceId" : "RGD:A45751"
    }, {
      "firstName" : "BG",
      "lastName" : "Winchester",
      "authorRank" : 3,
      "name" : "Winchester BG",
      "referenceId" : "RGD:A45752"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302238"
    } ]
  }, {
    "primaryId" : "PMID:1002129",
    "title" : "[Rule of antibody structure. the primary structure of a monoclonal IgG1 immunoglobulin (myeloma protein Nie), I: Purification and characterization of the protein, the L- and H-chains, the cyanogenbromide cleavage products, and the disulfide bridges (author's transl)].",
    "datePublished" : "1976-04-01T00:00:00.000-06:00",
    "citation" : "Dreker L, etal., Hoppe Seylers Z Physiol Chem. 1976 Nov;357(11):1515-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T13:37:29.000-05:00",
    "volume" : "357",
    "pages" : "1515-40",
    "abstract" : "Myeloma protein Nie has been isolated from the serum of a myeloma patient by free flow continuous high voltage electrophoresis or by Pevicon-block electrophoresis. It was further purified by ion-exchange chromatography and gel filtration, and characterized by amino acid analysis and end group determination. Serologically,  the protein belongs to the IgG1 subclass. It has been typed as Gm1+, 2-,4- and 17+. The L-chain is of the k-type. The L- and H-chains have been separated by gel-filtration after partial reduction and alkylation and characterized by amino  acid analysis and end group determination. The F(ab)- and Fc-fragments, prepared  by limited tryptic digestion, have been separated and characterized. Cyanogen bromide splitting products have been prepared both from the intact IgG and from the Fc-and the partially reduced and alkylated F(ab)-fragment. These splitting products have been purified and characterized by amino acid analysis and end group determination. By means of these cyanogen bromide splitting products and by partial reduction and alkylation, the disulfide bridges in the protein could be localized: one L-H-bridge, two inter-H-bridges and four loop forming intra-H-bridges.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Dreker",
      "authorRank" : 1,
      "name" : "Dreker",
      "referenceId" : "RGD:A221291"
    }, {
      "firstName" : "J",
      "lastName" : "Schwarz",
      "authorRank" : 2,
      "name" : "Schwarz",
      "referenceId" : "RGD:A192377"
    }, {
      "firstName" : "W",
      "lastName" : "Reichel",
      "authorRank" : 3,
      "name" : "Reichel",
      "referenceId" : "RGD:A221292"
    }, {
      "firstName" : "N",
      "lastName" : "Hilschmann",
      "authorRank" : 4,
      "name" : "Hilschmann",
      "referenceId" : "RGD:A217389"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11053260"
    } ]
  }, {
    "primaryId" : "PMID:10021345",
    "title" : "The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes  essential for heart development.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Tanaka M, etal., Development. 1999 Mar;126(6):1269-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-05-18T19:50:11.000-05:00",
    "volume" : "126",
    "pages" : "1269-80",
    "abstract" : "Csx/Nkx2.5 is a vertebrate homeobox gene with a sequence homology to the Drosophila tinman, which is required for the dorsal mesoderm specification. Recently, heterozygous mutations of this gene were found to cause human congenital heart disease (Schott, J.-J., Benson, D. W., Basson, C. T., Pease, W., Silberbach, G. M., Moak, J. P., Maron, B. J., Seidman, C. E. and Seidman, J. G. (1998) Science 281, 108-111). To investigate the functions of Csx/Nkx2.5 in cardiac and extracardiac development in the vertebrate, we have generated and analyzed mutant mice completely null for Csx/Nkx2.5. Homozygous null embryos showed arrest of cardiac development after looping and poor development of blood  vessels. Moreover, there were severe defects in vascular formation and hematopoiesis in the mutant yolk sac. Interestingly, TUNEL staining and PCNA staining showed neither enhanced apoptosis nor reduced cell proliferation in the  mutant myocardium. In situ hybridization studies demonstrated that, among 20 candidate genes examined, expression of ANF, BNP, MLC2V, N-myc, MEF2C, HAND1 and  Msx2 was disturbed in the mutant heart. Moreover, in the heart of adult chimeric  mice generated from Csx/Nkx2.5 null ES cells, there were almost no ES cell-derived cardiac myocytes, while there were substantial contributions of Csx  /Nkx2.5-deficient cells in other organs. Whole-mount &bgr;-gal staining of chimeric embryos showed that more than 20% contribution of Csx/Nkx2. 5-deficient  cells in the heart arrested cardiac development. These results indicate that (1)  the complete null mutation of Csx/Nkx2.5 did not abolish initial heart looping, (2) there was no enhanced apoptosis or defective cell cycle entry in Csx/Nkx2.5 null cardiac myocytes, (3) Csx/Nkx2.5 regulates expression of several essential transcription factors in the developing heart, (4) Csx/Nkx2.5 is required for later differentiation of cardiac myocytes, (5) Csx/Nkx2. 5 null cells exert dominant interfering effects on cardiac development, and (6) there were severe defects in yolk sac angiogenesis and hematopoiesis in the Csx/Nkx2.5 null embryos.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Tanaka",
      "authorRank" : 1,
      "name" : "Tanaka",
      "referenceId" : "RGD:A417009"
    }, {
      "firstName" : "Z",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen",
      "referenceId" : "RGD:A416768"
    }, {
      "firstName" : "S",
      "lastName" : "Bartunkova",
      "authorRank" : 3,
      "name" : "Bartunkova",
      "referenceId" : "RGD:A289343"
    }, {
      "firstName" : "N",
      "lastName" : "Yamasaki",
      "authorRank" : 4,
      "name" : "Yamasaki",
      "referenceId" : "RGD:A233387"
    }, {
      "firstName" : "S",
      "lastName" : "Izumo",
      "authorRank" : 5,
      "name" : "Izumo S",
      "referenceId" : "RGD:A14245"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11080395"
    } ]
  }, {
    "primaryId" : "PMID:10021368",
    "title" : "Identification of sonic hedgehog as a candidate gene responsible for the polydactylous mouse mutant Sasquatch.",
    "datePublished" : "1999-01-28T00:00:00.000-06:00",
    "citation" : "Sharpe J, etal., Curr Biol. 1999 Jan 28;9(2):97-100.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-03-30T13:24:17.000-05:00",
    "volume" : "9",
    "pages" : "97-100",
    "abstract" : "The mouse mutants of the hemimelia-luxate group (lx, lu, lst, Dh, Xt, and the more recently identified Hx, Xpl and Rim4; [1] [2] [3] [4] [5]) have in common preaxial polydactyly and longbone abnormalities. Associated with the duplication of digits are changes in the regulation of development of the anterior limb bud resulting in ectopic expression of signalling components such as Sonic hedgehog (Shh) and fibroblast growth factor-4 (Fgf4), but little is known about the molecular causes of this misregulation. We generated, by a transgene insertion event, a new member of this group of mutants, Sasquatch (Ssq), which disrupted aspects of both anteroposterior (AP) and dorsoventral (DV) patterning. The mutant displayed preaxial polydactyly in the hindlimbs of heterozygous embryos, and in both hindlimbs and forelimbs of homozygotes. The Shh, Fgf4, Fgf8, Hoxd12 and Hoxd13 genes were all ectopically expressed in the anterior region of affected limb buds. The insertion site was found to lie close to the Shh locus. Furthermore, expression from the transgene reporter has come under the control of a regulatory element that directs a pattern mirroring the endogenous expression pattern of Shh in limbs. In abnormal limbs, both Shh and the reporter were ectopically induced in the anterior region, whereas in normal limbs the reporter and Shh were restricted to the zone of polarising activity (ZPA). These data strongly suggest that Ssq is caused by direct interference with the cis regulation of the Shh gene.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Sharpe",
      "authorRank" : 1,
      "name" : "Sharpe J",
      "referenceId" : "RGD:A67759"
    }, {
      "firstName" : "L",
      "lastName" : "Lettice",
      "authorRank" : 2,
      "name" : "Lettice L",
      "referenceId" : "RGD:A441444"
    }, {
      "firstName" : "J",
      "lastName" : "Hecksher-Sorensen",
      "authorRank" : 3,
      "name" : "Hecksher-Sorensen J",
      "referenceId" : "RGD:A441445"
    }, {
      "firstName" : "M",
      "lastName" : "Fox",
      "authorRank" : 4,
      "name" : "Fox M",
      "referenceId" : "RGD:A5686"
    }, {
      "firstName" : "R",
      "lastName" : "Hill",
      "authorRank" : 5,
      "name" : "Hill R",
      "referenceId" : "RGD:A37873"
    }, {
      "firstName" : "R",
      "lastName" : "Krumlauf",
      "authorRank" : 6,
      "name" : "Krumlauf R",
      "referenceId" : "RGD:A75081"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12801429"
    } ]
  }, {
    "primaryId" : "PMID:10022303",
    "title" : "Expression of Fas system-related genes in the testis during development and after toxicant exposure.",
    "datePublished" : "1998-12-28T00:00:00.000-06:00",
    "citation" : "Boekelheide K, etal., Toxicol Lett. 1998 Dec 28;102-103:503-8. doi: 10.1016/s0378-4274(98)00242-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-05-27T15:08:20.000-05:00",
    "volume" : "102-103",
    "pages" : "503-8",
    "abstract" : "The Fas system has been identified as a key regulator of testicular germ cell apoptosis. The goal of these experiments was to explore the expression of Fas system-related genes in the testis during development and after toxicant exposure. Both Fas ligand (FasL) and Fas receptor (Fas) were expressed postnatally in rat testis with peak expression associated with the high levels of germ cell apoptosis found during the first wave of spermatogenesis. The testicular expression of RIP and FAP-1, components of the Fas activating complex, increased after exposure to mono-(2-ethylhexyl)phthalate (MEHP), a Sertoli cell toxicant which induces massive germ cell death. Finally, the expression of additional apoptosis-inducing genes, including tumor necrosis factor receptor (TNFR), FADD, TRAIL, and DR5, was detected in mammalian testis. These results provide additional support for the following concepts: (1) Sertoli-germ cell interactions are important in the control of germ cell apoptosis; and (2) the Fas system and similar paracrine systems are important modulators of testicular homeostasis.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Boekelheide",
      "authorRank" : 1,
      "name" : "Boekelheide K",
      "referenceId" : "RGD:A5735"
    }, {
      "firstName" : "J",
      "lastName" : "Lee",
      "authorRank" : 2,
      "name" : "Lee J",
      "referenceId" : "RGD:A41085"
    }, {
      "firstName" : "E B",
      "lastName" : "Shipp",
      "authorRank" : 3,
      "name" : "Shipp EB",
      "referenceId" : "RGD:A516273"
    }, {
      "firstName" : "J H",
      "lastName" : "Richburg",
      "authorRank" : 4,
      "name" : "Richburg JH",
      "referenceId" : "RGD:A516274"
    }, {
      "firstName" : "G",
      "lastName" : "Li",
      "authorRank" : 5,
      "name" : "Li G",
      "referenceId" : "RGD:A162013"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:152975630"
    } ]
  }, {
    "primaryId" : "PMID:10022408",
    "title" : "Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Reutens AT, etal., J Clin Endocrinol Metab. 1999 Feb;84(2):504-11. doi: 10.1210/jcem.84.2.5468.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:55:34.000-05:00",
    "volume" : "84",
    "pages" : "504-11",
    "abstract" : "Adrenal hypoplasia congenita (AHC) is an X-linked disorder caused by mutations in a gene referred to as DAX-1. AHC is characterized by adrenal insufficiency and failure to undergo puberty because of hypogonadotropic hypogonadism. The DAX-1 protein is structurally related to orphan nuclear receptors, although it lacks the characteristic zinc finger DNA-binding domain that is highly conserved in other members of this family. In this report, we describe the clinical features and genetic alterations in six families with AHC. These patients reveal the variable clinical presentation of adrenal insufficiency in AHC and underscore the importance of considering this diagnosis. Nonsense mutations that introduce a stop codon were found in three cases (W171X, W171X, Y399X). Frameshift mutations (405delT, 501delA, and 702delC), each of which resulted in a premature stop codon at amino acid 263, were found in the other three families. Three of these mutations (Y399X, 405delT, 702delC) are novel. Using transient gene expression assays to assess DAX-1 function, these mutations were shown to eliminate the ability of DAX-1 to repress the transcription of genes that are stimulated by a related nuclear receptor, steroidogenic factor-1. These studies reveal the variable clinical presentation of DAX-1 mutations and emphasize the value of genetic testing in boys with primary adrenal insufficiency and suspected X-linked AHC.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A T",
      "lastName" : "Reutens",
      "authorRank" : 1,
      "name" : "Reutens AT",
      "referenceId" : "RGD:A597299"
    }, {
      "firstName" : "J C",
      "lastName" : "Achermann",
      "authorRank" : 2,
      "name" : "Achermann JC",
      "referenceId" : "RGD:A597300"
    }, {
      "firstName" : "M",
      "lastName" : "Ito",
      "authorRank" : 3,
      "name" : "Ito M",
      "referenceId" : "RGD:A5288"
    }, {
      "firstName" : "M",
      "lastName" : "Ito",
      "authorRank" : 4,
      "name" : "Ito M",
      "referenceId" : "RGD:A5288"
    }, {
      "firstName" : "W X",
      "lastName" : "Gu",
      "authorRank" : 5,
      "name" : "Gu WX",
      "referenceId" : "RGD:A597301"
    }, {
      "firstName" : "R L",
      "lastName" : "Habiby",
      "authorRank" : 6,
      "name" : "Habiby RL",
      "referenceId" : "RGD:A597302"
    }, {
      "firstName" : "P A",
      "lastName" : "Donohoue",
      "authorRank" : 7,
      "name" : "Donohoue PA",
      "referenceId" : "RGD:A597303"
    }, {
      "firstName" : "S",
      "lastName" : "Pang",
      "authorRank" : 8,
      "name" : "Pang S",
      "referenceId" : "RGD:A17636"
    }, {
      "firstName" : "P C",
      "lastName" : "Hindmarsh",
      "authorRank" : 9,
      "name" : "Hindmarsh PC",
      "referenceId" : "RGD:A597304"
    }, {
      "firstName" : "J L",
      "lastName" : "Jameson",
      "authorRank" : 10,
      "name" : "Jameson JL",
      "referenceId" : "RGD:A565290"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118963"
    } ]
  }, {
    "primaryId" : "PMID:10022420",
    "title" : "Expression of growth hormone-releasing hormone (GHRH) messenger ribonucleic acid and the presence of biologically active GHRH in human breast, endometrial, and ovarian cancers.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Kahan Z, etal., J Clin Endocrinol Metab. 1999 Feb;84(2):582-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-02-21T14:25:08.000-06:00",
    "volume" : "84",
    "pages" : "582-9",
    "abstract" : "GHRH is produced in a variety of extrahypothalamic tissues, including some neoplasms. We have previously reported that GHRH antagonists can inhibit the growth of various human cancers xenografted into nude mice. These observations suggest that locally produced GHRH might directly affect tumor cell proliferation. To investigate this possibility, we have examined the local production of GHRH in human endometrial, ovarian, and breast cancers obtained after surgery or grown in nude mice as xenografts. We have also examined whether the GHRH produced in these tumors is biologically active. RT-PCR and Southern blotting showed expression of messenger ribonucleic acid for GHRH in 17 of 22 endometrial and 17 of 22 ovarian cancer specimens and in all of the human endometrial, ovarian, and breast cancer xenografts studied. Acid extracts of endometrial cancer specimens and breast cancer xenografts that expressed the GHRH gene contained immunoreactive GHRH peptide, as assessed by RIA for GHRH. The level of immunoreactive GHRH detected was equivalent to 2.7-6.4 ng GHRH-(1-29)/g tissue. Purified extract from one of these tumor samples induced a powerful stimulation of GH release from rat pituitary cells. The presence of biologically and immunologically active GHRH and messenger ribonucleic acid for GHRH in human breast, endometrial, and ovarian cancers supports the hypothesis that locally produced GHRH may play a role in the proliferation of these tumors.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Kahan",
      "authorRank" : 1,
      "name" : "Kahan Z",
      "referenceId" : "RGD:A92324"
    }, {
      "firstName" : "JM",
      "lastName" : "Arencibia",
      "authorRank" : 2,
      "name" : "Arencibia JM",
      "referenceId" : "RGD:A92325"
    }, {
      "firstName" : "VJ",
      "lastName" : "Csernus",
      "authorRank" : 3,
      "name" : "Csernus VJ",
      "referenceId" : "RGD:A92326"
    }, {
      "firstName" : "K",
      "lastName" : "Groot",
      "authorRank" : 4,
      "name" : "Groot K",
      "referenceId" : "RGD:A92327"
    }, {
      "firstName" : "RD",
      "lastName" : "Kineman",
      "authorRank" : 5,
      "name" : "Kineman RD",
      "referenceId" : "RGD:A80572"
    }, {
      "firstName" : "WR",
      "lastName" : "Robinson",
      "authorRank" : 6,
      "name" : "Robinson WR",
      "referenceId" : "RGD:A92328"
    }, {
      "firstName" : "AV",
      "lastName" : "Schally",
      "authorRank" : 7,
      "name" : "Schally AV",
      "referenceId" : "RGD:A6704"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289974"
    } ]
  }, {
    "primaryId" : "PMID:10022432",
    "title" : "Thyroid receptor alpha1 and alpha2 mutations in nonfunctioning pituitary tumors.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "McCabe CJ, etal., J Clin Endocrinol Metab. 1999 Feb;84(2):649-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-06-23T16:05:20.000-05:00",
    "volume" : "84",
    "pages" : "649-53",
    "abstract" : "We previously reported that nonfunctioning tumors of the anterior pituitary exhibit reduced expression of thyroid receptor (TR) alpha and beta isoforms, an observation that may account for abnormalities of T3-mediated negative regulation of the glycoprotein hormone common alpha-subunit. Reduced TR protein was associated with a parallel reduction in TRbeta messenger RNA (mRNA), although TRalpha1 and alpha2 mRNA levels were similar in nonfunctioning tumors and normal pituitaries. Because TRalpha shows aberrant posttranscriptional processing, and TRbeta is under ligand-dependent autoregulation, we hypothesized that aberrant TR expression in nonfunctioning tumors may reflect mutation in receptor coding and regulatory sequences, and therefore screened TRalpha mRNA and TRbeta T3 response elements and ligand binding domains for sequence anomalies. Screening TRalpha mRNA in 23 tumors and subsequently sequencing candidate fragments identified one silent change from published sequences and three novel missense mutations, two in the common TRalpha region (ser45ile and lys370asn) and one that was alpha2 specific (ser377leu). TRbeta response elements failed to show any differences from published sequences in 14 nonfunctioning tumors. Sequencing of TRbeta ligand binding domains were also identical to wild type in 23 nonfunctioning tumors. The functional significance of the novel TRalpha mutations is unknown; definition of mutant TR action may provide insight into the role of TRs in the growth control of pituitary cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CJ",
      "lastName" : "McCabe",
      "authorRank" : 1,
      "name" : "McCabe CJ",
      "referenceId" : "RGD:A61122"
    }, {
      "firstName" : "NJ",
      "lastName" : "Gittoes",
      "authorRank" : 2,
      "name" : "Gittoes NJ",
      "referenceId" : "RGD:A61123"
    }, {
      "firstName" : "MC",
      "lastName" : "Sheppard",
      "authorRank" : 3,
      "name" : "Sheppard MC",
      "referenceId" : "RGD:A61124"
    }, {
      "firstName" : "JA",
      "lastName" : "Franklyn",
      "authorRank" : 4,
      "name" : "Franklyn JA",
      "referenceId" : "RGD:A61125"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580114"
    } ]
  }, {
    "primaryId" : "PMID:10022440",
    "title" : "Diabetes alters the expression and activity of the human placental GLUT1 glucose transporter.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Gaither K, etal., J Clin Endocrinol Metab. 1999 Feb;84(2):695-701.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-04-24T13:34:00.000-05:00",
    "volume" : "84",
    "pages" : "695-701",
    "abstract" : "This study was designed to investigate the effects of maternal diabetes on glucose transporter expression and glucose transport activity in the human placenta. Syncytiotrophoblast microvillous and basal membranes were prepared from placental tissue obtained at term from pregestational diabetics (White class B) and gestational diabetics controlled either by diet alone (class A1) or by diet and insulin (class A2). These membranes were used to measure GLUT1 glucose transporter expression and D-glucose transport activity. Diabetic groups showed no differences in placental weights or neonatal birth weights compared to controls, although 8 of 25 diabetic fetuses were macrosomic. Glycemic control in the diabetics at term, as assessed by maternal glycosylated hemoglobin, was within normal limits. Basal membrane GLUT1 density was about 2-fold higher in all diabetic groups compared to that in controls, as measured by immunoblotting, whereas no changes were found for the microvillous membranes. D-Glucose uptake across the basal membrane was increased by 40% in the diabetic groups; no changes were observed for the microvillous membrane. These results demonstrate that diabetes causes an increase in basal membrane GLUT1 expression and activity that persists despite a lack of evidence for current or recent maternal hyperglycemia. This suggests the potential for an extended increase in transplacental glucose flux in the absence of maternal hyperglycemia, which may contribute to fetal macrosomia and the other consequences of diabetic pregnancy.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Gaither",
      "authorRank" : 1,
      "name" : "Gaither K",
      "referenceId" : "RGD:A442707"
    }, {
      "firstName" : "A N",
      "lastName" : "Quraishi",
      "authorRank" : 2,
      "name" : "Quraishi AN",
      "referenceId" : "RGD:A442708"
    }, {
      "firstName" : "N P",
      "lastName" : "Illsley",
      "authorRank" : 3,
      "name" : "Illsley NP",
      "referenceId" : "RGD:A442709"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12879500"
    } ]
  }, {
    "primaryId" : "PMID:10022499",
    "title" : "Identification of DERMO-1 as a member of helix-loop-helix type transcription factors expressed in osteoblastic cells.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Tamura M and Noda M, J Cell Biochem 1999 Feb 1;72(2):167-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:49.000-05:00",
    "volume" : "72",
    "pages" : "167-76",
    "abstract" : "Several members of the basic helix-loop-helix (bHLH) type of transcription factors have now been reported, and almost every member of this class has been implicated in transcriptional regulation in cell type determination and differentiation. Previously, we reported that dominant negative HLH proteins are involved in osteoblastic phenotype expression, such as osteocalcin, and hence differentiation (Tamura and Noda [1994] J. Cell Biol. 126:773-782). In this work, we used degenerate PCR cloning in order to identify cDNA clones encoding bHLH proteins expressed in osteoblastic osteosarcoma ROS17/2.8 cells. Sequence analyses of the 47 clones revealed that 11 clones encoded products with a characteristic motif of the bHLH transcription factor family. Of these clones, sequences in the amplified region of seven clones were homologous to the mouse twist, and three clones were homologous to the mouse twist-related HLH protein, Dermo-1. To confirm Dermo-1 mRNA expression in osteoblastic cells, we performed reverse transcription polymerase chain reaction (RT-PCR) analysis using mRNA from ROS17/2.8 cells and MC3T3-E1 cells by Dermo-1 specific primers and Northern blot analysis. These analyses demonstrated that Dermo-1 mRNA was expressed in these osteoblast-like cell lines. Nucleotide sequence analysis of the partial rat Dermo-1 cDNA cloned from ROS17/2.8 library revealed that it has the highest degree of homology with the mouse Dermo-1 cDNA, and the partial amino acid sequence deduced from the obtained rat Dermo-1 was identical with the corresponding region of the mouse Dermo-1 amino acid sequence. To further examine the role of Dermo-1 in the regulation of osteoblastic differentiation, we examined mRNA levels of Dermo-1 and twist in C3H10T1/2 cells treated with recombinant human bone morphogenetic protein (rhBMP)-2. Using the RT-PCR method, the mRNA levels of Dermo-1 and twist were found to be decreased by the treatment with rhBMP-2 in C3H10T1/2 cells. We also observed that the mRNA level of Dermo-1 was decreased about fourfold by the treatment with rhBMP-2 in C3H10T1/2 cells by Northern blot analysis. Moreover, Dermo-1 mRNA was detected at lower levels in 21-day-old differentiated MC3T3-E1 cells compared with 3-day-old undifferentiated MC3T3-E1 cells. These results suggested that Dermo-1 could be involved in the osteoblastic differentiation in a negative manner.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Tamura",
      "authorRank" : 1,
      "name" : "Tamura M",
      "referenceId" : "RGD:A32772"
    }, {
      "firstName" : "M",
      "lastName" : "Noda",
      "authorRank" : 2,
      "name" : "Noda M",
      "referenceId" : "RGD:A6115"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302335"
    } ]
  }, {
    "primaryId" : "PMID:10022522",
    "title" : "Dual posttranscriptional targets of retinoic acid-induced gene expression.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Manji SS, etal., J Cell Biochem. 1999 Mar 1;72(3):411-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-12-08T16:23:16.000-06:00",
    "volume" : "72",
    "pages" : "411-22",
    "abstract" : "Retinoic acid-induced differentiation of the pre-osteoblastic cell line, UMR 201, is associated with a marked increase in the proficiency of posttranscriptional nuclear processing of alkaline phosphatase mRNA. In this study we attempted to correlate the posttranscriptional actions of retinoic acid with changes in phosphorylation, or abundance of spliceosome components, or both. Treatment with  retinoic acid for periods of < or = 4 h resulted in dephosphorylation of nuclear  U1 70K protein without affecting its abundance. Peptide mapping showed that U1 70K dephosphorylation was related to the disappearance of one specific phosphopeptide out of four major U1 70K phosphopeptides. A twofold decrease in mRNA expression of an isoform of alternative splicing factor that inhibits splicing was also observed over the same period. Tumor necrosis factor-alpha, which enhances the posttranscriptional action of retinoic acid, reduced U1 70K mRNA expression, while an inhibition of retinoic acid action by transforming growth factor-beta was associated with a marked increase in U1 70K mRNA levels. Our results draw attention to the complex interactions between short- and long-term alterations in the abundance and functional status of U1 70K, as well as SR proteins by growth and/or differentiation factors in the regulation of spliceosome formation and function.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SS",
      "lastName" : "Manji",
      "authorRank" : 1,
      "name" : "Manji",
      "referenceId" : "RGD:A192692"
    }, {
      "firstName" : "RB",
      "lastName" : "Pearson",
      "authorRank" : 2,
      "name" : "Pearson RB",
      "referenceId" : "RGD:A110750"
    }, {
      "firstName" : "M",
      "lastName" : "Pardee",
      "authorRank" : 3,
      "name" : "Pardee",
      "referenceId" : "RGD:A209005"
    }, {
      "firstName" : "V",
      "lastName" : "Paspaliaris",
      "authorRank" : 4,
      "name" : "Paspaliaris",
      "referenceId" : "RGD:A209006"
    }, {
      "firstName" : "A",
      "lastName" : "D'Apice",
      "authorRank" : 5,
      "name" : "D'Apice A",
      "referenceId" : "RGD:A58132"
    }, {
      "firstName" : "TJ",
      "lastName" : "Martin",
      "authorRank" : 6,
      "name" : "Martin TJ",
      "referenceId" : "RGD:A9371"
    }, {
      "firstName" : "KW",
      "lastName" : "Ng",
      "authorRank" : 7,
      "name" : "Ng KW",
      "referenceId" : "RGD:A21102"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10448942"
    } ]
  }, {
    "primaryId" : "PMID:10022688",
    "title" : "Expression and prognostic value of CD44 isoforms in transitional cell carcinoma of renal pelvis and ureter.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Masuda M, etal., J Urol. 1999 Mar;161(3):805-8; discussion 808-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-01-30T15:24:46.000-06:00",
    "volume" : "161",
    "pages" : "805-8; discussion 808-9",
    "abstract" : "PURPOSE: We retrospectively evaluated the expression and prognostic value of CD44 isoforms in transitional cell carcinoma of the renal pelvis and ureter. MATERIALS AND METHODS: Using a labeled streptavidin-biotin-peroxidase method we performed immunohistochemical staining of archival tissue specimens from 62 men and 26 women with a mean age of 66.5 years who had transitional cell carcinoma of the renal pelvis and ureter. RESULTS: The expression of CD44 standard (CD44s) and splice variant 6 (CD44v6) proteins was significantly decreased in relation to histological grade and pathological stage, while expression of the CD44 splice variant 3 (CD44v3) protein was decreased in relation to histological grade. The prognosis was more favorable in patients with greater versus less than 25% CD44s positive cells. CD44v3 and CD44v6 proteins had no prognostic value. Multivariate analysis indicated that only pathological stage has an independent prognostic value. CONCLUSIONS: The expression of CD44 isoforms is closely associated with tumor differentiation and progression. However, it is not an independent marker and has no statistical significance greater than that of stage.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Masuda",
      "authorRank" : 1,
      "name" : "Masuda M",
      "referenceId" : "RGD:A7669"
    }, {
      "firstName" : "Y",
      "lastName" : "Takano",
      "authorRank" : 2,
      "name" : "Takano Y",
      "referenceId" : "RGD:A42575"
    }, {
      "firstName" : "M",
      "lastName" : "Iki",
      "authorRank" : 3,
      "name" : "Iki M",
      "referenceId" : "RGD:A91076"
    }, {
      "firstName" : "K",
      "lastName" : "Makiyama",
      "authorRank" : 4,
      "name" : "Makiyama K",
      "referenceId" : "RGD:A91077"
    }, {
      "firstName" : "S",
      "lastName" : "Noguchi",
      "authorRank" : 5,
      "name" : "Noguchi S",
      "referenceId" : "RGD:A15613"
    }, {
      "firstName" : "M",
      "lastName" : "Hosaka",
      "authorRank" : 6,
      "name" : "Hosaka M",
      "referenceId" : "RGD:A8099"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289363"
    } ]
  }, {
    "primaryId" : "PMID:10022766",
    "title" : "Estrogen-induced rat pituitary tumor is associated with loss of retinoblastoma susceptibility gene product.",
    "datePublished" : "1998-03-01T00:00:00.000-06:00",
    "citation" : "Chun TY, etal., Mol Cell Endocrinol. 1998 Nov 25;146(1-2):87-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-03-04T17:13:43.000-06:00",
    "volume" : "146",
    "pages" : "87-92",
    "abstract" : "Chronic treatment of rats with the estrogens 17beta-estradiol or diethylstilbestrol (DES) induces pituitary tumors in Fischer 344 but not Brown-Norway or Sprague-Dawley rats. Functional loss of retinoblastoma susceptibility gene product (pRb), a major regulatory protein for the G1 to S transition of the cell cycle, has been shown in several tumors. Here we report a  decreased level of pRb in pituitary tumors of the Fischer 344 rat as compared with resistant Sprague Dawley and Brown-Norway strains. pRb protein levels decreased 70% in Fischer 344 rats that were treated with diethylstilbestrol for 10 weeks as compared with tumor resistant control animals. Interestingly, the F1  hybrid (Fischer 344 x Norway) showed an intermediate range of pRb protein expression as compared with those of the parental strains. pRb expression levels  in nonhemorrhagic F2 (F1 x F1) rats correlated with the size of the tumors. One week withdrawal of DES increased pRb levels as compared with continuously treated rats. Also, there was a decreased association of cyclin D and cyclin dependent kinase in susceptible tumors, supporting the hypothesis of a physical and possibly functional loss of pRb in the diethylstilbestrol-induced pituitary tumor. These results suggest that the difference in pRb regulation, whether it is a direct or indirect effect of estrogen, is related to tumor resistance or susceptibility in these two rat strains.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TY",
      "lastName" : "Chun",
      "authorRank" : 1,
      "name" : "Chun TY",
      "referenceId" : "RGD:A135494"
    }, {
      "firstName" : "D",
      "lastName" : "Wendell",
      "authorRank" : 2,
      "name" : "Wendell",
      "referenceId" : "RGD:A180510"
    }, {
      "firstName" : "D",
      "lastName" : "Gregg",
      "authorRank" : 3,
      "name" : "Gregg",
      "referenceId" : "RGD:A180511"
    }, {
      "firstName" : "J",
      "lastName" : "Gorski",
      "authorRank" : 4,
      "name" : "Gorski",
      "referenceId" : "RGD:A376474"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547989"
    } ]
  }, {
    "primaryId" : "PMID:10022819",
    "title" : "Over-representation of a germline RET sequence variant in patients with sporadic  medullary thyroid carcinoma and somatic RET codon 918 mutation.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Gimm O, etal., Oncogene. 1999 Feb 11;18(6):1369-73.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:33:01.000-05:00",
    "volume" : "18",
    "pages" : "1369-73",
    "abstract" : "The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than  that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01). These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Gimm",
      "authorRank" : 1,
      "name" : "Gimm O",
      "referenceId" : "RGD:A39398"
    }, {
      "firstName" : "DS",
      "lastName" : "Neuberg",
      "authorRank" : 2,
      "name" : "Neuberg DS",
      "referenceId" : "RGD:A116234"
    }, {
      "firstName" : "DJ",
      "lastName" : "Marsh",
      "authorRank" : 3,
      "name" : "Marsh",
      "referenceId" : "RGD:A252775"
    }, {
      "firstName" : "PL",
      "lastName" : "Dahia",
      "authorRank" : 4,
      "name" : "Dahia PL",
      "referenceId" : "RGD:A39400"
    }, {
      "firstName" : "C",
      "lastName" : "Hoang-Vu",
      "authorRank" : 5,
      "name" : "Hoang-Vu",
      "referenceId" : "RGD:A259121"
    }, {
      "firstName" : "F",
      "lastName" : "Raue",
      "authorRank" : 6,
      "name" : "Raue",
      "referenceId" : "RGD:A251123"
    }, {
      "firstName" : "R",
      "lastName" : "Hinze",
      "authorRank" : 7,
      "name" : "Hinze R",
      "referenceId" : "RGD:A39402"
    }, {
      "firstName" : "H",
      "lastName" : "Dralle",
      "authorRank" : 8,
      "name" : "Dralle H",
      "referenceId" : "RGD:A7560"
    }, {
      "firstName" : "C",
      "lastName" : "Eng",
      "authorRank" : 9,
      "name" : "Eng",
      "referenceId" : "RGD:A405865"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069010"
    } ]
  }, {
    "primaryId" : "PMID:10022914",
    "title" : "Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Lev S, etal., Mol Cell Biol. 1999 Mar;19(3):2278-88.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-03-11T12:26:50.000-05:00",
    "volume" : "19",
    "pages" : "2278-88",
    "abstract" : "The protein tyrosine kinase PYK2 has been implicated in signaling pathways activated by G-protein-coupled receptors, intracellular calcium, and stress signals. Here we describe the molecular cloning and characterization of a novel family of PYK2-binding proteins designated Nirs (PYK2 N-terminal domain-interacting receptors). The three Nir proteins (Nir1, Nir2, and Nir3) bind to the amino-terminal domain of PYK2 via a conserved sequence motif located in the carboxy terminus. The primary structures of Nirs reveal six putative transmembrane domains, a region homologous to phosphatidylinositol (PI) transfer protein, and an acidic domain. The Nir proteins are the human homologues of the Drosophila retinal degeneration B protein (rdgB), a protein implicated in the visual transduction pathway in flies. We demonstrate that Nirs are calcium-binding proteins that exhibit PI transfer activity in vivo. Activation of PYK2 by agents that elevate intracellular calcium or by phorbol ester induce tyrosine phosphorylation of Nirs. Moreover, PYK2 and Nirs exhibit similar expression patterns in several regions of the brain and retina. In addition, PYK2-Nir complexes are detected in lysates prepared from cultured cells or from brain tissues. Finally, the Nir1-encoding gene is located at human chromosome 17p13.1, in proximity to a locus responsible for several human retinal diseases. We propose that the Nir and rdgB proteins represent a new family of evolutionarily conserved PYK2-binding proteins that play a role in the control of calcium and phosphoinositide metabolism downstream of G-protein-coupled receptors.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Lev",
      "authorRank" : 1,
      "name" : "Lev S",
      "referenceId" : "RGD:A88676"
    }, {
      "firstName" : "J",
      "lastName" : "Hernandez",
      "authorRank" : 2,
      "name" : "Hernandez J",
      "referenceId" : "RGD:A9570"
    }, {
      "firstName" : "R",
      "lastName" : "Martinez",
      "authorRank" : 3,
      "name" : "Martinez R",
      "referenceId" : "RGD:A9803"
    }, {
      "firstName" : "A",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen A",
      "referenceId" : "RGD:A10458"
    }, {
      "firstName" : "G",
      "lastName" : "Plowman",
      "authorRank" : 5,
      "name" : "Plowman G",
      "referenceId" : "RGD:A33499"
    }, {
      "firstName" : "J",
      "lastName" : "Schlessinger",
      "authorRank" : 6,
      "name" : "Schlessinger J",
      "referenceId" : "RGD:A9805"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2304238"
    } ]
  }, {
    "primaryId" : "PMID:10023073",
    "title" : "The human genome has only one functional hsp47 gene (CBP2) and a pseudogene (pshsp47).",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Nagai N, etal., Gene 1999 Feb 18;227(2):241-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-26T14:30:27.000-06:00",
    "volume" : "227",
    "pages" : "241-8",
    "abstract" : "Among all the species investigated to date, only in humans is hsp47 reported to exist as two separate genes. Here we examined whether hsp47 forms a gene family, and if so, how many genes constitute the family. Cloning and sequencing of human hsp47 cDNA revealed that only one gene, identical to CBP2, was transcribed. No transcript corresponding to colligin, which was reported to be a human homologue of hsp47, was found. Genomic southern hybridization using the exon III fragment of mouse hsp47 as a probe, however, showed two bands for several restriction enzyme digests. We cloned and sequenced the gene corresponding to the extra band and found that a pseudogene (pshsp47) existed in the human genome. We have mapped this pseudogene to chromosome 9p12-p13 by fluorescent in situ hybridization (FISH) using a 3.5kb genomic fragment containing the entire pshsp47 sequence as a probe. These results suggested that functional hsp47 exists as CBP2, not as colligin, and a highly conserved pseudogene is present in the human genome.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Nagai",
      "authorRank" : 1,
      "name" : "Nagai N",
      "referenceId" : "RGD:A39630"
    }, {
      "firstName" : "Y",
      "lastName" : "Tetuya",
      "authorRank" : 2,
      "name" : "Tetuya Y",
      "referenceId" : "RGD:A39631"
    }, {
      "firstName" : "N",
      "lastName" : "Hosokawa",
      "authorRank" : 3,
      "name" : "Hosokawa N",
      "referenceId" : "RGD:A39632"
    }, {
      "firstName" : "K",
      "lastName" : "Nagata",
      "authorRank" : 4,
      "name" : "Nagata K",
      "referenceId" : "RGD:A5190"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:737815"
    } ]
  }, {
    "primaryId" : "PMID:10023637",
    "title" : "Beneficial effects of calcium channel blockade on acute glomerular hemodynamic changes induced by cyclosporine.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Fassi A, etal., Am J Kidney Dis. 1999 Feb;33(2):267-75. doi: 10.1016/s0272-6386(99)70299-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-04-02T15:42:27.000-05:00",
    "volume" : "33",
    "pages" : "267-75",
    "abstract" : "Experimental and human studies have documented that cyclosporine (CsA) acutely reduces glomerular filtration rate (GFR). It has been reported that this effect can be partially prevented by calcium (Ca) channel blockade; however, the mechanisms by which this combination exerts its beneficial effects are unknown. We evaluated glomerular ultrafiltration determinants during acute CsA administration in the rat. First, we determined that maximal whole-kidney functional changes occur between 120 and 150 minutes after CsA administration and confirmed that pretreatment of MWF rats with the Ca channel blocker lacidipine effectively prevents a reduction in GFR. Micropuncture measurements in CsA-treated animals showed that a reduction in GFR (0.49 +/- 0.24 v 0.88 +/- 0.26 mL/min; P < 0.05; CsA-treated v untreated rats) is associated with a significant increase in glomerular capillary pressure (Pgc; 63.1 +/- 2.1 v 52.8 +/- 2.8 mm Hg; P < 0.01) and efferent arteriolar resistance, whereas single-nephron (SN) GFR and ultrafiltration coefficient (Kf) are both importantly reduced (34.0 +/- 11.7 v 68.9 +/- 23.8 nL/min; P < 0.05 and 1.04 +/- 0.33 v 4.40 +/- 2.36 nL/min/mm Hg; P < 0.01, respectively). Lacidipine partially prevented SNGFR (43.1 +/- 14.3 nL/min) and Kf decline (2.08 +/- 1.10 nl/min/mm Hg) despite the presence of elevated Pgc. This study further documents that Ca channel blockade has favorable effects on CsA-induced acute renal dysfunction. The mechanism of protection includes the prevention of glomerular hemodynamic changes induced by CsA, mainly GFR decline and reduction in glomerular Kf.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Fassi",
      "authorRank" : 1,
      "name" : "Fassi A",
      "referenceId" : "RGD:A480896"
    }, {
      "firstName" : "F",
      "lastName" : "Sangalli",
      "authorRank" : 2,
      "name" : "Sangalli F",
      "referenceId" : "RGD:A123851"
    }, {
      "firstName" : "F",
      "lastName" : "Colombi",
      "authorRank" : 3,
      "name" : "Colombi F",
      "referenceId" : "RGD:A480887"
    }, {
      "firstName" : "N",
      "lastName" : "Perico",
      "authorRank" : 4,
      "name" : "Perico N",
      "referenceId" : "RGD:A110397"
    }, {
      "firstName" : "G",
      "lastName" : "Remuzzi",
      "authorRank" : 5,
      "name" : "Remuzzi G",
      "referenceId" : "RGD:A27943"
    }, {
      "firstName" : "A",
      "lastName" : "Remuzzi",
      "authorRank" : 6,
      "name" : "Remuzzi A",
      "referenceId" : "RGD:A123856"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:25314253"
    } ]
  }, {
    "primaryId" : "PMID:10023681",
    "title" : "Increased expression of fibroblast growth factor 8 in human breast cancer.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Marsh SK, etal., Oncogene. 1999 Jan 28;18(4):1053-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-01-29T15:45:39.000-06:00",
    "volume" : "18",
    "pages" : "1053-60",
    "abstract" : "Fibroblast growth factor 8 (FGF8) is an important developmental protein which is oncogenic and able to cooperate with wnt-1 to produce mouse mammary carcinoma. The level of expression of FGF8 mRNA was measured in 68 breast cancers and 24 non-malignant breast tissues. Elevated levels of FGF8 mRNA were found in malignant compared to non-malignant breast tissues with significantly more malignant tissues expressing FGF8 (P=0.019) at significantly higher levels (P=0.031). In situ hybridization of breast cancer tissues and analysis of purified populations of normal epithelial cells and breast cancer cell lines showed that malignant epithelial cells expressed FGF8 mRNA at high levels compared to non-malignant epithelial and myoepithelial cells and fibroblasts. Although two of the receptors which FGF8 binds to (FGFR2-IIIc, FGFR3-IIIc) are not expressed in breast cancer cells, an autocrine activation loop is possible since expression of fibroblast growth factor receptor (FGFR) 4 and FGFR1 are retained in malignant epithelial cells. This is the first member of the FGF family to have increased expression in breast cancer and a potential autocrine role in its progression.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SK",
      "lastName" : "Marsh",
      "authorRank" : 1,
      "name" : "Marsh SK",
      "referenceId" : "RGD:A91007"
    }, {
      "firstName" : "GS",
      "lastName" : "Bansal",
      "authorRank" : 2,
      "name" : "Bansal GS",
      "referenceId" : "RGD:A91008"
    }, {
      "firstName" : "C",
      "lastName" : "Zammit",
      "authorRank" : 3,
      "name" : "Zammit C",
      "referenceId" : "RGD:A91009"
    }, {
      "firstName" : "R",
      "lastName" : "Barnard",
      "authorRank" : 4,
      "name" : "Barnard R",
      "referenceId" : "RGD:A9044"
    }, {
      "firstName" : "R",
      "lastName" : "Coope",
      "authorRank" : 5,
      "name" : "Coope R",
      "referenceId" : "RGD:A91010"
    }, {
      "firstName" : "D",
      "lastName" : "Roberts-Clarke",
      "authorRank" : 6,
      "name" : "Roberts-Clarke D",
      "referenceId" : "RGD:A91011"
    }, {
      "firstName" : "JJ",
      "lastName" : "Gomm",
      "authorRank" : 7,
      "name" : "Gomm JJ",
      "referenceId" : "RGD:A91012"
    }, {
      "firstName" : "RC",
      "lastName" : "Coombes",
      "authorRank" : 8,
      "name" : "Coombes RC",
      "referenceId" : "RGD:A91013"
    }, {
      "firstName" : "CL",
      "lastName" : "Johnston",
      "authorRank" : 9,
      "name" : "Johnston CL",
      "referenceId" : "RGD:A91014"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289344"
    } ]
  }, {
    "primaryId" : "PMID:10023766",
    "title" : "Prolonged eosinophil accumulation in allergic lung interstitium of ICAM-2 deficient mice results in extended hyperresponsiveness.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Gerwin N, etal., Immunity 1999 Jan;10(1):9-19.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-06T11:15:35.000-05:00",
    "volume" : "10",
    "pages" : "9-19",
    "abstract" : "ICAM-2-deficient mice exhibit prolonged accumulation of eosinophils in lung interstitium concomitant with a delayed increase in eosinophil numbers in the airway lumen during the development of allergic lung inflammation. The ICAM-2-dependent increased and prolonged accumulation of eosinophils in lung interstitium results in prolonged, heightened airway hyperresponsiveness. These findings reveal an essential role for ICAM-2 in the development of the inflammatory and respiratory components of allergic lung disease. This phenotype is caused by the lack of ICAM-2 expression on non-hematopoietic cells. ICAM-2 deficiency on endothelial cells causes reduced eosinophil transmigration in vitro. ICAM-2 is not essential for lymphocyte homing or the development of leukocytes, with the exception of megakaryocyte progenitors, which are significantly reduced.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Gerwin",
      "authorRank" : 1,
      "name" : "Gerwin N",
      "referenceId" : "RGD:A55621"
    }, {
      "firstName" : "JA",
      "lastName" : "Gonzalo",
      "authorRank" : 2,
      "name" : "Gonzalo JA",
      "referenceId" : "RGD:A55622"
    }, {
      "firstName" : "C",
      "lastName" : "Lloyd",
      "authorRank" : 3,
      "name" : "Lloyd C",
      "referenceId" : "RGD:A55623"
    }, {
      "firstName" : "AJ",
      "lastName" : "Coyle",
      "authorRank" : 4,
      "name" : "Coyle AJ",
      "referenceId" : "RGD:A55624"
    }, {
      "firstName" : "Y",
      "lastName" : "Reiss",
      "authorRank" : 5,
      "name" : "Reiss Y",
      "referenceId" : "RGD:A55625"
    }, {
      "firstName" : "N",
      "lastName" : "Banu",
      "authorRank" : 6,
      "name" : "Banu N",
      "referenceId" : "RGD:A55626"
    }, {
      "firstName" : "B",
      "lastName" : "Wang",
      "authorRank" : 7,
      "name" : "Wang B",
      "referenceId" : "RGD:A13107"
    }, {
      "firstName" : "H",
      "lastName" : "Xu",
      "authorRank" : 8,
      "name" : "Xu H",
      "referenceId" : "RGD:A14579"
    }, {
      "firstName" : "H",
      "lastName" : "Avraham",
      "authorRank" : 9,
      "name" : "Avraham H",
      "referenceId" : "RGD:A33903"
    }, {
      "firstName" : "B",
      "lastName" : "Engelhardt",
      "authorRank" : 10,
      "name" : "Engelhardt B",
      "referenceId" : "RGD:A55627"
    }, {
      "firstName" : "TA",
      "lastName" : "Springer",
      "authorRank" : 11,
      "name" : "Springer TA",
      "referenceId" : "RGD:A55628"
    }, {
      "firstName" : "JC",
      "lastName" : "Gutierrez-Ramos",
      "authorRank" : 12,
      "name" : "Gutierrez-Ramos JC",
      "referenceId" : "RGD:A55629"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549619"
    } ]
  }, {
    "primaryId" : "PMID:10023812",
    "title" : "Differential distribution of ionotropic glutamate receptor subunits in the rat olfactory bulb.",
    "datePublished" : "1999-03-08T00:00:00.000-06:00",
    "citation" : "Montague AA and Greer CA, J Comp Neurol. 1999 Mar 8;405(2):233-46. doi: 10.1002/(sici)1096-9861(19990308)405:2<233::aid-cne7>3.0.co;2-a.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-04-20T06:09:10.000-05:00",
    "volume" : "405",
    "pages" : "233-46",
    "abstract" : "The subcellular localization of ionotropic glutamate receptor (GluR) subunits was examined with light and electron microscopy in the rat olfactory bulb by using antibodies to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunits: GluR1, GluR2/3, and GluR4; and kainate (KA) receptor subunits: GluR5/6/7. Immunoreactivity to GluR1 was heavy in the glomerular layer, moderate in the external plexiform layer, and localized to periglomerular somata and dendrites, short axon somata and dendrites, mitral cell somata, and mitral/tufted dendrites. GluR2/3 immunoreactivity was heavy in the external plexiform and glomerular layers and localized to periglomerular somata and dendrites, mitral cell somata, mitral/tufted dendrites, granule cell somata, and olfactory nerve-associated glia. GluR4 immunoreactivity showed heavy staining in the external plexiform and olfactory nerve layers with localization to mitral cells, mitral/tufted dendritic processes, and olfactory nerve glial processes. GluR5/6/7 immunoreactivity was heavy in the external plexiform layer, moderate in the olfactory nerve and glomerular layers, and localized to granule cells, mitral cells, and mitral/tufted dendritic processes. Ultrastructural immunolabeling for all antibodies examined showed immunoreactivity in the postsynaptic membrane and densities, adjacent dendritic cytoplasm, and somatic cytoplasm. These data demonstrate a highly specific laminar, cellular, and subcellular distribution of ionotropic GluR subunits within the primary afferent and local synaptic circuits of the olfactory bulb. The results are consistent with the notion that the different roles subserved by glutamate in the olfactory bulb are actuated, in part, by a differential distribution of GluR subunits.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A A",
      "lastName" : "Montague",
      "authorRank" : 1,
      "name" : "Montague AA",
      "referenceId" : "RGD:A540993"
    }, {
      "firstName" : "C A",
      "lastName" : "Greer",
      "authorRank" : 2,
      "name" : "Greer CA",
      "referenceId" : "RGD:A540994"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:405650314"
    } ]
  }, {
    "primaryId" : "PMID:10023856",
    "title" : "Identification of arthritogenic adjuvants of self and foreign origin.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Lorentzen JC Scand J Immunol 1999 Jan;49(1):45-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T10:07:31.000-05:00",
    "volume" : "49",
    "pages" : "45-50",
    "abstract" : "The lack of defined triggers for human inflammatory joint diseases warrants efforts to identify candidate molecules. For this task, it may be an important lead that nonspecific activation of the immune system can precipitate arthritis in rats. Consequently, arthritis-prone rat strains were used to search for disease-triggering factors among molecules which initially induce innate defence reactions rather than specific immune responses. A variety of immunological adjuvants were investigated by intradermal injection into DA and LEW.1AV1 rats and monitoring of clinical signs for 30 days. Several arthritogenic cell-wall structures from yeast and bacteria were identified, such as beta-glucan, lipopolysaccharide and trehalosedimycolate. The test procedures also revealed arthritogens of chemical origin, such as dioctadecyldiammoniumbromide (DDA = C38H80NBr) and heptadecane (C17H36). Furthermore, it allowed the precise definition of arthritogenic determinants of lipids, since C16H34 induced arthritis, whereas the closely related linear hydrocarbons C16H32, C16H33Br and C15H32 did not. The observed pathogenicity of organic lipids raised the question of whether endogenous lipids can also precipitate arthritis. Indeed, this was true for the cholesterol precursor squalene (C30H50). In conclusion, this article describes the rational use of arthritis-prone rat strains to identify arthritogenic factors of both foreign and self origin. Although structurally unrelated, the pathogenic molecules defined here share the feature of being nonspecific triggers of the immune system. This consolidates a general principle for the induction of adjuvant arthritis which may provide clues to the aetiology of human arthritides, including rheumatoid arthritis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JC",
      "lastName" : "Lorentzen",
      "authorRank" : 1,
      "name" : "Lorentzen JC",
      "referenceId" : "RGD:A122872"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:737660"
    } ]
  }, {
    "primaryId" : "PMID:10024077",
    "title" : "Analysis of trinucleotide-repeat combination polymorphism at the rad gene in patients with type 2 diabetes mellitus.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Yuan X, etal., Metabolism. 1999 Feb;48(2):173-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-07-31T09:25:12.000-05:00",
    "volume" : "48",
    "pages" : "173-5",
    "abstract" : "A combined (GTT)n (ATT)n trinucleotide-repeat polymorphism designated as RAD1 has been identified at intron 2 of the rad gene on chromosome 16q. An association between the total length of the RAD1 locus and type 2 diabetes has been shown in white American subjects, but not in Finns. We genotyped 115 Japanese patients with type 2 diabetes and 114 nondiabetic control subjects at the RAD1 locus by the direct sequencing method, and found 16 RAD1 alleles composed of various combinations of GTTs and ATTs. Allele 14 consisting of four GTTs and seven ATTs accounted for the majority in both control subjects and diabetic patients, suggesting that RAD1 polymorphism is not a major genetic component for susceptibility to common forms of diabetes in the Japanese. There was no significant association between total repeat length and diabetes. However, the frequency of minor alleles containing five GTTs or three GTTs was significantly higher in diabetic patients versus nondiabetic subjects (4.8% v 0.9%, P = .012). Thus, genetic variability at the rad gene in linkage disequilibrium with RAD1 could be associated with a predisposition to type 2 diabetes in the Japanese population.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Yuan",
      "authorRank" : 1,
      "name" : "Yuan X",
      "referenceId" : "RGD:A9199"
    }, {
      "firstName" : "K",
      "lastName" : "Yamada",
      "authorRank" : 2,
      "name" : "Yamada K",
      "referenceId" : "RGD:A11181"
    }, {
      "firstName" : "S",
      "lastName" : "Ishiyama-Shigemoto",
      "authorRank" : 3,
      "name" : "Ishiyama-Shigemoto S",
      "referenceId" : "RGD:A110170"
    }, {
      "firstName" : "W",
      "lastName" : "Koyama",
      "authorRank" : 4,
      "name" : "Koyama W",
      "referenceId" : "RGD:A110171"
    }, {
      "firstName" : "K",
      "lastName" : "Nonaka",
      "authorRank" : 5,
      "name" : "Nonaka K",
      "referenceId" : "RGD:A110172"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311705"
    } ]
  }, {
    "primaryId" : "PMID:10024240",
    "title" : "A molecular pathway revealing a genetic basis for human cardiac and craniofacial defects.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Yamagishi H, etal., Science. 1999 Feb 19;283(5405):1158-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-25T16:42:08.000-05:00",
    "volume" : "283",
    "pages" : "1158-61",
    "abstract" : "Microdeletions of chromosome 22q11 are the most common genetic defects associated with cardiac and craniofacial anomalies in humans. A screen for mouse genes dependent on dHAND, a transcription factor implicated in neural crest development, identified Ufd1, which maps to human 22q11 and encodes a protein involved in degradation of ubiquitinated proteins. Mouse Ufd1 was specifically expressed in most tissues affected in patients with 22q11 deletion syndrome. The human UFD1L gene was deleted in all 182 patients studied with 22q11 deletion, and a smaller deletion of approximately 20 kilobases that removed exons 1 to 3 of UFD1L was found in one individual with features typical of 22q11 deletion syndrome. These data suggest that UFD1L haploinsufficiency contributes to the congenital heart and craniofacial defects seen in 22q11 deletion.",
    "issueName" : "5405",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Yamagishi",
      "authorRank" : 1,
      "name" : "Yamagishi H",
      "referenceId" : "RGD:A58730"
    }, {
      "firstName" : "V",
      "lastName" : "Garg",
      "authorRank" : 2,
      "name" : "Garg V",
      "referenceId" : "RGD:A62337"
    }, {
      "firstName" : "R",
      "lastName" : "Matsuoka",
      "authorRank" : 3,
      "name" : "Matsuoka R",
      "referenceId" : "RGD:A62346"
    }, {
      "firstName" : "T",
      "lastName" : "Thomas",
      "authorRank" : 4,
      "name" : "Thomas T",
      "referenceId" : "RGD:A34209"
    }, {
      "firstName" : "D",
      "lastName" : "Srivastava",
      "authorRank" : 5,
      "name" : "Srivastava D",
      "referenceId" : "RGD:A58733"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580803"
    } ]
  }, {
    "primaryId" : "PMID:10024302",
    "title" : "Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Neyroud N, etal., Circ Res. 1999 Feb 19;84(3):290-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:40:00.000-05:00",
    "volume" : "84",
    "pages" : "290-7",
    "abstract" : "The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of  the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval,  ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the  C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Neyroud",
      "authorRank" : 1,
      "name" : "Neyroud N",
      "referenceId" : "RGD:A62822"
    }, {
      "firstName" : "P",
      "lastName" : "Richard",
      "authorRank" : 2,
      "name" : "Richard P",
      "referenceId" : "RGD:A53382"
    }, {
      "firstName" : "N",
      "lastName" : "Vignier",
      "authorRank" : 3,
      "name" : "Vignier",
      "referenceId" : "RGD:A278838"
    }, {
      "firstName" : "C",
      "lastName" : "Donger",
      "authorRank" : 4,
      "name" : "Donger",
      "referenceId" : "RGD:A260376"
    }, {
      "firstName" : "I",
      "lastName" : "Denjoy",
      "authorRank" : 5,
      "name" : "Denjoy",
      "referenceId" : "RGD:A172939"
    }, {
      "firstName" : "L",
      "lastName" : "Demay",
      "authorRank" : 6,
      "name" : "Demay L",
      "referenceId" : "RGD:A62864"
    }, {
      "firstName" : "M",
      "lastName" : "Shkolnikova",
      "authorRank" : 7,
      "name" : "Shkolnikova",
      "referenceId" : "RGD:A279429"
    }, {
      "firstName" : "R",
      "lastName" : "Pesce",
      "authorRank" : 8,
      "name" : "Pesce",
      "referenceId" : "RGD:A279430"
    }, {
      "firstName" : "P",
      "lastName" : "Chevalier",
      "authorRank" : 9,
      "name" : "Chevalier",
      "referenceId" : "RGD:A250173"
    }, {
      "firstName" : "B",
      "lastName" : "Hainque",
      "authorRank" : 10,
      "name" : "Hainque B",
      "referenceId" : "RGD:A61722"
    }, {
      "firstName" : "P",
      "lastName" : "Coumel",
      "authorRank" : 11,
      "name" : "Coumel",
      "referenceId" : "RGD:A253160"
    }, {
      "firstName" : "K",
      "lastName" : "Schwartz",
      "authorRank" : 12,
      "name" : "Schwartz K",
      "referenceId" : "RGD:A7050"
    }, {
      "firstName" : "P",
      "lastName" : "Guicheney",
      "authorRank" : 13,
      "name" : "Guicheney P",
      "referenceId" : "RGD:A37505"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071415"
    } ]
  }, {
    "primaryId" : "PMID:10024308",
    "title" : "An alternative transcript of the rat renin gene can result in a truncated prorenin that is transported into adrenal mitochondria.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Clausmeyer S, etal., Circ Res 1999 Feb 19;84(3):337-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:42.000-05:00",
    "volume" : "84",
    "pages" : "337-44",
    "abstract" : "Characterization of the local renin-angiotensin system in the rat adrenal zona glomerulosa indicated a dual targeting of renin both to the secretory pathway and mitochondria. To investigate the transport of renin into mitochondria, we constructed a series of amino-terminal deletion variants of preprorenin. One of these variants, lacking the complete signal sequence for the endoplasmic reticulum and 10 amino acids of the profragment, was transported efficiently into isolated mitochondria. The transport was further shown to be dependent on mitochondrial membrane potential and ATP synthesis. Analysis of adrenal RNA revealed the existence of 2 renin transcripts. While one of the transcripts corresponds to the known full-length transcript, the other one lacks exon 1; instead, exon 2 is preceded by a domain of 80 nucleotides originating from intron 1. This domain, as well as the following region of intron 1 being excised, shows all essential sequence elements defining an additional, so-far-unknown exon. The second mRNA possibly derives from an additional transcription start in intron 1 and an alternative splicing process. Translation of this mRNA could result in a truncated prorenin representing a cytosolic form of renin, which is required for transport into mitochondria. This truncated prorenin corresponds exactly to the deletion variant being imported into mitochondria in vitro.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Clausmeyer",
      "authorRank" : 1,
      "name" : "Clausmeyer S",
      "referenceId" : "RGD:A10669"
    }, {
      "firstName" : "R",
      "lastName" : "Sturzebecher",
      "authorRank" : 2,
      "name" : "Sturzebecher R",
      "referenceId" : "RGD:A27172"
    }, {
      "firstName" : "J",
      "lastName" : "Peters",
      "authorRank" : 3,
      "name" : "Peters J",
      "referenceId" : "RGD:A10667"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727264"
    } ]
  }, {
    "primaryId" : "PMID:10024327",
    "title" : "Genetic and gender influences on sensitivity to focal cerebral ischemia in the stroke-prone spontaneously hypertensive rat.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Carswell HV, etal., Hypertension. 1999 Feb;33(2):681-5. doi: 10.1161/01.hyp.33.2.681.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-01-27T08:42:20.000-06:00",
    "volume" : "33",
    "pages" : "681-5",
    "abstract" : "We have investigated genetic transmission of increased sensitivity to focal cerebral ischemia and the influence of gender in the stroke-prone spontaneously hypertensive rat (SHRSP). Halothane-anesthetized, 3- to 5-month-old male and female Wistar-Kyoto rats (WKY), SHRSP, and the first filial generation rats (F1 crosses 1 and 2) underwent distal (2 mm) permanent middle cerebral artery occlusion (MCAO) by electrocoagulation. Infarct volume was measured by using hematoxylin-eosin-stained sections and image analysis 24 hours after ischemia and expressed as a percentage of the volume of the ipsilateral hemisphere. Infarct volume in males and females grouped together were significantly larger in SHRSP, F1 cross 1 (SHRSP father), and F1 cross 2 (WKY father), at 36.6+/-2.3% (mean+/-SEM, P<0.001, n=15), 25.4+/-2.4% (P<0.01, n=14), and 33. 9+/-1.6% (P<0.001, n=18), respectively, compared with WKY (14+/-2%, n=17). Male F1 cross 1 (18.9+/-2.4%, n=6) developed significantly smaller infarcts than male F1 cross 2 (32.8+/-2%, n=8, P<0.005). Females, which underwent ischemia during metestrus, developed larger infarcts than respective males. A group of females in which the cycle was not controlled for developed significantly smaller infarcts than females in metestrus. Thus, the increased sensitivity to MCAO in SHRSP is retained in both F1 cross 1 and cross 2 hybrids, suggesting a dominant or codominant trait; response to cerebral ischemia appears to be affected by gender and stage in the estrous cycle. In addition, the male progenitor of the cross (ie, SHRSP versus WKY) influences stroke sensitivity in male F1 cohorts.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H V",
      "lastName" : "Carswell",
      "authorRank" : 1,
      "name" : "Carswell HV",
      "referenceId" : "RGD:A478774"
    }, {
      "firstName" : "N H",
      "lastName" : "Anderson",
      "authorRank" : 2,
      "name" : "Anderson NH",
      "referenceId" : "RGD:A478775"
    }, {
      "firstName" : "J S",
      "lastName" : "Clark",
      "authorRank" : 3,
      "name" : "Clark JS",
      "referenceId" : "RGD:A478776"
    }, {
      "firstName" : "D",
      "lastName" : "Graham",
      "authorRank" : 4,
      "name" : "Graham D",
      "referenceId" : "RGD:A6414"
    }, {
      "firstName" : "B",
      "lastName" : "Jeffs",
      "authorRank" : 5,
      "name" : "Jeffs B",
      "referenceId" : "RGD:A486"
    }, {
      "firstName" : "A F",
      "lastName" : "Dominiczak",
      "authorRank" : 6,
      "name" : "Dominiczak AF",
      "referenceId" : "RGD:A478777"
    }, {
      "firstName" : "I M",
      "lastName" : "Macrae",
      "authorRank" : 7,
      "name" : "Macrae IM",
      "referenceId" : "RGD:A478778"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:18936990"
    } ]
  }, {
    "primaryId" : "PMID:10024332",
    "title" : "Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Davies E, etal., Hypertension. 1999 Feb;33(2):703-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-10T12:37:40.000-06:00",
    "volume" : "33",
    "pages" : "703-7",
    "abstract" : "Significant correlation of body sodium and potassium with blood pressure (BP) may suggest a role for aldosterone in essential hypertension. In patients with this disease, the ratio of plasma renin to plasma aldosterone may be lower than in control subjects and plasma aldosterone levels may be more sensitive to angiotensin II (Ang II) infusion. Because essential hypertension is partly genetic, it is possible that altered control of aldosterone synthase gene expression or translation may be responsible. We compared the frequency of 2 linked polymorphisms, one in the steroidogenic factor-1 (SF-1) binding site and the other an intronic conversion (IC), in groups of hypertensive and normotensive subjects. In a larger population, the relationship of aldosterone excretion rate to these polymorphisms was also evaluated. In 138 hypertensive subjects, there was a highly significant excess of TT homozygosity (SF-1) over CC homozygosity compared with a group of individually matched normotensive control subjects. The T allele was significantly more frequent than the C allele in the hypertensive group compared with the control group. Similarly, there was a highly significant relative excess of the conversion allele over the \"wild-type\" allele and of conversion homozygosity over wild-type homozygosity in the hypertensive group compared with the control group. In 486 subjects sampled from the North Glasgow Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) population, SF-1 and IC genotypes were compared with tetrahydroaldosterone excretion rate. Subjects with the SF-1 genotypes TT or TC had significantly higher excretion rates than those with the CC genotype. The T allele was associated with higher excretion rates than the C allele. However, no significant differences were found in excretion rate between subjects of different IC genotype. Urinary aldosterone excretion rate may be a useful intermediate phenotype linking these genotypes to raised BP. However, no causal relationship has yet been established, and it is possible that the polymorphisms may be in linkage with other causative mutations.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Davies",
      "authorRank" : 1,
      "name" : "Davies E",
      "referenceId" : "RGD:A58460"
    }, {
      "firstName" : "CD",
      "lastName" : "Holloway",
      "authorRank" : 2,
      "name" : "Holloway CD",
      "referenceId" : "RGD:A133288"
    }, {
      "firstName" : "MC",
      "lastName" : "Ingram",
      "authorRank" : 3,
      "name" : "Ingram MC",
      "referenceId" : "RGD:A133289"
    }, {
      "firstName" : "GC",
      "lastName" : "Inglis",
      "authorRank" : 4,
      "name" : "Inglis GC",
      "referenceId" : "RGD:A133290"
    }, {
      "firstName" : "EC",
      "lastName" : "Friel",
      "authorRank" : 5,
      "name" : "Friel EC",
      "referenceId" : "RGD:A133291"
    }, {
      "firstName" : "C",
      "lastName" : "Morrison",
      "authorRank" : 6,
      "name" : "Morrison C",
      "referenceId" : "RGD:A133292"
    }, {
      "firstName" : "NH",
      "lastName" : "Anderson",
      "authorRank" : 7,
      "name" : "Anderson NH",
      "referenceId" : "RGD:A133293"
    }, {
      "firstName" : "R",
      "lastName" : "Fraser",
      "authorRank" : 8,
      "name" : "Fraser R",
      "referenceId" : "RGD:A58457"
    }, {
      "firstName" : "JM",
      "lastName" : "Connell",
      "authorRank" : 9,
      "name" : "Connell JM",
      "referenceId" : "RGD:A11112"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4891152"
    } ]
  }, {
    "primaryId" : "PMID:10024361",
    "title" : "Fas/Apo -1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Cheema ZF, etal., J Neurosci. 1999 Mar 1;19(5):1754-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-26T10:35:58.000-05:00",
    "volume" : "19",
    "pages" : "1754-70",
    "abstract" : "The developing cerebral cortex undergoes a period of substantial cell death. The  present studies examine the role of the suicide receptor Fas/Apo[apoptosis]-1 in  cerebral cortical development. Fas mRNA and protein are transiently expressed in  subsets of cells within the developing rat cerebral cortex during the peak period of apoptosis. Fas-immunoreactive cells were localized in close proximity to Fas ligand (FasL)-expressing cells. The Fas-associated signaling protein receptor interacting protein (RIP) was expressed by some Fas-expressing cells, whereas Fas-associated death domain (FADD) was undetectable in the early postnatal cerebral cortex. FLICE-inhibitory protein (FLIP), an inhibitor of Fas activation, was also expressed in the postnatal cerebral cortex. Fas expression was more ubiquitous in embryonic cortical neuroblasts in dissociated culture compared to in situ within the developing brain, suggesting that the environmental milieu partly suppresses Fas expression at this developmental stage. Furthermore, FADD,  RIP, and FLIP were also expressed by subsets of dissociated cortical neuroblasts  in culture. Fas activation by ligand (FasL) or anti-Fas antibody induced caspase-dependent cell death in primary embryonic cortical neuroblast cultures. The activation of Fas was also accompanied by a rapid downregulation of Fas receptor expression, non-cell cycle-related incorporation of nucleic acids and nuclear translocation of the RelA/p65 subunit of the transcription factor NF-kappaB. Together, these data suggest that adult cortical cell number may be established, in part, by an active process of receptor-mediated cell suicide, initiated in situ by killer (FasL-expressing) cells and that Fas may have functions in addition to suicide in the developing brain.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ZF",
      "lastName" : "Cheema",
      "authorRank" : 1,
      "name" : "Cheema",
      "referenceId" : "RGD:A190591"
    }, {
      "firstName" : "SB",
      "lastName" : "Wade",
      "authorRank" : 2,
      "name" : "Wade",
      "referenceId" : "RGD:A190592"
    }, {
      "firstName" : "M",
      "lastName" : "Sata",
      "authorRank" : 3,
      "name" : "Sata M",
      "referenceId" : "RGD:A70317"
    }, {
      "firstName" : "K",
      "lastName" : "Walsh",
      "authorRank" : 4,
      "name" : "Walsh K",
      "referenceId" : "RGD:A7573"
    }, {
      "firstName" : "F",
      "lastName" : "Sohrabji",
      "authorRank" : 5,
      "name" : "Sohrabji F",
      "referenceId" : "RGD:A132231"
    }, {
      "firstName" : "RC",
      "lastName" : "Miranda",
      "authorRank" : 6,
      "name" : "Miranda",
      "referenceId" : "RGD:A190593"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662883"
    } ]
  }, {
    "primaryId" : "PMID:10024431",
    "title" : "Screening for hereditary fructose intolerance mutations by reverse dot-blot.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Lau J and Tolan DR, Mol Cell Probes. 1999 Feb;13(1):35-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:24:33.000-05:00",
    "volume" : "13",
    "pages" : "35-40",
    "abstract" : "An assay is described which is useful for genetic screening of the two most prevalent mutations that cause hereditary fructose intolerance (HFI). Both mutations lie within exon 5 of the aldolase B gene. Amplification of exon 5 from  genomic DNA isolated from peripheral lymphocytes using biotinylated aldolase B-specific primers yields a biotin-tagged probe. This probe is hybridized to complementary poly(dT)-tailed allele specific oligonucleotides (ASOs) that are bound to a nylon membrane. The length of the ASOs, the amount bound to the membrane and the time of hybridization are optimized for discrimination of all four alleles under the same hybridization conditions. Detection of biotinylated amplified DNA is performed by creating an avidin-alkaline phosphatase complex and visualization by chemiluminescence. This assay can rapidly detect the two mutations, A149P and A174D, which cause >70% of HFI worldwide, and offers a rapid and sensitive assay that is much less invasive for the diagnosis of this often difficult to diagnose disorder.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Lau",
      "authorRank" : 1,
      "name" : "Lau",
      "referenceId" : "RGD:A243641"
    }, {
      "firstName" : "DR",
      "lastName" : "Tolan",
      "authorRank" : 2,
      "name" : "Tolan DR",
      "referenceId" : "RGD:A35830"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064065"
    } ]
  }, {
    "primaryId" : "PMID:10024460",
    "title" : "Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Gruen M and Gautel M, J Mol Biol. 1999 Feb 26;286(3):933-49.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:27:24.000-05:00",
    "volume" : "286",
    "pages" : "933-49",
    "abstract" : "The myosin filaments of striated muscle contain a family of enigmatic myosin-binding proteins (MyBP), MyBP-C and MyBP-H. These modular proteins of the  intracellular immunoglobulin superfamily contain unique domains near their N termini. The N-terminal domain of cardiac MyBP-C, the MyBP-C motif, contains additional phosphorylation sites and may regulate contraction in a phosphorylation dependent way. In contrast to the C terminus, which binds to the  light meromyosin portion of the myosin rod, the interactions of this domain are unknown. We demonstrate that fragments of MyBP-C containing the MyBP-C motif localise to the sarcomeric A-band in cardiomyocytes and isolated myofibrils, without affecting sarcomere structure. The binding site for the MyBP-C motif resides in the N-terminal 126 residues of the S2 segment of the myosin rod. In this region, several mutations in beta-myosin are associated with FHC; however, their molecular implications remained unclear. We show that two representative FHC mutations in beta-myosin S2, R870H and E924K, drastically reduce MyBP-C binding (Kd approximately 60 microM for R870H compared with a Kd of approximately 5 microM for the wild-type) down to undetectable levels (E924K). These mutations  do not affect the coiled-coil structure of myosin. We suggest that the regulatory function of MyBP-C is mediated by the interaction with S2, and that mutations in  beta-myosin S2 may act by altering the interactions with MyBP-C.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Gruen",
      "authorRank" : 1,
      "name" : "Gruen M",
      "referenceId" : "RGD:A153653"
    }, {
      "firstName" : "M",
      "lastName" : "Gautel",
      "authorRank" : 2,
      "name" : "Gautel",
      "referenceId" : "RGD:A257891"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066049"
    } ]
  }, {
    "primaryId" : "PMID:10024498",
    "title" : "Upstream region of rat serum albumin gene promoter contributes to promoter activity: presence of functional binding site for hepatocyte nuclear factor-3.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Hsiang CH, etal., Biochem J. 1999 Mar 1;338 ( Pt 2):241-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-08-21T13:20:39.000-05:00",
    "volume" : "338 ( Pt 2)",
    "pages" : "241-9",
    "abstract" : "Transcription of the serum albumin gene occurs almost exclusively in the liver and is controlled in part by a strong liver-specific promoter. The upstream region of the serum albumin gene promoter is highly conserved among species and is footprinted in vitro by a number of nuclear proteins. However, the role of the upstream promoter region in regulating transcription and the identity of the transcription factors that bind to this region have not been established. In the present study, deletion analysis of the rat serum albumin promoter in transiently transfected HepG2 cells demonstrated that elimination of the region between -207 and -153 bp caused a two-fold decrease in promoter activity (P<0.05). Additional analysis of the -207 to -124 bp promoter interval led to the identification of two potential binding sites for hepatocyte nuclear factor-3 (HNF-3) located at -168 to -157 bp (site X) and -145 to -134 bp (site Y). Electrophoretic mobility-shift assays performed with the HNF-3 X and Y sites demonstrated that both sites are capable of binding HNF-3alpha and HNF-3beta. Placement of a single copy of the HNF-3 X site upstream from a minimal promoter increased promoter activity by about four-fold in HepG2 cells, and the reporter construct containing this site could be transactivated if co-transfected with an HNF-3 expression construct. Furthermore, inactivation of the HNF-3 X site by site-directed mutagenesis within the context of the -261 bp albumin promoter construct resulted in a 40% decrease in transcription (P<0.05). These results indicate that the positive effect of the -207 to -153 bp promoter interval is attributable to the presence of the HNF-3 X site within this interval. Additional results obtained with transfected HepG2 cells suggest that the HNF-3 Y site plays a lesser role in activation of transcription than the X site.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CH",
      "lastName" : "Hsiang",
      "authorRank" : 1,
      "name" : "Hsiang CH",
      "referenceId" : "RGD:A86828"
    }, {
      "firstName" : "NW",
      "lastName" : "Marten",
      "authorRank" : 2,
      "name" : "Marten NW",
      "referenceId" : "RGD:A86829"
    }, {
      "firstName" : "DS",
      "lastName" : "Straus",
      "authorRank" : 3,
      "name" : "Straus DS",
      "referenceId" : "RGD:A86830"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1627570"
    } ]
  }, {
    "primaryId" : "PMID:10024688",
    "title" : "Elevation of urokinase-type plasminogen activator and its receptor densities as new predictors of disease progression and prognosis in men with prostate cancer.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Miyake H, etal., Int J Oncol. 1999 Mar;14(3):535-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-03-07T11:56:16.000-06:00",
    "volume" : "14",
    "pages" : "535-41",
    "abstract" : "We examined whether two newly defined parameters, the density of urokinase-type plasminogen activator (uPAD) and the density of its receptor (uPARD), which were  determined by dividing the serum levels of uPA and uPAR by the prostate volume, respectively, could be used as predictors of the progression and prognosis of prostate cancer (PC). Serum levels of uPA and uPAR in 40 healthy controls, 70 patients with benign prostatic hypertrophy (BPH) and 80 patients with PC were measured by a sandwich enzyme immunoassay, and prostate volume was measured by ultrasonography. The mean levels of uPAD and uPARD in patients with PC were significantly higher than those in healthy controls and patients with BPH. Furthermore, the uPAD and uPARD levels in PC patients with metastasis were significantly elevated compared with those in patients without metastasis. Among  patients who underwent radical prostatectomy, the levels of uPAD and uPARD in patients with pathologically organ-confined disease were significantly lower than in those with advanced disease. The overall survival rate of PC cancer patients with elevated levels of either uPAD or uPARD, or of both, was significantly lower than that of patients with normal levels of uPAD and uPARD. In addition, Cox's multivariate analysis revealed that the elevation of uPAD or uPARD level, or of both, was strongly associated with overall survival in PC patients. These findings suggest that the elevation of uPAD or uPARD, or of both, could be used as new predictors of progression and prognosis in patients with PC.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Miyake",
      "authorRank" : 1,
      "name" : "Miyake H",
      "referenceId" : "RGD:A81036"
    }, {
      "firstName" : "I",
      "lastName" : "Hara",
      "authorRank" : 2,
      "name" : "Hara I",
      "referenceId" : "RGD:A48626"
    }, {
      "firstName" : "K",
      "lastName" : "Yamanaka",
      "authorRank" : 3,
      "name" : "Yamanaka K",
      "referenceId" : "RGD:A95926"
    }, {
      "firstName" : "S",
      "lastName" : "Arakawa",
      "authorRank" : 4,
      "name" : "Arakawa S",
      "referenceId" : "RGD:A120257"
    }, {
      "firstName" : "S",
      "lastName" : "Kamidono",
      "authorRank" : 5,
      "name" : "Kamidono S",
      "referenceId" : "RGD:A120258"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7241264"
    } ]
  }, {
    "primaryId" : "PMID:10024874",
    "title" : "Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Nishimura H, etal., Mol Cell 1999 Jan;3(1):1-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T12:09:31.000-05:00",
    "volume" : "3",
    "pages" : "1-10",
    "abstract" : "Angiotensin type 2 receptor gene null mutant mice display congenital anomalies of the kidney and urinary tract (CAKUT). Various features of mouse CAKUT impressively mimic human CAKUT. Studies of the human type 2 receptor (AGTR2) gene in two independent cohorts found that a significant association exists between CAKUT and a nucleotide transition within the lariat branchpoint motif of intron 1, which perturbs AGTR2 mRNA splicing efficiency. AGTR2, therefore, has a significant ontogenic role for the kidney and urinary tract system. Studies revealed that the establishment of CAKUT is preceded by delayed apoptosis of undifferentiated mesenchymal cells surrounding the urinary tract during key ontogenic events, from the ureteral budding to the expansive growth of the kidney and ureter.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Nishimura",
      "authorRank" : 1,
      "name" : "Nishimura H",
      "referenceId" : "RGD:A23369"
    }, {
      "firstName" : "E",
      "lastName" : "Yerkes",
      "authorRank" : 2,
      "name" : "Yerkes E",
      "referenceId" : "RGD:A44380"
    }, {
      "firstName" : "K",
      "lastName" : "Hohenfellner",
      "authorRank" : 3,
      "name" : "Hohenfellner K",
      "referenceId" : "RGD:A44381"
    }, {
      "firstName" : "Y",
      "lastName" : "Miyazaki",
      "authorRank" : 4,
      "name" : "Miyazaki Y",
      "referenceId" : "RGD:A7510"
    }, {
      "firstName" : "J",
      "lastName" : "Ma",
      "authorRank" : 5,
      "name" : "Ma J",
      "referenceId" : "RGD:A33899"
    }, {
      "firstName" : "TE",
      "lastName" : "Hunley",
      "authorRank" : 6,
      "name" : "Hunley TE",
      "referenceId" : "RGD:A44382"
    }, {
      "firstName" : "H",
      "lastName" : "Yoshida",
      "authorRank" : 7,
      "name" : "Yoshida H",
      "referenceId" : "RGD:A24062"
    }, {
      "firstName" : "T",
      "lastName" : "Ichiki",
      "authorRank" : 8,
      "name" : "Ichiki T",
      "referenceId" : "RGD:A6331"
    }, {
      "firstName" : "D",
      "lastName" : "Threadgill",
      "authorRank" : 9,
      "name" : "Threadgill D",
      "referenceId" : "RGD:A44383"
    }, {
      "firstName" : "3RD",
      "lastName" : "Phillips JA",
      "authorRank" : 10,
      "name" : "Phillips JA 3RD",
      "referenceId" : "RGD:A25346"
    }, {
      "firstName" : "BM",
      "lastName" : "Hogan",
      "authorRank" : 11,
      "name" : "Hogan BM",
      "referenceId" : "RGD:A44384"
    }, {
      "firstName" : "A",
      "lastName" : "Fogo",
      "authorRank" : 12,
      "name" : "Fogo A",
      "referenceId" : "RGD:A39456"
    }, {
      "firstName" : "3RD",
      "lastName" : "Brock JW",
      "authorRank" : 13,
      "name" : "Brock JW 3RD",
      "referenceId" : "RGD:A44385"
    }, {
      "firstName" : "T",
      "lastName" : "Inagami",
      "authorRank" : 14,
      "name" : "Inagami T",
      "referenceId" : "RGD:A118545"
    }, {
      "firstName" : "I",
      "lastName" : "Ichikawa",
      "authorRank" : 15,
      "name" : "Ichikawa I",
      "referenceId" : "RGD:A16561"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300275"
    } ]
  }, {
    "primaryId" : "PMID:10024875",
    "title" : "Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Dell'Angelica EC, etal., Mol Cell. 1999 Jan;3(1):11-21. doi: 10.1016/s1097-2765(00)80170-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:54:49.000-05:00",
    "volume" : "3",
    "pages" : "11-21",
    "abstract" : "Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defective lysosome-related organelles. Here, we report the identification of two HPS patients with mutations in the beta 3A subunit of the heterotetrameric AP-3 complex. The patients' fibroblasts exhibit drastically reduced levels of AP-3 due to enhanced degradation of mutant beta 3A. The AP-3 deficiency results in increased surface expression of the lysosomal membrane proteins CD63, lamp-1, and lamp-2, but not of nonlysosomal proteins. These differential effects are consistent with the preferential interaction of the AP-3 mu 3A subunit with tyrosine-based signals involved in lysosomal targeting. Our results suggest that AP-3 functions in protein sorting to lysosomes and provide an example of a human disease in which altered trafficking of integral membrane proteins is due to mutations in a component of the sorting machinery.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E C",
      "lastName" : "Dell'Angelica",
      "authorRank" : 1,
      "name" : "Dell'Angelica EC",
      "referenceId" : "RGD:A597153"
    }, {
      "firstName" : "V",
      "lastName" : "Shotelersuk",
      "authorRank" : 2,
      "name" : "Shotelersuk V",
      "referenceId" : "RGD:A52454"
    }, {
      "firstName" : "R C",
      "lastName" : "Aguilar",
      "authorRank" : 3,
      "name" : "Aguilar RC",
      "referenceId" : "RGD:A597154"
    }, {
      "firstName" : "W A",
      "lastName" : "Gahl",
      "authorRank" : 4,
      "name" : "Gahl WA",
      "referenceId" : "RGD:A446164"
    }, {
      "firstName" : "J S",
      "lastName" : "Bonifacino",
      "authorRank" : 5,
      "name" : "Bonifacino JS",
      "referenceId" : "RGD:A597155"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118939"
    } ]
  }, {
    "primaryId" : "PMID:10024914",
    "title" : "Pyrin/marenostrin mutations in familial Mediterranean fever.",
    "datePublished" : "1998-04-01T00:00:00.000-06:00",
    "citation" : "Booth DR, etal., QJM. 1998 Sep;91(9):603-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:32:03.000-05:00",
    "volume" : "91",
    "pages" : "603-6",
    "abstract" : "Familial Mediterranean fever (FMF) is an inherited inflammatory disease that is frequently complicated by reactive systemic (AA) amyloidosis. It is principally recognized in certain Mediterranean populations, and the diagnosis depends on clinical features. Four mutations strongly linked to FMF have lately been identified in a gene encoding a novel protein that has been named pyrin or marenostrin. We studied 27 consecutive patients of varied ethnic origin, including an English man, who had classical, probable or possible FMF. Pyrin/marenostrin genotypes were determined, and AA amyloidosis was sought using  serum amyloid P component scintigraphy. Among the 23 patients with classical or probable FMF, 17 were homozygotes or compound heterozygotes for pyrin/marenostrin mutations, and in five, only single allele mutations were identified. Two new mutations, T6811 and delta M694, were discovered in addition to the four described previously. No mutations were identified in three of the four patients  with possible FMF. Nine patients had AA amyloidosis, but this association was not restricted to any particular genotype. Most patients with FMF have mutations in both pyrin/marenostrin alleles, and genotyping at this locus is a valuable diagnostic test. Unidentified second mutations are likely to occur in FMF patients who have apparently solitary mutations, and therefore genotype results must be interpreted in conjunction with the clinical picture.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DR",
      "lastName" : "Booth",
      "authorRank" : 1,
      "name" : "Booth DR",
      "referenceId" : "RGD:A52655"
    }, {
      "firstName" : "JD",
      "lastName" : "Gillmore",
      "authorRank" : 2,
      "name" : "Gillmore",
      "referenceId" : "RGD:A276433"
    }, {
      "firstName" : "SE",
      "lastName" : "Booth",
      "authorRank" : 3,
      "name" : "Booth",
      "referenceId" : "RGD:A276434"
    }, {
      "firstName" : "MB",
      "lastName" : "Pepys",
      "authorRank" : 4,
      "name" : "Pepys MB",
      "referenceId" : "RGD:A44455"
    }, {
      "firstName" : "PN",
      "lastName" : "Hawkins",
      "authorRank" : 5,
      "name" : "Hawkins PN",
      "referenceId" : "RGD:A44473"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070303"
    } ]
  }, {
    "primaryId" : "PMID:10025402",
    "title" : "Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Ostermeier C and Brunger AT, Cell. 1999 Feb 5;96(3):363-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-12-08T14:14:42.000-06:00",
    "volume" : "96",
    "pages" : "363-74",
    "abstract" : "The small G protein Rab3A plays an important role in the regulation of neurotransmitter release. The crystal structure of activated Rab3A/GTP/Mg2+ bound to the effector domain of rabphilin-3A was solved to 2.6 A resolution. Rabphilin-3A contacts Rab3A in two distinct areas. The first interface involves the Rab3A switch I and switch II regions, which are sensitive to the nucleotide-binding state of Rab3A. The second interface consists of a deep pocket in Rab3A that interacts with a SGAWFF structural element of rabphilin-3A. Sequence and structure analysis, and biochemical data suggest that this pocket, or Rab complementarity-determining region (RabCDR), establishes a specific interaction between each Rab protein and its effectors. RabCDRs could be major determinants of effector specificity during vesicle trafficking and fusion.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Ostermeier",
      "authorRank" : 1,
      "name" : "Ostermeier C",
      "referenceId" : "RGD:A116027"
    }, {
      "firstName" : "AT",
      "lastName" : "Brunger",
      "authorRank" : 2,
      "name" : "Brunger AT",
      "referenceId" : "RGD:A34500"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2314908"
    } ]
  }, {
    "primaryId" : "PMID:10025671",
    "title" : "Regulation of lung surfactant secretion by phospholipase A2.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Liu L J Cell Biochem. 1999 Jan 1;72(1):103-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-09-18T15:26:26.000-05:00",
    "volume" : "72",
    "pages" : "103-10",
    "abstract" : "Arachidonic acid has been shown to stimulate lung surfactant secretion from alveolar epithelial type II cells. To identify the (phospho)lipases responsible for generating arachidonic acid during lung surfactant secretion, the effects of various (phospho)lipase inhibitors on phosphatidylcholine (PC) secretion from rat alveolar type II cells were investigated. N-(p-amylcinnamoyl)anthranilic acid (ACA), a general inhibitor of phsopholipase A2 (PLA2), inhibited ATP-stimulated PC secretion in a dose-dependent manner. ACA also blocked PC secretion from type II cells stimulated by other secretagogues including phorbol 12-myristate 13-acetate, Ca2+ ionophore A23187 and terbutaline, indicating that PLA2 acts at a late step distal to the generation of second messengers. To determine which PLA2 isoform(s) is involved in lung surfactant secretion, selective inhibitors to different types of PLA2 were used to inhibit PLA2 activity in type II cells. The cytosolic PLA2 (cPLA2) inhibitor, arachidonyl trifluoromethyl ketone, was found to inhibit ATP-stimulated PC secretion, whereas the secretory PLA2 inhibitors, oleoyloxyethylphosphocholine, aristolochic acid, or p-bromophenacyl bromide, and the Ca2+-independent PLA2 inhibitors, palmitoyl trifluoromethyl ketone, or haloenol lactone suicide substrate, had no effect. In addition to PLA2, arachidonic acid is released from diacylglycerol (DAG) by DAG and monoacylglycerol lipases. The DAG lipase inhibitor, RHC-80267 also blocked ATP-stimulated PC secretion. The results suggest that both pathways for generating arachidonic acid via cPLA2 and DAG lipase may participate in lung surfactant secretion.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu L",
      "referenceId" : "RGD:A161824"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642480"
    } ]
  }, {
    "primaryId" : "PMID:10025676",
    "title" : "Vitamin D3 metabolites regulate LTBP1 and latent TGF-beta1 expression and latent  TGF-beta1 incorporation in the extracellular matrix of chondrocytes.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Pedrozo HA, etal., J Cell Biochem. 1999 Jan 1;72(1):151-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-11-13T15:30:07.000-06:00",
    "volume" : "72",
    "pages" : "151-65",
    "abstract" : "Growth plate chondrocytes make TGF-beta1 in latent form (LTGF-beta1) and store it in the extracellular matrix via LTGF-beta1 binding protein (LTBP1). 1,25-(OH)2D3  (1,25) regulates matrix protein production in growth zone (GC) chondrocyte cultures, whereas 24,25-(OH)2D3 (24,25) does so in resting zone (RC) cell cultures. The aim of this study was to determine if 24,25 and 1,25 regulate LTBP1 expression as well as the LTBP1 -mediated storage of TGF-beta1 in the extracellular matrix of RC and GC cells. Expression of LTBP1 and TGF-beta1 in the growth plate and in cultured RC and GC cells was determined by in situ hybridization using sense and antisense oligonucleotide probes based on the published rat LTBP1 and TGF-beta1 cDNA sequences. Fourth passage male rat costochondral RC and GC chondrocytes were treated for 24 h with 10(-7)-10(-9) M 24,25 and 10(-8)-10(-10) M 1,25, respectively. LTBP1 and TGF-beta1 mRNA levels were measured by in situ hybridization; production of LTGF-beta1, LTGF-beta2, and LTBP1 protein in the conditioned media was verified by immunoassays of FPLC-purified fractions. In addition, ELISA assays were used to measure the effect of 1,25 and 24,25 on the level of TGF-beta1 in the media and matrix of the cultures. Matrix-bound LTGF-beta1 was released by digesting isolated matrices with 1 U/ml plasmin for 3 h at 37 degrees C. LTBP1 and TGF-beta1 mRNAs are co-expressed throughout the growth plate, except in the lower hypertrophic area.  Cultured GC cells express more LTBP1 and TGF-beta1 mRNAs than RC cells. FPLC purification of the conditioned media confirmed that RC cells produce LTGF-beta1, LTGF-beta2, and LTBP1. GC cells also produce LTGF-beta2, but at lower concentrations. 1,25 dose-dependently increased the number of GC cells with high  LTBP1 expression, as seen by in situ hybridization. 24,25 had a similar, but less pronounced, effect on RC cells. 1,25 also caused a dose-dependent increase in the amount of TGF-beta1 protein found in the matrix, significant at 10(-8) and 10(-9) M, and a corresponding decrease in TGF-beta1 in the media. 24,25 had no effect on the level of TGF-beta1 in the matrix or media produced by RC cells. This indicates that 1,25 induces the production of LTBP1 by GC cells and suggests that the TGF-beta1 content of the media is reduced through the formation of latent TGF-beta1 -LTBP1 complexes which mediates storage in the matrix. Although 24,25 induced the expression of LTBP1 by RCs, TGF-beta1 incorporation into the matrix is not regulated by this vitamin D3 metabolite. Thus, vitamin D3 metabolites may  play a role in regulating the availability of TGF-beta1 by modulating LTBP1 production.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HA",
      "lastName" : "Pedrozo",
      "authorRank" : 1,
      "name" : "Pedrozo",
      "referenceId" : "RGD:A208330"
    }, {
      "firstName" : "Z",
      "lastName" : "Schwartz",
      "authorRank" : 2,
      "name" : "Schwartz Z",
      "referenceId" : "RGD:A12923"
    }, {
      "firstName" : "T",
      "lastName" : "Mokeyev",
      "authorRank" : 3,
      "name" : "Mokeyev",
      "referenceId" : "RGD:A208331"
    }, {
      "firstName" : "A",
      "lastName" : "Ornoy",
      "authorRank" : 4,
      "name" : "Ornoy A",
      "referenceId" : "RGD:A51095"
    }, {
      "firstName" : "W",
      "lastName" : "Xin-Sheng",
      "authorRank" : 5,
      "name" : "Xin-Sheng",
      "referenceId" : "RGD:A208332"
    }, {
      "firstName" : "LF",
      "lastName" : "Bonewald",
      "authorRank" : 6,
      "name" : "Bonewald",
      "referenceId" : "RGD:A208333"
    }, {
      "firstName" : "DD",
      "lastName" : "Dean",
      "authorRank" : 7,
      "name" : "Dean DD",
      "referenceId" : "RGD:A12930"
    }, {
      "firstName" : "BD",
      "lastName" : "Boyan",
      "authorRank" : 8,
      "name" : "Boyan BD",
      "referenceId" : "RGD:A12931"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10412059"
    } ]
  }, {
    "primaryId" : "PMID:10025686",
    "title" : "A pharmacologic strategy for the treatment of nicotine addiction.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Dewey SL, etal., Synapse. 1999 Jan;31(1):76-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-02T09:47:41.000-06:00",
    "volume" : "31",
    "pages" : "76-86",
    "abstract" : "Like many psychostimulant drugs, nicotine elevates extracellular and synaptic dopamine (DA) concentrations in the nucleus accumbens (NAc). This elevation has been linked to its reinforcing properties. Dopaminergic transmission within the NAc is modulated by gamma-aminobutyric acid (GABA). Therefore, we examined the utility of gamma vinyl-GABA (GVG, Vigabatrin) for inhibiting nicotine's biochemical effects on NAc DA as well as its effects on behaviors associated with these biochemical changes. Given 2.5 hours prior to nicotine, GVG (75 mg/kg) had no effect on nicotine-induced increases in extracellular NAc DA. However, at 90 mg/kg, GVG significantly inhibited nicotine-induced increases by approximately 50% while at 100 or 150 mg/kg, GVG completely abolished nicotine-induced increases in both naive and chronically nicotine-treated animals. When given 12 or 24 hours prior to nicotine administration at a dose of 100 mg/kg, GVG-induced inhibition was diminished or abolished, respectively. In addition, at a dose of 18.75 mg/kg GVG abolished the expression of nicotine-induced conditioned place preference (CPP) while a dose of 75 mg/kg abolished the acquisition phase of CPP. Finally, using positron emission tomography (PET) and 11C-raclopride in primates, GVG (100 mg/kg) abolished nicotine-induced increases in synaptic DA while having no effect on the rate of metabolism of the radiotracer or its regional distribution. Together, these data suggest that GVG may be useful for the treatment of nicotine addiction and further support the strategy of targeting the GABAergic system with a suicide inhibitor of GABA-transaminase for the treatment of drug addiction.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SL",
      "lastName" : "Dewey",
      "authorRank" : 1,
      "name" : "Dewey SL",
      "referenceId" : "RGD:A70585"
    }, {
      "firstName" : "JD",
      "lastName" : "Brodie",
      "authorRank" : 2,
      "name" : "Brodie JD",
      "referenceId" : "RGD:A70586"
    }, {
      "firstName" : "M",
      "lastName" : "Gerasimov",
      "authorRank" : 3,
      "name" : "Gerasimov M",
      "referenceId" : "RGD:A70590"
    }, {
      "firstName" : "B",
      "lastName" : "Horan",
      "authorRank" : 4,
      "name" : "Horan B",
      "referenceId" : "RGD:A70591"
    }, {
      "firstName" : "EL",
      "lastName" : "Gardner",
      "authorRank" : 5,
      "name" : "Gardner EL",
      "referenceId" : "RGD:A70581"
    }, {
      "firstName" : "JR",
      "lastName" : "Ashby CR",
      "authorRank" : 6,
      "name" : "Ashby CR JR",
      "referenceId" : "RGD:A70587"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598517"
    } ]
  }, {
    "primaryId" : "PMID:10025723",
    "title" : "Light and electron microscopic immunohistochemical observations of p75 nerve growth factor receptor-immunoreactive dermal nerves in prurigo nodularis.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Liang Y, etal., Arch Dermatol Res. 1999 Jan;291(1):14-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-10-13T16:39:33.000-05:00",
    "volume" : "291",
    "pages" : "14-21",
    "abstract" : "Prurigo nodularis is an inflammatory skin disease characterized by neurohyperplasia. Neurotrophins and their receptors play a critical role in nerve growth, differentiation, maturation and maintenance, including cutaneous nerve fiber growth and innervation. They may also be responsible for events related to the growth and differentiation control of keratinocytes. To explore the exact distribution of the p75 low-affinity nerve growth factor receptor (p75 NGFr) in the cutaneous nerve components, p75 NGFr immunofluorescence as well as ultrastructural immunohistochemical studies were performed on prurigo nodularis lesional skin and normal human skin samples. The immunofluorescence results revealed that nerve fibers and bundles were increased in number and size in lesional upper dermis with stronger p75 NGFr immunoreactivity than in the corresponding normal tissue. At the ultrastructural level, a lot of nerve fibers clustered together in the prurigo nodularis dermal tissue. The axons were enlarged and branched, but the axons themselves seldom showed any NGFr immunoreactivity. The Schwann cell bodies were extended and irregularly shaped, and tended to separate into many branches enveloping the axons. The Schwann cell membrane showed strong p75 NGFr immunoreactivity. The perineurium cells also revealed strong p75 NGFr immunoreactivity. The Schwann cells inside the perineurium were less p75 NGFr-immunoreactive than those outside the perineurium. The membrane of certain basal keratinocytes showed NGFr immunoreactivity as well. The present results indicate that overexpression of p75 NGFr in Schwann cells and perineurium cells could contribute to the neurohyperplasia in prurigo nodularis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Liang",
      "authorRank" : 1,
      "name" : "Liang Y",
      "referenceId" : "RGD:A162007"
    }, {
      "firstName" : "JA",
      "lastName" : "Marcusson",
      "authorRank" : 2,
      "name" : "Marcusson JA",
      "referenceId" : "RGD:A145644"
    }, {
      "firstName" : "O",
      "lastName" : "Johansson",
      "authorRank" : 3,
      "name" : "Johansson O",
      "referenceId" : "RGD:A145645"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5508384"
    } ]
  }, {
    "primaryId" : "PMID:10025794",
    "title" : "Association of interleukin-1beta and interleukin-1 receptor antagonist genes with disease severity in MS.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Schrijver HM, etal., Neurology 1999 Feb;52(3):595-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-24T11:42:51.000-05:00",
    "volume" : "52",
    "pages" : "595-9",
    "abstract" : "OBJECTIVE: To investigate whether polymorphisms in the interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1RA) genes are associated with both susceptibility to and clinical characteristics of MS. BACKGROUND: Genetic susceptibility to MS is determined by many partially identified genes. The genes encoding various cytokines are logical candidates for MS susceptibility and phenotype. METHODS: Genotypes were determined from 148 patients with clinically definite MS and 98 healthy controls. All the patients were unrelated, Dutch, and white. Patient files were reviewed for disease type, initial symptoms, age at onset of disease, and rate of disease progression. RESULTS: No significant differences in genotypes, allele frequencies, or carrier frequencies were found between MS patients and healthy controls. Stratification for disease type (relapsing-remitting, primary progressive, or secondary progressive) did not provide significant differences between patients and controls. However, a specific IL-1RA/IL-1beta combination was associated with disease severity. MS patients with the IL-1RA allele 2+/IL-1beta allele 2- combination had a higher rate of progression on the Expanded Disability Status Scale when compared with the other possible combinations (p = 0.007). CONCLUSIONS: IL-1RA and IL-1beta are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HM",
      "lastName" : "Schrijver",
      "authorRank" : 1,
      "name" : "Schrijver HM",
      "referenceId" : "RGD:A53919"
    }, {
      "firstName" : "JB",
      "lastName" : "Crusius",
      "authorRank" : 2,
      "name" : "Crusius JB",
      "referenceId" : "RGD:A52640"
    }, {
      "firstName" : "BM",
      "lastName" : "Uitdehaag",
      "authorRank" : 3,
      "name" : "Uitdehaag BM",
      "referenceId" : "RGD:A52645"
    }, {
      "firstName" : "MA",
      "lastName" : "Garcia Gonzalez",
      "authorRank" : 4,
      "name" : "Garcia Gonzalez MA",
      "referenceId" : "RGD:A53920"
    }, {
      "firstName" : "PJ",
      "lastName" : "Kostense",
      "authorRank" : 5,
      "name" : "Kostense PJ",
      "referenceId" : "RGD:A53921"
    }, {
      "firstName" : "CH",
      "lastName" : "Polman",
      "authorRank" : 6,
      "name" : "Polman CH",
      "referenceId" : "RGD:A52644"
    }, {
      "firstName" : "AS",
      "lastName" : "Pena",
      "authorRank" : 7,
      "name" : "Pena AS",
      "referenceId" : "RGD:A53922"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358741"
    } ]
  }, {
    "primaryId" : "PMID:10025941",
    "title" : "Cloning of the peroxiredoxin gene family in rats and characterization of the fourth member.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Matsumoto A, etal., FEBS Lett 1999 Jan 29;443(3):246-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:39.000-05:00",
    "volume" : "443",
    "pages" : "246-50",
    "abstract" : "Peroxiredoxin (PRx) exhibits thioredoxin-dependent peroxidase activity and constitutes a family of proteins. Four members of genes from rat tissues were isolated by PCR using degenerated primers based on the sequences which encode a pair of highly conserved Cys-containing domains, and were then cloned to full-length cDNAs. These included two genes which have previously been isolated in rats, PRx I and PRx II, and two rat homologues of PRx III and PRx IV. We showed, for the first time, the simultaneous expression of all four genes in various rat tissues by Northern blotting. Since a discrepancy exists regarding cellular distribution, we further characterized PRx IV by expressing it in COS-1 cells. This clearly demonstrates that PRx IV is a secretory form and functions within the extracellular space.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Matsumoto",
      "authorRank" : 1,
      "name" : "Matsumoto A",
      "referenceId" : "RGD:A5762"
    }, {
      "firstName" : "A",
      "lastName" : "Okado",
      "authorRank" : 2,
      "name" : "Okado A",
      "referenceId" : "RGD:A21590"
    }, {
      "firstName" : "T",
      "lastName" : "Fujii",
      "authorRank" : 3,
      "name" : "Fujii T",
      "referenceId" : "RGD:A297692"
    }, {
      "firstName" : "J",
      "lastName" : "Fujii",
      "authorRank" : 4,
      "name" : "Fujii J",
      "referenceId" : "RGD:A4630"
    }, {
      "firstName" : "M",
      "lastName" : "Egashira",
      "authorRank" : 5,
      "name" : "Egashira M",
      "referenceId" : "RGD:A21592"
    }, {
      "firstName" : "N",
      "lastName" : "Niikawa",
      "authorRank" : 6,
      "name" : "Niikawa N",
      "referenceId" : "RGD:A21593"
    }, {
      "firstName" : "N",
      "lastName" : "Taniguchi",
      "authorRank" : 7,
      "name" : "Taniguchi N",
      "referenceId" : "RGD:A4634"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633622"
    } ]
  }, {
    "primaryId" : "PMID:10025961",
    "title" : "The latrophilin family: multiply spliced G protein-coupled receptors with differential tissue distribution.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Matsushita H, etal., FEBS Lett 1999 Jan 29;443(3):348-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:46.000-05:00",
    "volume" : "443",
    "pages" : "348-52",
    "abstract" : "Latrophilin is a brain-specific Ca2+-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin. We now report the finding of two novel latrophilin homologues. All three latrophilins are unusual G protein-coupled receptors. They exhibit strong similarities within their lectin, olfactomedin and transmembrane domains but possess variable C-termini. Latrophilins have up to seven sites of alternative splicing; some splice variants contain an altered third cytoplasmic loop or a truncated cytoplasmic tail. Only latrophilin-1 binds alpha-latrotoxin; it is abundant in brain and is present in endocrine cells. Latrophilin-3 is also brain-specific, whereas latrophilin-2 is ubiquitous. Together, latrophilins form a novel family of heterogeneous G protein-coupled receptors with distinct tissue distribution and functions.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Matsushita",
      "authorRank" : 1,
      "name" : "Matsushita H",
      "referenceId" : "RGD:A42641"
    }, {
      "firstName" : "VG",
      "lastName" : "Lelianova",
      "authorRank" : 2,
      "name" : "Lelianova VG",
      "referenceId" : "RGD:A17283"
    }, {
      "firstName" : "YA",
      "lastName" : "Ushkaryov",
      "authorRank" : 3,
      "name" : "Ushkaryov YA",
      "referenceId" : "RGD:A101845"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299288"
    } ]
  }, {
    "primaryId" : "PMID:10026131",
    "title" : "An intramembrane modulator of the ErbB2 receptor tyrosine kinase that potentiates neuregulin signaling.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Carraway KL 3rd, etal., J Biol Chem. 1999 Feb 26;274(9):5263-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-02-24T16:16:28.000-06:00",
    "volume" : "274",
    "pages" : "5263-6",
    "abstract" : "The ErbB2 receptor tyrosine kinase plays a critical role in a variety of developmental processes, and its aberrant activation may contribute to the progression of some breast and ovarian tumors. ASGP2, a transmembrane glycoprotein found on the surface of the highly metastatic ascites 13762 rat mammary adenocarcinoma cell line, is constitutively associated with ErbB2 in these cells and in mammary tissue from pregnant rats. Expression studies indicate that ASGP2 interacts directly and specifically with ErbB2 through one of its epidermal growth factor-like domains and that the co-expression of the two proteins in the same cell dramatically facilitates their direct stable interaction. Ectopic expression of ASGP2 in human melanoma tumor cells potentiates the response of endogenous ErbB2 to the neuregulin-1 growth factor. These observations point to a novel intramembrane mechanism for the modulation of receptor tyrosine kinase activity.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "3RD",
      "lastName" : "Carraway KL",
      "authorRank" : 1,
      "name" : "Carraway KL 3RD",
      "referenceId" : "RGD:A59359"
    }, {
      "firstName" : "EA",
      "lastName" : "Rossi",
      "authorRank" : 2,
      "name" : "Rossi EA",
      "referenceId" : "RGD:A103959"
    }, {
      "firstName" : "M",
      "lastName" : "Komatsu",
      "authorRank" : 3,
      "name" : "Komatsu M",
      "referenceId" : "RGD:A10325"
    }, {
      "firstName" : "SA",
      "lastName" : "Price-Schiavi",
      "authorRank" : 4,
      "name" : "Price-Schiavi SA",
      "referenceId" : "RGD:A67984"
    }, {
      "firstName" : "D",
      "lastName" : "Huang",
      "authorRank" : 5,
      "name" : "Huang D",
      "referenceId" : "RGD:A23973"
    }, {
      "firstName" : "PM",
      "lastName" : "Guy",
      "authorRank" : 6,
      "name" : "Guy PM",
      "referenceId" : "RGD:A103978"
    }, {
      "firstName" : "ME",
      "lastName" : "Carvajal",
      "authorRank" : 7,
      "name" : "Carvajal ME",
      "referenceId" : "RGD:A67997"
    }, {
      "firstName" : "N",
      "lastName" : "Fregien",
      "authorRank" : 8,
      "name" : "Fregien N",
      "referenceId" : "RGD:A161527"
    }, {
      "firstName" : "CA",
      "lastName" : "Carraway",
      "authorRank" : 9,
      "name" : "Carraway CA",
      "referenceId" : "RGD:A43380"
    }, {
      "firstName" : "KL",
      "lastName" : "Carraway",
      "authorRank" : 10,
      "name" : "Carraway KL",
      "referenceId" : "RGD:A20872"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303749"
    } ]
  }, {
    "primaryId" : "PMID:10026153",
    "title" : "C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor.",
    "datePublished" : "1999-02-26T00:00:00.000-06:00",
    "citation" : "Arbet-Engels C, etal., J Biol Chem. 1999 Feb 26;274(9):5422-8. doi: 10.1074/jbc.274.9.5422.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2026-03-07T06:08:15.000-06:00",
    "volume" : "274",
    "pages" : "5422-8",
    "abstract" : "Increased expression of the insulin-like growth factor-I receptor (IGF-IR) protein-tyrosine kinase occurs in several kinds of cancer and induces neoplastic transformation in fibroblast cell lines. The transformed phenotype can be reversed by interfering with the function of the IGF-IR. The IGF-IR is required for transformation by a number of viral and cellular oncoproteins, including SV40 large T antigen, Ras, Raf, and Src. The IGF-IR is a substrate for Src in vitro and is phosphorylated in v-Src-transformed cells. We observed that the IGF-IR and IR associated with the C-terminal Src kinase (CSK) following ligand stimulation. We found that the SH2 domain of CSK binds to the tyrosine-phosphorylated form of IGF-IR and IR. We determined the tyrosine residues in the IGF-IR and in the IR responsible for this interaction. We also observed that fibroblasts stimulated with IGF-I or insulin showed a rapid and transient decrease in c-Src tyrosine kinase activity. The results suggest that c-Src and CSK are involved in IGF-IR and IR signaling and that the interaction of CSK with the IGF-IR may play a role in the decrease in c-Src activity following IGF-I stimulation.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Arbet-Engels",
      "authorRank" : 1,
      "name" : "Arbet-Engels C",
      "referenceId" : "RGD:A615013"
    }, {
      "firstName" : "S",
      "lastName" : "Tartare-Deckert",
      "authorRank" : 2,
      "name" : "Tartare-Deckert S",
      "referenceId" : "RGD:A87292"
    }, {
      "firstName" : "W",
      "lastName" : "Eckhart",
      "authorRank" : 3,
      "name" : "Eckhart W",
      "referenceId" : "RGD:A507154"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:640476571"
    } ]
  }, {
    "primaryId" : "PMID:10026156",
    "title" : "Glucocorticoid down-regulation of fascin protein expression is required for the steroid-induced formation of tight junctions and cell-cell interactions in rat mammary epithelial tumor cells.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wong V, etal., J Biol Chem. 1999 Feb 26;274(9):5443-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-04-23T10:18:03.000-05:00",
    "volume" : "274",
    "pages" : "5443-53",
    "abstract" : "Glucocorticoid hormones, which are physiological regulators of mammary epithelium development, induce the formation of tight junctions in rat Con8 mammary epithelial tumor cells. We have discovered that, as part of this process, the synthetic glucocorticoid dexamethasone strongly and reversibly down-regulated the expression of fascin, an actin-bundling protein that also interacts with the adherens junction component beta-catenin. Ectopic constitutive expression of full-length mouse fascin containing a Myc epitope tag (Myc-fascin) in Con8 cells inhibited the dexamethasone stimulation of transepithelial electrical resistance, disrupted the induced localization of the tight junction protein occludin and the adherens junction protein beta-catenin to the cell periphery, and prevented the rearrangement of the actin cytoskeleton. Ectopic expression of either the carboxyl-terminal 213 amino acids of fascin, which includes the actin and beta-catenin-binding sites, or the amino-terminal 313 amino acids of fascin failed to disrupt the glucocorticoid induction of tight junction formation. Mammary tumor cells expressing the full-length Myc-fascin remained generally glucocorticoid responsive and displayed no changes in the levels or protein-protein interactions of junctional proteins or the amount of cytoskeletal associated actin filaments. However, a cell aggregation assay demonstrated that the expression of Myc-fascin abrogated the dexamethasone induction of cell-cell adhesion. Our results implicate the down-regulation of fascin as a key intermediate step that directly links glucocorticoid receptor signaling to the coordinate control of junctional complex formation and cell-cell interactions in mammary tumor epithelial cells.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Wong",
      "authorRank" : 1,
      "name" : "Wong V",
      "referenceId" : "RGD:A37302"
    }, {
      "firstName" : "D",
      "lastName" : "Ching",
      "authorRank" : 2,
      "name" : "Ching D",
      "referenceId" : "RGD:A122389"
    }, {
      "firstName" : "PD",
      "lastName" : "McCrea",
      "authorRank" : 3,
      "name" : "McCrea PD",
      "referenceId" : "RGD:A122382"
    }, {
      "firstName" : "GL",
      "lastName" : "Firestone",
      "authorRank" : 4,
      "name" : "Firestone GL",
      "referenceId" : "RGD:A7974"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317779"
    } ]
  }, {
    "primaryId" : "PMID:10026162",
    "title" : "A novel ubiquitously expressed alpha-latrotoxin receptor is a member of the CIRL family of G-protein-coupled receptors.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Ichtchenko K, etal., J Biol Chem 1999 Feb 26;274(9):5491-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:31.000-05:00",
    "volume" : "274",
    "pages" : "5491-8",
    "abstract" : "Poisoning with alpha-latrotoxin, a neurotoxic protein from black widow spider venom, results in a robust increase of spontaneous synaptic transmission and subsequent degeneration of affected nerve terminals. The neurotoxic action of alpha-latrotoxin involves extracellular binding to its high affinity receptors as a first step. One of these proteins, CIRL, is a neuronal G-protein-coupled receptor implicated in the regulation of secretion. We now demonstrate that CIRL has two close homologs with a similar domain structure and high degree of overall identity. These novel receptors, which we propose to name CIRL-2 and CIRL-3, together with CIRL (CIRL-1) belong to a recently identified subfamily of large orphan receptors with structural features typical of both G-protein-coupled receptors and cell adhesion proteins. Northern blotting experiments indicate that CIRL-2 is expressed ubiquitously with highest concentrations found in placenta, kidney, spleen, ovary, heart, and lung, whereas CIRL-3 is expressed predominantly in brain similarly to CIRL-1. It appears that CIRL-2 can also bind alpha-latrotoxin, although its affinity to the toxin is about 14 times less than that of CIRL-1. When overexpressed in chromaffin cells, CIRL-2 increases their sensitivity to alpha-latrotoxin stimulation but also inhibits Ca2+-regulated secretion. Thus, CIRL-2 is a functionally competent receptor of alpha-latrotoxin. Our findings suggest that although the nervous system is the primary target of low doses of alpha-latrotoxin, cells of other tissues are also susceptible to the toxic effects of alpha-latrotoxin because of the presence of CIRL-2, a low affinity receptor of the toxin.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Ichtchenko",
      "authorRank" : 1,
      "name" : "Ichtchenko K",
      "referenceId" : "RGD:A17139"
    }, {
      "firstName" : "MA",
      "lastName" : "Bittner",
      "authorRank" : 2,
      "name" : "Bittner MA",
      "referenceId" : "RGD:A17140"
    }, {
      "firstName" : "V",
      "lastName" : "Krasnoperov",
      "authorRank" : 3,
      "name" : "Krasnoperov V",
      "referenceId" : "RGD:A17141"
    }, {
      "firstName" : "AR",
      "lastName" : "Little",
      "authorRank" : 4,
      "name" : "Little AR",
      "referenceId" : "RGD:A17142"
    }, {
      "firstName" : "O",
      "lastName" : "Chepurny",
      "authorRank" : 5,
      "name" : "Chepurny O",
      "referenceId" : "RGD:A17143"
    }, {
      "firstName" : "RW",
      "lastName" : "Holz",
      "authorRank" : 6,
      "name" : "Holz RW",
      "referenceId" : "RGD:A17144"
    }, {
      "firstName" : "AG",
      "lastName" : "Petrenko",
      "authorRank" : 7,
      "name" : "Petrenko AG",
      "referenceId" : "RGD:A17145"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632388"
    } ]
  }, {
    "primaryId" : "PMID:10026167",
    "title" : "Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hiraiwa H, etal., J Biol Chem. 1999 Feb 26;274(9):5532-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:23:42.000-05:00",
    "volume" : "274",
    "pages" : "5532-6",
    "abstract" : "Glycogen storage disease type 1b (GSD-1b) is proposed to be caused by a deficiency in microsomal glucose 6-phosphate (G6P) transport, causing a loss of glucose-6-phosphatase activity and glucose homeostasis. However, for decades, this disorder has defied molecular characterization. In this study, we characterize the structural organization of the G6P transporter gene and identify mutations in the gene that segregate with the GSD-1b disorder. We report the functional characterization of the recombinant G6P transporter and demonstrate that mutations uncovered in GSD-1b patients disrupt G6P transport. Our results, for the first time, define a molecular basis for functional deficiency in GSD-1b  and raise the possibility that the defective G6P transporter contributes to neutropenia and neutrophil/monocyte dysfunctions characteristic of GSD-1b patients.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Hiraiwa",
      "authorRank" : 1,
      "name" : "Hiraiwa",
      "referenceId" : "RGD:A272147"
    }, {
      "firstName" : "CJ",
      "lastName" : "Pan",
      "authorRank" : 2,
      "name" : "Pan",
      "referenceId" : "RGD:A282347"
    }, {
      "firstName" : "B",
      "lastName" : "Lin",
      "authorRank" : 3,
      "name" : "Lin",
      "referenceId" : "RGD:A411997"
    }, {
      "firstName" : "SW",
      "lastName" : "Moses",
      "authorRank" : 4,
      "name" : "Moses SW",
      "referenceId" : "RGD:A75476"
    }, {
      "firstName" : "JY",
      "lastName" : "Chou",
      "authorRank" : 5,
      "name" : "Chou",
      "referenceId" : "RGD:A282348"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068817"
    } ]
  }, {
    "primaryId" : "PMID:10026172",
    "title" : "RNA antisense abrogation of MAT1 induces G1 phase arrest and triggers apoptosis in aortic smooth muscle cells.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Wu L, etal., J Biol Chem. 1999 Feb 26;274(9):5564-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-06-12T13:27:30.000-05:00",
    "volume" : "274",
    "pages" : "5564-72",
    "abstract" : "The human MAT1 gene (menage a trois 1) is an assembly factor and a targeting subunit of cyclin-dependent kinase (CDK)-activating kinase. The novel mechanisms by which MAT1 forms an active CDK-activating kinase and determines substrate specificity of CDK7-cyclin H are involved in the cell cycle, DNA repair, and transcription. Hyperplasia of vascular smooth muscle cells (SMC) is a fundamental pathologic feature of luminal narrowing in vascular occlusive diseases, and nothing is yet known regarding the cell cycle phase specificity of the MAT1 gene in its involvement in SMC proliferation. To investigate such novel regulatory pathways, MAT1 expression was abrogated by retrovirus-mediated gene transfer of antisense MAT1 RNA in cultured rat aortic SMCs. We show that abrogation of MAT1 expression retards SMC proliferation and inhibits cell activation from a nonproliferative state. Furthermore, we have demonstrated that these effects are due to G1 phase arrest and apoptotic cell death. Our studies indicate a link between cell cycle control and apoptosis and reveal a potential mechanism for coupling the regulation of MAT1 with G1 exit and prevention of apoptosis.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Wu",
      "authorRank" : 1,
      "name" : "Wu L",
      "referenceId" : "RGD:A52627"
    }, {
      "firstName" : "P",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen P",
      "referenceId" : "RGD:A9974"
    }, {
      "firstName" : "JJ",
      "lastName" : "Hwang",
      "authorRank" : 3,
      "name" : "Hwang JJ",
      "referenceId" : "RGD:A28259"
    }, {
      "firstName" : "LW",
      "lastName" : "Barsky",
      "authorRank" : 4,
      "name" : "Barsky LW",
      "referenceId" : "RGD:A91116"
    }, {
      "firstName" : "KI",
      "lastName" : "Weinberg",
      "authorRank" : 5,
      "name" : "Weinberg KI",
      "referenceId" : "RGD:A108200"
    }, {
      "firstName" : "A",
      "lastName" : "Jong",
      "authorRank" : 6,
      "name" : "Jong A",
      "referenceId" : "RGD:A108201"
    }, {
      "firstName" : "VA",
      "lastName" : "Starnes",
      "authorRank" : 7,
      "name" : "Starnes VA",
      "referenceId" : "RGD:A60719"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2308868"
    } ]
  }, {
    "primaryId" : "PMID:10026205",
    "title" : "Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Murphy M, etal., J Biol Chem 1999 Feb 26;274(9):5830-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T14:11:28.000-05:00",
    "volume" : "274",
    "pages" : "5830-4",
    "abstract" : "Accumulation of mesangial matrix is a pivotal event in the pathophysiology of diabetic nephropathy. The molecular triggers for matrix production are still being defined. Here, suppression subtractive hybridization identified 15 genes differentially induced when primary human mesangial cells are exposed to high glucose (30 mM versus 5 mM) in vitro. These genes included (a) known regulators of mesangial cell activation in diabetic nephropathy (fibronectin, caldesmon, thrombospondin, and plasminogen activator inhibitor-1), (b) novel genes, and (c) known genes whose induction by high glucose has not been reported. Prominent among the latter were genes encoding cytoskeleton-associated proteins and connective tissue growth factor (CTGF), a modulator of fibroblast matrix production. In parallel experiments, elevated CTGF mRNA levels were demonstrated in glomeruli of rats with streptozotocin-induced diabetic nephropathy. Mannitol provoked less mesangial cell CTGF expression in vitro than high glucose, excluding hyperosmolality as the key stimulus. The addition of recombinant CTGF to cultured mesangial cells enhanced expression of extracellular matrix proteins. High glucose stimulated expression of transforming growth factor beta1 (TGF-beta1), and addition of TGF-beta1 to mesangial cells triggered CTGF expression. CTGF expression induced by high glucose was partially suppressed by anti-TGF-beta1 antibody and by the protein kinase C inhibitor GF 109203X. Together, these data suggest that 1) high glucose stimulates mesangial CTGF expression by TGFbeta1-dependent and protein kinase C dependent pathways, and 2) CTGF may be a mediator of TGFbeta1-driven matrix production within a diabetic milieu.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Murphy",
      "authorRank" : 1,
      "name" : "Murphy M",
      "referenceId" : "RGD:A17683"
    }, {
      "firstName" : "C",
      "lastName" : "Godson",
      "authorRank" : 2,
      "name" : "Godson C",
      "referenceId" : "RGD:A17684"
    }, {
      "firstName" : "S",
      "lastName" : "Cannon",
      "authorRank" : 3,
      "name" : "Cannon S",
      "referenceId" : "RGD:A17685"
    }, {
      "firstName" : "S",
      "lastName" : "Kato",
      "authorRank" : 4,
      "name" : "Kato S",
      "referenceId" : "RGD:A17686"
    }, {
      "firstName" : "HS",
      "lastName" : "Mackenzie",
      "authorRank" : 5,
      "name" : "Mackenzie HS",
      "referenceId" : "RGD:A17687"
    }, {
      "firstName" : "F",
      "lastName" : "Martin",
      "authorRank" : 6,
      "name" : "Martin F",
      "referenceId" : "RGD:A17688"
    }, {
      "firstName" : "HR",
      "lastName" : "Brady",
      "authorRank" : 7,
      "name" : "Brady HR",
      "referenceId" : "RGD:A17689"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632526"
    } ]
  }, {
    "primaryId" : "PMID:10026214",
    "title" : "Role of class B scavenger receptor type I in phagocytosis of apoptotic rat spermatogenic cells by Sertoli cells.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Shiratsuchi A, etal., J Biol Chem 1999 Feb 26;274(9):5901-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-12-22T09:53:36.000-06:00",
    "volume" : "274",
    "pages" : "5901-8",
    "abstract" : "Rat Sertoli cells phagocytose apoptotic spermatogenic cells, which consist mostly of spermatocytes, in primary culture by recognizing phosphatidylserine (PS) exposed on the surface of degenerating spermatogenic cells. We compared the mode of phagocytosis using spermatogenic cells at different stages of spermatogenesis. Spermatogenic cells were separated into several groups based on their ploidy, with purities of 60-90%. When the fractionated spermatogenic cell populations were subjected to a phagocytosis assay, cells with ploidies of 1n, 2n, and 4n were almost equally phagocytosed by Sertoli cells. All the cell populations exposed PS on the cell surface, and phagocytosis of all cell populations was similarly inhibited by the addition of PS-containing liposomes. Class B scavenger receptor type I (SR-BI), a candidate for the PS receptor, was detected in Sertoli cells. Overexpression of the rat SR-BI cDNA increased the PS-mediated phagocytic activity of Sertoli cell-derived cell lines. Moreover, phagocytosis of spermatogenic cells by Sertoli cells was inhibited in the presence of an anti-SR-BI antibody. Finally, the addition of high density lipoprotein, a ligand specific for SR-BI, decreased both phagocytosis of spermatogenic cells and incorporation of PS-containing liposomes by Sertoli cells. In conclusion, SR-BI functions at least partly as a PS receptor, enabling Sertoli cells to recognize and phagocytose apoptotic spermatogenic cells at all stages of differentiation.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Shiratsuchi",
      "authorRank" : 1,
      "name" : "Shiratsuchi A",
      "referenceId" : "RGD:A30030"
    }, {
      "firstName" : "Y",
      "lastName" : "Kawasaki",
      "authorRank" : 2,
      "name" : "Kawasaki Y",
      "referenceId" : "RGD:A5065"
    }, {
      "firstName" : "M",
      "lastName" : "Ikemoto",
      "authorRank" : 3,
      "name" : "Ikemoto M",
      "referenceId" : "RGD:A9491"
    }, {
      "firstName" : "H",
      "lastName" : "Arai",
      "authorRank" : 4,
      "name" : "Arai H",
      "referenceId" : "RGD:A9492"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakanishi",
      "authorRank" : 5,
      "name" : "Nakanishi Y",
      "referenceId" : "RGD:A22150"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1304217"
    } ]
  }, {
    "primaryId" : "PMID:10026353",
    "title" : "Endogenous plasma endothelin concentrations and coronary circulation in patients  with mild dilated cardiomyopathy.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mundhenke M, etal., Heart. 1999 Mar;81(3):278-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-13T16:25:55.000-05:00",
    "volume" : "81",
    "pages" : "278-84",
    "abstract" : "OBJECTIVE: To determine whether increased plasma concentrations of endothelin-1 (ET-1) and big endothelin (BET) play a role in the regulation of coronary circulation in patients with idiopathic dilated cardiomyopathy (IDCM). SETTING: Tertiary referral centre for cardiac diseases. PATIENTS: Fourteen patients (eight male/six female; mean (SD) age 59 (9) years) with IDCM (ejection fraction 36 (9)%) and five normotensive subjects (two male/three female; age 52 (7) years) serving as controls were studied. METHODS: Functional status was classified according to New York Heart Association (NYHA) class. Endogenous ET-1 and BET plasma concentrations from the aorta and the coronary sinus were determined by radioimmunoassay. Coronary blood flow, using the inert chromatographic argon method, myocardial oxygen consumption, and coronary sinus oxygen content under basal conditions were determined. RESULTS: In the aorta, mean (SD) concentrations of ET-1 (IDCM 0.76 (0.25) v controls 0.31 (0.06) fmol/ml; p = 0.002) and BET (IDCM 3.58 (1.06) v controls 2.11 (0.58) fmol/ml; p = 0.014) were increased in patients with IDCM. Aortic ET-1 concentrations correlated positively with NYHA class (r = 0. 731; p < 0.001), myocardial oxygen consumption (r = 0.749; p < 0. 001), and coronary blood flow (r = 0.645; p = 0.003), but inversely with coronary sinus oxygen content (r = -0.633; p = 0.004), which was significantly decreased in IDCM patients (IDCM 4.68 (1.05) v controls 6.70 (1.06) vol%; p = 0.003). CONCLUSIONS: The coronary circulation in patients with IDCM is exposed to an increased endothelin load. ET-1 concentrations correlate with functional deterioration. A decrease of the coronary sinus content of oxygen suggests a mismatch between coronary blood flow and metabolic demand. Thus, ET-1 might be a  marker of a disequilibrium between myocardial oxygen demand and coronary blood flow in IDCM.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Mundhenke",
      "authorRank" : 1,
      "name" : "Mundhenke",
      "referenceId" : "RGD:A189791"
    }, {
      "firstName" : "B",
      "lastName" : "Schwartzkopff",
      "authorRank" : 2,
      "name" : "Schwartzkopff B",
      "referenceId" : "RGD:A69312"
    }, {
      "firstName" : "M",
      "lastName" : "Kostering",
      "authorRank" : 3,
      "name" : "Kostering",
      "referenceId" : "RGD:A189792"
    }, {
      "firstName" : "U",
      "lastName" : "Deska",
      "authorRank" : 4,
      "name" : "Deska",
      "referenceId" : "RGD:A189793"
    }, {
      "firstName" : "RM",
      "lastName" : "Klein",
      "authorRank" : 5,
      "name" : "Klein RM",
      "referenceId" : "RGD:A76715"
    }, {
      "firstName" : "BE",
      "lastName" : "Strauer",
      "authorRank" : 6,
      "name" : "Strauer BE",
      "referenceId" : "RGD:A69316"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8661756"
    } ]
  }, {
    "primaryId" : "PMID:10026829",
    "title" : "Mutations in the vasopressin V2 receptor and aquaporin-2 genes in twelve families with congenital nephrogenic diabetes insipidus.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Vargas-Poussou R, etal., Adv Exp Med Biol. 1998;449:387-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:15:41.000-05:00",
    "volume" : "449",
    "pages" : "387-90",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Vargas-Poussou",
      "authorRank" : 1,
      "name" : "Vargas-Poussou",
      "referenceId" : "RGD:A267077"
    }, {
      "firstName" : "L",
      "lastName" : "Forestier",
      "authorRank" : 2,
      "name" : "Forestier L",
      "referenceId" : "RGD:A79305"
    }, {
      "firstName" : "MD",
      "lastName" : "Dautzenberg",
      "authorRank" : 3,
      "name" : "Dautzenberg MD",
      "referenceId" : "RGD:A61138"
    }, {
      "firstName" : "P",
      "lastName" : "Niaudet",
      "authorRank" : 4,
      "name" : "Niaudet P",
      "referenceId" : "RGD:A77468"
    }, {
      "firstName" : "M",
      "lastName" : "Dechaux",
      "authorRank" : 5,
      "name" : "Dechaux",
      "referenceId" : "RGD:A267078"
    }, {
      "firstName" : "C",
      "lastName" : "Antignac",
      "authorRank" : 6,
      "name" : "Antignac C",
      "referenceId" : "RGD:A54238"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067100"
    } ]
  }, {
    "primaryId" : "PMID:10027080",
    "title" : "Glucose decreases steady state mRNA content of hydrophobic surfactant proteins B and C in fetal rat lung explants.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Rayani HH, etal., Exp Lung Res. 1999 Jan-Feb;25(1):69-79.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-24T11:24:02.000-05:00",
    "volume" : "25",
    "pages" : "69-79",
    "abstract" : "The streptozotocin-induced diabetic (STZ-DB) rat model is associated with fetal hyperglycemia, but with low to normal plasma insulin concentration. Because surfactant protein (SP) mRNA content in fetal rat lung is decreased in STZ-DB pregnancy, we investigated the effect of increasing concentrations of glucose on SP gene expression in lung organ cultures. SP mRNA content (SP-A, SP-B, SP-C) was assessed by Northern blot analysis in fetal day 20 lung explants (term = 22 days) cultured for 44 hours in medium containing 10, 25, 50, or 100 mM glucose. Our findings were (1) No consistent alteration in SP-A mRNA content was observed at different glucose concentrations (P > .05); (2) SP-B and SP-C mRNA content were reduced in a dose-dependent manner when glucose concentration was increased from 10 mM to 100 mM. The mRNA content, compared to 10 mM glucose, decreased to 50-60% at 25 mM glucose, to 20-25% at 50 mM glucose, and to lower than 10% at 100 mM glucose (P < .01). These findings indicate that the decrease in SP-B and SP-C mRNA in fetuses of STZ-DB rats may be, in part, due to a direct effect of hyperglycemia, whereas the decrease in SP-A mRNA content in STZ-DB rats appears to be due to other effects of diabetes in pregnancy.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HH",
      "lastName" : "Rayani",
      "authorRank" : 1,
      "name" : "Rayani HH",
      "referenceId" : "RGD:A128234"
    }, {
      "firstName" : "IH",
      "lastName" : "Gewolb",
      "authorRank" : 2,
      "name" : "Gewolb IH",
      "referenceId" : "RGD:A128235"
    }, {
      "firstName" : "J",
      "lastName" : "Floros",
      "authorRank" : 3,
      "name" : "Floros J",
      "referenceId" : "RGD:A128342"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4143477"
    } ]
  }, {
    "primaryId" : "PMID:1002715",
    "title" : "Isolation of eukaryotic ribosomal proteins. Purification and characterization of  the 60 S ribosomal subunit proteins L4, L5, L7, L9, L11, L12, L13, L21, L22, L23, L26, L27, L30, L33, L35', L37, and L39.",
    "datePublished" : "1976-02-01T00:00:00.000-06:00",
    "citation" : "Tsurugi K, etal., J Biol Chem. 1976 Dec 25;251(24):7940-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-02-17T14:15:37.000-06:00",
    "volume" : "251",
    "pages" : "7940-6",
    "abstract" : "The proteins of the large subunit of rat liver ribosomes were separated into seven groups by stepwise elution from carboxymethylcellulose with LiCl at pH 6.5. Seventeen proteins (L4, L5, L7, L9, L11, L12, L13, L21, L22, L23, L26, L27, L30,  L33, L35', L37, and L39) were isolated from three of the groups (B60, D60, G60) by ion exchange chromatography on carboxymethylcellulose and by filtration through Sephadex. The amount of protein obtained varied from 0.5 to 15 mg. Eight  of the proteins (L9, L11, L13, L21, L22, L35', L37 and L39) had no detectable contamination; the impurities in the others were no greater than 9%. The molecular weight of the proteins was estimated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; the amino acid composition was determined.",
    "issueName" : "24",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Tsurugi",
      "authorRank" : 1,
      "name" : "Tsurugi K",
      "referenceId" : "RGD:A99438"
    }, {
      "firstName" : "E",
      "lastName" : "Collatz",
      "authorRank" : 2,
      "name" : "Collatz E",
      "referenceId" : "RGD:A99424"
    }, {
      "firstName" : "EG",
      "lastName" : "Wool",
      "authorRank" : 3,
      "name" : "Wool",
      "referenceId" : "RGD:A212355"
    }, {
      "firstName" : "A",
      "lastName" : "Lin",
      "authorRank" : 4,
      "name" : "Lin",
      "referenceId" : "RGD:A391844"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11036093"
    } ]
  }, {
    "primaryId" : "PMID:10027300",
    "title" : "Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Xia J, etal., Neuron 1999 Jan;22(1):179-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-11-26T12:12:49.000-06:00",
    "volume" : "22",
    "pages" : "179-87",
    "abstract" : "Synaptic clustering of neurotransmitter receptors is crucial for efficient signal transduction and integration in neurons. PDZ domain-containing proteins such as PSD-95/SAP90 interact with the intracellular C termini of a variety of receptors and are thought to be important in the targeting and anchoring of receptors to specific synapses. Here, we show that PICK1 (protein interacting with C kinase), a PDZ domain-containing protein, interacts with the C termini of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptors in vitro and in vivo. In neurons, PICK1 specifically colocalizes with AMPA receptors at excitatory synapses. Furthermore, PICK1 induces clustering of AMPA receptors in heterologous expression systems. These results suggest that PICK1 may play an important role in the modulation of synaptic transmission by regulating the synaptic targeting of AMPA receptors.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Xia",
      "authorRank" : 1,
      "name" : "Xia J",
      "referenceId" : "RGD:A6543"
    }, {
      "firstName" : "X",
      "lastName" : "Zhang",
      "authorRank" : 2,
      "name" : "Zhang X",
      "referenceId" : "RGD:A6544"
    }, {
      "firstName" : "J",
      "lastName" : "Staudinger",
      "authorRank" : 3,
      "name" : "Staudinger J",
      "referenceId" : "RGD:A6545"
    }, {
      "firstName" : "RL",
      "lastName" : "Huganir",
      "authorRank" : 4,
      "name" : "Huganir RL",
      "referenceId" : "RGD:A6546"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69384"
    } ]
  }, {
    "primaryId" : "PMID:10027311",
    "title" : "Analysis of TSG101 tumour susceptibility gene transcripts in cervical and endometrial cancers.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Chang JG, etal., Br J Cancer. 1999 Feb;79(3-4):445-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-01T14:55:23.000-05:00",
    "volume" : "79",
    "pages" : "445-50",
    "abstract" : "Carcinoma of the uterine cervix is a common malignancy among women that has been found to show loss of heterozygosity in the chromosome 11p. Recent studies have localized the TSG101 gene in this region, and also demonstrated a high frequency of abnormalities of this gene in human breast cancer. To determine the role of the TSG101 gene in the carcinogenesis of cervical and uterine carcinoma, 19 cases of cervical carcinoma and five cases of endometrial carcinoma, as well as nearby non-cancerous tissue from the same patients, and 16 blood samples from healthy persons as normal control were analysed by Southern blot analysis of genomic DNA, reverse transcription of the TSG101 mRNA followed by PCR amplification and sequencing of the products. We found that abnormal transcripts of the TSG101 gene were common both in cancerous or non-cancerous tissues of the uterus and cervix and in normal peripheral mononuclear cells. There was no genomic deletion or rearrangement in spite of the presence of abnormal transcripts, and no definite relationship between the abnormal transcripts and HPV infection was found. Although the frequency of abnormal transcripts was higher in cancerous than in non-cancerous tissue, normal peripheral mononuclear cells also had abnormal transcripts. Given these findings, the role of the TSG101 gene as a tumour-suppressor gene should be re-evaluated. Because some aberrant transcripts could be found at the first PCR reaction, we suggest that the aberrant transcripts might be the result of imperfect minor splicesome products.",
    "issueName" : "3-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JG",
      "lastName" : "Chang",
      "authorRank" : 1,
      "name" : "Chang JG",
      "referenceId" : "RGD:A66796"
    }, {
      "firstName" : "TH",
      "lastName" : "Su",
      "authorRank" : 2,
      "name" : "Su TH",
      "referenceId" : "RGD:A93653"
    }, {
      "firstName" : "HJ",
      "lastName" : "Wei",
      "authorRank" : 3,
      "name" : "Wei HJ",
      "referenceId" : "RGD:A93654"
    }, {
      "firstName" : "JC",
      "lastName" : "Wang",
      "authorRank" : 4,
      "name" : "Wang JC",
      "referenceId" : "RGD:A93655"
    }, {
      "firstName" : "YJ",
      "lastName" : "Chen",
      "authorRank" : 5,
      "name" : "Chen YJ",
      "referenceId" : "RGD:A61969"
    }, {
      "firstName" : "CP",
      "lastName" : "Chang",
      "authorRank" : 6,
      "name" : "Chang CP",
      "referenceId" : "RGD:A5345"
    }, {
      "firstName" : "CJ",
      "lastName" : "Jeng",
      "authorRank" : 7,
      "name" : "Jeng CJ",
      "referenceId" : "RGD:A93656"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2291854"
    } ]
  }, {
    "primaryId" : "PMID:10027405",
    "title" : "Collagenase-3 (MMP-13) is expressed by tumor cells in invasive vulvar squamous cell carcinomas.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Johansson N, etal., Am J Pathol. 1999 Feb;154(2):469-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-06-09T15:06:18.000-05:00",
    "volume" : "154",
    "pages" : "469-80",
    "abstract" : "Collagenase-3 (MMP-13) is a human matrix metalloproteinase specifically expressed by invading tumor cells in squamous cell carcinomas (SCCs) of the head and neck. Here, we have further elucidated the role of MMP-13 in tumor invasion by examining its expression in invasive malignant tumors of the female genital tract. Using in situ hybridization, expression of MMP-13 mRNA was detected in 9 of 12 vulvar SCCs, primarily in tumor cells, but not in intact vulvar epithelium, in cervical SCCs (n = 12), or in endometrial (n = 11) or ovarian adenocarcinomas (n = 8). MMP-13 expression was especially abundant in vulvar carcinomas showing metastasis to lymph nodes and was associated with expression of membrane type 1 MMP by tumor cells and gelatinase-A (MMP-2) by stromal cells, as detected by immunohistochemistry. MMP-13 mRNAs were detected in 9 of 11 cell lines established from vulvar carcinomas and in 4 of 6 cell lines from cervical carcinomas, whereas endometrial (n = 10) and ovarian (n = 9) carcinoma cell lines were negative for MMP-13 mRNA. No correlation was detected between MMP-13 expression and p53 gene mutations in vulvar SCC cell lines. However, MMP-13 expression was detected in 5 of 6 vulvar and cervical SCC cell lines harboring HPV 16 or 68 DNA. These results show that MMP-13 is specifically expressed by malignantly transformed squamous epithelial cells, including vulvar SCC cells, and appears to serve as a marker for their invasive capacity.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Johansson",
      "authorRank" : 1,
      "name" : "Johansson N",
      "referenceId" : "RGD:A76295"
    }, {
      "firstName" : "M",
      "lastName" : "Vaalamo",
      "authorRank" : 2,
      "name" : "Vaalamo M",
      "referenceId" : "RGD:A96863"
    }, {
      "firstName" : "S",
      "lastName" : "Grenman",
      "authorRank" : 3,
      "name" : "Grenman S",
      "referenceId" : "RGD:A90998"
    }, {
      "firstName" : "S",
      "lastName" : "Hietanen",
      "authorRank" : 4,
      "name" : "Hietanen S",
      "referenceId" : "RGD:A96864"
    }, {
      "firstName" : "P",
      "lastName" : "Klemi",
      "authorRank" : 5,
      "name" : "Klemi P",
      "referenceId" : "RGD:A90999"
    }, {
      "firstName" : "U",
      "lastName" : "Saarialho-Kere",
      "authorRank" : 6,
      "name" : "Saarialho-Kere U",
      "referenceId" : "RGD:A71597"
    }, {
      "firstName" : "VM",
      "lastName" : "Kahari",
      "authorRank" : 7,
      "name" : "Kahari VM",
      "referenceId" : "RGD:A96855"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2293612"
    } ]
  }, {
    "primaryId" : "PMID:10027549",
    "title" : "Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Scacchi R, etal., Neurosci Lett. 1999 Jan 4;259(1):33-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-09-26T12:20:15.000-05:00",
    "volume" : "259",
    "pages" : "33-6",
    "abstract" : "Besides apolipoprotein E (APOE) polymorphism, whose association with Alzheimer's  disease (AD) has been confirmed in most of the numerous population samples studied, other markers have been investigated. In most cases the association firstly described was not confirmed in subsequent works. Since it is important to examine these associations in as many populations as possible, we investigated APOE, APOC1, APOC2, alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) polymorphisms in a series of elderly patients with late-onset sporadic AD from Northern Italy and in a sex and age-matched control group. We could not confirm the significantly higher frequency of the ACT*A allele among carriers of APOE e*4 allele described elsewhere, although a similar trend was observed. The APOC2 and  the PS-1 distributions were similar between patients and controls. However, we observed a significant difference in the genotype and allele frequencies of APOE  and APOC1: patients had higher e*4 and C1*2 allele frequencies. This finding confirms the important role for APOE in AD occurrence. In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk. In contrast to previously  reported data, plasma apoE concentrations were similar in patients and in controls. An interaction between APOE and APOC1 polymorphisms and apoE levels was observed in patients: subjects carrying the APOE E3/E2 or the APOC1 2-2 genotype  have higher apoE concentrations than those who do not.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Scacchi",
      "authorRank" : 1,
      "name" : "Scacchi R",
      "referenceId" : "RGD:A53789"
    }, {
      "firstName" : "G",
      "lastName" : "Gambina",
      "authorRank" : 2,
      "name" : "Gambina G",
      "referenceId" : "RGD:A158336"
    }, {
      "firstName" : "M",
      "lastName" : "Ruggeri",
      "authorRank" : 3,
      "name" : "Ruggeri M",
      "referenceId" : "RGD:A53940"
    }, {
      "firstName" : "MC",
      "lastName" : "Martini",
      "authorRank" : 4,
      "name" : "Martini MC",
      "referenceId" : "RGD:A158337"
    }, {
      "firstName" : "G",
      "lastName" : "Ferrari",
      "authorRank" : 5,
      "name" : "Ferrari G",
      "referenceId" : "RGD:A153148"
    }, {
      "firstName" : "M",
      "lastName" : "Silvestri",
      "authorRank" : 6,
      "name" : "Silvestri M",
      "referenceId" : "RGD:A158338"
    }, {
      "firstName" : "R",
      "lastName" : "Schiavon",
      "authorRank" : 7,
      "name" : "Schiavon R",
      "referenceId" : "RGD:A158339"
    }, {
      "firstName" : "RM",
      "lastName" : "Corbo",
      "authorRank" : 8,
      "name" : "Corbo RM",
      "referenceId" : "RGD:A53790"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6903233"
    } ]
  }, {
    "primaryId" : "PMID:10027563",
    "title" : "Retinoic acid and neurotrophins collaborate to regulate neurogenesis in adult-derived neural stem cell cultures.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Takahashi J, etal., J Neurobiol. 1999 Jan;38(1):65-81.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-04T11:06:30.000-05:00",
    "volume" : "38",
    "pages" : "65-81",
    "abstract" : "The adult rat hippocampus contains fibroblast growth factor 2-responsive stem cells that are self-renewing and have the ability to generate both neurons and glia in vitro, but little is known about the molecular events that regulate stem cell differentiation. Hippocampus-derived stem cell clones were used to examine the effects of retinoic acid (RA) on neuronal differentiation. Exposure to RA caused an immediate up-regulation of NeuroD, increased p21 expression, and concurrent exit from cell cycle. These changes were accompanied by a threefold increase in the number of cells differentiating into immature neurons. An accompanying effect of RA was to sustain or up-regulate trkA, trkB, trkC, and p75NGFR expression. Without RA treatment, cells were minimally responsive to neurotrophins (NTs), whereas the sequential application of RA followed by brain-derived neurotrophic factor or NT-3 led to a significant increase in neurons displaying mature y-a-minobutyric acid, acetylcholinesterase, tyrosine hydroxylase, or calbindin phenotypes. Although NTs promoted maturation, they had little effect on the total number of neurons generated, suggesting that RA and neurotrophins acted at distinct stages in neurogenesis. RA first promoted the acquisition of a neuronal fate, and NTs subsequently enhanced maturation by way of RA-dependent expression of the Trk receptors. In combination, these sequential effects were sufficient to stimulate stem cell-derived progenitors to differentiate into neurons displaying a variety of transmitter phenotypes.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Takahashi",
      "authorRank" : 1,
      "name" : "Takahashi J",
      "referenceId" : "RGD:A26539"
    }, {
      "firstName" : "TD",
      "lastName" : "Palmer",
      "authorRank" : 2,
      "name" : "Palmer TD",
      "referenceId" : "RGD:A26541"
    }, {
      "firstName" : "FH",
      "lastName" : "Gage",
      "authorRank" : 3,
      "name" : "Gage FH",
      "referenceId" : "RGD:A33912"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2325652"
    } ]
  }, {
    "primaryId" : "PMID:10027710",
    "title" : "Identification of a novel mutation in a non-Jewish factor XI deficient kindred.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Alhaq A, etal., Br J Haematol. 1999 Jan;104(1):44-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:22:26.000-05:00",
    "volume" : "104",
    "pages" : "44-9",
    "abstract" : "The role of factor XI (FXI) in blood coagulation has been clarified in recent years by descriptions of FXI-deficient patients who are prone to excessive bleeding after haemostatic challenge. We have studied a large kindred of an Italian FXI-deficient patient with a previously undescribed mutation. The propositus, a 68-year-old woman, presented with a cerebral thromboembolic event but had no history of bleeding (FXI activity 1.6 U/dl). A sensitive ELISA failed  to detect FXI antigen in the propositus. Sequence analysis of the entire FXI gene revealed a TGG to TGC transversion in codon 228 of exon 7 (FXI-W228C). This missense mutation results in a Trp to Cys substitution within the third apple domain of FXI. We conclude that this novel mutation occurred in a structurally conserved region and may therefore have interfered with either chain folding and  secretion or stability of FXI and was responsible for the inherited abnormality seen in this kindred. It is unclear why this kindred does not exhibit a bleeding  tendency but it may correlate with a FXI-like antigen and factor IX binding activity expressed on platelets.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Alhaq",
      "authorRank" : 1,
      "name" : "Alhaq A",
      "referenceId" : "RGD:A66137"
    }, {
      "firstName" : "M",
      "lastName" : "Mitchell",
      "authorRank" : 2,
      "name" : "Mitchell",
      "referenceId" : "RGD:A195140"
    }, {
      "firstName" : "M",
      "lastName" : "Sethi",
      "authorRank" : 3,
      "name" : "Sethi",
      "referenceId" : "RGD:A284176"
    }, {
      "firstName" : "S",
      "lastName" : "Rahman",
      "authorRank" : 4,
      "name" : "Rahman S",
      "referenceId" : "RGD:A26014"
    }, {
      "firstName" : "G",
      "lastName" : "Flynn",
      "authorRank" : 5,
      "name" : "Flynn G",
      "referenceId" : "RGD:A116185"
    }, {
      "firstName" : "P",
      "lastName" : "Boulton",
      "authorRank" : 6,
      "name" : "Boulton",
      "referenceId" : "RGD:A284177"
    }, {
      "firstName" : "G",
      "lastName" : "Caeno",
      "authorRank" : 7,
      "name" : "Caeno",
      "referenceId" : "RGD:A284178"
    }, {
      "firstName" : "M",
      "lastName" : "Smith",
      "authorRank" : 8,
      "name" : "Smith",
      "referenceId" : "RGD:A359038"
    }, {
      "firstName" : "G",
      "lastName" : "Savidge",
      "authorRank" : 9,
      "name" : "Savidge",
      "referenceId" : "RGD:A265107"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073304"
    } ]
  }, {
    "primaryId" : "PMID:10027744",
    "title" : "Caco-2 cells in culture synthesize and degrade dopamine and 5-hydroxytryptamine: a comparison with rat jejunal epithelial cells.",
    "datePublished" : "1000-03-01T00:00:00.000-06:00",
    "citation" : "Vieira-Coelho MA, etal., Life Sci. 1999;64(1):69-81.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-03-28T12:39:10.000-05:00",
    "volume" : "64",
    "pages" : "69-81",
    "abstract" : "To explore the usefulness of Caco-2 cells in the study of intestinal dopaminergic and 5-hydroxytryptaminergic physiology, we have undertaken the study of aromatic L-amino acid decarboxylase (AADC), catechol-O-methyltransferase (COMT) and type A and B monoamine oxidase (MAO-A and MAO-B) activities in these cells using specific substrates. The activity of these enzymes was also evaluated in isolated rat jejunal epithelial cells. The results showed that Vmax values (in nmol mg protein(-1) h(-1)) for AADC, using L-DOPA as the substrate, in rat jejunal epithelial cells (127.3+/-11.4) were found to be 6-fold higher than in Caco-2 cells (22.5+/-2.6). However, Km values in Caco-2 cells (1.24+/-0.37 mM) were similar to those observed in rat jejunal epithelial cells (1.30+/-0.29 mM). Similar results were obtained when AADC activity was evaluated using L-5HTP as substrate; in rat jejunal epithelial cells Vmax values (in nmol mg prot(-1) h(-1)) were found to be 5-fold that in Caco-2 cells (16.3+/-1.0 and 3.0+/-0.2, respectively), and Km values in Caco-2 cells (0.23+/-0.08 mM) were again similar to those observed in rat intestinal epithelial cells (0.09+/-0.03 mM). Caco-2 cells were not able to O-methylate dopamine, in contrast to rat jejunal epithelial cells (Vmax = 8.6+/-0.4 nmol mg protein(-1)(h-1); Km = 516+/-57 microM). Vmax values (in nmol mg protein(-1)(h-1)) for type A and B MAO in Caco-2 cells (19.0+/-0.6 and 5.4+/-0.6, respectively) were found to be significantly lower (P<0.05) than those in rat jejunal epithelial cells (46.9+/-3.1 and 9.6+/-1.2, respectively); however, no significant differences in the Km values were observed between Caco-2 and rat jejunal epithelial cells for both type A and B MAO. In conclusion, Caco-2 cells in culture are endowed with the synthetic and metabolic machinery needed to form and degrade DA and 5-HT, though, no COMT activity could be detected in these cells.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MA",
      "lastName" : "Vieira-Coelho",
      "authorRank" : 1,
      "name" : "Vieira-Coelho MA",
      "referenceId" : "RGD:A60831"
    }, {
      "firstName" : "VL",
      "lastName" : "Teixeira",
      "authorRank" : 2,
      "name" : "Teixeira VL",
      "referenceId" : "RGD:A137025"
    }, {
      "firstName" : "JT",
      "lastName" : "Guimaraes",
      "authorRank" : 3,
      "name" : "Guimaraes JT",
      "referenceId" : "RGD:A137026"
    }, {
      "firstName" : "MP",
      "lastName" : "Serrao",
      "authorRank" : 4,
      "name" : "Serrao MP",
      "referenceId" : "RGD:A75962"
    }, {
      "firstName" : "P",
      "lastName" : "Soares-da-Silva",
      "authorRank" : 5,
      "name" : "Soares-da-Silva P",
      "referenceId" : "RGD:A54374"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5129182"
    } ]
  }, {
    "primaryId" : "PMID:10027774",
    "title" : "Experimental axonal injury triggers interleukin-6 mRNA, protein synthesis and release into cerebrospinal fluid.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hans VH, etal., J Cereb Blood Flow Metab. 1999 Feb;19(2):184-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-08T15:46:57.000-05:00",
    "volume" : "19",
    "pages" : "184-94",
    "abstract" : "Diffuse axonal injury is a frequent pathologic sequel of head trauma, which, despite its devastating consequences for the patients, remains to be fully elucidated. Here we studied the release of interleukin-6 (IL-6) into CSF and serum, as well as the expression of IL-6 messenger ribonucleic acid (mRNA) and protein in a weight drop model of axonal injury in the rat. The IL-6 activity was elevated in CSF within 1 hour and peaked between 2 and 4 hours, reaching maximal  values of 82,108 pg/mL, and returned to control values after 24 hours. In serum,  the levels of IL-6 remained below increased CSF levels and did not exceed 393 pg/mL. In situ hybridization demonstrated augmented IL-6 mRNA expression in several regions including cortical pyramidal cells, neurons in thalamic nuclei, and macrophages in the basal subarachnoid spaces. A weak constitutive expression  of IL-6 protein was shown by immunohistochemical study in control brain. After injury, IL-6 increased at 1 hour and remained elevated through the first 24 hours, returning to normal afterward. Most cells producing IL-6 were cortical, thalamic, and hippocampal neurons as confirmed by staining for the neuronal marker NeuN. These results extend our previous studies showing IL-6 production in the cerebrospinal fluid of patients with severe head trauma and demonstrate that  neurons are the main source of IL-6 after experimental axonal injury.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "VH",
      "lastName" : "Hans",
      "authorRank" : 1,
      "name" : "Hans",
      "referenceId" : "RGD:A199196"
    }, {
      "firstName" : "T",
      "lastName" : "Kossmann",
      "authorRank" : 2,
      "name" : "Kossmann",
      "referenceId" : "RGD:A215865"
    }, {
      "firstName" : "PM",
      "lastName" : "Lenzlinger",
      "authorRank" : 3,
      "name" : "Lenzlinger",
      "referenceId" : "RGD:A215866"
    }, {
      "firstName" : "R",
      "lastName" : "Probstmeier",
      "authorRank" : 4,
      "name" : "Probstmeier",
      "referenceId" : "RGD:A197881"
    }, {
      "firstName" : "HG",
      "lastName" : "Imhof",
      "authorRank" : 5,
      "name" : "Imhof",
      "referenceId" : "RGD:A215867"
    }, {
      "firstName" : "O",
      "lastName" : "Trentz",
      "authorRank" : 6,
      "name" : "Trentz",
      "referenceId" : "RGD:A198520"
    }, {
      "firstName" : "MC",
      "lastName" : "Morganti-Kossmann",
      "authorRank" : 7,
      "name" : "Morganti-Kossmann",
      "referenceId" : "RGD:A206309"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11049549"
    } ]
  }, {
    "primaryId" : "PMID:10027934",
    "title" : "Effects of phosphate intake on distribution of type II Na/Pi cotransporter mRNA in rat kidney.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Ritthaler T, etal., Kidney Int. 1999 Mar;55(3):976-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-01T09:14:27.000-05:00",
    "volume" : "55",
    "pages" : "976-83",
    "abstract" : "BACKGROUND: Renal phosphate (Pi) reabsorption is regulated by dietary Pi intake,  as well as in other ways. Changes in Pi reabsorption are associated with the modulation of sodium/Pi cotransporter type II (NaPi-2) protein abundance in the brush border membrane (BBM) of proximal tubules (PTs) and of renal NaPi-2 mRNA levels. In this study, we address whether the NaPi-2 protein and NaPi-2 mRNA distribution patterns in the renal cortex vary in parallel with changes of dietary Pi intake. METHODS: We investigated in cryosections of perfusion-fixed rat kidneys by in situ hybridization (ISH) and immunohistochemistry (IHC) the distribution patterns of NaPi-2 mRNA and of NaPi-2 protein one week, two hours, and four hours after changes in dietary Pi intake. RESULTS: NaPi-2 mRNA and NaPi-2 protein were present in PTs exclusively. In rats adapted to one week of high Pi intake, signals for NaPi-2 mRNA and NaPi-2 protein in cortical PTs were weak, except in the convoluted parts of PTs of juxtamedullary nephrons. After one week of low Pi intake, the ISH and IHC signals for NaPi-2 were high in PT segments in all cortical levels. The switch from a chronic high to a low Pi intake within two and four hours induced no increase and a slight increase, respectively, in the NaPi-2 mRNA signal in PTs of midcortical and of superficial  nephrons, whereas in the BBM of these nephrons, NaPi-2 protein was markedly up-regulated. Two and four hours after switching from low to high Pi intake, the  overall high ISH signal for NaPi-2 mRNA was unchanged, whereas NaPi-2 protein staining was drastically down-regulated in the BBM of PTs from superficial and midcortical nephrons. CONCLUSIONS: The marked changes in NaPi-2 protein abundance in the BBM, following altered dietary Pi intake, precede corresponding changes at the RNA level by several hours. Thus, the early adaptation to altered Pi intake involves mRNA-independent mechanisms. The up- or down-regulation of NaPi-2 protein abundance in the BBM and NaPi-2 mRNA in PT affects mainly midcortical and superficial nephrons.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Ritthaler",
      "authorRank" : 1,
      "name" : "Ritthaler",
      "referenceId" : "RGD:A169475"
    }, {
      "firstName" : "M",
      "lastName" : "Traebert",
      "authorRank" : 2,
      "name" : "Traebert",
      "referenceId" : "RGD:A169472"
    }, {
      "firstName" : "M",
      "lastName" : "Lotscher",
      "authorRank" : 3,
      "name" : "Lotscher",
      "referenceId" : "RGD:A169473"
    }, {
      "firstName" : "J",
      "lastName" : "Biber",
      "authorRank" : 4,
      "name" : "Biber",
      "referenceId" : "RGD:A403617"
    }, {
      "firstName" : "H",
      "lastName" : "Murer",
      "authorRank" : 5,
      "name" : "Murer",
      "referenceId" : "RGD:A341576"
    }, {
      "firstName" : "B",
      "lastName" : "Kaissling",
      "authorRank" : 6,
      "name" : "Kaissling B",
      "referenceId" : "RGD:A89473"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7243095"
    } ]
  }, {
    "primaryId" : "PMID:10028916",
    "title" : "TGF-beta1-dependent differential expression of a rat homolog for latent TGF-beta binding protein in astrocytes and C6 glioma cells.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Krohn K Glia 1999 Feb 15;25(4):332-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-07-31T12:14:22.000-05:00",
    "volume" : "25",
    "pages" : "332-42",
    "abstract" : "Transforming growth factor-beta1 (TGF-beta1) is widely recognized for its multiple roles in development, cellular maintenance, and protection against injury. In the brain, TGF-beta1 upregulation in microglia/macrophages is a predominant response to lesion and during pathology. However, the precise functions of TGF-beta1 in this context are still enigmatic. The present study investigates changes in astroglial gene expression as a major target of TGF-beta1 signaling in the brain. Differential display reverse transcription-polymerase chain reaction (DDRT-PCR) was used to identify several gene fragments differentially regulated by TGF-beta1 in rat astrocytes and C6 glioma cells. Among the cDNAs regulated by TGF-beta1 in C6 cells two cDNAs showed homology to alpha-tropomyosin and glycerol-3-phosphate dehydrogenase, respectively. Cloning of a full length cDNA corresponding to a differentially regulated gene fragment revealed close homology to latent TGF-beta binding protein (LTBP)-2. Data using antisense LTBP-2 oligonucleotides to decrease LTBP-2 expression suggest that LTBP-2 functions to activate TGF-beta. Therefore, it is likely that upregulation of the rat LTBP-2 homolog mRNA in C6 cells and cortical astrocytes by TGF-1 might lead to self-activation and exaggeration of TGF-beta signaling. These data will extend our current understanding of TGF-beta1 functioning on lesion-related features of glial cells.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Krohn",
      "authorRank" : 1,
      "name" : "Krohn K",
      "referenceId" : "RGD:A4977"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68276"
    } ]
  }, {
    "primaryId" : "PMID:10029074",
    "title" : "Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (Tsc1) and analysis of its mutations in rat renal carcinomas.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Satake N, etal., Cancer Res 1999 Feb 15;59(4):849-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-08-14T16:46:10.000-05:00",
    "volume" : "59",
    "pages" : "849-55",
    "abstract" : "In the Eker rat, a germ-line mutation in the homologue of the human tuberous sclerosis gene (Tsc2) causes renal cell carcinomas (RCs) with a complete penetrance in all heterozygotes. Tsc2 mutations have also been found in a subset of chemically induced non-Eker rat RCs. Because tuberous sclerosis patients with alteration of either of the two predisposing genes (TSC1 and TSC2) show identical symptoms, the products of these two genes are thought to be involved in a common biological pathway. In this study, to analyze the possible overlap between the functions of Tsc2 and Tscl gene products, we isolated and characterized a rat homologue of the TSC1 gene (Tsc1). The rat Tsc1 gene, which has an identical exon-intron structure to that of human TSC1 and is localized on rat chromosome 3, has been shown to encode a protein (hamartin) that is highly homologous to the human counterpart with an approximately 86% amino acid sequence identity. Using PCR-single-strand conformational polymorphism analysis, we identified two splicing donor site mutations in one chemically induced rat RC (1 of 15). This suggests that alterations of the Tsc1 gene may be involved in the development of a subset of rat RCs.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Satake",
      "authorRank" : 1,
      "name" : "Satake N",
      "referenceId" : "RGD:A5221"
    }, {
      "firstName" : "T",
      "lastName" : "Kobayashi",
      "authorRank" : 2,
      "name" : "Kobayashi T",
      "referenceId" : "RGD:A5222"
    }, {
      "firstName" : "E",
      "lastName" : "Kobayashi",
      "authorRank" : 3,
      "name" : "Kobayashi E",
      "referenceId" : "RGD:A5223"
    }, {
      "firstName" : "K",
      "lastName" : "Izumi",
      "authorRank" : 4,
      "name" : "Izumi K",
      "referenceId" : "RGD:A5224"
    }, {
      "firstName" : "O",
      "lastName" : "Hino",
      "authorRank" : 5,
      "name" : "Hino O",
      "referenceId" : "RGD:A5225"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68666"
    } ]
  }, {
    "primaryId" : "PMID:10029085",
    "title" : "Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Astrom AK, etal., Cancer Res. 1999 Feb 15;59(4):918-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-16T13:48:48.000-06:00",
    "volume" : "59",
    "pages" : "918-23",
    "abstract" : "We have previously shown (K. Kas et al, Nat. Genet., 15: 170-174, 1997) that the developmentally regulated zinc finger gene pleomorphic adenoma gene 1 (PLAG1) is the target gene in 8q12 in pleomorphic adenomas of the salivary glands with t(3;8)(p21;q12) translocations. The t(3;8) results in promoter swapping between PLAG1 and the constitutively expressed gene for beta-catenin (CTNNB1), leading to activation of PLAG1 expression and reduced expression of CTNNB1. Here we have studied the expression of PLAG1 by Northern blot analysis in 47 primary benign and malignant human tumors with or without cytogenetic abnormalities of 8q12. Overexpression of PLAG1 was found in 23 tumors (49%). Thirteen of 17 pleomorphic adenomas with a normal karyotype and 5 of 10 with 12q13-15 abnormalities overexpressed PLAG1, which demonstrates that PLAG1 activation is a frequent event in adenomas irrespective of karyotype. In contrast, PLAG1 was overexpressed in only 2 of 11 malignant salivary gland tumors analyzed, which suggests that, at least in salivary gland tumors, PLAG1 activation preferentially occurs in benign tumors. PLAG1 over-expression was also found in three of nine mesenchymal tumors, i.e., in two uterine leiomyomas and one leiomyosarcoma. RNase protection, rapid amplification of 5'-cDNA ends (5'-RACE), and reverse transcription-PCR analyses of five adenomas with a normal karyotype revealed fusion transcripts in three tumors. Nucleotide sequence analysis of these showed that they contained fusions between PLAG1 and CTNNB1 (one case) or PLAG1 and a novel fusion partner gene, i.e., the gene encoding the transcription elongation factor SII (two cases). The fusions occurred in the 5' noncoding region of PLAG1, leading to exchange of regulatory control elements and, as a consequence, activation of PLAG1 gene expression. Because all of the cases had grossly normal karyotypes, the rearrangements must result from cryptic rearrangements. The results suggest that in addition to chromosomal translocations and cryptic rearrangements, PLAG1 may also be activated by mutations or indirect mechanisms. Our findings establish a conserved mechanism of PLAG1 activation in salivary gland tumors with and without 8q12 aberrations, which indicates that such activation is a frequent event in these tumors.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AK",
      "lastName" : "Astrom",
      "authorRank" : 1,
      "name" : "Astrom AK",
      "referenceId" : "RGD:A50768"
    }, {
      "firstName" : "ML",
      "lastName" : "Voz",
      "authorRank" : 2,
      "name" : "Voz ML",
      "referenceId" : "RGD:A72428"
    }, {
      "firstName" : "K",
      "lastName" : "Kas",
      "authorRank" : 3,
      "name" : "Kas K",
      "referenceId" : "RGD:A72429"
    }, {
      "firstName" : "E",
      "lastName" : "Roijer",
      "authorRank" : 4,
      "name" : "Roijer E",
      "referenceId" : "RGD:A50770"
    }, {
      "firstName" : "B",
      "lastName" : "Wedell",
      "authorRank" : 5,
      "name" : "Wedell B",
      "referenceId" : "RGD:A72430"
    }, {
      "firstName" : "N",
      "lastName" : "Mandahl",
      "authorRank" : 6,
      "name" : "Mandahl N",
      "referenceId" : "RGD:A25388"
    }, {
      "firstName" : "W",
      "lastName" : "Van de Ven",
      "authorRank" : 7,
      "name" : "Van de Ven W",
      "referenceId" : "RGD:A53764"
    }, {
      "firstName" : "J",
      "lastName" : "Mark",
      "authorRank" : 8,
      "name" : "Mark J",
      "referenceId" : "RGD:A72431"
    }, {
      "firstName" : "G",
      "lastName" : "Stenman",
      "authorRank" : 9,
      "name" : "Stenman G",
      "referenceId" : "RGD:A50773"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599086"
    } ]
  }, {
    "primaryId" : "PMID:10029567",
    "title" : "Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Dryden S, etal., Clin Sci (Lond). 1999 Mar;96(3):307-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-07-15T14:55:01.000-05:00",
    "volume" : "96",
    "pages" : "307-12",
    "abstract" : "Leptin inhibits feeding and decreases body weight. It may act partly by inhibiting hypothalamic neurons that express neuropeptide Y, a powerful inducer of feeding and obesity. These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat. The fa mutation affects the extracellular domain of the leptin receptor, but its impact on leptin action and neuropeptide Y neuronal activity is not fully known. We compared the effects of three doses of leptin given intracerebroventricularly and three doses  of leptin injected intraperitoneally on food intake and hypothalamic neuropeptide Y mRNA, in lean and fatty Zucker rats. In lean rats, 4-h food intake was reduced  in a dose-related fashion (P<0.01) by all intracerebroventricular leptin doses and by intraperitoneal doses of 300 and 600 microg/kg. Neuropeptide Y mRNA levels were reduced by 28% and 21% after the highest intracerebroventricular and intraperitoneal doses respectively (P<0. 01 for both). In fatty rats, only the highest intracerebroventricular leptin dose reduced food intake (by 22%; P<0. 01). Neuropeptide Y mRNA levels were 100% higher in fatty rats than in lean animals, and were reduced by 18% (P<0.01) after the highest intracerebroventricular leptin dose. Intraperitoneal injection had no effect on food intake and neuropeptide Y mRNA. The fa/fa Zucker rat is therefore less sensitive to leptin given intracerebroventricularly and particularly intraperitoneally, suggesting that the fa mutation interferes both with leptin's  direct effects on neurons and its transport into the central nervous system. Obesity in the fa/fa Zucker rat may be partly due to the inability of leptin to inhibit hypothalamic neuropeptide Y neurons.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Dryden",
      "authorRank" : 1,
      "name" : "Dryden",
      "referenceId" : "RGD:A204477"
    }, {
      "firstName" : "P",
      "lastName" : "King",
      "authorRank" : 2,
      "name" : "King P",
      "referenceId" : "RGD:A82567"
    }, {
      "firstName" : "L",
      "lastName" : "Pickavance",
      "authorRank" : 3,
      "name" : "Pickavance",
      "referenceId" : "RGD:A204478"
    }, {
      "firstName" : "P",
      "lastName" : "Doyle",
      "authorRank" : 4,
      "name" : "Doyle",
      "referenceId" : "RGD:A204479"
    }, {
      "firstName" : "G",
      "lastName" : "Williams",
      "authorRank" : 5,
      "name" : "Williams G",
      "referenceId" : "RGD:A82568"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10053612"
    } ]
  }, {
    "primaryId" : "PMID:10029626",
    "title" : "Involvement of CD95 (Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Müschen M, etal., Gastroenterology. 1999 Mar;116(3):666-77. doi: 10.1016/s0016-5085(99)70189-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-08-13T13:25:30.000-05:00",
    "volume" : "116",
    "pages" : "666-77",
    "abstract" : "<br><b>BACKGROUND & AIMS: </b>CD95 (Apo-1/Fas) ligand suppresses inflammatory responses in immune-privileged organs. In this study, modulation of the hepatic CD95 receptor/ligand system by interferon gamma and cyclosporin A was investigated.<br><b>METHODS: </b>CD95 receptor and ligand expression were measured at the messenger RNA level by using quantitative reverse-transcription polymerase chain reaction and immunocytochemistry in primary cultures of rat Kupffer cells, hepatocytes, and T lymphocytes. Soluble CD95 in culture supernatants was detected by enzyme-linked immunosorbent assay and apoptosis by the TUNEL method.<br><b>RESULTS: </b>Interferon gamma treatment led to an increase in CD95 ligand messenger RNA levels in Kupffer cells followed by an overexpression of the soluble CD95 receptor. Supernatants derived from 24-hour but not from 48-hour interferon gamma-treated Kupffer cells killed lymphocytes by a CD95-dependent mechanism. Cyclosporin A inhibited CD95 ligand expression in Kupffer cells and lymphocyte killing. In liver parenchymal cells, interferon gamma increased messenger RNA levels of the transmembrane CD95 isoform and sensitivity of these cells toward CD95-mediated apoptosis.<br><b>CONCLUSIONS: </b>The expression pattern of CD95 receptor and ligand in response to interferon gamma points to a coordinated interplay between Kupffer cells, hepatocytes, and T lymphocytes in which Kupffer cells may regulate programmed cell death of T lymphocytes and hepatocytes.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Müschen",
      "authorRank" : 1,
      "name" : "Müschen M",
      "referenceId" : "RGD:A472593"
    }, {
      "firstName" : "U",
      "lastName" : "Warskulat",
      "authorRank" : 2,
      "name" : "Warskulat U",
      "referenceId" : "RGD:A17362"
    }, {
      "firstName" : "T",
      "lastName" : "Peters-Regehr",
      "authorRank" : 3,
      "name" : "Peters-Regehr T",
      "referenceId" : "RGD:A472594"
    }, {
      "firstName" : "J G",
      "lastName" : "Bode",
      "authorRank" : 4,
      "name" : "Bode JG",
      "referenceId" : "RGD:A472595"
    }, {
      "firstName" : "R",
      "lastName" : "Kubitz",
      "authorRank" : 5,
      "name" : "Kubitz R",
      "referenceId" : "RGD:A70753"
    }, {
      "firstName" : "D",
      "lastName" : "Häussinger",
      "authorRank" : 6,
      "name" : "Häussinger D",
      "referenceId" : "RGD:A472596"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14700709"
    } ]
  }, {
    "primaryId" : "PMID:10030017",
    "title" : "Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Bhimani RS, etal., J Appl Microbiol. 1999 Jan;86(1):135-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-21T10:59:28.000-05:00",
    "volume" : "86",
    "pages" : "135-44",
    "abstract" : "Human and bovine lactoferrins (Lfs) and bovine lactoferrin hydrolysate (LH) were  assessed in vitro and in vivo for their antibacterial effects on Staphylococcus aureus. Lactoferrins showed weak in vitro antibacterial activity while Fe-saturated Lfs and LH showed no activity. Lactoferrin-treated mice (1 mg, i.v.) when injected i.v. with 10(6) staphylococci, showed 30-50% reduction in kidney infections, and viable bacterial counts in the kidneys decreased 5-12-fold. The inhibitory effect was dose-dependent up to 1 mg Lf. Lactoferrins were effective when given 1 day prior to the bacterial challenge, after which there was no significant effect even at doses up to 5 mg. Apo- and Fe-saturated forms of human and bovine Lfs were all equally effective, while LH was not protective. Human and bovine Lfs with different degrees of iron saturation (9-97%) were found to be equipotent. Feeding mice with 2% bLf in drinking water also reduced the kidney infections by 40-60%, and viable bacterial counts, 5-12-fold. The results suggest a potential for the use of Lfs as natural antibacterial proteins for preventing bacterial infections.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RS",
      "lastName" : "Bhimani",
      "authorRank" : 1,
      "name" : "Bhimani",
      "referenceId" : "RGD:A169952"
    }, {
      "firstName" : "Y",
      "lastName" : "Vendrov",
      "authorRank" : 2,
      "name" : "Vendrov",
      "referenceId" : "RGD:A169953"
    }, {
      "firstName" : "P",
      "lastName" : "Furmanski",
      "authorRank" : 3,
      "name" : "Furmanski",
      "referenceId" : "RGD:A169954"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7243953"
    } ]
  }, {
    "primaryId" : "PMID:10030835",
    "title" : "Antigen-induced airway hyperresponsiveness, pulmonary eosinophilia, and chemokine expression in B cell-deficient mice.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "MacLean JA, etal., Am J Respir Cell Mol Biol. 1999 Mar;20(3):379-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:34:40.000-05:00",
    "volume" : "20",
    "pages" : "379-87",
    "abstract" : "Murine models of allergen-induced pulmonary inflammation share many features with human asthma, including the development of antigen-induced pulmonary eosinophilia, airway hyperresponsiveness, antigen-specific cellular and antibody  responses, the elaboration of Th2 cytokines (interleukin [IL]-4 and IL-5), and the expression of chemokines with activity for eosinophils. We examined the role  of B cells and antigen-specific antibody responses in such a model by studying the histopathologic and physiologic responses of B cell-deficient mice compared with wild-type controls, following systemic immunization and airway challenge with ovalbumin (OVA). Both OVA-challenged wild-type and B cell-deficient mice developed (1) airway hyperresponsiveness, (2) pulmonary inflammation with activated T cells and eosinophils, (3) IL-4 and IL-5 secretion into the airway lumen, and (4) increased expression of the eosinophil active chemokines eotaxin and monocyte chemotactic protein-3. There were no significant differences in either the pathologic or physiologic responses in the B cell-deficient mice compared with wild-type mice. These data indicate that B cells and antigen-specific antibodies are not required for the development of airway hyperresponsiveness, eosinophilic pulmonary inflammation, and chemokine expression in sensitized mice following aerosol challenge with antigen.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "MacLean",
      "authorRank" : 1,
      "name" : "MacLean JA",
      "referenceId" : "RGD:A26297"
    }, {
      "firstName" : "A",
      "lastName" : "Sauty",
      "authorRank" : 2,
      "name" : "Sauty A",
      "referenceId" : "RGD:A141794"
    }, {
      "firstName" : "AD",
      "lastName" : "Luster",
      "authorRank" : 3,
      "name" : "Luster AD",
      "referenceId" : "RGD:A26624"
    }, {
      "firstName" : "JM",
      "lastName" : "Drazen",
      "authorRank" : 4,
      "name" : "Drazen JM",
      "referenceId" : "RGD:A35843"
    }, {
      "firstName" : "GT",
      "lastName" : "De Sanctis",
      "authorRank" : 5,
      "name" : "De Sanctis GT",
      "referenceId" : "RGD:A13484"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340559"
    } ]
  }, {
    "primaryId" : "PMID:10030843",
    "title" : "The role of alpha4 (CD49d) and beta2 (CD18) integrins in eosinophil and neutrophil migration to allergic lung inflammation in the Brown Norway rat.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Schneider T, etal., Am J Respir Cell Mol Biol. 1999 Mar;20(3):448-57.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-04-19T14:59:06.000-05:00",
    "volume" : "20",
    "pages" : "448-57",
    "abstract" : "We investigated the role of beta2 (CD18) and alpha4 (CD49d) integrins in eosinophil and neutrophil recruitment to lung parenchyma and bronchoalveolar lavage fluid (BALF) of allergen-challenged Brown Norway (BN) rats. Challenge of sensitized BN rats with ovalbumin induced an eosinophil- and neutrophil-rich infiltrate in BALF at 24 h, accompanied by an increase in BALF protein content. Treatment with either the TA-2 monoclonal antibody (mAb) against alpha4 (as an F[ab']2 fragment) or the WT.3 mAb against beta2 integrin significantly reduced eosinophil and neutrophil accumulation in BALF by 54 to 66% and eosinophil accumulation in the parenchyma by 48%. A significant difference in effect was observed between mAb TA-2 in intact immunoglobulin G or F(ab)2 form. Combined treatment with mAbs WT.3 plus TA-2 (F[ab]2) virtually abolished eosinophil accumulation in BALF and in the parenchyma, and reduced neutrophil accumulation in BALF by 91%. In contrast, neutrophil accumulation in the lung was not inhibited by these mAb treatments. The increase in BALF protein concentration was significantly inhibited by TA-2 (by 40%) and by WT.3 plus TA-2 in combination (71% inhibition). We conclude that eosinophil and neutrophil migration into the air space in allergic lung inflammation is partially CD18 (beta2)- and CD49d (alpha4)- dependent and that alpha4 integrins mediate essentially all of the CD18-independent migration. Similarly, eosinophil accumulation in the parenchyma  is completely alpha4 and CD18 (beta2) integrin-dependent. In marked contrast, neutrophil accumulation in the lung in this allergen model can occur independently of both alpha4 and beta2 integrins.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Schneider",
      "authorRank" : 1,
      "name" : "Schneider T",
      "referenceId" : "RGD:A6233"
    }, {
      "firstName" : "TB",
      "lastName" : "Issekutz",
      "authorRank" : 2,
      "name" : "Issekutz TB",
      "referenceId" : "RGD:A1165"
    }, {
      "firstName" : "AC",
      "lastName" : "Issekutz",
      "authorRank" : 3,
      "name" : "Issekutz AC",
      "referenceId" : "RGD:A118992"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6482228"
    } ]
  }, {
    "primaryId" : "PMID:10036219",
    "title" : "Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Abbott BD, etal., Toxicol Appl Pharmacol. 1999 Feb 15;155(1):62-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-02-22T15:44:37.000-06:00",
    "volume" : "155",
    "pages" : "62-70",
    "abstract" : "The aryl hydrocarbon receptor (AHR) is a transcriptional regulatory protein that binds to upstream DNA response elements of target genes. Activation of the AHR by binding of ligands such as polyhalogenated dioxins, furans, and PCBs is associated with a wide range of adverse biological outcomes, including cancer, immune deficiencies, embryo/fetotoxicity, and reproductive toxicity. Investigations of the diverse biological responses mediated by the AHR led to production of a transgenic mouse in which the gene coding for the AhR was inactivated. AHR-deficient mice were fertile and at maturity exhibited immune system impairment and hepatic fibrosis. Our laboratory received several of these homozygous knockout (-/-) mice and mated them with wild-type (+/+) C57BL/6N mice to generate large numbers of heterozygotes (+/-). The -/- males were then mated with a total of 45 heterozygous +/- females. Offspring of these matings were genotyped and mated in all genotypic combinations. Although male and female -/- adults were fertile, the -/- females had difficulty maintaining conceptuses during pregnancy, surviving pregnancy and lactation, and rearing pups to weaning. Only 46% of the 39 pregnant -/- females successfully raised pups to weaning. The -/- pups showed poor survival during lactation (average death rate per litter was 16%) and after weaning (26.5% of the 230 weaned -/- pups died within 2 weeks). Only 39% of the implantations in uteri of -/- dams resulted in offspring surviving to Postnatal Day 45. Across all litters the sex ratios and genotypic frequencies were comparable to expected values. Reproductive success was adversely affected in Ahr-null females and conceptuses. Additional study is needed to reveal the etiology of these effects.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BD",
      "lastName" : "Abbott",
      "authorRank" : 1,
      "name" : "Abbott BD",
      "referenceId" : "RGD:A58376"
    }, {
      "firstName" : "JE",
      "lastName" : "Schmid",
      "authorRank" : 2,
      "name" : "Schmid JE",
      "referenceId" : "RGD:A58377"
    }, {
      "firstName" : "JA",
      "lastName" : "Pitt",
      "authorRank" : 3,
      "name" : "Pitt JA",
      "referenceId" : "RGD:A58378"
    }, {
      "firstName" : "AR",
      "lastName" : "Buckalew",
      "authorRank" : 4,
      "name" : "Buckalew AR",
      "referenceId" : "RGD:A58379"
    }, {
      "firstName" : "CR",
      "lastName" : "Wood",
      "authorRank" : 5,
      "name" : "Wood CR",
      "referenceId" : "RGD:A58380"
    }, {
      "firstName" : "GA",
      "lastName" : "Held",
      "authorRank" : 6,
      "name" : "Held GA",
      "referenceId" : "RGD:A58381"
    }, {
      "firstName" : "JJ",
      "lastName" : "Diliberto",
      "authorRank" : 7,
      "name" : "Diliberto JJ",
      "referenceId" : "RGD:A58382"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1576353"
    } ]
  }, {
    "primaryId" : "PMID:10036231",
    "title" : "Presence of the vesicular inhibitory amino acid transporter in GABAergic and glycinergic synaptic terminal boutons.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Dumoulin A, etal., J Cell Sci. 1999 Mar;112 ( Pt 6):811-23. doi: 10.1242/jcs.112.6.811.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-03-30T01:55:42.000-05:00",
    "volume" : "112 ( Pt 6)",
    "pages" : "811-23",
    "abstract" : "The characterization of the Caenorhabditis elegans unc-47 gene recently allowed the identification of a mammalian (gamma)-amino butyric acid (GABA) transporter, presumed to be located in the synaptic vesicle membrane. In situ hybridization data in rat brain suggested that it might also take up glycine and thus represent a general Vesicular Inhibitory Amino Acid Transporter (VIAAT). In the present study, we have investigated the localization of VIAAT in neurons by using a polyclonal antibody raised against the hydrophilic N-terminal domain of the protein. Light microscopy and immunocytochemistry in primary cultures or tissue sections of the rat spinal cord revealed that VIAAT was localized in a subset (63-65%) of synaptophysin-immunoreactive terminal boutons; among the VIAAT-positive terminals around motoneuronal somata, 32.9% of them were also immunoreactive for GAD65, a marker of GABAergic presynaptic endings. Labelling was also found apposed to clusters positive for the glycine receptor or for its associated protein gephyrin. At the ultrastructural level, VIAAT immunoreactivity was restricted to presynaptic boutons exhibiting classical inhibitory features and, within the boutons, concentrated over synaptic vesicle clusters. Pre-embedding detection of VIAAT followed by post-embedding detection of GABA or glycine on serial sections of the spinal cord or cerebellar cortex indicated that VIAAT was present in glycine-, GABA- or GABA- and glycine-containing boutons. Taken together, these data further support the view of a common vesicular transporter for these two inhibitory transmitters, which would be responsible for their costorage in the same synaptic vesicle and subsequent corelease at mixed GABA-and-glycine synapses.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Dumoulin",
      "authorRank" : 1,
      "name" : "Dumoulin A",
      "referenceId" : "RGD:A24327"
    }, {
      "firstName" : "P",
      "lastName" : "Rostaing",
      "authorRank" : 2,
      "name" : "Rostaing P",
      "referenceId" : "RGD:A13338"
    }, {
      "firstName" : "C",
      "lastName" : "Bedet",
      "authorRank" : 3,
      "name" : "Bedet C",
      "referenceId" : "RGD:A513742"
    }, {
      "firstName" : "S",
      "lastName" : "Lévi",
      "authorRank" : 4,
      "name" : "Lévi S",
      "referenceId" : "RGD:A513760"
    }, {
      "firstName" : "M F",
      "lastName" : "Isambert",
      "authorRank" : 5,
      "name" : "Isambert MF",
      "referenceId" : "RGD:A513761"
    }, {
      "firstName" : "J P",
      "lastName" : "Henry",
      "authorRank" : 6,
      "name" : "Henry JP",
      "referenceId" : "RGD:A513762"
    }, {
      "firstName" : "A",
      "lastName" : "Triller",
      "authorRank" : 7,
      "name" : "Triller A",
      "referenceId" : "RGD:A13340"
    }, {
      "firstName" : "B",
      "lastName" : "Gasnier",
      "authorRank" : 8,
      "name" : "Gasnier B",
      "referenceId" : "RGD:A13785"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:151665723"
    } ]
  }, {
    "primaryId" : "PMID:10037107",
    "title" : "Genetic mapping of the thymoma susceptible locus, Tsr1, in BUF/Mna rats.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Oyabu A, etal., J Natl Cancer Inst 1999 Feb 3;91(3):279-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-10-12T08:05:03.000-05:00",
    "volume" : "91",
    "pages" : "279-82",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Oyabu",
      "authorRank" : 1,
      "name" : "Oyabu A",
      "referenceId" : "RGD:A10760"
    }, {
      "firstName" : "K",
      "lastName" : "Higo",
      "authorRank" : 2,
      "name" : "Higo K",
      "referenceId" : "RGD:A10477"
    }, {
      "firstName" : "C",
      "lastName" : "Ye",
      "authorRank" : 3,
      "name" : "Ye C",
      "referenceId" : "RGD:A10476"
    }, {
      "firstName" : "H",
      "lastName" : "Amo",
      "authorRank" : 4,
      "name" : "Amo H",
      "referenceId" : "RGD:A24866"
    }, {
      "firstName" : "M",
      "lastName" : "Saito",
      "authorRank" : 5,
      "name" : "Saito M",
      "referenceId" : "RGD:A24865"
    }, {
      "firstName" : "S",
      "lastName" : "Yagyu",
      "authorRank" : 6,
      "name" : "Yagyu S",
      "referenceId" : "RGD:A10758"
    }, {
      "firstName" : "H",
      "lastName" : "Morita",
      "authorRank" : 7,
      "name" : "Morita H",
      "referenceId" : "RGD:A10761"
    }, {
      "firstName" : "K",
      "lastName" : "Maeda",
      "authorRank" : 8,
      "name" : "Maeda K",
      "referenceId" : "RGD:A10762"
    }, {
      "firstName" : "T",
      "lastName" : "Serikawa",
      "authorRank" : 9,
      "name" : "Serikawa T",
      "referenceId" : "RGD:A130780"
    }, {
      "firstName" : "M",
      "lastName" : "Takahashi",
      "authorRank" : 10,
      "name" : "Takahashi M",
      "referenceId" : "RGD:A4629"
    }, {
      "firstName" : "M",
      "lastName" : "Matsuyama",
      "authorRank" : 11,
      "name" : "Matsuyama M",
      "referenceId" : "RGD:A10478"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302468"
    } ]
  }, {
    "primaryId" : "PMID:10037450",
    "title" : "Mono- and Diglucuronide formation from benzopyrene and chrysene diphenols by AHH-1 cell-expressed UDP-glucuronosyltransferase UGT1A7.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Bock KW, etal., Biochem Pharmacol. 1999 Mar 15;57(6):653-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-12T08:33:11.000-06:00",
    "volume" : "57",
    "pages" : "653-6",
    "abstract" : "Polycyclic aromatic hydrocarbon (PAH)-type compounds induce at least two rat UDP-glucuronosyltransferase isoforms, UGT1A6 and UGT1A7. Among the glucuronidation reactions of PAH metabolites studied, mono- and diglucuronide formation of benzo[a]pyrene and chrysene-3,6-diphenol showed the highest induction factors in rat liver microsomes. Availability of AHH-1 cells stably expressing UGT1A7 allowed us to study whether this PAH-inducible isoform could catalyze benzo[a]pyrene and chrysene-3,6-diphenol glucuronidation. It was found that UGT1A7 indeed catalyzed mono- and diglucuronide formation of both benzo[a]pyrene and chrysene 3,6-diphenols. V79 cell-expressed rat UGT1A6 also catalyzed these reactions, except for chrysene diphenol diglucronide formation (Bock et al., Mol Pharmacol 42: 613-618, 1992). Enzyme kinetic studies of the glucuronidation of 6-hydroxychrysene (used as a stable PAH phenol) indicated that UGT1A7 conjugated this compound with a lower apparent Km value (0.1 microM) than UGT1A6 (10 microM). The results suggest that the two PAH-inducible UGTs may cooperate in conjugating PAH metabolites, but that UGT1A7 is more efficient.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KW",
      "lastName" : "Bock",
      "authorRank" : 1,
      "name" : "Bock KW",
      "referenceId" : "RGD:A19565"
    }, {
      "firstName" : "FT",
      "lastName" : "Raschko",
      "authorRank" : 2,
      "name" : "Raschko FT",
      "referenceId" : "RGD:A120278"
    }, {
      "firstName" : "H",
      "lastName" : "Gschaidmeier",
      "authorRank" : 3,
      "name" : "Gschaidmeier H",
      "referenceId" : "RGD:A120279"
    }, {
      "firstName" : "A",
      "lastName" : "Seidel",
      "authorRank" : 4,
      "name" : "Seidel A",
      "referenceId" : "RGD:A103475"
    }, {
      "firstName" : "F",
      "lastName" : "Oesch",
      "authorRank" : 5,
      "name" : "Oesch F",
      "referenceId" : "RGD:A18076"
    }, {
      "firstName" : "AD",
      "lastName" : "Grove",
      "authorRank" : 6,
      "name" : "Grove AD",
      "referenceId" : "RGD:A24094"
    }, {
      "firstName" : "JK",
      "lastName" : "Ritter",
      "authorRank" : 7,
      "name" : "Ritter JK",
      "referenceId" : "RGD:A24038"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317075"
    } ]
  }, {
    "primaryId" : "PMID:10037502",
    "title" : "Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Bassan M, etal., J Neurochem. 1999 Mar;72(3):1283-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-03T09:09:35.000-05:00",
    "volume" : "72",
    "pages" : "1283-93",
    "abstract" : "The vulnerability of neurons and the irreversibility of loss make discoveries of neuroprotective compounds fundamentally important. Here, the complete coding sequence of a novel protein (828 amino acids, pI 5.99), derived from mouse neuroglial cells, is revealed. The sequence contained (1) a neuroprotective peptide, NAPVSIPQ, sharing structural and immunological homologies with the previously reported, activity-dependent neurotrophic factor; (2) a glutaredoxin active site; and (3) a zinc binding domain. Gene expression was enriched in the mouse hippocampus and cerebellum and augmented in the presence of the neuropeptide vasoactive intestinal peptide, in cerebral cortical astrocytes. In mixed neuron-astrocyte cultures, NAPVSIPQ provided neuroprotection at subfemtomolar concentrations against toxicity associated with tetrodotoxin (electrical blockade), the beta-amyloid peptide (the Alzheimer's disease neurotoxin), N-methyl-D-aspartate (excitotoxicity), and the human immunodeficiency virus envelope protein. Daily NAPVSIPQ injections to newborn apolipoprotein E-deficient mice accelerated the acquisition of developmental reflexes and prevented short-term memory deficits. Comparative studies suggested that NAPVSIPQ was more efficacious than other neuroprotective peptides in the apolipoprotein E-deficiency model. A potential basis for rational drug design against neurodegeneration is suggested with NAPVSIPQ as a lead compound. The relative enrichment of the novel mRNA transcripts in the brain and the increases found in the presence of vasoactive intestinal peptide, an established neuroprotective substance, imply a role for the cloned protein in neuronal function.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Bassan",
      "authorRank" : 1,
      "name" : "Bassan M",
      "referenceId" : "RGD:A51845"
    }, {
      "firstName" : "R",
      "lastName" : "Zamostiano",
      "authorRank" : 2,
      "name" : "Zamostiano R",
      "referenceId" : "RGD:A51824"
    }, {
      "firstName" : "A",
      "lastName" : "Davidson",
      "authorRank" : 3,
      "name" : "Davidson A",
      "referenceId" : "RGD:A111539"
    }, {
      "firstName" : "A",
      "lastName" : "Pinhasov",
      "authorRank" : 4,
      "name" : "Pinhasov A",
      "referenceId" : "RGD:A51836"
    }, {
      "firstName" : "E",
      "lastName" : "Giladi",
      "authorRank" : 5,
      "name" : "Giladi E",
      "referenceId" : "RGD:A51834"
    }, {
      "firstName" : "O",
      "lastName" : "Perl",
      "authorRank" : 6,
      "name" : "Perl O",
      "referenceId" : "RGD:A111540"
    }, {
      "firstName" : "H",
      "lastName" : "Bassan",
      "authorRank" : 7,
      "name" : "Bassan H",
      "referenceId" : "RGD:A111541"
    }, {
      "firstName" : "C",
      "lastName" : "Blat",
      "authorRank" : 8,
      "name" : "Blat C",
      "referenceId" : "RGD:A111542"
    }, {
      "firstName" : "G",
      "lastName" : "Gibney",
      "authorRank" : 9,
      "name" : "Gibney G",
      "referenceId" : "RGD:A111543"
    }, {
      "firstName" : "G",
      "lastName" : "Glazner",
      "authorRank" : 10,
      "name" : "Glazner G",
      "referenceId" : "RGD:A111544"
    }, {
      "firstName" : "DE",
      "lastName" : "Brenneman",
      "authorRank" : 11,
      "name" : "Brenneman DE",
      "referenceId" : "RGD:A17583"
    }, {
      "firstName" : "I",
      "lastName" : "Gozes",
      "authorRank" : 12,
      "name" : "Gozes I",
      "referenceId" : "RGD:A17584"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2312794"
    } ]
  }, {
    "primaryId" : "PMID:10037570",
    "title" : "GLC1F, a new primary open-angle glaucoma locus, maps to 7q35-q36.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wirtz MK, etal., Arch Ophthalmol. 1999 Feb;117(2):237-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:00:31.000-05:00",
    "volume" : "117",
    "pages" : "237-41",
    "abstract" : "BACKGROUND: A large family with adult-onset primary open-angle glaucoma (POAG) was identified. OBJECTIVE: To initiate a genome-wide scan to map the POAG locus in this family. METHODS: Blood samples or buccal swabs were obtained from 25 members of a large family with POAG after informed consent was obtained. Members  and their spouses were evaluated clinically for POAG on the basis of intraocular  pressures, cupping of discs, and visual fields. DNA samples were used for a genome-wide screen using microsatellite markers. RESULTS: Ten affected family members in 4 generations showed evidence of POAG including intraocular pressures  of 22 mm Hg or more, and/or optic cup-disc ratios of 0.6 or more, and/or visual field defects consistent with glaucomatous damage. Primary open-angle glaucoma segregated as an autosomal dominant trait, with the disease locus mapping to 7q35-q36 between markers D7S2442 and D7S483 with a multipoint lod score of 4.06.  CONCLUSION: A sixth gene for POAG (GLC1F) has been mapped to 7q35-q36 in a family with at least 4 generations affected. CLINICAL RELEVANCE: The mapping of this locus further confirms that primary open-angle glaucoma is a heterogeneous group  of diseases with at least 6 different loci resulting in a similar phenotype. The  eventual ability to classify which major POAG gene an affected person carries could have ramifications for selecting the most effective treatment regimen for that person.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MK",
      "lastName" : "Wirtz",
      "authorRank" : 1,
      "name" : "Wirtz MK",
      "referenceId" : "RGD:A79832"
    }, {
      "firstName" : "JR",
      "lastName" : "Samples",
      "authorRank" : 2,
      "name" : "Samples JR",
      "referenceId" : "RGD:A79834"
    }, {
      "firstName" : "K",
      "lastName" : "Rust",
      "authorRank" : 3,
      "name" : "Rust",
      "referenceId" : "RGD:A175398"
    }, {
      "firstName" : "J",
      "lastName" : "Lie",
      "authorRank" : 4,
      "name" : "Lie J",
      "referenceId" : "RGD:A65234"
    }, {
      "firstName" : "L",
      "lastName" : "Nordling",
      "authorRank" : 5,
      "name" : "Nordling",
      "referenceId" : "RGD:A254199"
    }, {
      "firstName" : "K",
      "lastName" : "Schilling",
      "authorRank" : 6,
      "name" : "Schilling",
      "referenceId" : "RGD:A185127"
    }, {
      "firstName" : "TS",
      "lastName" : "Acott",
      "authorRank" : 7,
      "name" : "Acott",
      "referenceId" : "RGD:A254200"
    }, {
      "firstName" : "PL",
      "lastName" : "Kramer",
      "authorRank" : 8,
      "name" : "Kramer PL",
      "referenceId" : "RGD:A40819"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063202"
    } ]
  }, {
    "primaryId" : "PMID:10037722",
    "title" : "Cloning of a stretch-inhibitable nonselective cation channel.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Suzuki M, etal., J Biol Chem 1999 Mar 5;274(10):6330-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:34:42.000-05:00",
    "volume" : "274",
    "pages" : "6330-5",
    "abstract" : "A homologue of the capsaicin receptor-nonselective cation channel was cloned from the rat kidney to investigate a mechanosensitive channel. We found this channel to be inactivated by membrane stretch and have designated it stretch-inactivated channel (SIC). SIC encodes a 563-amino acid protein with putative six transmembrane segments. The cDNA was expressed in mammalian cells, and electophysiological studies were performed. SIC-induced large cation currents were found to be regulated by cell volume, with currents being stimulated by cell shrinkage and inhibited by cell swelling. Single channel analysis showed a conductance of 250 pS with cation permeability (PCl/PNa < 0.1), and the channel possessed some of the characteristics of a stretch-inactivated channel in that it was permeable to calcium, sensitive to membrane stretch, and blocked by Gd3+. Therefore, we cloned one of the mechanosensitive cation channels of mammals, which is considered to regulate Ca2+ influx in response to mechanical stress on the cell membrane.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Suzuki",
      "authorRank" : 1,
      "name" : "Suzuki M",
      "referenceId" : "RGD:A299767"
    }, {
      "firstName" : "J",
      "lastName" : "Sato",
      "authorRank" : 2,
      "name" : "Sato J",
      "referenceId" : "RGD:A23911"
    }, {
      "firstName" : "K",
      "lastName" : "Kutsuwada",
      "authorRank" : 3,
      "name" : "Kutsuwada K",
      "referenceId" : "RGD:A23912"
    }, {
      "firstName" : "G",
      "lastName" : "Ooki",
      "authorRank" : 4,
      "name" : "Ooki G",
      "referenceId" : "RGD:A23913"
    }, {
      "firstName" : "M",
      "lastName" : "Imai",
      "authorRank" : 5,
      "name" : "Imai M",
      "referenceId" : "RGD:A160808"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634421"
    } ]
  }, {
    "primaryId" : "PMID:10037757",
    "title" : "Physiological role of the N-terminal processed P4501A1 targeted to mitochondria in erythromycin metabolism and reversal of erythromycin-mediated inhibition of mitochondrial protein synthesis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Anandatheerthavarada HK, etal., J Biol Chem. 1999 Mar 5;274(10):6617-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-04-30T09:57:46.000-05:00",
    "volume" : "274",
    "pages" : "6617-25",
    "abstract" : "Recently, we showed that the major species of beta-naphthoflavone-inducible rat liver mitochondrial P450MT2 consists of N-terminal truncated microsomal P4501A1 (+33/1A1) and that the truncated enzyme exhibits different substrate specificity as compared with intact P4501A1. The results of the present study show that P450MT2 targeted to COS cell mitochondria by transient transfection of P4501A1 cDNA is localized inside the mitochondrial inner membrane in a membrane-extrinsic orientation. Co-expression with wild type P4501A1 and adrenodoxin (Adx) cDNAs resulted in 5-7-fold higher erythromycin N-demethylation (ERND) in the mitochondrial fraction but minimal changes in the microsomal fraction of transfected cells. Erythromycin, a potent inhibitor of bacterial and mitochondrial protein synthesis, caused 8-12-fold higher accumulation of CYP1A1 mRNA, preferential accumulation of P450MT2, and 5-6-fold higher ERND activity in the mitochondrial compartment of rat C6 glioma cells. Consistent with the increased mitochondrial ERND activity, co-expression with P4501A1 and Adx in COS cells rendered complete protection against erythromycin-mediated mitochondrial translation inhibition. Mutations that specifically affect the mitochondrial targeting of P4501A1 also abolished protection against mitochondrial translation inhibition. These results for the first time suggest a physiological function for the xenobiotic inducible cytochrome P4501A1 against drug-mediated mitochondrial toxicity.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HK",
      "lastName" : "Anandatheerthavarada",
      "authorRank" : 1,
      "name" : "Anandatheerthavarada HK",
      "referenceId" : "RGD:A43978"
    }, {
      "firstName" : "C",
      "lastName" : "Vijayasarathy",
      "authorRank" : 2,
      "name" : "Vijayasarathy C",
      "referenceId" : "RGD:A46560"
    }, {
      "firstName" : "SV",
      "lastName" : "Bhagwat",
      "authorRank" : 3,
      "name" : "Bhagwat SV",
      "referenceId" : "RGD:A43980"
    }, {
      "firstName" : "G",
      "lastName" : "Biswas",
      "authorRank" : 4,
      "name" : "Biswas G",
      "referenceId" : "RGD:A43981"
    }, {
      "firstName" : "J",
      "lastName" : "Mullick",
      "authorRank" : 5,
      "name" : "Mullick J",
      "referenceId" : "RGD:A28903"
    }, {
      "firstName" : "NG",
      "lastName" : "Avadhani",
      "authorRank" : 6,
      "name" : "Avadhani NG",
      "referenceId" : "RGD:A28904"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306685"
    } ]
  }, {
    "primaryId" : "PMID:10037764",
    "title" : "Competition between thyroid hormone receptor-associated protein (TRAP) 220 and transcriptional intermediary factor (TIF) 2 for binding to nuclear receptors. Implications for the recruitment of TRAP and p160 coactivator complexes.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Treuter E, etal., J Biol Chem. 1999 Mar 5;274(10):6667-77.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-07-07T11:28:52.000-05:00",
    "volume" : "274",
    "pages" : "6667-77",
    "abstract" : "Transcriptional activation by nuclear receptors (NRs) involves the concerted action of coactivators, chromatin components, and the basal transcription machinery. Crucial NR coactivators, which target primarily the conserved ligand-regulated activation (AF-2) domain, include p160 family members, such as TIF2, as well as p160-associated coactivators, such as CBP/p300. Because these coactivators possess intrinsic histone acetyltransferase activity, they are believed to function mainly by regulating chromatin-dependent transcriptional activation. Recent evidence suggests the existence of an additional NR coactivator complex, referred to as the thyroid hormone receptor-associated protein (TRAP) complex, which may function more directly as a bridging complex to the basal transcription machinery. TRAP220, the 220-kDa NR-binding subunit of the complex, has been identified in independent studies using both biochemical and genetic approaches. In light of the functional differences identified between p160 and TRAP coactivator complexes in NR activation, we have attempted to compare interaction and functional characteristics of TIF 2 and TRAP220. Our findings imply that competition between the NR-binding subunits of distinct coactivator complexes may act as a putative regulatory step in establishing either a sequential activation cascade or the formation of independent coactivator complexes.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Treuter",
      "authorRank" : 1,
      "name" : "Treuter E",
      "referenceId" : "RGD:A20678"
    }, {
      "firstName" : "L",
      "lastName" : "Johansson",
      "authorRank" : 2,
      "name" : "Johansson L",
      "referenceId" : "RGD:A60023"
    }, {
      "firstName" : "JS",
      "lastName" : "Thomsen",
      "authorRank" : 3,
      "name" : "Thomsen JS",
      "referenceId" : "RGD:A109932"
    }, {
      "firstName" : "A",
      "lastName" : "Warnmark",
      "authorRank" : 4,
      "name" : "Warnmark A",
      "referenceId" : "RGD:A141214"
    }, {
      "firstName" : "J",
      "lastName" : "Leers",
      "authorRank" : 5,
      "name" : "Leers J",
      "referenceId" : "RGD:A20677"
    }, {
      "firstName" : "M",
      "lastName" : "Pelto-Huikko",
      "authorRank" : 6,
      "name" : "Pelto-Huikko M",
      "referenceId" : "RGD:A24661"
    }, {
      "firstName" : "M",
      "lastName" : "Sjoberg",
      "authorRank" : 7,
      "name" : "Sjoberg M",
      "referenceId" : "RGD:A141215"
    }, {
      "firstName" : "AP",
      "lastName" : "Wright",
      "authorRank" : 8,
      "name" : "Wright AP",
      "referenceId" : "RGD:A141216"
    }, {
      "firstName" : "G",
      "lastName" : "Spyrou",
      "authorRank" : 9,
      "name" : "Spyrou G",
      "referenceId" : "RGD:A9411"
    }, {
      "firstName" : "JA",
      "lastName" : "Gustafsson",
      "authorRank" : 10,
      "name" : "Gustafsson JA",
      "referenceId" : "RGD:A5567"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5134969"
    } ]
  }, {
    "primaryId" : "PMID:10037815",
    "title" : "Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Yang GP, etal., Nucleic Acids Res. 1999 Mar 15;27(6):1517-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:32:53.000-05:00",
    "volume" : "27",
    "pages" : "1517-23",
    "abstract" : "Comparing patterns of gene expression in cell lines and tissues has important applications in a variety of biological systems. In this study we have examined whether the emerging technology of cDNA microarrays will allow a high throughput  analysis of expression of cDNA clones generated by suppression subtractive hybridization (SSH). A set of cDNA clones including 332 SSH inserts amplified by  PCR was arrayed using robotic printing. The cDNA arrays were hybridized with fluorescent labeled probes prepared from RNA from ER-positive (MCF7 and T47D) and ER-negative (MDA-MB-231 and HBL-100) breast cancer cell lines. Ten clones were identified that were over-expressed by at least a factor of five in the ER-positive cell lines. Northern blot analysis confirmed over-expression of these 10 cDNAs. Sequence analysis identified four of these clones as cytokeratin 19, GATA-3, CD24 and glutathione-S-transferase mu-3. Of the remaining six cDNA clones, four clones matched EST sequences from two different genes and two clones were novel sequences. Flow cytometry and immunofluorescence confirmed that CD24 protein was over-expressed in the ER-positive cell lines. We conclude that SSH and microarray technology can be successfully applied to identify differentially  expressed genes. This approach allowed the identification of differentially expressed genes without the need to obtain previously cloned cDNAs.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GP",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang",
      "referenceId" : "RGD:A183936"
    }, {
      "firstName" : "DT",
      "lastName" : "Ross",
      "authorRank" : 2,
      "name" : "Ross",
      "referenceId" : "RGD:A183937"
    }, {
      "firstName" : "WW",
      "lastName" : "Kuang",
      "authorRank" : 3,
      "name" : "Kuang",
      "referenceId" : "RGD:A183938"
    }, {
      "firstName" : "PO",
      "lastName" : "Brown",
      "authorRank" : 4,
      "name" : "Brown PO",
      "referenceId" : "RGD:A50066"
    }, {
      "firstName" : "RJ",
      "lastName" : "Weigel",
      "authorRank" : 5,
      "name" : "Weigel RJ",
      "referenceId" : "RGD:A59234"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553422"
    } ]
  }, {
    "primaryId" : "PMID:10041004",
    "title" : "Scanning-tunneling-microscopy studies of Ag on Si(100)-(2 x 1).",
    "datePublished" : "1989-05-01T00:00:00.000-05:00",
    "citation" : "Samsavar A, etal., Phys Rev Lett. 1989 Dec 25;63(26):2830-2833.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-05-07T18:07:53.000-05:00",
    "volume" : "63",
    "pages" : "2830-2833",
    "issueName" : "26",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Samsavar",
      "authorRank" : 1,
      "name" : "Samsavar",
      "referenceId" : "RGD:A201630"
    }, {
      "firstName" : "ES",
      "lastName" : "Hirschorn",
      "authorRank" : 2,
      "name" : "Hirschorn",
      "referenceId" : "RGD:A201631"
    }, {
      "firstName" : "FM",
      "lastName" : "Leibsle",
      "authorRank" : 3,
      "name" : "Leibsle",
      "referenceId" : "RGD:A201632"
    }, {
      "firstName" : "T",
      "lastName" : "Chiang",
      "authorRank" : 4,
      "name" : "Chiang",
      "referenceId" : "RGD:A201633"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10041008"
    } ]
  }, {
    "primaryId" : "PMID:10045945",
    "title" : "Dynamics and memory effects in rupture of thermal fuse networks.",
    "datePublished" : "1992-02-03T00:00:00.000-06:00",
    "citation" : "Sornette D and Vanneste C, Phys Rev Lett. 1992 Feb 3;68(5):612-615. doi: 10.1103/PhysRevLett.68.612.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-01-26T10:32:41.000-06:00",
    "volume" : "68",
    "pages" : "612-615",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "lastName" : "Sornette",
      "authorRank" : 1,
      "name" : "Sornette D",
      "referenceId" : "RGD:A455009"
    }, {
      "lastName" : "Vanneste",
      "authorRank" : 2,
      "name" : "Vanneste C",
      "referenceId" : "RGD:A455010"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13504821"
    } ]
  }, {
    "primaryId" : "PMID:10047462",
    "title" : "Overexpression of anti-apoptotic gene BAG-1 in human cervical cancer.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Yang X, etal., Exp Cell Res. 1999 Feb 25;247(1):200-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-06-20T15:01:29.000-05:00",
    "volume" : "247",
    "pages" : "200-7",
    "abstract" : "Apoptosis is a programmed cell death process in which cells commit suicide under certain environmental conditions. Recent studies suggest that apoptosis is controlled by a variety of cellular genes, and dysregulation of these genes plays an important role in the pathogenesis of human diseases, including cancer. BAG-1 is a novel anti-apoptotic protein isolated by its interaction with another anti-apoptotic protein, Bcl-2. It binds to several hormone receptors and growth factor receptors and modulates their function in apoptosis. However, the role of BAG-1 in the oncogenesis of human cervical cancer has yet to be illustrated. In this study, we examined the expression of BAG-1 in cervical normal and carcinoma cultured cells and tissues. BAG-1 was overexpressed in human cervical carcinoma cell lines and tissues. Overexpression was regulated at the transcriptional level. The increased expression of BAG-1 was correlated with enhanced resistance of cervical carcinoma cells to apoptosis induced by a DNA-damaging reagent. In addition, overexpression of BAG-1 enhanced the resistance of cervical cells to apoptosis. This study provided the first evidence that BAG-1 is upregulated in human cervical cancer and may play an important role in apoptosis and human cervical carcinogenesis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang X",
      "referenceId" : "RGD:A9368"
    }, {
      "firstName" : "Y",
      "lastName" : "Hao",
      "authorRank" : 2,
      "name" : "Hao Y",
      "referenceId" : "RGD:A60844"
    }, {
      "firstName" : "A",
      "lastName" : "Ferenczy",
      "authorRank" : 3,
      "name" : "Ferenczy A",
      "referenceId" : "RGD:A97447"
    }, {
      "firstName" : "SC",
      "lastName" : "Tang",
      "authorRank" : 4,
      "name" : "Tang SC",
      "referenceId" : "RGD:A63931"
    }, {
      "firstName" : "A",
      "lastName" : "Pater",
      "authorRank" : 5,
      "name" : "Pater A",
      "referenceId" : "RGD:A97448"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2293889"
    } ]
  }, {
    "primaryId" : "PMID:10047530",
    "title" : "Functions of gelsolin: motility, signaling, apoptosis, cancer.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Kwiatkowski DJ Curr Opin Cell Biol 1999 Feb;11(1):103-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-18T10:21:39.000-06:00",
    "volume" : "11",
    "pages" : "103-8",
    "abstract" : "Several new members of the gelsolin family have been discovered in the past year. Determination of the structure of gelsolin and identification of lysophosphatidic acid as a negative regulator provide novel functional insights. Gelsolin is an obligate downstream effector of Rac for motility in dermal fibroblasts, regulates phosphoinositide signaling pathways and ion channel function in vivo, and acts as both a regulator and effector of apoptosis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Kwiatkowski",
      "authorRank" : 1,
      "name" : "Kwiatkowski DJ",
      "referenceId" : "RGD:A11930"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556782"
    } ]
  }, {
    "primaryId" : "PMID:10048142",
    "title" : "Contribution of serum and cellular semicarbazide-sensitive amine oxidase to amine metabolism and cardiovascular toxicity.",
    "datePublished" : "1998-10-01T00:00:00.000-05:00",
    "citation" : "Conklin DJ, etal., Toxicol Sci. 1998 Dec;46(2):386-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-10-16T17:15:05.000-05:00",
    "volume" : "46",
    "pages" : "386-92",
    "abstract" : "Semicarbazide-sensitive amine oxidase (SSAO) plays a role in the in vivo and in vitro toxicity of several environmental and endogenous amines. We investigated the role of SSAO as a component of cell culture medium (through addition of fetal calf serum (FCS)) compared to intracellular SSAO in the in vitro cytotoxicity of three amines and metabolites. Smooth muscle cells and beating cardiac myocytes were grown in 96-well plates and exposed to various concentrations and combinations of FCS in medium, amines (allylamine, AA; benzylamine, BZA; and methylamine, MA), and amine metabolites (aldehydes: acrolein, benzaldehyde, and formaldehyde; hydrogen peroxide, H2O2; ammonia, NH3). Amine and amine metabolite cytotoxicity was quantified by monitoring cell viability. SSAO activity was measured in FCS, cardiovascular cells, or rat plasma by a radioenzymatic assay using [14C]BZA. Our data show that AA and its aldehyde metabolite, acrolein, were the most toxic compounds to both cell types. However, AA toxicity was FCS-dependent in both cell types, while BZA, MA, and amine metabolite (i.e., aldehydes, H2O2, and NH3) cytotoxicity showed little FCS dependence. In these experiments, medium containing 10% FCS had a calculated amine metabolic capacity that was 30- to 50-fold that of the cultured smooth muscle cellular content in a single well of a 96-well plate. Our study demonstrates that SSAO in FCS contributes to amine metabolism and cytotoxicity to rat cardiovascular cells in vitro and how critical it is to evaluate serum for its role in mechanisms of amine toxicity in vitro and in vivo.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Conklin",
      "authorRank" : 1,
      "name" : "Conklin DJ",
      "referenceId" : "RGD:A113756"
    }, {
      "firstName" : "SD",
      "lastName" : "Langford",
      "authorRank" : 2,
      "name" : "Langford SD",
      "referenceId" : "RGD:A113757"
    }, {
      "firstName" : "PJ",
      "lastName" : "Boor",
      "authorRank" : 3,
      "name" : "Boor PJ",
      "referenceId" : "RGD:A113758"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313829"
    } ]
  }, {
    "primaryId" : "PMID:10048463",
    "title" : "Ontogeny of diazepam binding inhibitor/acyl-CoA binding protein mRNA and peripheral benzodiazepine receptor mRNA expression in the rat.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Burgi B, etal., J Neuroendocrinol. 1999 Feb;11(2):85-100.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-03T14:37:49.000-06:00",
    "volume" : "11",
    "pages" : "85-100",
    "abstract" : "The Diazepam Binding Inhibitor/Acyl-CoA Binding Protein (DBI/ACBP) has been implicated in different functions, as acyl-CoA transporter and as an endogenous ligand at the GABA(A) receptor and the peripheral benzodiazepine receptor (PBR). The latter is thought to be involved in control of steroidogenesis. We studied the ontogeny of DBI/ACBP and PBR mRNA expression in embryos and offspring of time-pregnant Long Evans rats by in-situ hybridization with 33P-endlabelled oligonucleotides. Both mRNAs were present in embryo and placenta at gestational day (G)11, the earliest stage studied. DBI/ACBP mRNA was strongly expressed from embryonic through mid-foetal stages in central nervous system (maximum in neuroepithelium), cranial and sympathetic ganglia, anterior pituitary, adrenal cortex, thyroid, thymus, liver and (late foetal) brown adipose tissue, moderately in testis, heart, lung and kidney. In brain, a late foetal decrease of DBI/ACBP mRNA was followed by an increase at postnatal day 6. Peripheral benzodiazepine receptor mRNA expression started very low and increased to moderate levels in adrenal cortex and medulla, testis, thyroid, brown adipose tissue, liver, heart, lung, salivary gland at mid- to late-foetal stages. Data suggest a significant role of DBI/ACBP at early developmental stages. Both proteins may be involved in the control of foetal steroidogenesis. However, differences in developmental patterns indicate that additional functions may be equally important during ontogeny, such as the involvement in lipid metabolism in the case of DBI/ACBP.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Burgi",
      "authorRank" : 1,
      "name" : "Burgi B",
      "referenceId" : "RGD:A118840"
    }, {
      "firstName" : "W",
      "lastName" : "Lichtensteiger",
      "authorRank" : 2,
      "name" : "Lichtensteiger W",
      "referenceId" : "RGD:A76185"
    }, {
      "firstName" : "ME",
      "lastName" : "Lauber",
      "authorRank" : 3,
      "name" : "Lauber ME",
      "referenceId" : "RGD:A118841"
    }, {
      "firstName" : "M",
      "lastName" : "Schlumpf",
      "authorRank" : 4,
      "name" : "Schlumpf M",
      "referenceId" : "RGD:A76187"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316283"
    } ]
  }, {
    "primaryId" : "PMID:10048466",
    "title" : "Induction of pituitary cytokine transcripts by peripheral lipopolysaccharide.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Whiteside MB, etal., J Neuroendocrinol. 1999 Feb;11(2):115-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-11-21T09:33:57.000-06:00",
    "volume" : "11",
    "pages" : "115-20",
    "abstract" : "Systemically administered lipopolysaccharide (LPS) elicits profound changes in pituitary hormone secretion. Pro-inflammatory cytokines have been proposed as mediators of these responses. In this study, we used in-situ hybridization histochemistry to investigate LPS-induced cytokine gene expression in the rat pituitary. After i.p. or i.v. injection of various doses of LPS, mRNA for the immediate-early gene IkappaBu (an inhibitor of NF-kappaB, a transcription factor  that regulates the expression of many pro-inflammatory cytokines) was induced in  the anterior lobe as early as 0.5 h. The induced IkappaBalpha mRNA expression peaked at 1 h. In the posterior lobe, IkappaBalpha mRNA was first induced at 0.5  h and peaked at 2 h. A similar spatiotemporal pattern of interleukin-1b (IL-1) mRNA induction was observed. In addition, at 2 h after injection, TNFalpha, IL-1beta converting enzyme (ICE), and IL-1 receptor antagonist (IL-1RA) mRNAs were induced in both anterior and posterior lobes. Type 1 IL-1 receptor (IL-1R1)  mRNA was constitutively expressed in the pituitary, and its expression level did  not change after the LPS injection. Interestingly, the mRNA coding for glial fibrillary acidic protein (GFAP), an astrocyte marker, was selectively induced in the posterior lobe at 2 h after LPS injection, suggesting that LPS affects pituicyte function. Together, these results suggest that LPS acts directly on the pituitary to rapidly induce cytokine expression. Locally synthesized cytokines may activate cytokine receptor bearing cells to modulate the endocrine activities of the pituitary.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MB",
      "lastName" : "Whiteside",
      "authorRank" : 1,
      "name" : "Whiteside MB",
      "referenceId" : "RGD:A159769"
    }, {
      "firstName" : "N",
      "lastName" : "Quan",
      "authorRank" : 2,
      "name" : "Quan N",
      "referenceId" : "RGD:A91415"
    }, {
      "firstName" : "M",
      "lastName" : "Herkenharn",
      "authorRank" : 3,
      "name" : "Herkenharn M",
      "referenceId" : "RGD:A159770"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7175061"
    } ]
  }, {
    "primaryId" : "PMID:10048754",
    "title" : "Effect of dienogest on bleeding time, coagulation, fibrinolysis, and platelet aggregation in female rats.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Nobukata H, etal., Toxicol Lett. 1999 Jan 11;104(1-2):93-101.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-02-27T15:09:43.000-06:00",
    "volume" : "104",
    "pages" : "93-101",
    "abstract" : "We investigated the effect of dienogest on bleeding time, coagulation, fibrinolysis, and platelet aggregation in female rats compared with that of medroxyprogesterone acetate (MPA) and danazol, in order to elucidate the reason for relatively high incidence of bleeding in dienogest-treated patients with endometriosis. Dienogest caused no change in the bleeding time at a single dose of 100 mg/kg or at a repeated dose of 10 mg/kg per day for 2 weeks. The drug increased the fibrinogen level, coagulation factor II and V activities, and antithrombin III activity, but had no effect on fibrinolysis or on platelet aggregation at repeated doses of 1 and 10 mg/kg per day for 4 weeks. MPA significantly shortened the bleeding time at the same doses as dienogest. MPA increased the fibrinogen level and plasminogen activity, potentiated the platelet aggregation, and increased the platelet cholesterol-to-phospholipid ratio at a repeated dose of 10 mg/kg per day for 4 weeks. Danazol significantly shortened the bleeding time like MPA. Danazol increased the fibrinogen level, coagulation factor II, V, VII, VIII, IX, X, XI, and XII activities, and antithrombin III activity, but had no influence on the platelet aggregation at repeated doses of 10 and 100 mg/kg per day for 4 weeks. In comparison with MPA and danazol, dienogest may induce a relatively high incidence of bleeding in patients with endometriosis partially because of its minimal effect on hemostasis.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Nobukata",
      "authorRank" : 1,
      "name" : "Nobukata H",
      "referenceId" : "RGD:A71756"
    }, {
      "firstName" : "Y",
      "lastName" : "Katsuki",
      "authorRank" : 2,
      "name" : "Katsuki Y",
      "referenceId" : "RGD:A92643"
    }, {
      "firstName" : "T",
      "lastName" : "Ishikawa",
      "authorRank" : 3,
      "name" : "Ishikawa T",
      "referenceId" : "RGD:A299703"
    }, {
      "firstName" : "M",
      "lastName" : "Inokuma",
      "authorRank" : 4,
      "name" : "Inokuma M",
      "referenceId" : "RGD:A92644"
    }, {
      "firstName" : "Y",
      "lastName" : "Shibutani",
      "authorRank" : 5,
      "name" : "Shibutani Y",
      "referenceId" : "RGD:A71758"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2290183"
    } ]
  }, {
    "primaryId" : "PMID:10049528",
    "title" : "Cloning and characterization of a novel class VI semaphorin, semaphorin Y.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Kikuchi K, etal., Mol Cell Neurosci 1999 Jan;13(1):9-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-11T15:05:31.000-06:00",
    "volume" : "13",
    "pages" : "9-23",
    "abstract" : "Semaphorins comprise a large family of proteins implicated in axonal guidance. We cloned a novel transmembrane semaphorin, semaphorin Y (Sema Y), which has a class VI sema domain. Sema Y shows growth cone collapsing activity on DRG neurons in vitro, and the target regions of the DRG neurons express sema Y mRNA during development. Sema Y may be a stop signal for these neurons in their target areas. Interestingly, sema Y mRNA was also detected in other neurons and their targets. Two isoforms of Sema Y derived from alternative splicing were identified and their expression was found to be regulated in a tissue- and age-dependent manner. Distribution of sema Y mRNA suggests that Sema Y might also be important during maintenance of axonal connections and/or differentiation and migration of cells. Sequence comparison among class VI semaphorins revealed two short conserved sequence stretches in their cytoplasmic domains, suggesting interaction of these semaphorins with a common intracellular component(s).",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Kikuchi",
      "authorRank" : 1,
      "name" : "Kikuchi K",
      "referenceId" : "RGD:A148367"
    }, {
      "firstName" : "A",
      "lastName" : "Chedotal",
      "authorRank" : 2,
      "name" : "Chedotal A",
      "referenceId" : "RGD:A7960"
    }, {
      "firstName" : "H",
      "lastName" : "Hanafusa",
      "authorRank" : 3,
      "name" : "Hanafusa H",
      "referenceId" : "RGD:A7962"
    }, {
      "firstName" : "Y",
      "lastName" : "Ujimasa",
      "authorRank" : 4,
      "name" : "Ujimasa Y",
      "referenceId" : "RGD:A7963"
    }, {
      "firstName" : "F",
      "lastName" : "De Castro",
      "authorRank" : 5,
      "name" : "De Castro F",
      "referenceId" : "RGD:A7961"
    }, {
      "firstName" : "CS",
      "lastName" : "Goodman",
      "authorRank" : 6,
      "name" : "Goodman CS",
      "referenceId" : "RGD:A52302"
    }, {
      "firstName" : "T",
      "lastName" : "Kimura",
      "authorRank" : 7,
      "name" : "Kimura T",
      "referenceId" : "RGD:A6130"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69992"
    } ]
  }, {
    "primaryId" : "PMID:10049584",
    "title" : "GPR56, a novel secretin-like human G-protein-coupled receptor gene.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Liu M, etal., Genomics 1999 Feb 1;55(3):296-305.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-23T14:20:40.000-05:00",
    "volume" : "55",
    "pages" : "296-305",
    "abstract" : "A novel gene product, GPR56, with homology to the seven transmembrane-domain receptor superfamily, has been cloned by PCR amplification using degenerate oligonucleotide primers and subsequent screening of a human heart cDNA library. The isolated 2.8-kb cDNA clone encodes a protein of 693 amino acids that shows highest identity (32%) to HE6, a member of a subclass of the class B secretin-like G-protein-coupled receptors. Northern analysis of various human tissues revealed a wide distribution of the transcript with highest levels found in thyroid gland, brain, and heart. In situ hybridization analysis of human thyroid gland as well as rat heart and brain tissue confirms these results and identifies the hippocampus and hypothalamic nuclei as brain areas with particularly high expression of GPR56 mRNA. The high level of mRNA expression, its wide distribution, and the mucin-like extracellular domain of the receptor protein suggest a possible role for this receptor in cell-cell interaction processes. The human gene for GPR56 has been isolated and its exon-intron structure determined. The total length of the human GPR56 gene is approximately 15 kb, and it consists of 13 exons. Fluorescence in situ hybridization, PCR analysis of somatic cell hybrids, and interspecific mouse backcross mapping have localized the genes to human chromosome 16q13 and mouse chromosome 8.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu M",
      "referenceId" : "RGD:A12294"
    }, {
      "firstName" : "RM",
      "lastName" : "Parker",
      "authorRank" : 2,
      "name" : "Parker RM",
      "referenceId" : "RGD:A25861"
    }, {
      "firstName" : "K",
      "lastName" : "Darby",
      "authorRank" : 3,
      "name" : "Darby K",
      "referenceId" : "RGD:A25862"
    }, {
      "firstName" : "HJ",
      "lastName" : "Eyre",
      "authorRank" : 4,
      "name" : "Eyre HJ",
      "referenceId" : "RGD:A25863"
    }, {
      "firstName" : "NG",
      "lastName" : "Copeland",
      "authorRank" : 5,
      "name" : "Copeland NG",
      "referenceId" : "RGD:A57268"
    }, {
      "firstName" : "J",
      "lastName" : "Crawford",
      "authorRank" : 6,
      "name" : "Crawford J",
      "referenceId" : "RGD:A25865"
    }, {
      "firstName" : "DJ",
      "lastName" : "Gilbert",
      "authorRank" : 7,
      "name" : "Gilbert DJ",
      "referenceId" : "RGD:A57269"
    }, {
      "firstName" : "GR",
      "lastName" : "Sutherland",
      "authorRank" : 8,
      "name" : "Sutherland GR",
      "referenceId" : "RGD:A25867"
    }, {
      "firstName" : "NA",
      "lastName" : "Jenkins",
      "authorRank" : 9,
      "name" : "Jenkins NA",
      "referenceId" : "RGD:A57270"
    }, {
      "firstName" : "H",
      "lastName" : "Herzog",
      "authorRank" : 10,
      "name" : "Herzog H",
      "referenceId" : "RGD:A21153"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:708336"
    } ]
  }, {
    "primaryId" : "PMID:10049691",
    "title" : "The N-terminus of KIR6.2 limits spontaneous bursting and modulates the ATP-inhibition of KATP channels.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Babenko AP, etal., Biochem Biophys Res Commun. 1999 Feb 16;255(2):231-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:10:09.000-05:00",
    "volume" : "255",
    "pages" : "231-8",
    "abstract" : "KATP channels are heteromultimers of a sulfonylurea receptor SUR and KIR6.2 with  the inward rectifier forming the pore which is regulated by SUR. We have examined the contributions of the cytoplasmic domains of KIR6.2 to control of spontaneous  bursting and ATP-inhibition in human SUR1/KIR6.2 KATP channels. Truncations of the N-terminus of KIR6.2 nearly eliminate transitions to interburst closed states without affecting the open or intraburst closed states, thus producing SUR1/DeltaNKIR6.2 channels with an extremely high open probability in the absence of nucleotides. These channels have a decrease apparent ATP-sensitivity which is  consistent with the involvement of the N-terminus in a transition to an interburst closed state that preferentially binds inhibitory ATP. Mutations in both the N- and proximal C-termini of KIR6.2 can synergistically attenuate the ATP-inhibition. The results identify the N-terminus of KIR6.2 as a determinant of the interburst kinetics of KATP channels and suggest that the two cytoplasmic domains of KIR6.2 participate in ATP-inhibitory gating through distinct mechanisms.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AP",
      "lastName" : "Babenko",
      "authorRank" : 1,
      "name" : "Babenko",
      "referenceId" : "RGD:A252587"
    }, {
      "firstName" : "G",
      "lastName" : "Gonzalez",
      "authorRank" : 2,
      "name" : "Gonzalez",
      "referenceId" : "RGD:A272330"
    }, {
      "firstName" : "J",
      "lastName" : "Bryan",
      "authorRank" : 3,
      "name" : "Bryan J",
      "referenceId" : "RGD:A25417"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073083"
    } ]
  }, {
    "primaryId" : "PMID:10049700",
    "title" : "Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function.",
    "datePublished" : "1999-02-16T00:00:00.000-06:00",
    "citation" : "Prasad PD, etal., Biochem Biophys Res Commun. 1999 Feb 16;255(2):283-8. doi: 10.1006/bbrc.1999.0206.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-09-21T01:57:54.000-05:00",
    "volume" : "255",
    "pages" : "283-8",
    "abstract" : "We report here on the cloning and functional characterization of human LAT1, a subunit of the amino acid transport system L. The hLAT1 cDNA, obtained from a human placental cDNA library, codes for a protein of 507 amino acids. When functionally expressed in mammalian cells together with the heavy chain of the rat 4F2 antigen (r4F2hc), hLAT1 induces the transport of neutral amino acids. When expressed independently, neither hLAT1 nor r4F2hc was capable of amino acid transport to any significant extent. Thus, the hLAT1-r4F2hc heterodimeric complex is responsible for the observed amino acid transport. The transport process induced by the heterodimer is Na+ independent and is not influenced by pH. It recognizes exclusively neutral amino acids with high affinity. LAT1-specific mRNA is expressed in most human tissues with the notable exception of the intestine.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P D",
      "lastName" : "Prasad",
      "authorRank" : 1,
      "name" : "Prasad PD",
      "referenceId" : "RGD:A521126"
    }, {
      "firstName" : "H",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang H",
      "referenceId" : "RGD:A160751"
    }, {
      "firstName" : "W",
      "lastName" : "Huang",
      "authorRank" : 3,
      "name" : "Huang W",
      "referenceId" : "RGD:A5009"
    }, {
      "firstName" : "R",
      "lastName" : "Kekuda",
      "authorRank" : 4,
      "name" : "Kekuda R",
      "referenceId" : "RGD:A6424"
    }, {
      "firstName" : "D P",
      "lastName" : "Rajan",
      "authorRank" : 5,
      "name" : "Rajan DP",
      "referenceId" : "RGD:A521127"
    }, {
      "firstName" : "F H",
      "lastName" : "Leibach",
      "authorRank" : 6,
      "name" : "Leibach FH",
      "referenceId" : "RGD:A485659"
    }, {
      "firstName" : "V",
      "lastName" : "Ganapathy",
      "authorRank" : 7,
      "name" : "Ganapathy V",
      "referenceId" : "RGD:A5011"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:155230758"
    } ]
  }, {
    "primaryId" : "PMID:10049703",
    "title" : "Altered expression of hepatic CYP2E1 and CYP4A in obese, diabetic ob/ob mice, and fa/fa Zucker rats.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Enriquez A, etal., Biochem Biophys Res Commun. 1999 Feb 16;255(2):300-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-10-08T18:47:07.000-05:00",
    "volume" : "255",
    "pages" : "300-6",
    "abstract" : "Hepatic levels of the cytochrome P450 (CYP) proteins 2E1 and 4A are often increased in obesity, diabetes and fasting. In such states of nutritional imbalance, CYPs 2E1 and 4A may play a more significant role in fatty acid oxidation. In order to more fully characterize the regulation of CYP2E1 and CYP4A in obesity and obesity-related (type II) diabetes, we analyzed the hepatic expression of CYP2E1 and CYP4A in ob/ob mice which are leptin deficient, and fa/fa Zucker rats which have defective leptin receptor function. CYP2E1 protein and mRNA were either unchanged or reduced in both models. Conversely, expression of murine Cyp4a10 and 4a14 in the obese mice, and 4A2 in the male fatty Zucker rat, were greatly increased. The levels of other CYP4As were either unchanged or reduced. These results show that CYP2E1 is not inevitably increased by obesity and diabetes and indicate differential regulation of CYP4A subfamily genes in rodent models. Further, they implicate leptin receptor signaling as a factor that may modulate expression of CYP gene products involved in fatty acid oxidation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Enriquez",
      "authorRank" : 1,
      "name" : "Enriquez A",
      "referenceId" : "RGD:A113325"
    }, {
      "firstName" : "I",
      "lastName" : "Leclercq",
      "authorRank" : 2,
      "name" : "Leclercq I",
      "referenceId" : "RGD:A100840"
    }, {
      "firstName" : "GC",
      "lastName" : "Farrell",
      "authorRank" : 3,
      "name" : "Farrell GC",
      "referenceId" : "RGD:A113326"
    }, {
      "firstName" : "G",
      "lastName" : "Robertson",
      "authorRank" : 4,
      "name" : "Robertson G",
      "referenceId" : "RGD:A113328"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313688"
    } ]
  }, {
    "primaryId" : "PMID:10049752",
    "title" : "Molecular cloning and functional characterization of rat delta-6 fatty acid desaturase.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Aki T, etal., Biochem Biophys Res Commun 1999 Feb 24;255(3):575-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-07-31T12:14:20.000-05:00",
    "volume" : "255",
    "pages" : "575-9",
    "abstract" : "Mammalian cDNA fragments putatively encoding amino acid sequences characteristic of the fatty acid desaturase were obtained using expressed sequence tag (EST) sequence informations. These fragments were subsequently used to screen a rat liver cDNA library, yielding a 1573-bp clone. Expression of DNA fragment containing either of two possible open reading frames (nucleotide numbers 97-1431 and 148-1431) of the isolated clone in yeast led to the accumulation of gamma-linolenic acid in the presence of exogenous linoleic acid. In this system, the addition of alpha-linolenic acid also resulted in the accumulation of its Delta-6 desaturated product whereas dihomo-gamma-linolenic acid failed to be a substrate. These results indicate that the protein encoded by the rat cDNA is Delta-6 fatty acid desaturase, and the first 17 amino acids corresponding to the coding region 97-147 of the clone are not required to function in yeast.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Aki",
      "authorRank" : 1,
      "name" : "Aki T",
      "referenceId" : "RGD:A4800"
    }, {
      "firstName" : "Y",
      "lastName" : "Shimada",
      "authorRank" : 2,
      "name" : "Shimada Y",
      "referenceId" : "RGD:A4801"
    }, {
      "firstName" : "K",
      "lastName" : "Inagaki",
      "authorRank" : 3,
      "name" : "Inagaki K",
      "referenceId" : "RGD:A4802"
    }, {
      "firstName" : "H",
      "lastName" : "Higashimoto",
      "authorRank" : 4,
      "name" : "Higashimoto H",
      "referenceId" : "RGD:A4803"
    }, {
      "firstName" : "S",
      "lastName" : "Kawamoto",
      "authorRank" : 5,
      "name" : "Kawamoto S",
      "referenceId" : "RGD:A4804"
    }, {
      "firstName" : "S",
      "lastName" : "Shigeta",
      "authorRank" : 6,
      "name" : "Shigeta S",
      "referenceId" : "RGD:A4805"
    }, {
      "firstName" : "K",
      "lastName" : "Ono",
      "authorRank" : 7,
      "name" : "Ono K",
      "referenceId" : "RGD:A147194"
    }, {
      "firstName" : "O",
      "lastName" : "Suzuki",
      "authorRank" : 8,
      "name" : "Suzuki O",
      "referenceId" : "RGD:A4807"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68244"
    } ]
  }, {
    "primaryId" : "PMID:10049754",
    "title" : "Mechanism of Ret activation by a mutation at aspartic acid 631 identified in sporadic pheochromocytoma.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Asai N, etal., Biochem Biophys Res Commun. 1999 Feb 24;255(3):587-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:29:22.000-05:00",
    "volume" : "255",
    "pages" : "587-90",
    "abstract" : "Mutations at aspartic acid 631 in Ret were reported in sporadic pheochromocytoma  and medullary thyroid carcinoma. We replaced this aspartic acid with four other amino acids including tyrosine, glycine, asparagine, and alanine and investigated the transforming activity of these mutant cDNAs. Among them, RET cDNA with a mutation of aspartic acid to tyrosine (D631Y) that was reported in sporadic pheochromocytoma showed high transforming activity. The D631Y mutation activated  Ret by inducing its disulfide-linked dimerization in the transfectant as observed for multiple endocrine neoplasia (MEN) 2A mutations at cysteine 609, 611, 618, 620, 630, or 634. Further mutation analysis suggested that cysteine 630 or 634 could be involved in the disulfide-linked Ret dimerization induced by the D631Y mutation.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Asai",
      "authorRank" : 1,
      "name" : "Asai N",
      "referenceId" : "RGD:A139566"
    }, {
      "firstName" : "T",
      "lastName" : "Iwashita",
      "authorRank" : 2,
      "name" : "Iwashita T",
      "referenceId" : "RGD:A49656"
    }, {
      "firstName" : "H",
      "lastName" : "Murakami",
      "authorRank" : 3,
      "name" : "Murakami H",
      "referenceId" : "RGD:A5055"
    }, {
      "firstName" : "H",
      "lastName" : "Takanari",
      "authorRank" : 4,
      "name" : "Takanari",
      "referenceId" : "RGD:A278978"
    }, {
      "firstName" : "K",
      "lastName" : "Ohmori",
      "authorRank" : 5,
      "name" : "Ohmori K",
      "referenceId" : "RGD:A113511"
    }, {
      "firstName" : "M",
      "lastName" : "Ichihara",
      "authorRank" : 6,
      "name" : "Ichihara M",
      "referenceId" : "RGD:A46044"
    }, {
      "firstName" : "M",
      "lastName" : "Takahashi",
      "authorRank" : 7,
      "name" : "Takahashi M",
      "referenceId" : "RGD:A4629"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071227"
    } ]
  }, {
    "primaryId" : "PMID:10049954",
    "title" : "Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1)",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Cohn ES, etal., Pediatrics. 1999 Mar;103(3):546-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:50:03.000-05:00",
    "volume" : "103",
    "pages" : "546-50",
    "abstract" : "OBJECTIVE: This retrospective study describes the phenotype associated with the single most common cause of genetic hearing loss. The frequency of childhood deafness is estimated at 1/500. Half of this hearing loss is genetic and approximately 80% of genetic hearing loss is nonsyndromic and inherited in an autosomal recessive manner. Approximately 50% of childhood nonsyndromic recessive hearing loss is caused by mutations in the connexin 26 (Cx26) gene (GJB2/DFNB1),  making it the most common form of autosomal recessive nonsyndromic hearing loss with a carrier rate estimated to be as high as 2.8%. One mutation, 35delG, accounts for approximately 75% to 80% of mutations at this gene. METHODS: Hearing loss was examined in 46 individuals from 24 families who were either homozygous or compound heterozygous for Cx26 mutations. A subset of these individuals were examined for vestibular function, otoacoustic emissions, auditory brainstem response, temporal bone computed tomography, electrocardiography, urinalyses, dysmorphology, and thyroid function. RESULTS: Although all persons had hearing impairment, no consistent audiologic phenotype was observed. Hearing loss varied  from mild-moderate to profound, even within the group of families homozygous for  the common mutation 35delG, suggesting that other factors modify the phenotypic effects of mutations in Cx26. Furthermore, the hearing loss was observed to be progressive in a number of cases. No associations with inner ear abnormality, thyroid dysfunction, heart conduction defect, urinalyses, dysmorphic features, or retinal abnormality were noted. CONCLUSION: Newborns with confirmed hearing loss  should have Cx26 testing. Cx26 testing will help define a group in which approximately 60% will have profound or severe-profound hearing loss and require  aggressive language intervention (many of these patients will be candidates for cochlear implants).",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ES",
      "lastName" : "Cohn",
      "authorRank" : 1,
      "name" : "Cohn",
      "referenceId" : "RGD:A251941"
    }, {
      "firstName" : "PM",
      "lastName" : "Kelley",
      "authorRank" : 2,
      "name" : "Kelley PM",
      "referenceId" : "RGD:A75641"
    }, {
      "firstName" : "TW",
      "lastName" : "Fowler",
      "authorRank" : 3,
      "name" : "Fowler",
      "referenceId" : "RGD:A282728"
    }, {
      "firstName" : "MP",
      "lastName" : "Gorga",
      "authorRank" : 4,
      "name" : "Gorga",
      "referenceId" : "RGD:A282729"
    }, {
      "firstName" : "DM",
      "lastName" : "Lefkowitz",
      "authorRank" : 5,
      "name" : "Lefkowitz",
      "referenceId" : "RGD:A282730"
    }, {
      "firstName" : "HJ",
      "lastName" : "Kuehn",
      "authorRank" : 6,
      "name" : "Kuehn",
      "referenceId" : "RGD:A282731"
    }, {
      "firstName" : "GB",
      "lastName" : "Schaefer",
      "authorRank" : 7,
      "name" : "Schaefer",
      "referenceId" : "RGD:A282732"
    }, {
      "firstName" : "LS",
      "lastName" : "Gobar",
      "authorRank" : 8,
      "name" : "Gobar",
      "referenceId" : "RGD:A282733"
    }, {
      "firstName" : "FJ",
      "lastName" : "Hahn",
      "authorRank" : 9,
      "name" : "Hahn",
      "referenceId" : "RGD:A282734"
    }, {
      "firstName" : "DJ",
      "lastName" : "Harris",
      "authorRank" : 10,
      "name" : "Harris",
      "referenceId" : "RGD:A251842"
    }, {
      "firstName" : "WJ",
      "lastName" : "Kimberling",
      "authorRank" : 11,
      "name" : "Kimberling WJ",
      "referenceId" : "RGD:A23983"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072730"
    } ]
  }, {
    "primaryId" : "PMID:10050036",
    "title" : "Molecular shape and ATP binding activity of rat p50, a putative mammalian homologue of RuvB DNA helicase.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Kikuchi N, etal., J Biochem (Tokyo) 1999 Mar;125(3):487-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-07-31T12:14:24.000-05:00",
    "volume" : "125",
    "pages" : "487-94",
    "abstract" : "Based on partial amino acid sequences of p50 purified from a high-salt buffer extract of a rat liver nuclear matrix fraction, p50 cDNA was cloned and sequenced, and its amino acid sequence was predicted. The sequence contained helicase motifs, and showed homology with RuvB DNA helicase of Thermus thermophilus and an open reading frame for an unknown 50.5 k protein of Saccharomyces cerevisiae. p50 was expressed as a GST-fusion protein and antiserum against the protein was generated. p50 was localized to the nuclear matrix by cell fractionation and immunoblotting. p50 bound to ATP-Sepharose beads. Ultracentrifugation and gel filtration analyses showed that p50 in rat liver and Xenopus egg mitotic extracts exists as large complexes corresponding to 697 k and 447 k, respectively. A 50 k protein reactive with p50 antibodies was detected not only in rat liver nuclei, but also in a Xenopus egg cytoplasm fraction and a S. cerevisiae extract. This suggests that this putative DNA helicase is present in a wide variety of species ranging from yeast to mammals.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Kikuchi",
      "authorRank" : 1,
      "name" : "Kikuchi N",
      "referenceId" : "RGD:A101263"
    }, {
      "firstName" : "T",
      "lastName" : "Gohshi",
      "authorRank" : 2,
      "name" : "Gohshi T",
      "referenceId" : "RGD:A5114"
    }, {
      "firstName" : "S",
      "lastName" : "Kawahire",
      "authorRank" : 3,
      "name" : "Kawahire S",
      "referenceId" : "RGD:A5115"
    }, {
      "firstName" : "T",
      "lastName" : "Tachibana",
      "authorRank" : 4,
      "name" : "Tachibana T",
      "referenceId" : "RGD:A5116"
    }, {
      "firstName" : "Y",
      "lastName" : "Yoneda",
      "authorRank" : 5,
      "name" : "Yoneda Y",
      "referenceId" : "RGD:A5117"
    }, {
      "firstName" : "T",
      "lastName" : "Isobe",
      "authorRank" : 6,
      "name" : "Isobe T",
      "referenceId" : "RGD:A131425"
    }, {
      "firstName" : "CR",
      "lastName" : "Lim",
      "authorRank" : 7,
      "name" : "Lim CR",
      "referenceId" : "RGD:A5119"
    }, {
      "firstName" : "K",
      "lastName" : "Kohno",
      "authorRank" : 8,
      "name" : "Kohno K",
      "referenceId" : "RGD:A5120"
    }, {
      "firstName" : "T",
      "lastName" : "Ichimura",
      "authorRank" : 9,
      "name" : "Ichimura T",
      "referenceId" : "RGD:A119384"
    }, {
      "firstName" : "S",
      "lastName" : "Omata",
      "authorRank" : 10,
      "name" : "Omata S",
      "referenceId" : "RGD:A5122"
    }, {
      "firstName" : "T",
      "lastName" : "Horigome",
      "authorRank" : 11,
      "name" : "Horigome T",
      "referenceId" : "RGD:A5123"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68302"
    } ]
  }, {
    "primaryId" : "PMID:10050048",
    "title" : "Expression of arginase II and related enzymes in the rat small intestine and kidney.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Ozaki M, etal., J Biochem. 1999 Mar;125(3):586-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-30T11:39:55.000-05:00",
    "volume" : "125",
    "pages" : "586-93",
    "abstract" : "Arginase, which catalyzes the conversion of arginine to urea and ornithine, and consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Arginine is also used for the synthesis of nitric oxide and creatine phosphate, while ornithine is used for the synthesis of polyamines and proline, and thus collagen. Arginase II mRNA and protein are abundant in the intestine (most abundant in the jejunum and less abundant in the ileum, duodenum, and colon) and kidney of the rat. In the kidney, the levels of arginase II mRNA do not change appreciably from 0 to 8 weeks of age. In contrast, arginase II mRNA and protein in the small intestine are not detectable at birth, appear at 3 weeks of age, the weaning period, and their levels increase up to 8 weeks. On the other hand, mRNAs for ornithine aminotransferase (OAT), ornithine decarboxylase, and ornithine carbamoyltransferase (OCT) are present at birth and their levels do not change much during development. Arginase II is elevated in response to a combination of bacterial lipopolysaccharide, dibutyryl cAMP, and dexamethasone in the kidney, but is not affected by these treatments in the small intestine. Immunohistochemical analysis of arginase II, OAT, and OCT in the jejunum revealed their co-localization in absorptive epithelial cells. These results show that the arginase II gene is regulated differentially in the small intestine and kidney, and suggest different roles of the enzyme in these two tissues. The co-localization of arginase II and the three ornithine-utilizing enzymes in the small intestine suggests that the enzyme is involved in the synthesis of proline, polyamines, and/or citrulline in this tissue.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Ozaki",
      "authorRank" : 1,
      "name" : "Ozaki M",
      "referenceId" : "RGD:A87276"
    }, {
      "firstName" : "T",
      "lastName" : "Gotoh",
      "authorRank" : 2,
      "name" : "Gotoh T",
      "referenceId" : "RGD:A15184"
    }, {
      "firstName" : "A",
      "lastName" : "Nagasaki",
      "authorRank" : 3,
      "name" : "Nagasaki A",
      "referenceId" : "RGD:A72811"
    }, {
      "firstName" : "K",
      "lastName" : "Miyanaka",
      "authorRank" : 4,
      "name" : "Miyanaka K",
      "referenceId" : "RGD:A73154"
    }, {
      "firstName" : "M",
      "lastName" : "Takeya",
      "authorRank" : 5,
      "name" : "Takeya M",
      "referenceId" : "RGD:A22984"
    }, {
      "firstName" : "S",
      "lastName" : "Fujiyama",
      "authorRank" : 6,
      "name" : "Fujiyama S",
      "referenceId" : "RGD:A103635"
    }, {
      "firstName" : "K",
      "lastName" : "Tomita",
      "authorRank" : 7,
      "name" : "Tomita K",
      "referenceId" : "RGD:A162352"
    }, {
      "firstName" : "M",
      "lastName" : "Mori",
      "authorRank" : 8,
      "name" : "Mori M",
      "referenceId" : "RGD:A7028"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4144052"
    } ]
  }, {
    "primaryId" : "PMID:10050756",
    "title" : "Enhanced mitochondrial biogenesis is associated with increased expression of the mitochondrial ATP-dependent Lon protease.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Luciakova K, etal., FEBS Lett. 1999 Feb 12;444(2-3):186-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-21T09:13:59.000-05:00",
    "volume" : "444",
    "pages" : "186-8",
    "abstract" : "Rats bearing the Zajdela hepatoma tumor and T3-treated hypothyroid rats were used to study the role of protein degradation in the process of mitochondrial biogenesis. It was shown that the activity, protein and mRNA levels of the ATP-dependent Lon protease increased in rapidly growing Zajdela hepatoma cells. The increase in the rate of mitochondrial biogenesis by thyroid hormone was similarly accompanied by enhanced expression of the Lon protease. The results imply that mitochondrial biogenesis in mammalian cells is, at least partially, regulated by the matrix Lon protease.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Luciakova",
      "authorRank" : 1,
      "name" : "Luciakova K",
      "referenceId" : "RGD:A63514"
    }, {
      "firstName" : "B",
      "lastName" : "Sokolikova",
      "authorRank" : 2,
      "name" : "Sokolikova B",
      "referenceId" : "RGD:A63515"
    }, {
      "firstName" : "M",
      "lastName" : "Chloupkova",
      "authorRank" : 3,
      "name" : "Chloupkova M",
      "referenceId" : "RGD:A63516"
    }, {
      "firstName" : "BD",
      "lastName" : "Nelson",
      "authorRank" : 4,
      "name" : "Nelson BD",
      "referenceId" : "RGD:A63517"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580666"
    } ]
  }, {
    "primaryId" : "PMID:10050766",
    "title" : "Cytosolic phospholipase A2 in rat decidual cells: evidence for its role in decidualization.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Kurusu S, etal., FEBS Lett. 1999 Feb 12;444(2-3):235-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-09-18T15:18:43.000-05:00",
    "volume" : "444",
    "pages" : "235-8",
    "abstract" : "We investigated the existence and possible role of cytosolic phospholipase A2 (cPLA2) in rat decidualized uteri. PLA2 activity in the cytosol of a decidualized uterine horn, induced by intraluminal oil infusion, was significantly higher than that in contralateral intact horn. The activity was almost completely depressed by cPLA2 inhibitors including arachidonyl trifluoromethyl ketone (ATK). The immunoreactive signals for cPLA2 were intense in decidua and glandular epithelial cells. In vivo administration of ATK (0.1-100 microg) caused a dose-dependent inhibition of decidualization. These results show the presence of cPLA2 and its probable implication in decidualization in rat uterus.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kurusu",
      "authorRank" : 1,
      "name" : "Kurusu S",
      "referenceId" : "RGD:A11566"
    }, {
      "firstName" : "M",
      "lastName" : "Endo",
      "authorRank" : 2,
      "name" : "Endo M",
      "referenceId" : "RGD:A37840"
    }, {
      "firstName" : "H",
      "lastName" : "Madarame",
      "authorRank" : 3,
      "name" : "Madarame H",
      "referenceId" : "RGD:A88163"
    }, {
      "firstName" : "M",
      "lastName" : "Kawaminami",
      "authorRank" : 4,
      "name" : "Kawaminami M",
      "referenceId" : "RGD:A11563"
    }, {
      "firstName" : "I",
      "lastName" : "Hashimoto",
      "authorRank" : 5,
      "name" : "Hashimoto I",
      "referenceId" : "RGD:A11567"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642479"
    } ]
  }, {
    "primaryId" : "PMID:10050892",
    "title" : "Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Dalmau J, etal., Brain 1999 Jan;122 ( Pt 1):27-39.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-09T17:54:41.000-05:00",
    "volume" : "122 ( Pt 1)",
    "pages" : "27-39",
    "abstract" : "The identification of antineuronal antibodies has facilitated the diagnosis of paraneoplastic neurological disorders and the early detection of the associated tumours. It has also led to the cloning of possibly important neuron-specific proteins. In this study we wanted to identify novel antineuronal antibodies in the sera of patients with paraneoplastic neurological disorders and to clone the corresponding antigens. Serological studies of 1705 sera from patients with suspected paraneoplastic neurological disorders resulted in the identification of four patients with antibodies that reacted with 37 and 40 kDa neuronal proteins (anti-Ma antibodies). Three patients had brainstem and cerebellar dysfunction, and one had dysphagia and motor weakness. Autopsy of two patients showed loss of Purkinje cells, Bergmann gliosis and deep cerebellar white matter inflammatory infiltrates. Extensive neuronal degeneration, gliosis and infiltrates mainly composed of CD8+ T cells were also found in the brainstem of one patient. In normal human and rat tissues, the anti-Ma antibodies reacted exclusively with neurons and with testicular germ cells; the reaction was mainly with subnuclear elements (including the nucleoli) and to a lesser degree the cytoplasm. Anti-Ma antibodies also reacted with the cancers (breast, colon and parotid) available from three anti-Ma patients, but not with 66 other tumours of varying histological types. Preincubation of tissues with any of the anti-Ma sera abrogated the reactivity of the other anti-Ma immunoglobulins. Probing of a human complementary DNA library with anti-Ma serum resulted in the cloning of a gene that encodes a novel 37 kDa protein (Mal). Recombinant Mal was specifically recognized by the four anti-Ma sera but not by 337 control sera, including those from 52 normal individuals, 179 cancer patients without paraneoplastic neurological symptoms, 96 patients with paraneoplastic syndromes and 10 patients with non-cancer-related neurological disorders. The expression of Mal mRNA is highly restricted to the brain and testis. Subsequent analysis suggested that Mal is likely to be a phosphoprotein. Our study demonstrates that some patients with paraneoplastic neurological disorders develop antibodies against Mal, a new member of an expanding family of 'brain/testis' proteins.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Dalmau",
      "authorRank" : 1,
      "name" : "Dalmau J",
      "referenceId" : "RGD:A26275"
    }, {
      "firstName" : "SH",
      "lastName" : "Gultekin",
      "authorRank" : 2,
      "name" : "Gultekin SH",
      "referenceId" : "RGD:A26276"
    }, {
      "firstName" : "R",
      "lastName" : "Voltz",
      "authorRank" : 3,
      "name" : "Voltz R",
      "referenceId" : "RGD:A26277"
    }, {
      "firstName" : "R",
      "lastName" : "Hoard",
      "authorRank" : 4,
      "name" : "Hoard R",
      "referenceId" : "RGD:A26278"
    }, {
      "firstName" : "T",
      "lastName" : "DesChamps",
      "authorRank" : 5,
      "name" : "DesChamps T",
      "referenceId" : "RGD:A26279"
    }, {
      "firstName" : "C",
      "lastName" : "Balmaceda",
      "authorRank" : 6,
      "name" : "Balmaceda C",
      "referenceId" : "RGD:A26280"
    }, {
      "firstName" : "T",
      "lastName" : "Batchelor",
      "authorRank" : 7,
      "name" : "Batchelor T",
      "referenceId" : "RGD:A26281"
    }, {
      "firstName" : "E",
      "lastName" : "Gerstner",
      "authorRank" : 8,
      "name" : "Gerstner E",
      "referenceId" : "RGD:A26282"
    }, {
      "firstName" : "J",
      "lastName" : "Eichen",
      "authorRank" : 9,
      "name" : "Eichen J",
      "referenceId" : "RGD:A26283"
    }, {
      "firstName" : "J",
      "lastName" : "Frennier",
      "authorRank" : 10,
      "name" : "Frennier J",
      "referenceId" : "RGD:A26284"
    }, {
      "firstName" : "JB",
      "lastName" : "Posner",
      "authorRank" : 11,
      "name" : "Posner JB",
      "referenceId" : "RGD:A26285"
    }, {
      "firstName" : "MR",
      "lastName" : "Rosenfeld",
      "authorRank" : 12,
      "name" : "Rosenfeld MR",
      "referenceId" : "RGD:A26286"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:724595"
    } ]
  }, {
    "primaryId" : "PMID:10051009",
    "title" : "Mutation screening of the RYR1 gene and identification of two novel mutations in  Italian malignant hyperthermia families.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Barone V, etal., J Med Genet. 1999 Feb;36(2):115-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:02:43.000-05:00",
    "volume" : "36",
    "pages" : "115-8",
    "abstract" : "Point mutations in the ryanodine receptor (RYR1) gene are associated with malignant hyperthermia, an autosomal dominant disorder triggered in susceptible people (MHS) by volatile anaesthetics and depolarising skeletal muscle relaxants. To date, 17 missense point mutations have been identified in the human RYR1 gene  by screening of the cDNA obtained from muscle biopsies. Here we report single strand conformation polymorphism (SSCP) screening for nine of the most frequent RYR1 mutations using genomic DNA isolated from MHS patients. In addition, the Argl63Cys mutation was analysed by restriction enzyme digestion. We analysed 57 unrelated patients and detected seven of the known RYR1 point mutations. Furthermore, we found a new mutation, Arg2454His, segregating with the MHS phenotype in a large pedigree and a novel amino acid substitution at position 2436 in another patient, indicating a 15.8% frequency of these mutations in Italian patients. A new polymorphic site in intron 16 that causes the substitution of a G at position -7 with a C residue was identified.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Barone",
      "authorRank" : 1,
      "name" : "Barone V",
      "referenceId" : "RGD:A42744"
    }, {
      "firstName" : "O",
      "lastName" : "Massa",
      "authorRank" : 2,
      "name" : "Massa O",
      "referenceId" : "RGD:A60615"
    }, {
      "firstName" : "E",
      "lastName" : "Intravaia",
      "authorRank" : 3,
      "name" : "Intravaia",
      "referenceId" : "RGD:A283301"
    }, {
      "firstName" : "A",
      "lastName" : "Bracco",
      "authorRank" : 4,
      "name" : "Bracco",
      "referenceId" : "RGD:A255489"
    }, {
      "firstName" : "A",
      "lastName" : "Di Martino",
      "authorRank" : 5,
      "name" : "Di Martino",
      "referenceId" : "RGD:A255488"
    }, {
      "firstName" : "V",
      "lastName" : "Tegazzin",
      "authorRank" : 6,
      "name" : "Tegazzin",
      "referenceId" : "RGD:A250560"
    }, {
      "firstName" : "S",
      "lastName" : "Cozzolino",
      "authorRank" : 7,
      "name" : "Cozzolino",
      "referenceId" : "RGD:A255476"
    }, {
      "firstName" : "V",
      "lastName" : "Sorrentino",
      "authorRank" : 8,
      "name" : "Sorrentino V",
      "referenceId" : "RGD:A42746"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072953"
    } ]
  }, {
    "primaryId" : "PMID:10051017",
    "title" : "A mutation in the RIEG1 gene associated with Peters' anomaly.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Doward W, etal., J Med Genet. 1999 Feb;36(2):152-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-07T20:10:34.000-06:00",
    "volume" : "36",
    "pages" : "152-5",
    "abstract" : "Mutations within the RIEG1 homeobox gene on chromosome 4q25 have previously been  reported in association with Rieger syndrome. We report a 3' splice site mutation within the 3rd intron of the RIEG1 gene which is associated with unilateral Peters' anomaly. The mutation is a single base substition of A to T at the invariant -2 site of the 3' splice site. Peters' anomaly, which is characterised  by ocular anterior segment dysgenesis and central corneal opacification, is distinct from Rieger anomaly. This is the first description of a RIEG1 mutation associated with Peters' anomaly.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Doward",
      "authorRank" : 1,
      "name" : "Doward",
      "referenceId" : "RGD:A415041"
    }, {
      "firstName" : "R",
      "lastName" : "Perveen",
      "authorRank" : 2,
      "name" : "Perveen R",
      "referenceId" : "RGD:A51345"
    }, {
      "firstName" : "IC",
      "lastName" : "Lloyd",
      "authorRank" : 3,
      "name" : "Lloyd",
      "referenceId" : "RGD:A415042"
    }, {
      "firstName" : "AE",
      "lastName" : "Ridgway",
      "authorRank" : 4,
      "name" : "Ridgway",
      "referenceId" : "RGD:A415043"
    }, {
      "firstName" : "L",
      "lastName" : "Wilson",
      "authorRank" : 5,
      "name" : "Wilson L",
      "referenceId" : "RGD:A77303"
    }, {
      "firstName" : "GC",
      "lastName" : "Black",
      "authorRank" : 6,
      "name" : "Black GC",
      "referenceId" : "RGD:A45496"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568202"
    } ]
  }, {
    "primaryId" : "PMID:10051108",
    "title" : "Glial gene expression during aging in rat striatum and in long-term responses to 6-OHDA lesions.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Pasinetti GM, etal., Synapse. 1999 Mar 15;31(4):278-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-06T16:08:37.000-06:00",
    "volume" : "31",
    "pages" : "278-84",
    "abstract" : "The male rat striatum was examined for age-related changes in mRNAs expressed in astrocytes and microglia in two rat genotypes that differ by 35% in mean and maximum life spans: F344 and the longer-lived F1 (BN x F344) hybrid. The findings extend the established age-related increases in GFAP (glial fibrillary acidic protein) to other glial mRNAs: two lipoprotein mRNAs that are predominantly expressed in striatal astrocytes, apoE (apolipoprotein E) and apoJ (apolipoprotein J, clusterin, CLI, or SGP-2), and two mRNAs expressed in striatal microglia, TGF-beta1 and complement C1qB. By Northern blot hybridization, both genotypes showed progressive increases of GFAP mRNA to > 2.5-fold by the lifespan. Although the rat strains differed 35% in life span, the slope of the GFAP mRNA regression on age did not differ. Relative to GFAP, the increases of apoE, apoJ, C1q, and TGF-beta1 mRNAs were smaller, < or = 1.5-fold. Because prior studies showed that acute damage to striatal afferents induced astrocyte gene expression increases resembling those that also occur during aging, we examined long-term effects of damage to substantia nigra neurons on striatal astrocyte changes during aging. Young F344 rats were given 6-OHDA lesions that cause striatal dopamine deficits and induce GFAP. When examined 15 months later at age 18 months, there was no effect during prior lesions on the age-related elevation of GFAP mRNA. We conclude that aging changes in striatal GFAP mRNAs do not interact with loss of dopaminergic output to the striatum from 6-OHDA lesions and may be independent of the relatively modest dopaminergic losses during normal aging.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GM",
      "lastName" : "Pasinetti",
      "authorRank" : 1,
      "name" : "Pasinetti GM",
      "referenceId" : "RGD:A74156"
    }, {
      "firstName" : "M",
      "lastName" : "Hassler",
      "authorRank" : 2,
      "name" : "Hassler M",
      "referenceId" : "RGD:A74157"
    }, {
      "firstName" : "D",
      "lastName" : "Stone",
      "authorRank" : 3,
      "name" : "Stone D",
      "referenceId" : "RGD:A41755"
    }, {
      "firstName" : "CE",
      "lastName" : "Finch",
      "authorRank" : 4,
      "name" : "Finch CE",
      "referenceId" : "RGD:A8805"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599511"
    } ]
  }, {
    "primaryId" : "PMID:10051168",
    "title" : "Child with velocardiofacial syndrome and del (4)(q34.2): another critical region  associated with a velocardiofacial syndrome-like phenotype.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Tsai CH, etal., Am J Med Genet. 1999 Feb 12;82(4):336-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-07T20:19:53.000-06:00",
    "volume" : "82",
    "pages" : "336-9",
    "abstract" : "We report on a child with congenital heart disease (atrial septal defect, ventricular septal defect, pulmonic stenosis), submucosal cleft palate, hypernasal speech, learning difficulties, and right fifth finger anomaly manifestations, consistent with velocardiofacial syndrome (VCFS); however, cytogenetic analysis demonstrated a small terminal deletion of the segment 4q34.2 to 4qter. Fluorescent in situ hybridization did not identify a deletion of the critical region associated with VCFS. In previously reported 4q deletions with a  breakpoint distal to 4q34.2, no cardiac defects or cleft of palate were reported. Our patient has a deletion of 4q34.2 to 4qter and has palate and cardiac involvement and minor learning difficulties, which implies that genes involved in heart and palate development lie distal to 4q34.2, and that the critical region for more severe mental retardation on 4q may reside proximal to 4q34.2. These results suggest that a distal 4q deletion can lead to a phenotype similar to VCFS and emphasizes the importance of searching for other karyotype abnormalities when a VCFS-like phenotype is present and a 22q deletion is not identified.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CH",
      "lastName" : "Tsai",
      "authorRank" : 1,
      "name" : "Tsai CH",
      "referenceId" : "RGD:A58671"
    }, {
      "firstName" : "DL",
      "lastName" : "Van Dyke",
      "authorRank" : 2,
      "name" : "Van Dyke",
      "referenceId" : "RGD:A278336"
    }, {
      "firstName" : "GL",
      "lastName" : "Feldman",
      "authorRank" : 3,
      "name" : "Feldman",
      "referenceId" : "RGD:A253802"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568578"
    } ]
  }, {
    "primaryId" : "PMID:10051208",
    "title" : "Distinct regional distribution in the brain of messenger RNAs for the two isoforms of synaphin associated with the docking/fusion complex.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Ishizuka T, etal., Neuroscience 1999 Jan;88(1):295-306.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:17:14.000-05:00",
    "volume" : "88",
    "pages" : "295-306",
    "abstract" : "Synaphin is a 19,000 mol. wt cytosolic protein we first found to co-purify with the docking/fusion complex crucial to neurotransmitter release from presynaptic terminals. Two isoforms of synaphin (synaphins 1 and 2) (also called complexins II and I, respectively) exist in the rat brain. On density gradient centrifugation of a Triton X-100 extract of brain membranes, synaphin was found to be associated with the 7S complex that contains synaptotagmin, syntaxin, synaptosomal-associated protein of 25,000 mol. wt and vesicle-associated membrane protein. A smaller complex devoid of synaphins was also identified by immunoprecipitation with a monoclonal antibody against synaptosomal-associated protein of 25,000 mol. wt. Messenger RNAs for synaphins 1 and 2 were expressed predominantly in the brain. In situ hybridization using probes specific to synaphins 1 and 2 indicated that the distribution of their mRNAs was significantly different in brain regions such as olfactory bulb, hippocampus, cerebral cortex, piriform cortex, cerebellum, thalamus and facial nuclei. These results show synaphin as a component of the 7S complex and suggest different physiological implications for the two isoforms.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Ishizuka",
      "authorRank" : 1,
      "name" : "Ishizuka T",
      "referenceId" : "RGD:A9836"
    }, {
      "firstName" : "H",
      "lastName" : "Saisu",
      "authorRank" : 2,
      "name" : "Saisu H",
      "referenceId" : "RGD:A9837"
    }, {
      "firstName" : "S",
      "lastName" : "Odani",
      "authorRank" : 3,
      "name" : "Odani S",
      "referenceId" : "RGD:A5706"
    }, {
      "firstName" : "T",
      "lastName" : "Kumanishi",
      "authorRank" : 4,
      "name" : "Kumanishi T",
      "referenceId" : "RGD:A27236"
    }, {
      "firstName" : "T",
      "lastName" : "Abe",
      "authorRank" : 5,
      "name" : "Abe T",
      "referenceId" : "RGD:A8476"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70696"
    } ]
  }, {
    "primaryId" : "PMID:10051231",
    "title" : "D1- and D2-like dopamine receptors are co-localized on the presynaptic varicosities of striatal and nucleus accumbens neurons in vitro.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Wong AC, etal., Neuroscience. 1999 Mar;89(1):221-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:39:44.000-05:00",
    "volume" : "89",
    "pages" : "221-33",
    "abstract" : "The neuromodulatory actions of dopamine in the striatum and nucleus accumbens are likely to depend on the distribution of dopamine receptors on individual postsynaptic cells. To address this, we have visualized D1- and D2-like receptors on living medium-spiny GABAergic neurons in cultures from the striatum and nucleus accumbens using receptor antagonist fluoroprobes. We labeled D1-like receptors with rhodamine-SCH23390, D2-like receptors with rhodamine-N-(p-aminophenethyl)spiperone and synaptic sites with K+-stimulated uptake of the activity-dependent endocytic tracer FM-143. The fluoroprobes were applied in sequence to assess co-localization. We found that D1- or D2-like receptors were present on about two-thirds of the cells, and co-localized on 22+/-3% (mean +/- S.E.M.) of striatal and 38+/-6% of nucleus accumbens cells. On  either D1 or D2 labeled cells, postsynaptic labeling continuously outlined the cell body membrane and extended to proximal dendrites, but not axons. About two-thirds of synaptic varicosities showed D1 or D2 labeling. D1- and D2-like receptors were co-localized on 21+/-4% of striatal and 27+/-3% of nucleus accumbens varicosities. Presynaptic labeling was typically more intense than postsynaptic labeling. The distribution of presynaptic dopamine receptors contrasted with that of postsynaptic GABA(A) receptors, which were clustered in longer patches on neighboring postsynaptic membranes. The extensive presence of D1- and D2-like receptors on presynaptic varicosities of medium-spiny neurons suggests that the receptors are likely to play an important and interacting role  in the presynaptic modulation of inhibitory synaptic transmission in the striatum and nucleus accumbens. The significant overlap in labeling suggests that D1-D2 interactions, which occur at the level of individual postsynaptic cells, the circuit level and the systems level, may also be mediated at the presynaptic level. Finally, the ability to visualize dopamine, as well as GABA(A), receptors  on the individual synapses of living neurons now makes possible physiological studies of individual mesolimbic system synapses with known receptor expression.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AC",
      "lastName" : "Wong",
      "authorRank" : 1,
      "name" : "Wong AC",
      "referenceId" : "RGD:A72928"
    }, {
      "firstName" : "ME",
      "lastName" : "Shetreat",
      "authorRank" : 2,
      "name" : "Shetreat",
      "referenceId" : "RGD:A185590"
    }, {
      "firstName" : "JO",
      "lastName" : "Clarke",
      "authorRank" : 3,
      "name" : "Clarke",
      "referenceId" : "RGD:A185591"
    }, {
      "firstName" : "S",
      "lastName" : "Rayport",
      "authorRank" : 4,
      "name" : "Rayport",
      "referenceId" : "RGD:A185592"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554073"
    } ]
  }, {
    "primaryId" : "PMID:10051295",
    "title" : "Familial dilated cardiomyopathy locus maps to chromosome 2q31.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Siu BL, etal., Circulation 1999 Mar 2;99(8):1022-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-10-28T09:30:13.000-05:00",
    "volume" : "99",
    "pages" : "1022-6",
    "abstract" : "BACKGROUND: Inherited gene defects are an important cause of dilated cardiomyopathy. Although the chromosome locations of some defects and 1 disease gene (actin) have been identified, the genetic etiologies of most cases of familial dilated cardiomyopathy remain unknown. METHODS AND RESULTS: We clinically evaluated 3 generations of a kindred with autosomal dominant transmission of dilated cardiomyopathy. Nine surviving and affected individuals had early-onset disease (ventricular chamber dilation during the teenage years and congestive heart failure during the third decade of life). The disease was nonpenetrant in 2 obligate carriers. To identify the causal gene defect, linkage studies were performed. A new dilated cardiomyopathy locus was identified on chromosome 2 between loci GCG and D2S72 (maximum logarithm of odds [LOD] score=4.86 at theta=0). Because the massive gene encoding titin, a cytoskeletal muscle protein, resides in this disease interval, sequences encoding 900 amino acid residues of the cardiac-specific (N2-B) domain were analyzed. Five sequence variants were identified, but none segregated with disease in this family. CONCLUSIONS: A dilated cardiomyopathy locus (designated CMD1G) is located on chromosome 2q31 and causes early-onset congestive heart failure. Although titin remains an intriguing candidate gene for this disorder, a disease-causing mutation is not present in its cardiac-specific N2-B domain.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BL",
      "lastName" : "Siu",
      "authorRank" : 1,
      "name" : "Siu BL",
      "referenceId" : "RGD:A56258"
    }, {
      "firstName" : "H",
      "lastName" : "Niimura",
      "authorRank" : 2,
      "name" : "Niimura H",
      "referenceId" : "RGD:A56259"
    }, {
      "firstName" : "JA",
      "lastName" : "Osborne",
      "authorRank" : 3,
      "name" : "Osborne JA",
      "referenceId" : "RGD:A56260"
    }, {
      "firstName" : "D",
      "lastName" : "Fatkin",
      "authorRank" : 4,
      "name" : "Fatkin D",
      "referenceId" : "RGD:A56261"
    }, {
      "firstName" : "C",
      "lastName" : "MacRae",
      "authorRank" : 5,
      "name" : "MacRae C",
      "referenceId" : "RGD:A56262"
    }, {
      "firstName" : "S",
      "lastName" : "Solomon",
      "authorRank" : 6,
      "name" : "Solomon S",
      "referenceId" : "RGD:A50418"
    }, {
      "firstName" : "DW",
      "lastName" : "Benson",
      "authorRank" : 7,
      "name" : "Benson DW",
      "referenceId" : "RGD:A56263"
    }, {
      "firstName" : "JG",
      "lastName" : "Seidman",
      "authorRank" : 8,
      "name" : "Seidman JG",
      "referenceId" : "RGD:A32536"
    }, {
      "firstName" : "CE",
      "lastName" : "Seidman",
      "authorRank" : 9,
      "name" : "Seidman CE",
      "referenceId" : "RGD:A32532"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556474"
    } ]
  }, {
    "primaryId" : "PMID:10051311",
    "title" : "The mouse mutation Pdn (Polydactyly Nagoya) is caused by the integration of a retrotransposon into the Gli3 gene.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Thien H and Rüther U, Mamm Genome. 1999 Mar;10(3):205-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-01-27T16:30:45.000-06:00",
    "volume" : "10",
    "pages" : "205-9",
    "abstract" : "Mutations in the Gli3 gene are associated with a preaxial polydactyly in several mouse mutants such as extra-toes (Xt). The semidominant mouse mutant Pdn (Polydactyly Nagoya) is characterized by a mild polydactyly on the anterior side of the hind limbs. Homozygous Pdn mice show a more severe polydactyly, additional skeletal malformations, and abnormal brain development. Herein, we report the molecular basis of Pdn, being the integration of an Early Transposon (ETn) into the Gli3 gene. As a consequence, several novel Gli3 mRNAs are generated by alternatively spliced transcripts.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Thien",
      "authorRank" : 1,
      "name" : "Thien H",
      "referenceId" : "RGD:A438258"
    }, {
      "firstName" : "U",
      "lastName" : "Rüther",
      "authorRank" : 2,
      "name" : "Rüther U",
      "referenceId" : "RGD:A438259"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12738140"
    } ]
  }, {
    "primaryId" : "PMID:10051315",
    "title" : "Quantitative trait loci for growth traits in C57BL/6J x DBA/2J mice.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Morris KH, etal., Mamm Genome 1999 Mar;10(3):225-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-03-31T20:58:40.000-06:00",
    "volume" : "10",
    "pages" : "225-8",
    "abstract" : "Quantitative trait loci (QTLs) for body weight and tail length are mapped in an F2 population of 927 C57BL/6J x DBA/2J mice. We test the concordance between the locations of the mapped QTLs with those detected by changes of marker frequency under artificial selection in a previous experiment with the same base population. The directions of effects of the QTLs are generally in agreement, and in many cases significant QTLs are found in similar map positions, but there are also discrepancies between the two experiments. There are indications of age-specific QTL effects on growth. For body weight traits, the genetic variation in the F2 appears to result from many loci with relatively small effects. For tail length at 10 weeks, however, a single QTL on Chromosome (Chr) 1 with a peak LOD score of approximately 33 contributes most of the genetic variation detected, changes the trait value by about 6%, and explains about 20% of the phenotypic variance of the trait.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KH",
      "lastName" : "Morris",
      "authorRank" : 1,
      "name" : "Morris KH",
      "referenceId" : "RGD:A51385"
    }, {
      "firstName" : "A",
      "lastName" : "Ishikawa",
      "authorRank" : 2,
      "name" : "Ishikawa A",
      "referenceId" : "RGD:A37983"
    }, {
      "firstName" : "PD",
      "lastName" : "Keightley",
      "authorRank" : 3,
      "name" : "Keightley PD",
      "referenceId" : "RGD:A51384"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1357232"
    } ]
  }, {
    "primaryId" : "PMID:10051320",
    "title" : "Mapping and characterization of quantitative trait loci for non-insulin-dependent diabetes mellitus with an improved genetic map in the Otsuka Long-Evans Tokushima fatty rat.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wei S, etal., Mamm Genome 1999 Mar;10(3):249-58",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-08-24T10:41:26.000-05:00",
    "volume" : "10",
    "pages" : "249-58",
    "abstract" : "The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, non-insulin-dependent diabetes mellitus (NIDDM) in humans. We have previously reported four quantitative trait loci (QTLs) responsible for NIDDM on Chromosomes (Chrs) 7, 14, 8, and 11 (Nidd1-4/of for Non-insulin-dependent diabetes1-4/oletf) by a whole-genome search in 160 F2 progenies obtained by mating the OLETF and the Fischer-344 (F344) rats. Our present investigation was designed to identify and characterize novel QTLs affecting NIDDM by performing a genome-wide linkage analysis of genes for glucose levels and body weight and analysis for gene-to-gene and gene-to-body-weight interactions on an improved genetic map with a set of 382 informative markers in the 160 F2 progenies. We have identified seven novel QTLs on rat Chrs 1 (Nidd5 and 6/of), 5 (Nidd7/of), 9 (Nidd8/of), 12 (Nidd9/of), 14 (Nidd10/of) and 16 (Nidd11/of) which, together with the Nidd1-4/of, account for a total of approximately 60% and approximately 75% of the genetic variance of the fasting and postprandial glucose levels, respectively, in the F2. While the OLETF allele corresponds with increased glucose levels as expected for the novel QTLs except Nidd8 and 9/of, the Nidd8 and 9/of exhibit heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. There are epistatic interactions between Nidd1 and 10/of and between Nidd2 and 8/of. Additionally, our results indicated that the Nidd6 and 11/of could also contribute to an increase of body weight, and that the other five QTLs could show no linkage with body weight, but Nidd8,9, and 10/of have an interaction with body weight.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Wei",
      "authorRank" : 1,
      "name" : "Wei S",
      "referenceId" : "RGD:A152512"
    }, {
      "firstName" : "K",
      "lastName" : "Wei",
      "authorRank" : 2,
      "name" : "Wei K",
      "referenceId" : "RGD:A128356"
    }, {
      "firstName" : "DH",
      "lastName" : "Moralejo",
      "authorRank" : 3,
      "name" : "Moralejo DH",
      "referenceId" : "RGD:A157573"
    }, {
      "firstName" : "T",
      "lastName" : "Ogino",
      "authorRank" : 4,
      "name" : "Ogino T",
      "referenceId" : "RGD:A137306"
    }, {
      "firstName" : "G",
      "lastName" : "Koike",
      "authorRank" : 5,
      "name" : "Koike G",
      "referenceId" : "RGD:A51179"
    }, {
      "firstName" : "HJ",
      "lastName" : "Jacob",
      "authorRank" : 6,
      "name" : "Jacob HJ",
      "referenceId" : "RGD:A160476"
    }, {
      "firstName" : "K",
      "lastName" : "Sugiura",
      "authorRank" : 7,
      "name" : "Sugiura K",
      "referenceId" : "RGD:A299747"
    }, {
      "firstName" : "Y",
      "lastName" : "Sasaki",
      "authorRank" : 8,
      "name" : "Sasaki Y",
      "referenceId" : "RGD:A135358"
    }, {
      "firstName" : "T",
      "lastName" : "Yamada",
      "authorRank" : 9,
      "name" : "Yamada T",
      "referenceId" : "RGD:A159941"
    }, {
      "firstName" : "K",
      "lastName" : "Matsumoto",
      "authorRank" : 10,
      "name" : "Matsumoto K",
      "referenceId" : "RGD:A159245"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61021"
    } ]
  }, {
    "primaryId" : "PMID:10051321",
    "title" : "Complete genome searches for quantitative trait loci controlling blood pressure and related traits in four segregating populations derived from Dahl hypertensive rats.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kato N, etal., Mamm Genome 1999 Mar;10(3):259-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-05T10:58:19.000-05:00",
    "volume" : "10",
    "pages" : "259-65",
    "abstract" : "The Dahl salt-sensitive rat is one of the principal animal models of hereditary hypertension. Genome-wide searches were undertaken to detect quantitative trait loci (QTLs) that influence blood pressure, cardiac mass, and body weight in four F2 populations derived from Dahl salt-sensitive rats and different inbred normotensive control strains of rat. We detected three QTLs associated with one or more of the phenotypes, using a stringent statistical criterion for linkage (p < 0.00003). These included a novel QTL linked to blood pressure on rat Chromosome (Chr) 12, and another QTL on rat Chr 3 linked to body weight. A QTL on rat Chr 10 for which linkage to blood pressure has been described in other crosses was found to be a principal determinant of blood pressure and cardiac mass in some but not all of the crosses examined here. Three other regions showed evidence of linkage to these phenotypes with a less stringent statistical criterion of linkage at QTLs previously reported in other studies. As part of our study, microsatellite markers have been developed for three candidate genes for investigation in hypertension, and the genes have been localized by linkage mapping. These are: the rat Gs alpha subunit (Gnas) gene, the alpha-1B adrenergic receptor (Adra1b), and the Na+, K+-ATPase beta2 subunit (Atp1b2) gene.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Kato",
      "authorRank" : 1,
      "name" : "Kato N",
      "referenceId" : "RGD:A159893"
    }, {
      "firstName" : "G",
      "lastName" : "Hyne",
      "authorRank" : 2,
      "name" : "Hyne G",
      "referenceId" : "RGD:A8662"
    }, {
      "firstName" : "MT",
      "lastName" : "Bihoreau",
      "authorRank" : 3,
      "name" : "Bihoreau MT",
      "referenceId" : "RGD:A156487"
    }, {
      "firstName" : "D",
      "lastName" : "Gauguier",
      "authorRank" : 4,
      "name" : "Gauguier D",
      "referenceId" : "RGD:A131574"
    }, {
      "firstName" : "GM",
      "lastName" : "Lathrop",
      "authorRank" : 5,
      "name" : "Lathrop GM",
      "referenceId" : "RGD:A134841"
    }, {
      "firstName" : "JP",
      "lastName" : "Rapp",
      "authorRank" : 6,
      "name" : "Rapp JP",
      "referenceId" : "RGD:A111210"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619631"
    } ]
  }, {
    "primaryId" : "PMID:10051328",
    "title" : "Chromosomal localization of three human genes encoding bone morphogenetic protein receptors.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Astrom AK, etal., Mamm Genome 1999 Mar;10(3):299-302.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-02-16T15:44:15.000-06:00",
    "volume" : "10",
    "pages" : "299-302",
    "abstract" : "Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily that play a pivotal role in bone formation during embryogenesis and fracture repair. BMP signaling occurs via hetero-oligomeric serine/threonine kinase complexes of BMP type I (BMPR-IA or BMPR-IB) and type II receptors (BMPR-II). BMPR-IA and IB are closely related receptors, with sequence differences conserved between different species, suggesting that they serve distinct functions. Here we report the cDNA cloning of human BMPR1B and the chromosomal localization of all three BMPR genes. Using somatic cell hybrid and FISH analyses, the BMPR1A, BMPR1B, and BMPR2 genes were assigned to 10q23, 4q22-24, and 2q33-34, respectively. A processed BMPR1A pseudogene was mapped to 6q23.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AK",
      "lastName" : "Astrom",
      "authorRank" : 1,
      "name" : "Astrom AK",
      "referenceId" : "RGD:A50768"
    }, {
      "firstName" : "D",
      "lastName" : "Jin",
      "authorRank" : 2,
      "name" : "Jin D",
      "referenceId" : "RGD:A50769"
    }, {
      "firstName" : "T",
      "lastName" : "Imamura",
      "authorRank" : 3,
      "name" : "Imamura T",
      "referenceId" : "RGD:A9093"
    }, {
      "firstName" : "E",
      "lastName" : "Roijer",
      "authorRank" : 4,
      "name" : "Roijer E",
      "referenceId" : "RGD:A50770"
    }, {
      "firstName" : "B",
      "lastName" : "Rosenzweig",
      "authorRank" : 5,
      "name" : "Rosenzweig B",
      "referenceId" : "RGD:A50771"
    }, {
      "firstName" : "K",
      "lastName" : "Miyazono",
      "authorRank" : 6,
      "name" : "Miyazono K",
      "referenceId" : "RGD:A50772"
    }, {
      "firstName" : "P",
      "lastName" : "Ten Dijke",
      "authorRank" : 7,
      "name" : "Ten Dijke P",
      "referenceId" : "RGD:A15560"
    }, {
      "firstName" : "G",
      "lastName" : "Stenman",
      "authorRank" : 8,
      "name" : "Stenman G",
      "referenceId" : "RGD:A50773"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1334467"
    } ]
  }, {
    "primaryId" : "PMID:10051400",
    "title" : "Physical and transcriptional map of a 3-Mb region of mouse chromosome 1 containing the gene for the neural tube defect mutant loop-tail (Lp).",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Eddleston J, etal., Genomics 1999 Mar 1;56(2):149-59.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-18T10:21:40.000-06:00",
    "volume" : "56",
    "pages" : "149-59",
    "abstract" : "The Lp mouse mutant provides a model for the severe human neural tube defect (NTD), cranio-rachischisis. To identify the Lp gene, a positional cloning approach has been adopted. Previously, linkage analysis in a large intraspecific backcross was used to map the Lp locus to distal mouse chromosome 1. Here we report a detailed physical map of this region. The interval surrounding Lp has been cloned in a yeast artificial chromosome (YAC) contig consisting of 63 clones spanning approximately 3.2 Mb. Fifty sequence tagged sites (STSs) have been used to construct the contig and establish marker order across the interval. Based on the high level of conserved synteny between distal mouse chromosome 1 and human 1q21-q24, many of these STSs were designed from expressed sequences identified by cross-screening human and mouse databases of expressed sequence tags. Added to other known genes in the region, a total of 29 genes were located and ordered within the contig. Seven novel polymorphisms were identified within the region, allowing refinement of the genetic map and a reduction in the size of the physical interval containing the Lp gene. The Lp interval, between D1Mit113 and Tagln2, can be spanned by two nonchimeric overlapping YACs that define a physical distance of approximately 1 Mb. Within this region, 10 potential candidate genes have been mapped. The materials and genes described here will provide a resource for the identification and further study of the mutated Lp gene that causes this severe neural tube defect and will provide candidates for other defects known to map to the homologous region on human chromosome 1q.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Eddleston",
      "authorRank" : 1,
      "name" : "Eddleston J",
      "referenceId" : "RGD:A57321"
    }, {
      "firstName" : "JN",
      "lastName" : "Murdoch",
      "authorRank" : 2,
      "name" : "Murdoch JN",
      "referenceId" : "RGD:A57322"
    }, {
      "firstName" : "AJ",
      "lastName" : "Copp",
      "authorRank" : 3,
      "name" : "Copp AJ",
      "referenceId" : "RGD:A37184"
    }, {
      "firstName" : "P",
      "lastName" : "Stanier",
      "authorRank" : 4,
      "name" : "Stanier P",
      "referenceId" : "RGD:A26714"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556783"
    } ]
  }, {
    "primaryId" : "PMID:10051439",
    "title" : "Stress- and cell type-dependent regulation of transfected c-Jun N-terminal kinase and mitogen-activated protein kinase kinase isoforms.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Butterfield L, etal., Biochem J. 1999 Mar 15;338 ( Pt 3):681-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-07-11T10:37:32.000-05:00",
    "volume" : "338 ( Pt 3)",
    "pages" : "681-6",
    "abstract" : "The cJun N-terminal kinases (JNKs) are encoded by three genes generating ten protein kinase polypeptides and are activated in settings of cell stress, mitogenesis, differentiation and morphogenesis. The specific role of the JNK family members in these diverse cell programmes is largely undefined. In this study, we tested the hypothesis that individual JNK isoforms would exhibit distinct patterns of regulation within cells. The cDNAs encoding five haemagglutinin (HA)-tagged JNK isoforms (p46JNK1alpha, p54JNK2alpha, p54JNK2beta, p46JNK3 and p54JNK3) were expressed in cultured rat PC12 phaeochromocytoma cells and human small-cell lung cancer (SCLC) cells by retrovirus-mediated gene transfer. In addition, HA-tagged forms of the dual-specificity mitogen-activated protein kinase kinases (MKKs), MKK4 and MKK7, which are specific activators of the JNK enzymes, were similarly expressed. Reverse transcription and PCR revealed that JNK3 is endogenously expressed in SCLC cells, but not in either chromaffin or neuronally differentiated PC12 cells. MKK4 and MKK7 were endogenously expressed in both PC12 cells and SHP77 cells. Immunoprecipitation and analysis of the JNKs expressed in SCLC cells revealed strong stimulation of all five JNK isoforms by UV radiation. Hypertonic stress, elicited by mannitol, also significantly stimulated these same JNKs, although the JNK3 isoforms were most strongly activated. In PC12 cell transfectants, however, selective and equal activation of p54JNK2alpha and p54JNK3 by UV and osmotic stress was observed, with little or no activation of JNK1alpha or JNK2beta. In contrast with the broad activation of the JNK enzymes by UV in SCLC cells, only HA-MKK4 was stimulated by UV exposure in these cells, whereas osmotic stress stimulated both HA-MKK4 and HA-MKK7. These findings indicate selective activation of JNK and MKK isoforms in a manner that is dependent upon the specific cell stress and the cell type.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Butterfield",
      "authorRank" : 1,
      "name" : "Butterfield L",
      "referenceId" : "RGD:A97865"
    }, {
      "firstName" : "E",
      "lastName" : "Zentrich",
      "authorRank" : 2,
      "name" : "Zentrich E",
      "referenceId" : "RGD:A97866"
    }, {
      "firstName" : "A",
      "lastName" : "Beekman",
      "authorRank" : 3,
      "name" : "Beekman A",
      "referenceId" : "RGD:A97867"
    }, {
      "firstName" : "LE",
      "lastName" : "Heasley",
      "authorRank" : 4,
      "name" : "Heasley LE",
      "referenceId" : "RGD:A21328"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2298561"
    } ]
  }, {
    "primaryId" : "PMID:10051443",
    "title" : "SNAP-23 participates in SNARE complex assembly in rat adipose cells.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "St-Denis JF, etal., Biochem J 1999 Mar 15;338 ( Pt 3):709-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:52.000-05:00",
    "volume" : "338 ( Pt 3)",
    "pages" : "709-15",
    "abstract" : "SNARE proteins are required for vesicle docking and fusion in eukaryotic cells in processes as diverse as homotypic membrane fusion and synaptic vesicle exocytosis [SNARE stands for SNAP receptor, where SNAP is soluble NSF attachment protein]. The SNARE proteins syntaxin 4 and vesicle-associated membrane protein (VAMP) 2/3 also participate in the insulin-stimulated translocation of GLUT4 from intracellular vesicles to the plasma membrane in adipose cells. We now report the molecular cloning and characterization of rat SNAP-23, a ubiquitously expressed homologue of the essential neuronal SNARE protein SNAP-25 (synaptosomal-associated protein of 25 kDa). Rat SNAP-23 is 86% and 98% identical respectively to human and mouse SNAP-23. Southern blot analysis reveals that the rat, mouse and human SNAP-23 genes encode species-specific isoforms of the same protein. Co-immunoprecipitation of syntaxin 4 and SNAP-23 shows association of these two proteins in rat adipose cell plasma membranes, and insulin stimulation does not alter the SNAP-23/syntaxin 4 complex. In addition, we demonstrate for the first time the participation of SNAP-23, along with syntaxin 4 and VAMP2/3, in the formation of 20S SNARE complexes prepared using rat adipose cell membranes and recombinant alpha-SNAP and NSF proteins. The stoichiometry of the SNARE complexes formed is essentially identical using membranes from either unstimulated or insulin-stimulated adipose cells. These data demonstrate that rat SNAP-23 associates with syntaxin 4 before insulin stimulation and is present in the SNARE complexes known to mediate the translocation of GLUT4 from intracellular vesicles to the plasma membrane of rat adipose cells.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JF",
      "lastName" : "St-Denis",
      "authorRank" : 1,
      "name" : "St-Denis JF",
      "referenceId" : "RGD:A23355"
    }, {
      "firstName" : "JP",
      "lastName" : "Cabaniols",
      "authorRank" : 2,
      "name" : "Cabaniols JP",
      "referenceId" : "RGD:A23356"
    }, {
      "firstName" : "SW",
      "lastName" : "Cushman",
      "authorRank" : 3,
      "name" : "Cushman SW",
      "referenceId" : "RGD:A21359"
    }, {
      "firstName" : "PA",
      "lastName" : "Roche",
      "authorRank" : 4,
      "name" : "Roche PA",
      "referenceId" : "RGD:A23357"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634161"
    } ]
  }, {
    "primaryId" : "PMID:10051478",
    "title" : "Role of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 during nonsuppurative destructive cholangitis in a mouse graft-versus-host disease model.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Howell CD, etal., Hepatology. 1999 Mar;29(3):766-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-03T11:40:07.000-05:00",
    "volume" : "29",
    "pages" : "766-76",
    "abstract" : "Intercellular adhesion molecule-1 (ICAM-1) is expressed abnormally on the bile duct epithelium during the course of primary biliary cirrhosis (PBC), but the importance of ICAM-1 and its lymphocyte function-associated antigen-1 (LFA-1) receptor during the course of nonsuppurative destructive cholangitis (NSDC) has not been defined. To address this question, we defined the relationship between ICAM-1 on the intrahepatic bile duct epithelium and the evolution of NSDC lesions in a mouse graft-versus-host disease (GVHD) model. We also determined the effects of anti-ICAM-1 and anti-LFA-1 treatments on NSDC, intrahepatic lymphokine production, and the homing of lymphocytes to the livers of GVHD mice. ICAM-1 was  initially detected on the bile duct epithelium and portal vein endothelium on day 7 of GVHD. There was a significant positive correlation between the intensity of  ICAM-1 staining and histological bile duct damage (r =.58, P <.05) between day 3  and 28. Treatment with anti-ICAM-1 (but not anti-LFA-1) decreased both the mean grades of portal inflammation (P =.003) and NSDC (P =.002) lesions compared with  control immunoglobulin G (IgG) treatments. Combined treatment with anti-ICAM-1 and anti-LFA-1 caused a further decrease in the amount of portal inflammation and bile duct damage compared with anti-ICAM-1, alone (P =.02). Anti-ICAM-1 treatment also decreased both the percentage of T cells and the production of interleukin-2 (IL-2) and IL-12 in the liver (P <.01), but had no effect on IL-4, IL-10, and interferon gamma. Neither anti-ICAM-1 nor anti-LFA-1 prevented lymphocytes from homing to the liver. These results indicate that both ICAM-1 and LFA-1 are important to the pathogenesis of NSDC.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CD",
      "lastName" : "Howell",
      "authorRank" : 1,
      "name" : "Howell",
      "referenceId" : "RGD:A315747"
    }, {
      "firstName" : "J",
      "lastName" : "Li",
      "authorRank" : 2,
      "name" : "Li J",
      "referenceId" : "RGD:A13064"
    }, {
      "firstName" : "W",
      "lastName" : "Chen",
      "authorRank" : 3,
      "name" : "Chen",
      "referenceId" : "RGD:A413058"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11520783"
    } ]
  }, {
    "primaryId" : "PMID:10051504",
    "title" : "Transforming growth factor beta1 induces the expression of alpha1(I) procollagen mRNA by a hydrogen peroxide-C/EBPbeta-dependent mechanism in rat hepatic stellate cells.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Garcia-Trevijano ER, etal., Hepatology. 1999 Mar;29(3):960-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-30T15:24:13.000-05:00",
    "volume" : "29",
    "pages" : "960-70",
    "abstract" : "Oxidative stress plays a key role in liver fibrosis. Both inflammatory cells and activated Kupffer cells produce H2O2, an oxidant involved in the activation of hepatic stellate cells (HSC). Increased production of reactive oxygen intermediates (ROIs) in fibrotic livers is associated in part with the up-regulation of transforming growth factor beta (TGF-beta), and this cytokine enhances collagen production by cultured HSC. However, the possible link between oxidative stress and the molecular mechanisms by which TGF-beta induces collagen gene expression in HSC remains to be elucidated. To address this question, we investigated whether H2O2 is a mediator of TGF-beta-elicited alpha1(I) collagen gene (col1a1) up-regulation. We demonstrated that TGF-beta induces the accumulation of H2O2, and that this oxidant is, in turn, directly involved in up-regulating the expression of the col1a1 gene. While the addition of H2O2 to HSC induced the expression of alpha1(I) procollagen mRNA, catalase, an H2O2 enzyme scavenger, abrogated TGF-beta-mediated col1a1 gene up-regulation. We transfected HSC with chimeric plasmids driven by different segments of the mouse col1a1 promoter and mapped a cis-acting element (-370 to -344) essential for TGF-beta responsiveness. We further showed that TGF-beta induced the activation and binding of a C/EBPbeta-containing transcriptional complex to this sequence, an effect that was also mimicked by the addition of H2O2. Taken together, these data demonstrate a direct connection between TGF-beta-mediated accumulation of H2O2 and the up-regulation of col1a1 gene in HSC.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ER",
      "lastName" : "Garcia-Trevijano",
      "authorRank" : 1,
      "name" : "Garcia-Trevijano ER",
      "referenceId" : "RGD:A54218"
    }, {
      "firstName" : "MJ",
      "lastName" : "Iraburu",
      "authorRank" : 2,
      "name" : "Iraburu MJ",
      "referenceId" : "RGD:A42103"
    }, {
      "firstName" : "L",
      "lastName" : "Fontana",
      "authorRank" : 3,
      "name" : "Fontana L",
      "referenceId" : "RGD:A78966"
    }, {
      "firstName" : "JA",
      "lastName" : "Dominguez-Rosales",
      "authorRank" : 4,
      "name" : "Dominguez-Rosales JA",
      "referenceId" : "RGD:A78967"
    }, {
      "firstName" : "A",
      "lastName" : "Auster",
      "authorRank" : 5,
      "name" : "Auster A",
      "referenceId" : "RGD:A78968"
    }, {
      "firstName" : "A",
      "lastName" : "Covarrubias-Pinedo",
      "authorRank" : 6,
      "name" : "Covarrubias-Pinedo A",
      "referenceId" : "RGD:A78969"
    }, {
      "firstName" : "M",
      "lastName" : "Rojkind",
      "authorRank" : 7,
      "name" : "Rojkind M",
      "referenceId" : "RGD:A33133"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600921"
    } ]
  }, {
    "primaryId" : "PMID:10051629",
    "title" : "Predominant VH genes expressed in innate antibodies are associated with distinctive antigen-binding sites.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Seidl KJ, etal., Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2262-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:56:11.000-05:00",
    "volume" : "96",
    "pages" : "2262-7",
    "abstract" : "Antibodies to phosphatidylcholine (PtC), a common constituent of mammalian and bacterial cell membranes, represent a large proportion of the natural antibody repertoire in mice. Previous studies of several mouse strains (e.g., C57BL/6) have shown that anti-PtC antibodies are mainly encoded by the VH11 and VH12 immunoglobulin heavy chain variable region gene families. We show here, however,  that VH11 and VH12 encode only a small proportion of the anti-PtC antibodies in BALB/c mice. Instead, VHQ52-encoded antibodies predominate in this strain. In addition, two-thirds of the cells expressing VHQ52 family genes use a single gene (which, interestingly, has been previously shown to predominate in the anti-oxazolone response). We also show here that in anti-PtC antibodies from all  strains, the distinctive antigen-binding sites associated with VHQ52 differ substantially from those associated with VH11 and VH12. That is, VHQ52-containing transcripts preferentially use the joining region JH4 rather than JH1 and exhibit more diverse complementarity-determining region 3 (CDR3) junctions with more N-region nucleotide additions at the gene segment junctions. Thus, the VH gene family that predominates in the anti-PtC repertoire differs among mouse strains,  whereas the distinctive VHDJH rearrangements (CDR3, JH) associated with each VH gene family are similar in all strains. We discuss these findings in the context  of a recent hypothesis suggesting that CDR3 structure, independent of VH framework, is sufficient to define the specificity of an antibody.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KJ",
      "lastName" : "Seidl",
      "authorRank" : 1,
      "name" : "Seidl KJ",
      "referenceId" : "RGD:A56827"
    }, {
      "firstName" : "JA",
      "lastName" : "Wilshire",
      "authorRank" : 2,
      "name" : "Wilshire",
      "referenceId" : "RGD:A332898"
    }, {
      "firstName" : "JD",
      "lastName" : "MacKenzie",
      "authorRank" : 3,
      "name" : "MacKenzie",
      "referenceId" : "RGD:A332899"
    }, {
      "firstName" : "AB",
      "lastName" : "Kantor",
      "authorRank" : 4,
      "name" : "Kantor",
      "referenceId" : "RGD:A332900"
    }, {
      "firstName" : "LA",
      "lastName" : "Herzenberg",
      "authorRank" : 5,
      "name" : "Herzenberg LA",
      "referenceId" : "RGD:A31079"
    }, {
      "firstName" : "LA",
      "lastName" : "Herzenberg",
      "authorRank" : 6,
      "name" : "Herzenberg LA",
      "referenceId" : "RGD:A31079"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11341188"
    } ]
  }, {
    "primaryId" : "PMID:10051633",
    "title" : "Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Suzuki K, etal., Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2285-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-04-24T10:58:03.000-05:00",
    "volume" : "96",
    "pages" : "2285-90",
    "abstract" : "Abnormal expression of major histocompatibility complex (MHC) class I and class II in various tissues is associated with autoimmune disease. Autoimmune responses can be triggered by viral infections or tissue injuries. We show that the ability of a virus or a tissue injury to increase MHC gene expression is duplicated by any fragment of double-stranded (ds) DNA or dsRNA introduced into the cytoplasm of nonimmune cells. Activation is sequence-independent, is induced by ds polynucleotides as small as 25 bp in length, and is not duplicated by single-stranded polynucleotides. In addition to causing abnormal MHC expression,  the ds nucleic acids increase the expression of genes necessary for antigen processing and presentation: proteasome proteins (e.g., LMP2), transporters of antigen peptides; invariant chain, HLA-DM, and the costimulatory molecule B7.1. The mechanism is different from and additive to that of gamma-interferon (gammaIFN), i.e., ds polynucleotides increase class I much more than class II, whereas gammaIFN increases class II more than class I. The ds nucleic acids also  induce or activate Stat1, Stat3, mitogen-activated protein kinase, NF-kappaB, the class II transactivator, RFX5, and the IFN regulatory factor 1 differently from gammaIFN. CpG residues are not responsible for this effect, and the action of the ds polynucleotides could be shown in a variety of cell types in addition to thyrocytes. We suggest that this phenomenon is a plausible mechanism that might explain how viral infection of tissues or tissue injury triggers autoimmune disease; it is potentially relevant to host immune responses induced during gene  therapy.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Suzuki",
      "authorRank" : 1,
      "name" : "Suzuki",
      "referenceId" : "RGD:A399969"
    }, {
      "firstName" : "A",
      "lastName" : "Mori",
      "authorRank" : 2,
      "name" : "Mori A",
      "referenceId" : "RGD:A52888"
    }, {
      "firstName" : "KJ",
      "lastName" : "Ishii",
      "authorRank" : 3,
      "name" : "Ishii",
      "referenceId" : "RGD:A169275"
    }, {
      "firstName" : "J",
      "lastName" : "Saito",
      "authorRank" : 4,
      "name" : "Saito J",
      "referenceId" : "RGD:A142407"
    }, {
      "firstName" : "DS",
      "lastName" : "Singer",
      "authorRank" : 5,
      "name" : "Singer DS",
      "referenceId" : "RGD:A57056"
    }, {
      "firstName" : "DM",
      "lastName" : "Klinman",
      "authorRank" : 6,
      "name" : "Klinman",
      "referenceId" : "RGD:A169276"
    }, {
      "firstName" : "PR",
      "lastName" : "Krause",
      "authorRank" : 7,
      "name" : "Krause",
      "referenceId" : "RGD:A169277"
    }, {
      "firstName" : "LD",
      "lastName" : "Kohn",
      "authorRank" : 8,
      "name" : "Kohn LD",
      "referenceId" : "RGD:A17541"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7242894"
    } ]
  }, {
    "primaryId" : "PMID:10051637",
    "title" : "Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.",
    "datePublished" : "1999-03-02T00:00:00.000-06:00",
    "citation" : "Pelin K, etal., Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2305-10. doi: 10.1073/pnas.96.5.2305.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:38:26.000-05:00",
    "volume" : "96",
    "pages" : "2305-10",
    "abstract" : "The congenital nemaline myopathies are rare hereditary muscle disorders characterized by the presence in the muscle fibers of nemaline bodies consisting of proteins derived from the Z disc and thin filament. In a single large Australian family with an autosomal dominant form of nemaline myopathy, the disease is caused by a mutation in the alpha-tropomyosin gene TPM3. The typical form of nemaline myopathy is inherited as an autosomal recessive trait, the locus of which we previously assigned to chromosome 2q21.2-q22. We show here that mutations in the nebulin gene located within this region are associated with the disease. The nebulin protein is a giant protein found in the thin filaments of striated muscle. A variety of nebulin isoforms are thought to contribute to the molecular diversity of Z discs. We have studied the 3' end of the 20. 8-kb cDNA encoding the Z disc part of the 800-kDa protein and describe six disease-associated mutations in patients from five families of different ethnic origins. In two families with consanguineous parents, the patients were homozygous for point mutations. In one family with nonconsanguineous parents, the affected siblings were compound heterozygotes for two different mutations, and in two further families with one detected mutation each, haplotypes are compatible with compound heterozygosity. Immunofluorescence studies with antibodies specific to the C-terminal region of nebulin indicate that the mutations may cause protein truncation possibly associated with loss of fiber-type diversity, which may be relevant to disease pathogenesis.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Pelin",
      "authorRank" : 1,
      "name" : "Pelin K",
      "referenceId" : "RGD:A485484"
    }, {
      "firstName" : "P",
      "lastName" : "Hilpelä",
      "authorRank" : 2,
      "name" : "Hilpelä P",
      "referenceId" : "RGD:A568632"
    }, {
      "firstName" : "K",
      "lastName" : "Donner",
      "authorRank" : 3,
      "name" : "Donner K",
      "referenceId" : "RGD:A485485"
    }, {
      "firstName" : "C",
      "lastName" : "Sewry",
      "authorRank" : 4,
      "name" : "Sewry C",
      "referenceId" : "RGD:A73443"
    }, {
      "firstName" : "P A",
      "lastName" : "Akkari",
      "authorRank" : 5,
      "name" : "Akkari PA",
      "referenceId" : "RGD:A568633"
    }, {
      "firstName" : "S D",
      "lastName" : "Wilton",
      "authorRank" : 6,
      "name" : "Wilton SD",
      "referenceId" : "RGD:A568634"
    }, {
      "firstName" : "D",
      "lastName" : "Wattanasirichaigoon",
      "authorRank" : 7,
      "name" : "Wattanasirichaigoon D",
      "referenceId" : "RGD:A62775"
    }, {
      "firstName" : "M L",
      "lastName" : "Bang",
      "authorRank" : 8,
      "name" : "Bang ML",
      "referenceId" : "RGD:A568635"
    }, {
      "firstName" : "T",
      "lastName" : "Centner",
      "authorRank" : 9,
      "name" : "Centner T",
      "referenceId" : "RGD:A568636"
    }, {
      "firstName" : "F",
      "lastName" : "Hanefeld",
      "authorRank" : 10,
      "name" : "Hanefeld F",
      "referenceId" : "RGD:A80356"
    }, {
      "firstName" : "S",
      "lastName" : "Odent",
      "authorRank" : 11,
      "name" : "Odent S",
      "referenceId" : "RGD:A44749"
    }, {
      "firstName" : "M",
      "lastName" : "Fardeau",
      "authorRank" : 12,
      "name" : "Fardeau M",
      "referenceId" : "RGD:A37513"
    }, {
      "firstName" : "J A",
      "lastName" : "Urtizberea",
      "authorRank" : 13,
      "name" : "Urtizberea JA",
      "referenceId" : "RGD:A439657"
    }, {
      "firstName" : "F",
      "lastName" : "Muntoni",
      "authorRank" : 14,
      "name" : "Muntoni F",
      "referenceId" : "RGD:A39236"
    }, {
      "firstName" : "V",
      "lastName" : "Dubowitz",
      "authorRank" : 15,
      "name" : "Dubowitz V",
      "referenceId" : "RGD:A568637"
    }, {
      "firstName" : "A H",
      "lastName" : "Beggs",
      "authorRank" : 16,
      "name" : "Beggs AH",
      "referenceId" : "RGD:A460930"
    }, {
      "firstName" : "N G",
      "lastName" : "Laing",
      "authorRank" : 17,
      "name" : "Laing NG",
      "referenceId" : "RGD:A485495"
    }, {
      "firstName" : "S",
      "lastName" : "Labeit",
      "authorRank" : 18,
      "name" : "Labeit S",
      "referenceId" : "RGD:A24003"
    }, {
      "firstName" : "A",
      "lastName" : "de la Chapelle",
      "authorRank" : 19,
      "name" : "de la Chapelle A",
      "referenceId" : "RGD:A449296"
    }, {
      "firstName" : "C",
      "lastName" : "Wallgren-Pettersson",
      "authorRank" : 20,
      "name" : "Wallgren-Pettersson C",
      "referenceId" : "RGD:A57786"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598114940"
    } ]
  }, {
    "primaryId" : "PMID:10051646",
    "title" : "Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine  deficiency.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wang Y, etal., Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2356-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:43:05.000-05:00",
    "volume" : "96",
    "pages" : "2356-60",
    "abstract" : "Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. This disease presents early in life with hypoketotic hypoglycemia or later in life with skeletal myopathy or cardiomyopathy. The gene for this condition maps to 5q31.2-32 and OCTN2, an organic cation/carnitine transporter, also maps to the same chromosomal region. Here we test the causative role of OCTN2 in primary carnitine deficiency by searching for mutations in this gene in affected patients. Fibroblasts from patients with primary carnitine deficiency lacked mediated carnitine transport. Transfection of patient's fibroblasts with the OCTN2 cDNA partially restored carnitine transport. Sequencing of the OCTN2 gene revealed different mutations in two unrelated patients. The first patient was homozygous (and both parents heterozygous) for a single base pair substitution converting the codon for Arg-282 to a STOP codon (R282X). The second patient was a compound heterozygote for a paternal 1-bp insertion producing a STOP codon (Y401X) and a maternal 1-bp  deletion that produced a frameshift creating a subsequent STOP codon (458X). These mutations decreased the levels of mature OCTN2 mRNA and resulted in nonfunctional transporters, confirming that defects in the organic cation/carnitine transporter OCTN2 are responsible for primary carnitine deficiency.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang",
      "referenceId" : "RGD:A417031"
    }, {
      "firstName" : "J",
      "lastName" : "Ye",
      "authorRank" : 2,
      "name" : "Ye J",
      "referenceId" : "RGD:A22589"
    }, {
      "firstName" : "V",
      "lastName" : "Ganapathy",
      "authorRank" : 3,
      "name" : "Ganapathy V",
      "referenceId" : "RGD:A5011"
    }, {
      "firstName" : "N",
      "lastName" : "Longo",
      "authorRank" : 4,
      "name" : "Longo N",
      "referenceId" : "RGD:A137795"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069237"
    } ]
  }, {
    "primaryId" : "PMID:10051670",
    "title" : "Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Encinas JA, etal., Proc Natl Acad Sci U S A 1999 Mar 2;96(5):2491-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-11T15:05:31.000-06:00",
    "volume" : "96",
    "pages" : "2491-6",
    "abstract" : "The semaphorins comprise a large family of membrane-bound and secreted proteins, some of which have been shown to function in axon guidance. We have cloned a transmembrane semaphorin, Sema W, that belongs to the class IV subgroup of the semaphorin family. The mouse and rat forms of Sema W show 97% amino acid sequence identity with each other, and each shows about 91% identity with the human form. The gene for Sema W is divided into 15 exons, up to 4 of which are absent in the human cDNAs that we sequenced. Unlike many other semaphorins, Sema W is expressed at low levels in the developing embryo but was found to be expressed at high levels in the adult central nervous system and lung. Functional studies with purified membrane fractions from COS7 cells transfected with a Sema W expression plasmid showed that Sema W has growth-cone collapse activity against retinal ganglion-cell axons, indicating that vertebrate transmembrane semaphorins, like secreted semaphorins, can collapse growth cones. Genetic mapping of human SEMAW with human/hamster radiation hybrids localized the gene to chromosome 2p13. Genetic mapping of mouse Semaw with mouse/hamster radiation hybrids localized the gene to chromosome 6, and physical mapping placed the gene on bacteria artificial chromosomes carrying microsatellite markers D6Mit70 and D6Mit189. This localization places Semaw within the locus for motor neuron degeneration 2, making it an attractive candidate gene for this disease.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Encinas",
      "authorRank" : 1,
      "name" : "Encinas JA",
      "referenceId" : "RGD:A48343"
    }, {
      "firstName" : "K",
      "lastName" : "Kikuchi",
      "authorRank" : 2,
      "name" : "Kikuchi K",
      "referenceId" : "RGD:A148367"
    }, {
      "firstName" : "A",
      "lastName" : "Chedotal",
      "authorRank" : 3,
      "name" : "Chedotal A",
      "referenceId" : "RGD:A7960"
    }, {
      "firstName" : "F",
      "lastName" : "De Castro",
      "authorRank" : 4,
      "name" : "De Castro F",
      "referenceId" : "RGD:A7961"
    }, {
      "firstName" : "CS",
      "lastName" : "Goodman",
      "authorRank" : 5,
      "name" : "Goodman CS",
      "referenceId" : "RGD:A52302"
    }, {
      "firstName" : "T",
      "lastName" : "Kimura",
      "authorRank" : 6,
      "name" : "Kimura T",
      "referenceId" : "RGD:A6130"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69991"
    } ]
  }, {
    "primaryId" : "PMID:10051703",
    "title" : "Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Lara-Marquez ML, etal., Clin Exp Allergy 1999 Jan;29(1):60-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-01-27T11:49:17.000-06:00",
    "volume" : "29",
    "pages" : "60-71",
    "abstract" : "BACKGROUND: Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezuelan population (estimated at 20%) and genetic markers are needed to identify populations at risk and plan intervention strategies. OBJECTIVE: To study the influence of the MHC class I and class II genes in the susceptibility to atopic asthma. METHODS: MHC-class I HLA-A, -C, -B and MHC-class II HLA-DR, -DQ, -DP gene haplotype frequencies were determined in 135 Venezuelan mestizos, 71 belong to 20 atopic asthmatic families and 64 unrelated controls. The index cases were 20 atopic asthmatics with positive skin-prick tests and specific serum immunoglobulin E (IgE) for Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). To ascertain the genes associated with susceptibility to atopy and/or asthma, two control groups were studied, 41 non-atopic subjects with skin-prick negative test, and undetectable levels of specific IgE and 23 non-asthmatic atopic subjects with detectable specific IgE to Der p and Der f. A linkage analysis was performed in those families with two or more atopic siblings (with or without asthma). RESULTS: MHC-class I genes analysis showed that HLA-Cw7 was absent in the asthmatic patients studied, whereas the frequency of this allele was 14.3% in non-atopic controls (P = 0.0 17, PC = 0.19) and 20.8% in the atopic controls (P = 0.0066, PC = 0.07). MHC-class II gene analysis showed a significant increase of the HLA-DRB1*11 in the asthmatic patients compared with non-atopic controls (allele frequencies of 25.6 vs 4.4% P = 0.0017, PC = 0.02). There were no significant differences among asthmatic and atopic controls in the frequency of HLA-DRB1*11 (25.6 vs 17.4%). In contrast, the HLA-DRB1*1101+ haplotypes were significantly higher in asthmatics compared with atopic and non-atopic controls (19.6% vs 2.2% vs 2.3%, PC<0.05). The HLA-DRB1*1101, DQA1*0501, DQB1*0301 haplotype was found significantly increased in the patients vs non-atopic controls (15.4 vs 1.1%, PC< 0.01). The serum levels of specific IgE were detectable in both atopic asthmatics and atopic controls; however, it was higher in atopic asthmatics vs atopic controls Der p (median, 58.7 vs 2.7 kU/L, P<0.001) and Der f (median, 46.9 vs 2.7 kU/L, P<0.001). No linkage between MHC genes and mite-atopy could be documented on informative families with two or more atopic siblings. CONCLUSIONS: We have identified an association between the haplotype HLA-DRB1*1101, DQA1*0501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequencies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, it may have a protective role for developing atopic asthma in the population studied.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ML",
      "lastName" : "Lara-Marquez",
      "authorRank" : 1,
      "name" : "Lara-Marquez ML",
      "referenceId" : "RGD:A50497"
    }, {
      "firstName" : "JJ",
      "lastName" : "Yunis",
      "authorRank" : 2,
      "name" : "Yunis JJ",
      "referenceId" : "RGD:A50498"
    }, {
      "firstName" : "Z",
      "lastName" : "Layrisse",
      "authorRank" : 3,
      "name" : "Layrisse Z",
      "referenceId" : "RGD:A50499"
    }, {
      "firstName" : "F",
      "lastName" : "Ortega",
      "authorRank" : 4,
      "name" : "Ortega F",
      "referenceId" : "RGD:A50500"
    }, {
      "firstName" : "E",
      "lastName" : "Carvallo-Gil",
      "authorRank" : 5,
      "name" : "Carvallo-Gil E",
      "referenceId" : "RGD:A50501"
    }, {
      "firstName" : "S",
      "lastName" : "Montagnani",
      "authorRank" : 6,
      "name" : "Montagnani S",
      "referenceId" : "RGD:A50502"
    }, {
      "firstName" : "NJ",
      "lastName" : "Makhatadze",
      "authorRank" : 7,
      "name" : "Makhatadze NJ",
      "referenceId" : "RGD:A50503"
    }, {
      "firstName" : "M",
      "lastName" : "Pocino",
      "authorRank" : 8,
      "name" : "Pocino M",
      "referenceId" : "RGD:A50504"
    }, {
      "firstName" : "C",
      "lastName" : "Granja",
      "authorRank" : 9,
      "name" : "Granja C",
      "referenceId" : "RGD:A50505"
    }, {
      "firstName" : "E",
      "lastName" : "Yunis",
      "authorRank" : 10,
      "name" : "Yunis E",
      "referenceId" : "RGD:A50506"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1331670"
    } ]
  }, {
    "primaryId" : "PMID:10051750",
    "title" : "Heparan sulphate and HB-GAM (heparin-binding growth-associated molecule) in the development of the thalamocortical pathway of rat brain.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kinnunen A, etal., Eur J Neurosci. 1999 Feb;11(2):491-502.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-05-29T15:48:59.000-05:00",
    "volume" : "11",
    "pages" : "491-502",
    "abstract" : "Extracellular matrix (ECM) molecules, such as laminin, tenascin, chondroitin sulphate proteoglycans and heparan sulphate proteoglycans have been suggested to  have 'signpost' and directing roles in the formation of axonal projections in cortical development. We show here that the expression of the neurite outgrowth-promoting protein heparin-binding growth-associated molecule (HB-GAM) and N-syndecan, a transmembrane heparan sulphate proteoglycan previously isolated as a receptor for HB-GAM, is spatiotemporally associated with the developing thalamocortical pathway in the rat brain. Using in situ hybridization, thalamic neurons were shown to express mRNA for N-syndecan, and in vitro, thalamic neurons grew more neurites on HB-GAM than on laminin. The HB-GAM-induced neurite outgrowth in thalamic neurons was inhibited by heparitinase, heparin, soluble N-syndecan and by an excess of soluble HB-GAM in the culture medium. In a pathway assay, thalamic neurons selectively preferred attaching and growing neurites on matrices containing HB-GAM than on those containing fibronectin or laminin alone, suggesting that HB-GAM may modulate the effect of other ECM proteins. On an unfixed brain slice preparation, thalamic neurons repeatedly showed a typical neurite outgrowth and attachment pattern resembling the expression pattern of HB-GAM. On the brain slices, the neurite outgrowth was significantly inhibited by heparitinase, heparin and soluble HB-GAM, thus displaying features of neurite outgrowth on matrix-bound HB-GAM. Our results suggest that HB-GAM is important for the neurite outgrowth of thalamic neurons and it may function as an ECM-bound guidance cue for thalamic neurons that possess HB-GAM-binding heparan sulphates on their cell membrane.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Kinnunen",
      "authorRank" : 1,
      "name" : "Kinnunen",
      "referenceId" : "RGD:A199945"
    }, {
      "firstName" : "M",
      "lastName" : "Niemi",
      "authorRank" : 2,
      "name" : "Niemi M",
      "referenceId" : "RGD:A134515"
    }, {
      "firstName" : "T",
      "lastName" : "Kinnunen",
      "authorRank" : 3,
      "name" : "Kinnunen",
      "referenceId" : "RGD:A199946"
    }, {
      "firstName" : "M",
      "lastName" : "Kaksonen",
      "authorRank" : 4,
      "name" : "Kaksonen",
      "referenceId" : "RGD:A199947"
    }, {
      "firstName" : "R",
      "lastName" : "Nolo",
      "authorRank" : 5,
      "name" : "Nolo",
      "referenceId" : "RGD:A199948"
    }, {
      "firstName" : "H",
      "lastName" : "Rauvala",
      "authorRank" : 6,
      "name" : "Rauvala H",
      "referenceId" : "RGD:A24472"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10043838"
    } ]
  }, {
    "primaryId" : "PMID:10052456",
    "title" : "Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hoon MA, etal., Cell 1999 Feb 19;96(4):541-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-10T11:27:24.000-05:00",
    "volume" : "96",
    "pages" : "541-51",
    "abstract" : "Taste represents a major form of sensory input in the animal kingdom. In mammals, taste perception begins with the recognition of tastant molecules by unknown membrane receptors localized on the apical surface of receptor cells of the tongue and palate epithelium. We report the cloning and characterization of two novel seven-transmembrane domain proteins expressed in topographically distinct subpopulations of taste receptor cells and taste buds. These proteins are specifically localized to the taste pore and are members of a new group of G protein-coupled receptors distantly related to putative mammalian pheromone receptors. We propose that these genes encode taste receptors.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MA",
      "lastName" : "Hoon",
      "authorRank" : 1,
      "name" : "Hoon MA",
      "referenceId" : "RGD:A102162"
    }, {
      "firstName" : "E",
      "lastName" : "Adler",
      "authorRank" : 2,
      "name" : "Adler E",
      "referenceId" : "RGD:A23332"
    }, {
      "firstName" : "J",
      "lastName" : "Lindemeier",
      "authorRank" : 3,
      "name" : "Lindemeier J",
      "referenceId" : "RGD:A3124"
    }, {
      "firstName" : "JF",
      "lastName" : "Battey",
      "authorRank" : 4,
      "name" : "Battey JF",
      "referenceId" : "RGD:A87906"
    }, {
      "firstName" : "NJ",
      "lastName" : "Ryba",
      "authorRank" : 5,
      "name" : "Ryba NJ",
      "referenceId" : "RGD:A102164"
    }, {
      "firstName" : "CS",
      "lastName" : "Zuker",
      "authorRank" : 6,
      "name" : "Zuker CS",
      "referenceId" : "RGD:A47115"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61615"
    } ]
  }, {
    "primaryId" : "PMID:10053003",
    "title" : "Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Stallmeyer B, etal., Am J Hum Genet 1999 Mar;64(3):698-705.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-07T12:39:10.000-06:00",
    "volume" : "64",
    "pages" : "698-705",
    "abstract" : "A universal molybdenum-containing cofactor (MoCo) is essential for the activity of all human molybdoenzymes, including sulphite oxidase. The free cofactor is highly unstable, and all organisms share a similar biosynthetic pathway. The involved enzymes exhibit homologies, even between bacteria and humans. We have exploited these homologies to isolate a cDNA for the heterodimeric molybdopterin (MPT)-synthase. This enzyme is necessary for the conversion of an unstable precursor into molybdopterin, the organic moiety of MoCo. The corresponding transcript shows a bicistronic structure, encoding the small and large subunits of the MPT-synthase in two different open reading frames (ORFs) that overlap by 77 nucleotides. In various human tissues, only one size of mRNA coinciding with the bicistronic transcript was detected. In vitro translation and mutagenesis experiments demonstrated that each ORF is translated independently, leading to the synthesis of a 10-kDa protein and a 21-kDa protein for the small and large subunits, respectively, and indicated that the 3'-proximal ORF of the bicistronic transcript is translated by leaky scanning.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Stallmeyer",
      "authorRank" : 1,
      "name" : "Stallmeyer B",
      "referenceId" : "RGD:A56330"
    }, {
      "firstName" : "G",
      "lastName" : "Drugeon",
      "authorRank" : 2,
      "name" : "Drugeon G",
      "referenceId" : "RGD:A56798"
    }, {
      "firstName" : "J",
      "lastName" : "Reiss",
      "authorRank" : 3,
      "name" : "Reiss J",
      "referenceId" : "RGD:A5295"
    }, {
      "firstName" : "AL",
      "lastName" : "Haenni",
      "authorRank" : 4,
      "name" : "Haenni AL",
      "referenceId" : "RGD:A56799"
    }, {
      "firstName" : "RR",
      "lastName" : "Mendel",
      "authorRank" : 5,
      "name" : "Mendel RR",
      "referenceId" : "RGD:A5299"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556603"
    } ]
  }, {
    "primaryId" : "PMID:10053004",
    "title" : "Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Reiss J, etal., Am J Hum Genet 1999 Mar;64(3):706-11.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-10-31T09:11:05.000-06:00",
    "volume" : "64",
    "pages" : "706-11",
    "abstract" : "Biosynthesis of the molybdenum cofactor (MoCo) can be divided into (1) the formation of a precursor and (2) the latter's subsequent conversion, by molybdopterin synthase, into the organic moiety of MoCo. These two steps are reflected by the complementation groups A and B and the two formally distinguished types of MoCo deficiency that have an identical phenotype. Both types of MoCo deficiency result in a pleiotropic loss of all molybdoenzyme activities and cause severe neurological damage. MOCS1 is defective in patients with group A deficiency and has been shown to encode two enzymes for early synthesis via a bicistronic transcript with two consecutive open reading frames (ORFs). MOCS2 encodes the small and large subunits of molybdopterin synthase via a single transcript with two overlapping reading frames. This gene was mapped to 5q and comprises seven exons. The coding sequence and all splice site-junction sequences were screened for mutations, in MoCo-deficient patients in whom a previous search for MOCS1 mutations had been negative. In seven of the eight patients whom we investigated, we identified MOCS2 mutations that, by their nature, are most likely responsible for the deficiency. Three different frameshift mutations were observed, with one of them found on 7 of 14 identified alleles. Furthermore, a start-codon mutation and a missense mutation of a highly conserved amino acid residue were found. The locations of the mutations confirm the functional role of both ORFs. One of the patients with identified MOCS2 mutations had been classified as type B, in complementation studies. These findings support the hypothetical mechanism, for both forms of MoCo deficiency, that formerly had been established by cell-culture experiments.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Reiss",
      "authorRank" : 1,
      "name" : "Reiss J",
      "referenceId" : "RGD:A5295"
    }, {
      "firstName" : "C",
      "lastName" : "Dorche",
      "authorRank" : 2,
      "name" : "Dorche C",
      "referenceId" : "RGD:A56329"
    }, {
      "firstName" : "B",
      "lastName" : "Stallmeyer",
      "authorRank" : 3,
      "name" : "Stallmeyer B",
      "referenceId" : "RGD:A56330"
    }, {
      "firstName" : "RR",
      "lastName" : "Mendel",
      "authorRank" : 4,
      "name" : "Mendel RR",
      "referenceId" : "RGD:A5299"
    }, {
      "firstName" : "N",
      "lastName" : "Cohen",
      "authorRank" : 5,
      "name" : "Cohen N",
      "referenceId" : "RGD:A56331"
    }, {
      "firstName" : "MT",
      "lastName" : "Zabot",
      "authorRank" : 6,
      "name" : "Zabot MT",
      "referenceId" : "RGD:A23264"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556492"
    } ]
  }, {
    "primaryId" : "PMID:10053006",
    "title" : "A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Tavormina PL, etal., Am J Hum Genet. 1999 Mar;64(3):722-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-07T10:35:49.000-06:00",
    "volume" : "64",
    "pages" : "722-31",
    "abstract" : "We have identified a novel fibroblast growth factor receptor 3 (FGFR3) missense mutation in four unrelated individuals with skeletal dysplasia that approaches the severity observed in thanatophoric dysplasia type I (TD1). However, three of  the four individuals developed extensive areas of acanthosis nigricans beginning  in early childhood, suffer from severe neurological impairments, and have survived past infancy without prolonged life-support measures. The FGFR3 mutation (A1949T: Lys650Met) occurs at the nucleotide adjacent to the TD type II (TD2) mutation (A1948G: Lys650Glu) and results in a different amino acid substitution at a highly conserved codon in the kinase domain activation loop. Transient transfection studies with FGFR3 mutant constructs show that the Lys650Met mutation causes a dramatic increase in constitutive receptor kinase activity, approximately three times greater than that observed with the Lys650Glu mutation. We refer to the phenotype caused by the Lys650Met mutation as \"severe achondroplasia with developmental delay and acanthosis nigricans\" (SADDAN) because it differs significantly from the phenotypes of other known FGFR3 mutations.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PL",
      "lastName" : "Tavormina",
      "authorRank" : 1,
      "name" : "Tavormina",
      "referenceId" : "RGD:A414598"
    }, {
      "firstName" : "GA",
      "lastName" : "Bellus",
      "authorRank" : 2,
      "name" : "Bellus",
      "referenceId" : "RGD:A267750"
    }, {
      "firstName" : "MK",
      "lastName" : "Webster",
      "authorRank" : 3,
      "name" : "Webster MK",
      "referenceId" : "RGD:A7970"
    }, {
      "firstName" : "MJ",
      "lastName" : "Bamshad",
      "authorRank" : 4,
      "name" : "Bamshad MJ",
      "referenceId" : "RGD:A85609"
    }, {
      "firstName" : "AE",
      "lastName" : "Fraley",
      "authorRank" : 5,
      "name" : "Fraley",
      "referenceId" : "RGD:A414599"
    }, {
      "firstName" : "I",
      "lastName" : "McIntosh",
      "authorRank" : 6,
      "name" : "McIntosh I",
      "referenceId" : "RGD:A75042"
    }, {
      "firstName" : "J",
      "lastName" : "Szabo",
      "authorRank" : 7,
      "name" : "Szabo",
      "referenceId" : "RGD:A414600"
    }, {
      "firstName" : "W",
      "lastName" : "Jiang",
      "authorRank" : 8,
      "name" : "Jiang W",
      "referenceId" : "RGD:A51614"
    }, {
      "firstName" : "EW",
      "lastName" : "Jabs",
      "authorRank" : 9,
      "name" : "Jabs EW",
      "referenceId" : "RGD:A15495"
    }, {
      "firstName" : "WR",
      "lastName" : "Wilcox",
      "authorRank" : 10,
      "name" : "Wilcox WR",
      "referenceId" : "RGD:A37391"
    }, {
      "firstName" : "JJ",
      "lastName" : "Wasmuth",
      "authorRank" : 11,
      "name" : "Wasmuth JJ",
      "referenceId" : "RGD:A56703"
    }, {
      "firstName" : "DJ",
      "lastName" : "Donoghue",
      "authorRank" : 12,
      "name" : "Donoghue",
      "referenceId" : "RGD:A414601"
    }, {
      "firstName" : "LM",
      "lastName" : "Thompson",
      "authorRank" : 13,
      "name" : "Thompson LM",
      "referenceId" : "RGD:A50743"
    }, {
      "firstName" : "CA",
      "lastName" : "Francomano",
      "authorRank" : 14,
      "name" : "Francomano CA",
      "referenceId" : "RGD:A39144"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568046"
    } ]
  }, {
    "primaryId" : "PMID:10053007",
    "title" : "Cyclic ichthyosis with epidermolytic hyperkeratosis: A phenotype conferred by mutations in the 2B domain of keratin K1.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Sybert VP, etal., Am J Hum Genet. 1999 Mar;64(3):732-8. doi: 10.1086/302278.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:10:15.000-05:00",
    "volume" : "64",
    "pages" : "732-8",
    "abstract" : "Bullous congenital ichthyosiform erythroderma (BCIE) is characterized by blistering and erythroderma in infancy and by erythroderma and ichthyosis thereafter. Epidermolytic hyperkeratosis is a hallmark feature of light and electron microscopy. Here we report on four individuals from two families with a unique clinical disorder with histological findings of epidermolytic hyperkeratosis. Manifesting erythema and superficial erosions at birth, which improved during the first few months of life, affected individuals later developed palmoplantar hyperkeratosis with patchy erythema and scale elsewhere on the body. Three affected individuals exhibit dramatic episodic flares of annular, polycyclic erythematous plaques with scale, which coalesce to involve most of the body surface. The flares last weeks to months. In the interim periods the skin may be normal, except for palmoplantar hyperkeratosis. Abnormal keratin-filament aggregates were observed in suprabasal keratinocytes from both probands, suggesting that the causative mutation might reside in keratin K1 or keratin K10. In one proband, sequencing of K1 revealed a heterozygous mutation, 1436T-->C, predicting a change of isoleucine to threonine in the highly conserved helix-termination motif. In the second family, a heterozygous mutation, 1435A-->T, was found in K1, predicting an isoleucine-to-phenylalanine substitution in the same codon. Both mutations were excluded in both a control population and all unaffected family members tested. These findings reveal that a clinical phenotype distinct from classic BCIE but with similar histology can result from K1 mutations and that mutations at this codon give rise to a clinically unique condition.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V P",
      "lastName" : "Sybert",
      "authorRank" : 1,
      "name" : "Sybert VP",
      "referenceId" : "RGD:A599857"
    }, {
      "firstName" : "J S",
      "lastName" : "Francis",
      "authorRank" : 2,
      "name" : "Francis JS",
      "referenceId" : "RGD:A599858"
    }, {
      "firstName" : "L D",
      "lastName" : "Corden",
      "authorRank" : 3,
      "name" : "Corden LD",
      "referenceId" : "RGD:A599859"
    }, {
      "firstName" : "L T",
      "lastName" : "Smith",
      "authorRank" : 4,
      "name" : "Smith LT",
      "referenceId" : "RGD:A599860"
    }, {
      "firstName" : "M",
      "lastName" : "Weaver",
      "authorRank" : 5,
      "name" : "Weaver M",
      "referenceId" : "RGD:A599861"
    }, {
      "firstName" : "K",
      "lastName" : "Stephens",
      "authorRank" : 6,
      "name" : "Stephens K",
      "referenceId" : "RGD:A56689"
    }, {
      "firstName" : "W H",
      "lastName" : "McLean",
      "authorRank" : 7,
      "name" : "McLean WH",
      "referenceId" : "RGD:A575790"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119401"
    } ]
  }, {
    "primaryId" : "PMID:10053008",
    "title" : "Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Toh S, etal., Am J Hum Genet. 1999 Mar;64(3):739-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-07T12:03:49.000-06:00",
    "volume" : "64",
    "pages" : "739-46",
    "abstract" : "Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (MRP2/cMOAT) in patients with DJS have suggested that the gene defects are responsible for DJS. In this study, we determined the exon/intron structure of the human MRP2/cMOAT gene and further characterized mutations in patients with DJS. The human MRP2/cMOAT gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP-binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that MRP2/cMOAT is the gene responsible for DJS. The finding that mutations are concentrated in the first ATP-binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Toh",
      "authorRank" : 1,
      "name" : "Toh S",
      "referenceId" : "RGD:A54614"
    }, {
      "firstName" : "M",
      "lastName" : "Wada",
      "authorRank" : 2,
      "name" : "Wada M",
      "referenceId" : "RGD:A10407"
    }, {
      "firstName" : "T",
      "lastName" : "Uchiumi",
      "authorRank" : 3,
      "name" : "Uchiumi T",
      "referenceId" : "RGD:A54609"
    }, {
      "firstName" : "A",
      "lastName" : "Inokuchi",
      "authorRank" : 4,
      "name" : "Inokuchi A",
      "referenceId" : "RGD:A70919"
    }, {
      "firstName" : "Y",
      "lastName" : "Makino",
      "authorRank" : 5,
      "name" : "Makino Y",
      "referenceId" : "RGD:A5103"
    }, {
      "firstName" : "Y",
      "lastName" : "Horie",
      "authorRank" : 6,
      "name" : "Horie Y",
      "referenceId" : "RGD:A46937"
    }, {
      "firstName" : "Y",
      "lastName" : "Adachi",
      "authorRank" : 7,
      "name" : "Adachi Y",
      "referenceId" : "RGD:A26833"
    }, {
      "firstName" : "S",
      "lastName" : "Sakisaka",
      "authorRank" : 8,
      "name" : "Sakisaka S",
      "referenceId" : "RGD:A70920"
    }, {
      "firstName" : "M",
      "lastName" : "Kuwano",
      "authorRank" : 9,
      "name" : "Kuwano M",
      "referenceId" : "RGD:A37823"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598616"
    } ]
  }, {
    "primaryId" : "PMID:10053012",
    "title" : "Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Gibbs M, etal., Am J Hum Genet. 1999 Mar;64(3):776-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-05-05T08:40:16.000-05:00",
    "volume" : "64",
    "pages" : "776-87",
    "abstract" : "Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Gibbs",
      "authorRank" : 1,
      "name" : "Gibbs M",
      "referenceId" : "RGD:A95704"
    }, {
      "firstName" : "JL",
      "lastName" : "Stanford",
      "authorRank" : 2,
      "name" : "Stanford JL",
      "referenceId" : "RGD:A93270"
    }, {
      "firstName" : "RA",
      "lastName" : "McIndoe",
      "authorRank" : 3,
      "name" : "McIndoe RA",
      "referenceId" : "RGD:A95705"
    }, {
      "firstName" : "GP",
      "lastName" : "Jarvik",
      "authorRank" : 4,
      "name" : "Jarvik GP",
      "referenceId" : "RGD:A57246"
    }, {
      "firstName" : "S",
      "lastName" : "Kolb",
      "authorRank" : 5,
      "name" : "Kolb S",
      "referenceId" : "RGD:A93591"
    }, {
      "firstName" : "EL",
      "lastName" : "Goode",
      "authorRank" : 6,
      "name" : "Goode EL",
      "referenceId" : "RGD:A91342"
    }, {
      "firstName" : "L",
      "lastName" : "Chakrabarti",
      "authorRank" : 7,
      "name" : "Chakrabarti L",
      "referenceId" : "RGD:A95706"
    }, {
      "firstName" : "EF",
      "lastName" : "Schuster",
      "authorRank" : 8,
      "name" : "Schuster EF",
      "referenceId" : "RGD:A95707"
    }, {
      "firstName" : "VA",
      "lastName" : "Buckley",
      "authorRank" : 9,
      "name" : "Buckley VA",
      "referenceId" : "RGD:A95708"
    }, {
      "firstName" : "EL",
      "lastName" : "Miller",
      "authorRank" : 10,
      "name" : "Miller EL",
      "referenceId" : "RGD:A95709"
    }, {
      "firstName" : "S",
      "lastName" : "Brandzel",
      "authorRank" : 11,
      "name" : "Brandzel S",
      "referenceId" : "RGD:A95710"
    }, {
      "firstName" : "S",
      "lastName" : "Li",
      "authorRank" : 12,
      "name" : "Li S",
      "referenceId" : "RGD:A12216"
    }, {
      "firstName" : "L",
      "lastName" : "Hood",
      "authorRank" : 13,
      "name" : "Hood L",
      "referenceId" : "RGD:A55620"
    }, {
      "firstName" : "EA",
      "lastName" : "Ostrander",
      "authorRank" : 14,
      "name" : "Ostrander EA",
      "referenceId" : "RGD:A93274"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292707"
    } ]
  }, {
    "primaryId" : "PMID:10053014",
    "title" : "The predisposition to type 1 diabetes linked to the human leukocyte antigen complex includes at least one non-class II gene.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Lie BA, etal., Am J Hum Genet 1999 Mar;64(3):793-800.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-13T10:40:22.000-05:00",
    "volume" : "64",
    "pages" : "793-800",
    "abstract" : "The human leukocyte antigen (HLA) complex, encompassing 3.5 Mb of DNA from the centromeric HLA-DPB2 locus to the telomeric HLA-F locus on chromosome 6p21, encodes a major part of the genetic predisposition to develop type 1 diabetes, designated \"IDDM1.\" A primary role for allelic variation of the class II HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci has been established. However, studies of animals and humans have indicated that other, unmapped, major histocompatibility complex (MHC)-linked genes are participating in IDDM1. The strong linkage disequilibrium between genes in this complex makes mapping a difficult task. In the present paper, we report on the approach we have devised to circumvent the confounding effects of disequilibrium between class II alleles and alleles at other MHC loci. We have scanned 12 Mb of the MHC and flanking chromosome regions with microsatellite polymorphisms and analyzed the transmission of these marker alleles to diabetic probands from parents who were homozygous for the alleles of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Our analysis, using three independent family sets, suggests the presence of an additional type I diabetes gene (or genes). This approach is useful for the analysis of other loci linked to common diseases, to verify if a candidate polymorphism can explain all of the association of a region or if the association is due to two or more loci in linkage disequilibrium with each other.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BA",
      "lastName" : "Lie",
      "authorRank" : 1,
      "name" : "Lie BA",
      "referenceId" : "RGD:A35664"
    }, {
      "firstName" : "JA",
      "lastName" : "Todd",
      "authorRank" : 2,
      "name" : "Todd JA",
      "referenceId" : "RGD:A35675"
    }, {
      "firstName" : "F",
      "lastName" : "Pociot",
      "authorRank" : 3,
      "name" : "Pociot F",
      "referenceId" : "RGD:A192521"
    }, {
      "firstName" : "J",
      "lastName" : "Nerup",
      "authorRank" : 4,
      "name" : "Nerup J",
      "referenceId" : "RGD:A192520"
    }, {
      "firstName" : "HE",
      "lastName" : "Akselsen",
      "authorRank" : 5,
      "name" : "Akselsen HE",
      "referenceId" : "RGD:A40338"
    }, {
      "firstName" : "G",
      "lastName" : "Joner",
      "authorRank" : 6,
      "name" : "Joner G",
      "referenceId" : "RGD:A161950"
    }, {
      "firstName" : "K",
      "lastName" : "Dahl-Jorgensen",
      "authorRank" : 7,
      "name" : "Dahl-Jorgensen K",
      "referenceId" : "RGD:A40339"
    }, {
      "firstName" : "KS",
      "lastName" : "Ronningen",
      "authorRank" : 8,
      "name" : "Ronningen KS",
      "referenceId" : "RGD:A40294"
    }, {
      "firstName" : "E",
      "lastName" : "Thorsby",
      "authorRank" : 9,
      "name" : "Thorsby E",
      "referenceId" : "RGD:A161951"
    }, {
      "firstName" : "DE",
      "lastName" : "Undlien",
      "authorRank" : 10,
      "name" : "Undlien DE",
      "referenceId" : "RGD:A35669"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298357"
    } ]
  }, {
    "primaryId" : "PMID:10053027",
    "title" : "A fifth locus for Bardet-Biedl syndrome maps to chromosome 2q31.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Young TL, etal., Am J Hum Genet. 1999 Mar;64(3):900-4. doi: 10.1086/302301.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:40:07.000-05:00",
    "volume" : "64",
    "pages" : "900-4",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T L",
      "lastName" : "Young",
      "authorRank" : 1,
      "name" : "Young TL",
      "referenceId" : "RGD:A568198"
    }, {
      "firstName" : "L",
      "lastName" : "Penney",
      "authorRank" : 2,
      "name" : "Penney L",
      "referenceId" : "RGD:A604563"
    }, {
      "firstName" : "M O",
      "lastName" : "Woods",
      "authorRank" : 3,
      "name" : "Woods MO",
      "referenceId" : "RGD:A604564"
    }, {
      "firstName" : "P S",
      "lastName" : "Parfrey",
      "authorRank" : 4,
      "name" : "Parfrey PS",
      "referenceId" : "RGD:A564596"
    }, {
      "firstName" : "J S",
      "lastName" : "Green",
      "authorRank" : 5,
      "name" : "Green JS",
      "referenceId" : "RGD:A564594"
    }, {
      "firstName" : "D",
      "lastName" : "Hefferton",
      "authorRank" : 6,
      "name" : "Hefferton D",
      "referenceId" : "RGD:A80494"
    }, {
      "firstName" : "W S",
      "lastName" : "Davidson",
      "authorRank" : 7,
      "name" : "Davidson WS",
      "referenceId" : "RGD:A604565"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598120226"
    } ]
  }, {
    "primaryId" : "PMID:10053028",
    "title" : "Autosomal dominant (Beukes) premature degenerative osteoarthropathy of the hip joint maps to an 11-cM region on chromosome 4q35.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Roby P, etal., Am J Hum Genet 1999 Mar;64(3):904-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-04-22T15:59:58.000-05:00",
    "volume" : "64",
    "pages" : "904-8",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Roby",
      "authorRank" : 1,
      "name" : "Roby P",
      "referenceId" : "RGD:A40046"
    }, {
      "firstName" : "S",
      "lastName" : "Eyre",
      "authorRank" : 2,
      "name" : "Eyre S",
      "referenceId" : "RGD:A161314"
    }, {
      "firstName" : "J",
      "lastName" : "Worthington",
      "authorRank" : 3,
      "name" : "Worthington J",
      "referenceId" : "RGD:A183442"
    }, {
      "firstName" : "R",
      "lastName" : "Ramesar",
      "authorRank" : 4,
      "name" : "Ramesar R",
      "referenceId" : "RGD:A38352"
    }, {
      "firstName" : "H",
      "lastName" : "Cilliers",
      "authorRank" : 5,
      "name" : "Cilliers H",
      "referenceId" : "RGD:A40047"
    }, {
      "firstName" : "P",
      "lastName" : "Beighton",
      "authorRank" : 6,
      "name" : "Beighton P",
      "referenceId" : "RGD:A6201"
    }, {
      "firstName" : "M",
      "lastName" : "Grant",
      "authorRank" : 7,
      "name" : "Grant M",
      "referenceId" : "RGD:A40048"
    }, {
      "firstName" : "G",
      "lastName" : "Wallis",
      "authorRank" : 8,
      "name" : "Wallis G",
      "referenceId" : "RGD:A40049"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298026"
    } ]
  }, {
    "primaryId" : "PMID:10053172",
    "title" : "Ah receptor and ARNT protein and mRNA concentrations in rat prostate: effects of stage of development and 2,3,7, 8-tetrachlorodibenzo-p-dioxin treatment.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Sommer RJ, etal., Toxicol Appl Pharmacol. 1999 Mar 1;155(2):177-89. doi: 10.1006/taap.1998.8597.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-07-02T14:59:21.000-05:00",
    "volume" : "155",
    "pages" : "177-89",
    "abstract" : "Effects of stage of development and 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) protein concentrations in reproductive organs of male rats were determined. AhR protein levels in developing rat ventral and dorsolateral prostate decreased with age, declining approximately 70% between Postnatal Days (PND) 1 and 21. ARNT protein levels also decreased with age in dorsolateral, but not ventral prostate. The developmental decreases in prostatic AhR and ARNT protein were associated with decreases in AhR and ARNT mRNA. AhR and ARNT protein concentrations in fetal urogenital sinus on Gestation Days (GD) 16, 18, and 20 were similar to levels in ventral prostate on PND 7. TCDD exposure of adult male rats (0.2, 1, 5, or 25 micrograms/kg po, 24 h) decreased AhR but not ARNT protein in ventral and dorsolateral prostate, vas deferens, and epididymis. In utero and lactational TCDD exposure (1.0 micrograms/kg dam po, GD 15) did not alter ARNT levels but reduced prostatic AhR protein levels on PND 7 and delayed the developmental decrease in AhR protein in ventral and dorsolateral prostate. Finally, pretreatment of rat pups for 24 h with TCDD (5 micrograms/kg ip) down-regulated prostatic AhR protein on PND 7, but not on PND 1. Thus, prostatic AhR and ARNT protein and mRNA levels are regulated with age, whereas only AhR protein concentration is altered by TCDD exposure. Because in utero and lactational TCDD exposure only decreased prostatic AhR on PND 7, it is unlikely that down-regulation of AhR is the mechanism by which perinatal TCDD exposure impairs prostate development.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R J",
      "lastName" : "Sommer",
      "authorRank" : 1,
      "name" : "Sommer RJ",
      "referenceId" : "RGD:A542505"
    }, {
      "firstName" : "K M",
      "lastName" : "Sojka",
      "authorRank" : 2,
      "name" : "Sojka KM",
      "referenceId" : "RGD:A542506"
    }, {
      "firstName" : "R S",
      "lastName" : "Pollenz",
      "authorRank" : 3,
      "name" : "Pollenz RS",
      "referenceId" : "RGD:A542507"
    }, {
      "firstName" : "P S",
      "lastName" : "Cooke",
      "authorRank" : 4,
      "name" : "Cooke PS",
      "referenceId" : "RGD:A542508"
    }, {
      "firstName" : "R E",
      "lastName" : "Peterson",
      "authorRank" : 5,
      "name" : "Peterson RE",
      "referenceId" : "RGD:A542509"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:405866382"
    } ]
  }, {
    "primaryId" : "PMID:10063411",
    "title" : "Is there a relationship between abdominal aortic aneurysms and alpha1-antitrypsin deficiency (PiZ)?",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Elzouki AN, etal., Eur J Vasc Endovasc Surg. 1999 Feb;17(2):149-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-12-05T13:41:08.000-06:00",
    "volume" : "17",
    "pages" : "149-54",
    "abstract" : "OBJECTIVE: To determine if the frequency of alpha 1AT deficiency (PiZ) is increased in patients with abdominal aortic aneurysm (AAA), and, to investigate whether aneurysmal stiffness and other clinical characteristics differ in AAA patients with and without alpha 1AT deficiency. METHODS: We identified alpha 1AT-deficient individuals by a monoclonal-antibody ELISA technique, in 102 consecutive patients with AAA. Positive ELISA samples were further phenotyped by isoelectric focusing to differentiate between the heterozygosity (PiZ) and homozygosity (PiZZ) state. Aneurysmal diameter and stiffness was measured using echotracking sonography and blood pressure measurements. RESULTS: The frequency of heterozygous alpha 1AT deficiency (PiZ) in patients with AAA was similar to that in the general population (6.8% and 4.7%, respectively, p > 0.3). The frequency of popliteal and femoral aneurysm was similar in male PiZ-carriers and non-carriers with AAA, as were age at diagnosis of AAA, aneurysmal diameter, aneurysmal stiffness, and presence of factors that may be associated with AAA (i.e. smoking, hypertension, diabetes mellitus, and family history of AAA). Occurrence of ischaemic heart disease was more frequent in male non-PiZ-carriers than in male PiZ-carriers with AAA (p = 0.03). CONCLUSIONS: The frequency of alpha 1AT deficiency (PiZ) was not increased in our series of patients with AAA and patients in whom the two disorders coexisted did not appear to have different clinical characteristics except for the lower occurrence of ischaemic heart disease among the PiZ-carriers.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AN",
      "lastName" : "Elzouki",
      "authorRank" : 1,
      "name" : "Elzouki AN",
      "referenceId" : "RGD:A89538"
    }, {
      "firstName" : "A",
      "lastName" : "Ryden Ahlgren",
      "authorRank" : 2,
      "name" : "Ryden Ahlgren A",
      "referenceId" : "RGD:A89539"
    }, {
      "firstName" : "T",
      "lastName" : "Lanne",
      "authorRank" : 3,
      "name" : "Lanne T",
      "referenceId" : "RGD:A89540"
    }, {
      "firstName" : "B",
      "lastName" : "Sonesson",
      "authorRank" : 4,
      "name" : "Sonesson B",
      "referenceId" : "RGD:A89541"
    }, {
      "firstName" : "S",
      "lastName" : "Eriksson",
      "authorRank" : 5,
      "name" : "Eriksson S",
      "referenceId" : "RGD:A79422"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1643148"
    } ]
  }, {
    "primaryId" : "PMID:10063835",
    "title" : "Characterization of 34 novel and six known MTM1 gene mutations in 47 unrelated X-linked myotubular myopathy patients.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Tanner SM, etal., Neuromuscul Disord. 1999 Jan;9(1):41-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:16:12.000-05:00",
    "volume" : "9",
    "pages" : "41-9",
    "abstract" : "X-linked myotubular myopathy (XLMTM) is a congenital muscle disorder mainly affecting newborn males. Neonatal muscle weakness and hypotonia usually leads to  a rapid demise. The responsible gene, MTM1, was isolated in 1996, and mutational  data derived from 90 patients have been published. We report on our findings in a further 53 patients, using genomic DNA and mRNA screening protocols. Thirty-four  novel mutations were identified in 37 cases, and six known mutations found in 10  other patients. The 34 new mutations include five large deletions, eight nonsense, six frameshift, five missense, and eight splice-site mutations, whereas two intronic variants causing partial exon skipping represent the first report on such a mechanism in MTM1. Two deletions, one involving exon 1, and the second exon 15, are the first defects to be identified in these exons. The heterogeneity of the mutations, their mutational origins, and the varied ethnic backgrounds of  the patients, indicate that the majority of XLMTM families are affected by unique MTM1 mutations.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SM",
      "lastName" : "Tanner",
      "authorRank" : 1,
      "name" : "Tanner SM",
      "referenceId" : "RGD:A16926"
    }, {
      "firstName" : "V",
      "lastName" : "Schneider",
      "authorRank" : 2,
      "name" : "Schneider V",
      "referenceId" : "RGD:A89286"
    }, {
      "firstName" : "NS",
      "lastName" : "Thomas",
      "authorRank" : 3,
      "name" : "Thomas NS",
      "referenceId" : "RGD:A50459"
    }, {
      "firstName" : "A",
      "lastName" : "Clarke",
      "authorRank" : 4,
      "name" : "Clarke A",
      "referenceId" : "RGD:A71595"
    }, {
      "firstName" : "L",
      "lastName" : "Lazarou",
      "authorRank" : 5,
      "name" : "Lazarou L",
      "referenceId" : "RGD:A80524"
    }, {
      "firstName" : "S",
      "lastName" : "Liechti-Gallati",
      "authorRank" : 6,
      "name" : "Liechti-Gallati S",
      "referenceId" : "RGD:A79216"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069949"
    } ]
  }, {
    "primaryId" : "PMID:10064059",
    "title" : "Anti-Vbeta8 antibodies induce and maintain staphylococcal enterotoxin B-triggered Vbeta8+ T cell anergy.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Aroeira LS, etal., Eur J Immunol. 1999 Feb;29(2):437-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:37:17.000-05:00",
    "volume" : "29",
    "pages" : "437-45",
    "abstract" : "The mechanism involved in the maintenance of staphylococcal enterotoxin B (SEB)-induced T cell anergy is poorly understood. We demonstrated earlier that B  cells play an important role in the maintenance of SEB-induced T cell anergy in vivo and in vitro. Here, we demonstrate that B cells are not essential in SEB-induced T cell activation, but are important for the maintenance of T cell memory phenotype and anergy in vivo. Studying the activated B cell repertoire, we observe that SEB treatment increases serum anti-Vbeta8 antibody titer as detected by enzyme-linked immunosorbent assay using soluble Vbeta8 chains as antigens, and by staining of a Vbeta8-expressing thymoma. These antibodies disappear gradually  after immunization with SEB, whereas the capacity of the T cells to respond to SEB in vitro is restored. Anti-Vbeta8 monoclonal antibody treatment causes Vbeta8+ T cell unresponsiveness to SEB in vitro (anergy), without affecting CD4Vbeta8+ T cell frequency. Together, these results suggest a new mechanism to explain the maintenance of SEB-induced T cell anergy, which is dependent on B cells and on anti-Vbeta8 antibody that specifically interacts with Vbeta8+ T cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LS",
      "lastName" : "Aroeira",
      "authorRank" : 1,
      "name" : "Aroeira",
      "referenceId" : "RGD:A331576"
    }, {
      "firstName" : "CG",
      "lastName" : "Mouton",
      "authorRank" : 2,
      "name" : "Mouton",
      "referenceId" : "RGD:A331577"
    }, {
      "firstName" : "JL",
      "lastName" : "Toran",
      "authorRank" : 3,
      "name" : "Toran",
      "referenceId" : "RGD:A331578"
    }, {
      "firstName" : "ES",
      "lastName" : "Ward",
      "authorRank" : 4,
      "name" : "Ward",
      "referenceId" : "RGD:A331579"
    }, {
      "firstName" : "C",
      "lastName" : "Martinez",
      "authorRank" : 5,
      "name" : "Martinez C",
      "referenceId" : "RGD:A15384"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340717"
    } ]
  }, {
    "primaryId" : "PMID:10064338",
    "title" : "Modulation of estrogen action in the rat pituitary and mammary glands by dietary energy consumption.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Spady TJ, etal., J Nutr 1999 Feb;129(2S Suppl):587S-590S.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-07-19T07:42:32.000-05:00",
    "volume" : "129",
    "pages" : "587S-590S",
    "abstract" : "We are investigating the mechanisms through which estrogens induce development of prolactin (PRL)-producing pituitary tumors and mammary carcinomas in rats and how these mechanisms are affected by dietary energy consumption. The hypothesis under examination is that dietary energy restriction inhibits tumorigenesis in estrogen-responsive tissues by altering cellular responsiveness to estrogenic hormones. In the Fischer 344 (F344) rat strain, a 40% restriction of energy consumption virtually abolishes development of estrogen-induced pituitary tumors. Inhibition of pituitary tumorigenesis in the F344 strain by energy restriction results from modulation of estrogen regulation of cell survival, not cell proliferation. In contrast, energy restriction has no inhibitory effect on estrogen-induced pituitary tumor development in the ACI rat strain. However, energy restriction markedly inhibits induction of mammary carcinomas in female ACI rats treated with 17beta-estradiol. Data presented herein indicate that dietary energy restriction modulates the responsiveness of specific cell populations to estrogenic hormones and thereby inhibits estrogen-induced tumorigenesis in a manner specific to both rat strain and tissue.",
    "issueName" : "2S Suppl",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TJ",
      "lastName" : "Spady",
      "authorRank" : 1,
      "name" : "Spady TJ",
      "referenceId" : "RGD:A50704"
    }, {
      "firstName" : "DM",
      "lastName" : "Harvell",
      "authorRank" : 2,
      "name" : "Harvell DM",
      "referenceId" : "RGD:A54123"
    }, {
      "firstName" : "A",
      "lastName" : "Lemus-Wilson",
      "authorRank" : 3,
      "name" : "Lemus-Wilson A",
      "referenceId" : "RGD:A54160"
    }, {
      "firstName" : "TE",
      "lastName" : "Strecker",
      "authorRank" : 4,
      "name" : "Strecker TE",
      "referenceId" : "RGD:A50703"
    }, {
      "firstName" : "KL",
      "lastName" : "Pennington",
      "authorRank" : 5,
      "name" : "Pennington KL",
      "referenceId" : "RGD:A20810"
    }, {
      "firstName" : "EA",
      "lastName" : "Vander Woude",
      "authorRank" : 6,
      "name" : "Vander Woude EA",
      "referenceId" : "RGD:A54161"
    }, {
      "firstName" : "DF",
      "lastName" : "Birt",
      "authorRank" : 7,
      "name" : "Birt DF",
      "referenceId" : "RGD:A54162"
    }, {
      "firstName" : "RD",
      "lastName" : "McComb",
      "authorRank" : 8,
      "name" : "McComb RD",
      "referenceId" : "RGD:A54125"
    }, {
      "firstName" : "JD",
      "lastName" : "Shull",
      "authorRank" : 9,
      "name" : "Shull JD",
      "referenceId" : "RGD:A20809"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358973"
    } ]
  }, {
    "primaryId" : "PMID:10064590",
    "title" : "Increased neurodegeneration during ageing in mice lacking high-affinity nicotine receptors.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Zoli M, etal., EMBO J 1999 Mar 1;18(5):1235-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-26T14:27:58.000-06:00",
    "volume" : "18",
    "pages" : "1235-44",
    "abstract" : "We have examined neuroanatomical, biochemical and endocrine parameters and spatial learning in mice lacking the beta2 subunit of the nicotinic acetylcholine receptor (nAChR) during ageing. Aged beta2(-/-) mutant mice showed region-specific alterations in cortical regions, including neocortical hypotrophy, loss of hippocampal pyramidal neurons, astro- and microgliosis and elevation of serum corticosterone levels. Whereas adult mutant and control animals performed well in the Morris maze, 22- to 24-month-old beta2(-/-) mice were significantly impaired in spatial learning. These data show that beta2 subunit-containing nAChRs can contribute to both neuronal survival and maintenance of cognitive performance during ageing. beta2(-/-) mice may thus serve as one possible animal model for some of the cognitive deficits and degenerative processes which take place during physiological ageing and in Alzheimer's disease, particularly those associated with dysfunction of the cholinergic system.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Zoli",
      "authorRank" : 1,
      "name" : "Zoli M",
      "referenceId" : "RGD:A39616"
    }, {
      "firstName" : "MR",
      "lastName" : "Picciotto",
      "authorRank" : 2,
      "name" : "Picciotto MR",
      "referenceId" : "RGD:A29328"
    }, {
      "firstName" : "R",
      "lastName" : "Ferrari",
      "authorRank" : 3,
      "name" : "Ferrari R",
      "referenceId" : "RGD:A31582"
    }, {
      "firstName" : "D",
      "lastName" : "Cocchi",
      "authorRank" : 4,
      "name" : "Cocchi D",
      "referenceId" : "RGD:A39617"
    }, {
      "firstName" : "JP",
      "lastName" : "Changeux",
      "authorRank" : 5,
      "name" : "Changeux JP",
      "referenceId" : "RGD:A39618"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:737811"
    } ]
  }, {
    "primaryId" : "PMID:10064618",
    "title" : "Carbonic anhydrase III protects cells from hydrogen peroxide-induced apoptosis.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Räisänen SR, etal., FASEB J. 1999 Mar;13(3):513-22. doi: 10.1096/fasebj.13.3.513.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-11-20T14:51:17.000-06:00",
    "volume" : "13",
    "pages" : "513-22",
    "abstract" : "Carbonic anhydrase III (CA III; EC 4.2.1.1) is a cytoplasmic enzyme that exhibits a relatively low carbon dioxide hydratase activity. It is expressed at a very high level in skeletal muscle, where physical exercise has been shown to increase free radical production. In this work we show the effect of overexpression of CA III on cellular response to oxidative stress. Rat CA III cDNA was transfected to NIH/3T3 cells, which have no endogenous CA III expression. The isolated clones expressed CA III mRNA and protein. The protein was localized to cytoplasm and nuclei. Compared to parental cells, transfected cells showed lower basal oxidized state as judged by measurement of intracellular reactive oxygen species (ROS) using fluorescent dye and an image analysis system. Addition of exogenous H2O2 to cells induced a rapid increase of ROS in control but not in CA III overexpressing cells. Association of this phenomenon with CA III expression was further confirmed by showing that overexpression of CA II could not prevent H2O2-stimulated increase of ROS. In proliferation assays, CA III overexpressing cells grew faster and were more resistant to cytotoxic concentrations of H2O2 than control cells. After a 16 h exposure to oxidative stress, the number of apoptotic cells was also reduced in transfectants. Our results suggest that CA III functions as an oxyradical scavenger and thus protects cells from oxidative damage. A lower level of free radicals in CA III overexpressing cells may also affect growth signaling pathways.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S R",
      "lastName" : "Räisänen",
      "authorRank" : 1,
      "name" : "Räisänen SR",
      "referenceId" : "RGD:A559226"
    }, {
      "firstName" : "P",
      "lastName" : "Lehenkari",
      "authorRank" : 2,
      "name" : "Lehenkari P",
      "referenceId" : "RGD:A50960"
    }, {
      "firstName" : "M",
      "lastName" : "Tasanen",
      "authorRank" : 3,
      "name" : "Tasanen M",
      "referenceId" : "RGD:A559227"
    }, {
      "firstName" : "P",
      "lastName" : "Rahkila",
      "authorRank" : 4,
      "name" : "Rahkila P",
      "referenceId" : "RGD:A559228"
    }, {
      "firstName" : "P L",
      "lastName" : "Härkönen",
      "authorRank" : 5,
      "name" : "Härkönen PL",
      "referenceId" : "RGD:A559229"
    }, {
      "firstName" : "H K",
      "lastName" : "Väänänen",
      "authorRank" : 6,
      "name" : "Väänänen HK",
      "referenceId" : "RGD:A559230"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:408426008"
    } ]
  }, {
    "primaryId" : "PMID:10064727",
    "title" : "Paradoxical effect on atherosclerosis of hormone-sensitive lipase overexpression in macrophages.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Escary JL, etal., J Lipid Res. 1999 Mar;40(3):397-404.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-10-28T12:56:00.000-05:00",
    "volume" : "40",
    "pages" : "397-404",
    "abstract" : "Foam cells formed from receptor-mediated uptake of lipoprotein cholesterol by macrophages in the arterial intima are critical in the initiation, progression, and stability of atherosclerotic lesions. Macrophages accumulate cholesterol when conditions favor esterification by acyl-CoA:cholesterol acyltransferase (ACAT) over cholesteryl-ester hydrolysis by a neutral cholesteryl-ester hydrolase, such as hormone-sensitive lipase (HSL), and subsequent cholesterol efflux mediated by extracellular acceptors. We recently made stable transfectants of a murine macrophage cell line, RAW 264.7, that overexpressed a rat HSL cDNA and had a 5-fold higher rate of cholesteryl-ester hydrolysis than control cells. The current study examined the effect of macrophage-specific HSL overexpression on susceptibility to diet-induced atherosclerosis in mice. A transgenic line overexpressing the rat HSL cDNA regulated with a macrophage-specific scavenger receptor promoter-enhancer was established by breeding with C57BL/6J mice. Transgenic peritoneal macrophages exhibited macrophage-specific 7-fold overexpression of HSL cholesterol esterase activity. Total plasma cholesterol levels in transgenic mice fed a chow diet were modestly elevated 16% compared to control littermates. After 14 weeks on a high-fat, high-cholesterol diet, total cholesterol increased 3-fold, with no difference between transgenics and controls. However, HSL overexpression resulted in thicker aortic fatty lesions that were 2.5-times larger in transgenic mice. HSL expression in the aortic lesions was shown by immunocytochemistry. Atherosclerosis was more advanced in transgenic mice exhibiting raised lesions involving the aortic wall, along with lipid accumulation in coronary arteries occurring only in transgenics. Thus, increasing cholesteryl-ester hydrolysis, without concomitantly decreasing ACAT activity or increasing cholesterol efflux, is not sufficient to protect against atherosclerosis. hormone-sensitive lipase overexpression in macrophages.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JL",
      "lastName" : "Escary",
      "authorRank" : 1,
      "name" : "Escary JL",
      "referenceId" : "RGD:A67686"
    }, {
      "firstName" : "HA",
      "lastName" : "Choy",
      "authorRank" : 2,
      "name" : "Choy HA",
      "referenceId" : "RGD:A67687"
    }, {
      "firstName" : "K",
      "lastName" : "Reue",
      "authorRank" : 3,
      "name" : "Reue K",
      "referenceId" : "RGD:A35994"
    }, {
      "firstName" : "XP",
      "lastName" : "Wang",
      "authorRank" : 4,
      "name" : "Wang XP",
      "referenceId" : "RGD:A37571"
    }, {
      "firstName" : "LW",
      "lastName" : "Castellani",
      "authorRank" : 5,
      "name" : "Castellani LW",
      "referenceId" : "RGD:A35991"
    }, {
      "firstName" : "CK",
      "lastName" : "Glass",
      "authorRank" : 6,
      "name" : "Glass CK",
      "referenceId" : "RGD:A33344"
    }, {
      "firstName" : "AJ",
      "lastName" : "Lusis",
      "authorRank" : 7,
      "name" : "Lusis AJ",
      "referenceId" : "RGD:A7267"
    }, {
      "firstName" : "MC",
      "lastName" : "Schotz",
      "authorRank" : 8,
      "name" : "Schotz MC",
      "referenceId" : "RGD:A31093"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581868"
    } ]
  }, {
    "primaryId" : "PMID:10064895",
    "title" : "Identity of heart and liver L-3-hydroxyacyl coenzyme A dehydrogenase.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "He XY, etal., Biochim Biophys Acta 1999 Feb 25;1437(2):119-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:55.000-05:00",
    "volume" : "1437",
    "pages" : "119-23",
    "abstract" : "Rat heart and liver cDNAs for precursor of L-3-hydroxyacyl-CoA dehydrogenase have been cloned and sequenced. The results indicate that these different rat organs express identical dehydrogenases. Furthermore, pig heart mRNA for L-3-hydroxyacyl-CoA dehydrogenase precursor was amplified by reverse transcription-polymerase chain reaction, and all the cDNA clones were found to encode a precursor of liver L-3-hydroxyacyl-CoA dehydrogenase (X.-Y. He, S.-Y. Yang, Biochim. Biophys. Acta 1392 (1998) 119-126) but not the well-documented heart form of the dehydrogenase (K.G. Bitar et al., FEBS Lett. 116 (1980) 196-198). Sequencing data and other evidence establish that the pig, like the rat, has the same dehydrogenase in heart and liver. Since the size and structure of pig heart L-3-hydroxyacyl-CoA dehydrogenase are identical to the pig liver dehydrogenase, reports that relied on the published sequence of the pig heart dehydrogenase need to be re-evaluated. For example, the signature pattern of the L-3-hydroxyacyl-CoA dehydrogenase family is HXFXPX3MXLXE. Furthermore, the published crystal structure of the pig heart dehydrogenase that substantiated each subunit comprising 307 residues with a mercury-binding residue at position 204 (J.J. Birktoft et al., Proc. Natl. Acad. Sci. U.S.A. 84 (1987) 8262-8266) must be re-examined in accordance with this revelation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "XY",
      "lastName" : "He",
      "authorRank" : 1,
      "name" : "He XY",
      "referenceId" : "RGD:A137754"
    }, {
      "firstName" : "G",
      "lastName" : "Zhang",
      "authorRank" : 2,
      "name" : "Zhang G",
      "referenceId" : "RGD:A5911"
    }, {
      "firstName" : "F",
      "lastName" : "Blecha",
      "authorRank" : 3,
      "name" : "Blecha F",
      "referenceId" : "RGD:A5912"
    }, {
      "firstName" : "SY",
      "lastName" : "Yang",
      "authorRank" : 4,
      "name" : "Yang SY",
      "referenceId" : "RGD:A5909"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68799"
    } ]
  }, {
    "primaryId" : "PMID:10064901",
    "title" : "Sequence, expression in Escherichia coli, and characterization of lysophospholipase II.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Toyoda T, etal., Biochim Biophys Acta 1999 Feb 25;1437(2):182-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-02T12:49:40.000-05:00",
    "volume" : "1437",
    "pages" : "182-93",
    "abstract" : "Here we report the sequence, expression in Escherichia coli cells, and characterization of a new small-form lysophospholipase named lysophospholipase II from mouse embryo. The cDNA clone was found and identified among mouse expressed sequence tags in the database search for the homologue of lysophospholipase I previously cloned from rat liver (H. Sugimoto et al., J. Biol. Chem. 271 (1996) 7705-7711). The predicted amino acids sequence contained 231 residues with a calculated molecular weight of 24794, and showed 64% identity to that of lysophospholipase I with the Gly-X-Ser-X-Gly esterase/lipase consensus. The lacZ fusion protein expressed in E. coli cells exhibited lysophospholipase activity and reacted with antibody raised against previously purified pig gastric lysophospholipase II (H. Sunaga et al., Biochem. J. 308 (1995) 551-557), but not with antibody against rat liver lysophospholipase I. The expressed enzyme was purified to a specific activity of 0.15 micromol/min per mg by DEAE-Sepharose A-500 chromatography. The enzyme preferentially utilized zwitterionic lysophospholipids in the order of lysophosphatidylcholine>lysophosphatidylethanolamine, but poorly acidic lysophospholipids, such as lysophosphatidylserine, lysophosphatidylinositol, and lysophosphatidic acid. Not only the 1-acyl isomer, but also the 2-acyl isomer were deacylated. Northern blot analysis and reverse transcription-polymerase chain reaction revealed that lysophospholipase II transcript as well as lysophospholipase I transcript was widely distributed in mouse tissues.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Toyoda",
      "authorRank" : 1,
      "name" : "Toyoda T",
      "referenceId" : "RGD:A26029"
    }, {
      "firstName" : "H",
      "lastName" : "Sugimoto",
      "authorRank" : 2,
      "name" : "Sugimoto H",
      "referenceId" : "RGD:A8616"
    }, {
      "firstName" : "S",
      "lastName" : "Yamashita",
      "authorRank" : 3,
      "name" : "Yamashita S",
      "referenceId" : "RGD:A125020"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:724409"
    } ]
  }, {
    "primaryId" : "PMID:10065021",
    "title" : "Coexistence of mitochondrial DNA and beta myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure.",
    "datePublished" : "1998-04-01T00:00:00.000-06:00",
    "citation" : "Arbustini E, etal., Heart. 1998 Dec;80(6):548-58.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:07:46.000-05:00",
    "volume" : "80",
    "pages" : "548-58",
    "abstract" : "OBJECTIVE: To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patients with beta myosin heavy chain (beta MHC) linked hypertrophic cardiomyopathy (HCM) who develop congestive heart failure. DESIGN: Molecular analysis of beta MHC and mtDNA gene defects in patients with HCM. SETTING: Cardiovascular molecular diagnostic and heart transplantation reference centre in north Italy. PATIENTS: Four patients with HCM who underwent heart transplantation for end stage heart failure, and after pedigree analysis of 60 relatives, eight additional affected patients and 27 unaffected relatives. A total of 111 unrelated healthy adult volunteers served as controls. Disease controls included  an additional 27 patients with HCM and 102 with dilated cardiomyopathy. INTERVENTION: Molecular analysis of DNA from myocardial and skeletal muscle tissue and from peripheral blood specimens. MAIN OUTCOME MEASURES: Screening for  mutations in beta MHC (exons 3-23) and mtDNA tRNA (n = 22) genes with denaturing  gradient gel electrophoresis or single strand conformational polymorphism followed by automated DNA sequencing. RESULTS: One proband (kindred A) (plus seven affected relatives) had arginine 249 glutamine (Arg249Gln) beta MHC and heteroplasmic mtDNA tRNAIle A4300G mutations. Another unrelated patient (kindred  B) with sporadic HCM had identical mutations. The remaining two patients (kindred C), a mother and son, had a novel beta MHC mutation (lysine 450 glutamic acid) (Lys450Glu) and a heteroplasmic missense (T9957C, phenylalanine (Phe)-->leucine (Leu)) mtDNA mutation in subunit III of the cytochrome C oxidase gene. The amount of mutant mtDNA was higher in the myocardium than in skeletal muscle or peripheral blood and in affected patients than in asymptomatic relatives. Mutations were absent in the controls. Pathological and biochemical characteristics of patients with mutations Arg249Gln plus A4300G (kindreds A and  B) were identical, but different from those of the two patients with Lys450Glu plus T9957C(Phe-->Leu) mutations (kindred C). Cytochrome C oxidase activity and histoenzymatic staining were severely decreased in the two patients in kindreds A and B, but were unaffected in the two in kindred C. CONCLUSIONS: beta MHC gene and mtDNA mutations may coexist in patients with HCM and end stage congestive heart failure. Although beta MHC gene mutations seem to be the true determinants  of HCM, both mtDNA mutations in these patients have known prerequisites for pathogenicity. Coexistence of other genetic abnormalities in beta MHC linked HCM, such as mtDNA mutations, may contribute to variable phenotypic expression and explain the heterogeneous behaviour of HCM.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Arbustini",
      "authorRank" : 1,
      "name" : "Arbustini E",
      "referenceId" : "RGD:A104894"
    }, {
      "firstName" : "R",
      "lastName" : "Fasani",
      "authorRank" : 2,
      "name" : "Fasani",
      "referenceId" : "RGD:A283509"
    }, {
      "firstName" : "P",
      "lastName" : "Morbini",
      "authorRank" : 3,
      "name" : "Morbini",
      "referenceId" : "RGD:A283510"
    }, {
      "firstName" : "M",
      "lastName" : "Diegoli",
      "authorRank" : 4,
      "name" : "Diegoli",
      "referenceId" : "RGD:A261447"
    }, {
      "firstName" : "M",
      "lastName" : "Grasso",
      "authorRank" : 5,
      "name" : "Grasso M",
      "referenceId" : "RGD:A104883"
    }, {
      "firstName" : "B",
      "lastName" : "Dal Bello",
      "authorRank" : 6,
      "name" : "Dal Bello",
      "referenceId" : "RGD:A283511"
    }, {
      "firstName" : "E",
      "lastName" : "Marangoni",
      "authorRank" : 7,
      "name" : "Marangoni",
      "referenceId" : "RGD:A283512"
    }, {
      "firstName" : "P",
      "lastName" : "Banfi",
      "authorRank" : 8,
      "name" : "Banfi",
      "referenceId" : "RGD:A283513"
    }, {
      "firstName" : "N",
      "lastName" : "Banchieri",
      "authorRank" : 9,
      "name" : "Banchieri",
      "referenceId" : "RGD:A283514"
    }, {
      "firstName" : "O",
      "lastName" : "Bellini",
      "authorRank" : 10,
      "name" : "Bellini",
      "referenceId" : "RGD:A283515"
    }, {
      "firstName" : "G",
      "lastName" : "Comi",
      "authorRank" : 11,
      "name" : "Comi G",
      "referenceId" : "RGD:A53941"
    }, {
      "firstName" : "J",
      "lastName" : "Narula",
      "authorRank" : 12,
      "name" : "Narula",
      "referenceId" : "RGD:A283516"
    }, {
      "firstName" : "C",
      "lastName" : "Campana",
      "authorRank" : 13,
      "name" : "Campana C",
      "referenceId" : "RGD:A104885"
    }, {
      "firstName" : "A",
      "lastName" : "Gavazzi",
      "authorRank" : 14,
      "name" : "Gavazzi A",
      "referenceId" : "RGD:A104886"
    }, {
      "firstName" : "C",
      "lastName" : "Danesino",
      "authorRank" : 15,
      "name" : "Danesino C",
      "referenceId" : "RGD:A44828"
    }, {
      "firstName" : "M",
      "lastName" : "Vigano",
      "authorRank" : 16,
      "name" : "Vigano M",
      "referenceId" : "RGD:A104892"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073040"
    } ]
  }, {
    "primaryId" : "PMID:10066032",
    "title" : "Missense mutations in phosphomannomutase 2 gene in two Japanese families with carbohydrate-deficient glycoprotein syndrome type 1.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Kondo I, etal., Clin Genet. 1999 Jan;55(1):50-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-17T14:18:25.000-06:00",
    "volume" : "55",
    "pages" : "50-4",
    "abstract" : "Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1) (MIM: 212065) is an autosomal recessive disorder with psychomotor retardation, strokelike episodes, ataxia, and olivopontocerebellar atrophy (OPCA) of neonatal onset. Recently, DNA substitutions in a gene for phosphomannomutase 2 (PMM2), mapped to 16p13, were identified in patients with CDG1. Biochemical findings in previously reported Japanese patients with CDG1 were slightly different from those of Caucasians, suggesting genetic heterogeneity of CDG1 in Japanese patients. We investigated the DNA sequence of PMM2 in two unrelated Japanese families with CDG1. Missense mutations in exon 5 (Phe144Leu) and exon 8 (Tyr229Ser, Arg238Pro) of the PMM2 gene were present in two families, but they were not present in 72 unrelated healthy Japanese individuals. One of the missense mutations, Phe144Leu in exon 5, was common to two families with CDG1. Our findings confirm that mutations in the PMM2 gene account for at least some Japanese patients with CDG1 similar to that seen in Caucasians and that exons 5 and 8 are hot spots of mutations of CDG1 caused by the PMM2 gene.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Kondo",
      "authorRank" : 1,
      "name" : "Kondo I",
      "referenceId" : "RGD:A72596"
    }, {
      "firstName" : "K",
      "lastName" : "Mizugishi",
      "authorRank" : 2,
      "name" : "Mizugishi K",
      "referenceId" : "RGD:A72597"
    }, {
      "firstName" : "Y",
      "lastName" : "Yoneda",
      "authorRank" : 3,
      "name" : "Yoneda Y",
      "referenceId" : "RGD:A5117"
    }, {
      "firstName" : "T",
      "lastName" : "Hashimoto",
      "authorRank" : 4,
      "name" : "Hashimoto T",
      "referenceId" : "RGD:A6042"
    }, {
      "firstName" : "K",
      "lastName" : "Kuwajima",
      "authorRank" : 5,
      "name" : "Kuwajima K",
      "referenceId" : "RGD:A72598"
    }, {
      "firstName" : "I",
      "lastName" : "Yuasa",
      "authorRank" : 6,
      "name" : "Yuasa I",
      "referenceId" : "RGD:A72599"
    }, {
      "firstName" : "K",
      "lastName" : "Shigemoto",
      "authorRank" : 7,
      "name" : "Shigemoto K",
      "referenceId" : "RGD:A72600"
    }, {
      "firstName" : "Y",
      "lastName" : "Kuroda",
      "authorRank" : 8,
      "name" : "Kuroda Y",
      "referenceId" : "RGD:A27926"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599134"
    } ]
  }, {
    "primaryId" : "PMID:10066037",
    "title" : "Genetic investigation of patients with hypercholesterolemia type IIa.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Szalai C, etal., Clin Genet. 1999 Jan;55(1):67-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:23:58.000-05:00",
    "volume" : "55",
    "pages" : "67-8",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Szalai",
      "authorRank" : 1,
      "name" : "Szalai C",
      "referenceId" : "RGD:A84120"
    }, {
      "firstName" : "A",
      "lastName" : "Csaszar",
      "authorRank" : 2,
      "name" : "Csaszar A",
      "referenceId" : "RGD:A59187"
    }, {
      "firstName" : "A",
      "lastName" : "Czinner",
      "authorRank" : 3,
      "name" : "Czinner A",
      "referenceId" : "RGD:A112366"
    }, {
      "firstName" : "T",
      "lastName" : "Palicz",
      "authorRank" : 4,
      "name" : "Palicz",
      "referenceId" : "RGD:A361995"
    }, {
      "firstName" : "B",
      "lastName" : "Halmos",
      "authorRank" : 5,
      "name" : "Halmos",
      "referenceId" : "RGD:A262797"
    }, {
      "firstName" : "L",
      "lastName" : "Romics",
      "authorRank" : 6,
      "name" : "Romics L",
      "referenceId" : "RGD:A59186"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11526864"
    } ]
  }, {
    "primaryId" : "PMID:10066244",
    "title" : "Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Lee JH, etal., J Neurosci 1999 Mar 15;19(6):1912-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:56.000-05:00",
    "volume" : "19",
    "pages" : "1912-21",
    "abstract" : "Low voltage-activated Ca2+ channels play important roles in pacing neuronal firing and producing network oscillations, such as those that occur during sleep and epilepsy. Here we describe the cloning and expression of the third member of the T-type family, alpha1I or CavT.3, from rat brain. Northern analysis indicated that it is predominantly expressed in brain. Expression of the cloned channel in either Xenopus oocytes or stably transfected human embryonic kidney-293 cells revealed novel gating properties. We compared these electrophysiological properties to those of the cloned T-type channels alpha1G and alpha1H and to the high voltage-activated channels formed by alpha1Ebeta3. The alpha1I channels opened after small depolarizations of the membrane similar to alpha1G and alpha1H but at more depolarized potentials. The kinetics of activation and inactivation were dramatically slower, which allows the channel to act as a Ca2+ injector. In oocytes, the kinetics were even slower, suggesting that components of the expression system modulate its gating properties. Steady-state inactivation occurred at higher potentials than any of the other T channels, endowing the channel with a substantial window current. The alpha1I channel could still be classified as T-type by virtue of its criss-crossing kinetics, its slow deactivation (tail current), and its small (11 pS) conductance in 110 mM Ba2+ solutions. Based on its brain distribution and novel gating properties, we suggest that alpha1I plays important roles in determining the electroresponsiveness of neurons, and hence, may be a novel drug target.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JH",
      "lastName" : "Lee",
      "authorRank" : 1,
      "name" : "Lee JH",
      "referenceId" : "RGD:A5688"
    }, {
      "firstName" : "AN",
      "lastName" : "Daud",
      "authorRank" : 2,
      "name" : "Daud AN",
      "referenceId" : "RGD:A6230"
    }, {
      "firstName" : "LL",
      "lastName" : "Cribbs",
      "authorRank" : 3,
      "name" : "Cribbs LL",
      "referenceId" : "RGD:A5681"
    }, {
      "firstName" : "AE",
      "lastName" : "Lacerda",
      "authorRank" : 4,
      "name" : "Lacerda AE",
      "referenceId" : "RGD:A5683"
    }, {
      "firstName" : "A",
      "lastName" : "Pereverzev",
      "authorRank" : 5,
      "name" : "Pereverzev A",
      "referenceId" : "RGD:A6231"
    }, {
      "firstName" : "U",
      "lastName" : "Klockner",
      "authorRank" : 6,
      "name" : "Klockner U",
      "referenceId" : "RGD:A6232"
    }, {
      "firstName" : "T",
      "lastName" : "Schneider",
      "authorRank" : 7,
      "name" : "Schneider T",
      "referenceId" : "RGD:A6233"
    }, {
      "firstName" : "E",
      "lastName" : "Perez-Reyes",
      "authorRank" : 8,
      "name" : "Perez-Reyes E",
      "referenceId" : "RGD:A5680"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68867"
    } ]
  }, {
    "primaryId" : "PMID:10066450",
    "title" : "Three splicing variants of tomosyn and identification of their syntaxin-binding region.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Yokoyama S, etal., Biochem Biophys Res Commun 1999 Mar 5;256(1):218-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:44:01.000-05:00",
    "volume" : "256",
    "pages" : "218-22",
    "abstract" : "We have recently isolated a neural tissue-specific syntaxin-1-binding protein, named tomosyn, which is capable of dissociating Munc18/n-Sec1/rbSec1 from syntaxin-1 to form a 10S tomosyn complex, an intermediate complex converted to the 7S SNARE complex. We isolated here two splicing variants of tomosyn: one had 36 amino acids (aa) insertion and another had 17 aa deletion. We named original one m-tomosyn, big one b-tomosyn, and small one s-tomosyn. s-Tomosyn as well as m-tomosyn was mainly expressed in brain whereas b-tomosyn was ubiquitously expressed. All the isoforms bound to syntaxin-1, but not to syntaxin-2, -3, or -4, and had a region highly homologous to VAMP, another syntaxin-binding protein. This region was necessary but not sufficient for high-affinity binding of tomosyn to syntaxin-1.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Yokoyama",
      "authorRank" : 1,
      "name" : "Yokoyama S",
      "referenceId" : "RGD:A16805"
    }, {
      "firstName" : "H",
      "lastName" : "Shirataki",
      "authorRank" : 2,
      "name" : "Shirataki H",
      "referenceId" : "RGD:A43225"
    }, {
      "firstName" : "T",
      "lastName" : "Sakisaka",
      "authorRank" : 3,
      "name" : "Sakisaka T",
      "referenceId" : "RGD:A17757"
    }, {
      "firstName" : "Y",
      "lastName" : "Takai",
      "authorRank" : 4,
      "name" : "Takai Y",
      "referenceId" : "RGD:A151861"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299497"
    } ]
  }, {
    "primaryId" : "PMID:10066767",
    "title" : "Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Hu MC, etal., J Biol Chem 1999 Mar 12;274(11):7095-102.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:05.000-06:00",
    "volume" : "274",
    "pages" : "7095-102",
    "abstract" : "The p38 mitogen-activated protein kinases (MAPK) play a crucial role in stress and inflammatory responses and are also involved in activation of the human immunodeficiency virus gene expression. We have isolated the murine cDNA clones encoding p38-delta MAPK, and we have localized the p38-delta gene to mouse chromosome 17A3-B and human chromosome 6p21.3. By using Northern and in situ hybridization, we have examined the expression of p38-delta in the mouse adult tissues and embryos. p38-delta was expressed primarily in the lung, testis, kidney, and gut epithelium in the adult tissues. Although p38-delta was expressed predominantly in the developing gut and the septum transversum in the mouse embryo at 9.5 days, its expression began to be expanded to many specific tissues in the 12.5-day embryo. At 15.5 days, p38-delta was expressed virtually in most developing epithelia in embryos, suggesting that p38-delta is a developmentally regulated MAPK. Interestingly, p38-delta and p38-alpha were similar serine/threonine kinases but differed in substrate specificity. Overall, p38-delta resembles p38-gamma, whereas p38-beta resembles p38-alpha. Moreover, p38-delta is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7, suggesting that p38-delta is a unique stress-responsive protein kinase.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MC",
      "lastName" : "Hu",
      "authorRank" : 1,
      "name" : "Hu MC",
      "referenceId" : "RGD:A7518"
    }, {
      "firstName" : "YP",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang YP",
      "referenceId" : "RGD:A7519"
    }, {
      "firstName" : "A",
      "lastName" : "Mikhail",
      "authorRank" : 3,
      "name" : "Mikhail A",
      "referenceId" : "RGD:A7520"
    }, {
      "firstName" : "WR",
      "lastName" : "Qiu",
      "authorRank" : 4,
      "name" : "Qiu WR",
      "referenceId" : "RGD:A7521"
    }, {
      "firstName" : "TH",
      "lastName" : "Tan",
      "authorRank" : 5,
      "name" : "Tan TH",
      "referenceId" : "RGD:A7522"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69880"
    } ]
  }, {
    "primaryId" : "PMID:10066787",
    "title" : "Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum- and glucocorticoid-inducible protein kinase, Sgk, in mammary tumor cells. A novel convergence point of anti-proliferative and proliferative cell signaling pathways.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Buse P, etal., J Biol Chem. 1999 Mar 12;274(11):7253-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-10-15T16:45:06.000-05:00",
    "volume" : "274",
    "pages" : "7253-63",
    "abstract" : "The serum- and glucocorticoid-inducible kinase (sgk) is a novel serine/threonine protein kinase that is transcriptionally regulated in rat mammary tumor cells by serum under proliferative conditions or by glucocorticoids that induce a G1 cell cycle arrest. Our results establish that the subcellular distribution of Sgk is under stringent cell cycle and hormonal control. Sgk is localized to the perinuclear or cytoplasmic compartment as a 50-kDa hypophosphorylated protein in cells arrested in G1 by treatment with the synthetic glucocorticoid dexamethasone. In serum-stimulated cells, Sgk was transiently hyperphosphorylated and resided in the nucleus. Laser scanning cytometry, which monitors Sgk localization and DNA content in individual mammary tumor cells of an asynchronously growing population, revealed that Sgk actively shuttles between the nucleus (in S and G2/M) and the cytoplasm (in G1) in synchrony with the cell cycle. In cells synchronously released from the G1/S boundary, Sgk localized to the nucleus during progression through S phase. The forced retention of exogenous Sgk in either the cytoplasmic compartment, using a wild type sgk gene, or the nucleus, using a nuclear localization signal-containing sgk gene (NLS-Sgk), suppressed the growth and DNA synthesis of serum-stimulated cells. Thus, our study implicates the nuclear-cytoplasmic shuttling of sgk as a requirement for cell cycle progression and represents a novel convergence point of anti-proliferative and proliferative signaling in mammary tumor cells.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Buse",
      "authorRank" : 1,
      "name" : "Buse P",
      "referenceId" : "RGD:A88987"
    }, {
      "firstName" : "SH",
      "lastName" : "Tran",
      "authorRank" : 2,
      "name" : "Tran SH",
      "referenceId" : "RGD:A89019"
    }, {
      "firstName" : "E",
      "lastName" : "Luther",
      "authorRank" : 3,
      "name" : "Luther E",
      "referenceId" : "RGD:A89020"
    }, {
      "firstName" : "PT",
      "lastName" : "Phu",
      "authorRank" : 4,
      "name" : "Phu PT",
      "referenceId" : "RGD:A89021"
    }, {
      "firstName" : "GW",
      "lastName" : "Aponte",
      "authorRank" : 5,
      "name" : "Aponte GW",
      "referenceId" : "RGD:A89022"
    }, {
      "firstName" : "GL",
      "lastName" : "Firestone",
      "authorRank" : 6,
      "name" : "Firestone GL",
      "referenceId" : "RGD:A7974"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642789"
    } ]
  }, {
    "primaryId" : "PMID:10066862",
    "title" : "Thrombolysis with tissue plasminogen activator alters adhesion molecule expression in the ischemic rat brain.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Zhang RL, etal., Stroke. 1999 Mar;30(3):624-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-04T09:47:12.000-05:00",
    "volume" : "30",
    "pages" : "624-9",
    "abstract" : "BACKGROUND AND PURPOSE: We tested the hypothesis that treatment of embolic stroke with recombinant human tissue plasminogen activator (rhtPA) alters cerebral expression of adhesion molecules. METHODS: Male Wistar rats were subjected to middle cerebral artery occlusion by a single fibrin-rich clot. P-selectin, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) immunoreactivity was measured at 6 or 24 hours after embolic stroke in control rats and in rats treated with rhtPA at 1 or 4 hours after stroke. To examine the therapeutic efficacy of combined rhtPA and anti-ICAM-1 antibody treatment at 4 hours after embolization, ischemic lesion volumes were measured in rats treated with rhtPA alone, rats treated with rhtPA and anti-ICAM-1 antibody, and nontreated rats. RESULTS: Administration of rhtPA at 1 hour after embolization resulted in a significant reduction of adhesion molecule vascular immunoreactivity after embolization in the ipsilateral hemisphere compared with corresponding control rats. However, when rhtPA was administered to rats at 4 hours after embolization, significant increases of adhesion molecule immunoreactivity in the ipsilateral hemisphere were detected. A significant increase of ICAM-1 immunoreactivity was also detected in the contralateral hemisphere at 24 hours after ischemia. A significant reduction in lesion volume was found in rats treated with the combination of rhtPA and anti-ICAM-1 antibody compared with rats treated only with rhtPA. CONCLUSIONS: The present study suggests that the time of initiation of thrombolytic therapy alters vascular immunoreactivity of inflammatory adhesion molecules in the ischemic brain and that therapeutic benefit can be obtained by combining rhtPA and anti-ICAM-1 antibody treatment 4 hours after stroke.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RL",
      "lastName" : "Zhang",
      "authorRank" : 1,
      "name" : "Zhang RL",
      "referenceId" : "RGD:A85366"
    }, {
      "firstName" : "ZG",
      "lastName" : "Zhang",
      "authorRank" : 2,
      "name" : "Zhang ZG",
      "referenceId" : "RGD:A23737"
    }, {
      "firstName" : "M",
      "lastName" : "Chopp",
      "authorRank" : 3,
      "name" : "Chopp M",
      "referenceId" : "RGD:A23744"
    }, {
      "firstName" : "JA",
      "lastName" : "Zivin",
      "authorRank" : 4,
      "name" : "Zivin",
      "referenceId" : "RGD:A204382"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11522710"
    } ]
  }, {
    "primaryId" : "PMID:10067205",
    "title" : "A genetic linkage map of rat chromosome 9 with a new locus for variant activity of liver aldehyde oxidase.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kunieda T, etal., Exp Anim 1999 Jan;48(1):43-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:50.000-05:00",
    "volume" : "48",
    "pages" : "43-5",
    "abstract" : "A genetic linkage map of rat chromosome 9 consisting of five loci including a new biochemical marker representing a genetic variation of the activity of the liver aldehyde oxidase, (Aox) was constructed. Linkage analysis of the five loci among 92 backcross progeny of (WKS/Iar x IS/Iar)F1 x WKS/Iar revealed significant linkages between these loci. Minimizing crossover frequency resulted in the best gene order: Aox-D9Mit4-Gls-Cryg-Tp53l1. The homologues of the Cryg, Gls, and Aox genes have been mapped on mouse chromosome 1 and human chromosome 2q. The present findings provide further evidence for the conservation of synteny among these regions of rat, mouse, and human chromosomes.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kunieda",
      "authorRank" : 1,
      "name" : "Kunieda T",
      "referenceId" : "RGD:A15113"
    }, {
      "firstName" : "E",
      "lastName" : "Kobayashi",
      "authorRank" : 2,
      "name" : "Kobayashi E",
      "referenceId" : "RGD:A5223"
    }, {
      "firstName" : "M",
      "lastName" : "Tachibana",
      "authorRank" : 3,
      "name" : "Tachibana M",
      "referenceId" : "RGD:A31263"
    }, {
      "firstName" : "H",
      "lastName" : "Ikadai",
      "authorRank" : 4,
      "name" : "Ikadai H",
      "referenceId" : "RGD:A15116"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300498"
    } ]
  }, {
    "primaryId" : "PMID:10067796",
    "title" : "Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Mujumdar VS and Tyagi SC, J Hypertens. 1999 Feb;17(2):261-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-03-13T15:02:11.000-05:00",
    "volume" : "17",
    "pages" : "261-70",
    "abstract" : "OBJECTIVE: Extracellular matrix, particularly type I fibrillar collagen, provides tensile strength that allows cardiac muscle to perform systolic and diastolic functions. Collagen is induced during the transition from compensatory hypertrophy to heart failure. We hypothesized that cardiac stiffness during decompensatory hypertrophy is partly due to a decreased elastin:collagen ratio. MATERIALS AND METHODS: We prepared left ventricular tissue homogenates from spontaneously hypertensive rats (SHR) aged 30-36 weeks, which had compensatory hypertrophy with no heart failure, and from SHR aged 70-92 weeks, which had decompensatory hypertrophy with heart failure. Age- and sex-matched Wistar-Kyoto (WKY) rats were used as normotensive controls. In both SHR groups, increased levels of collagen were detected by immuno-blot analysis using type I collagen antibody. Elastin and collagen were quantitated by measuring desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively. To determine whether the decrease in elastin content was due to increased elastinolytic activity of matrix metalloproteinase-2, we performed gelatin and elastin zymography on left ventricular tissue homogenates from control rats, SHR with compensatory hypertrophy and SHR with heart failure. RESULTS: The elastin:collagen ratio was 0.242 +/- 0.008 in hearts from WKY rats. In SHR without heart failure, the ratio was decreased to 0.073 +/- 0.003 and in decompensatory hypertrophy with heart failure, the ratio decreased to 0.012 +/- 0.005. Matrix metalloproteinase-2 activity was increased significantly in SHR with heart failure compared with controls (P < 0.001). The level of tissue inhibitor of metalloproteinase-4 was increased in compensatory hypertrophy and markedly reduced in heart failure. Decorin was strongly reduced in decompensatory heart failure compared with control hearts. CONCLUSIONS: Since collagen was induced in SHR with heart failure, decorin and elastin were decreased and the ratios of gelatinase A and elastase to tissue inhibitor of metalloproteinase-4 were increased, we conclude that heart failure is associated with adverse extracellular matrix remodeling.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "VS",
      "lastName" : "Mujumdar",
      "authorRank" : 1,
      "name" : "Mujumdar VS",
      "referenceId" : "RGD:A93112"
    }, {
      "firstName" : "SC",
      "lastName" : "Tyagi",
      "authorRank" : 2,
      "name" : "Tyagi SC",
      "referenceId" : "RGD:A46057"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2290471"
    } ]
  }, {
    "primaryId" : "PMID:10067818",
    "title" : "Glutathione S-transferase GSTM3 and GSTP1 genotypes and larynx cancer risk.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Jourenkova-Mironova N, etal., Cancer Epidemiol Biomarkers Prev. 1999 Feb;8(2):185-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-07-11T16:47:31.000-05:00",
    "volume" : "8",
    "pages" : "185-8",
    "abstract" : "Glutathione S-transferases (GSTs) are involved in detoxification of reactive metabolites of carcinogens and, therefore, could be potentially important in susceptibility to cancer. The associations between larynx cancer risk and GSTM3 and GSTP1 gene polymorphisms, either separately or in combination with GSTM1 and GSTT1 gene polymorphisms, were evaluated using peripheral blood DNA from 129 cancer patients and 172 controls, all regular smokers. The frequencies of GSTM3 AA, AB, and BB genotypes were 60.5%, 36.4%, and 3.1% in cases and 72.7%, 24.4%, and 2.9% in controls, respectively. The frequencies of GSTP1 AA, AG, and GG genotypes were 48.1%, 40.3%, and 11.6% in cases and 50.0%, 37.2%, and 12.8% in controls, respectively. Multivariate logistic regression analyses did not reveal any association between the GSTP1 (AG or GG) genotype and larynx cancer [odds ratio, 1.1; 95% confidence interval (CI), 0.7-2.0]. In contrast, a significant increase in risk was related to the GSTM3 (AB or BB) genotype (odds ratio, 2.0; 95% CI, 1.1-3.4). The combined GSTM3 (AB or BB) and GSTM1-null genotype conferred a 4-fold risk (95% CI, 1.6-10.1) of larynx cancer as compared with the combined GSTM3 AA and GSTM1-positive genotype. However, the effect of GSTM3 (AB or BB) genotype was similar among individuals with GSTM1-positive or GSTM1-null genotypes.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Jourenkova-Mironova",
      "authorRank" : 1,
      "name" : "Jourenkova-Mironova N",
      "referenceId" : "RGD:A141433"
    }, {
      "firstName" : "A",
      "lastName" : "Voho",
      "authorRank" : 2,
      "name" : "Voho A",
      "referenceId" : "RGD:A141434"
    }, {
      "firstName" : "C",
      "lastName" : "Bouchardy",
      "authorRank" : 3,
      "name" : "Bouchardy C",
      "referenceId" : "RGD:A141435"
    }, {
      "firstName" : "H",
      "lastName" : "Wikman",
      "authorRank" : 4,
      "name" : "Wikman H",
      "referenceId" : "RGD:A140211"
    }, {
      "firstName" : "P",
      "lastName" : "Dayer",
      "authorRank" : 5,
      "name" : "Dayer P",
      "referenceId" : "RGD:A141436"
    }, {
      "firstName" : "S",
      "lastName" : "Benhamou",
      "authorRank" : 6,
      "name" : "Benhamou S",
      "referenceId" : "RGD:A141437"
    }, {
      "firstName" : "A",
      "lastName" : "Hirvonen",
      "authorRank" : 7,
      "name" : "Hirvonen A",
      "referenceId" : "RGD:A59870"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5135043"
    } ]
  }, {
    "primaryId" : "PMID:10067849",
    "title" : "Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Hayashi M, etal., Endocrinology 1999 Mar;140(3):1236-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:11:48.000-05:00",
    "volume" : "140",
    "pages" : "1236-44",
    "abstract" : "Transgenic mice with deletion of the GDF-9 (growth differentiation factor-9) gene are characterized by the arrest of ovarian follicle development at the primary stage. Based on the hypothesis that GDF-9 is important for early follicle development, we isolated rat GDF-9 complementary DNA (cDNA) and generated recombinant GDF-9 protein to study its physiological role. Using bacteria-derived GDF-9-glutathione S-transferase (GST) fusion protein, specific antibodies to the mature form of GDF-9 was generated. Immunohistochemical staining of ovarian sections indicated the localization of GDF-9 protein in the oocyte of primary, secondary and preantral follicles, whereas immunoblotting demonstrated the secretion of GDF-9 by mammalian cells transfected with GDF-9 cDNAs. Recombinant GDF-9 was shown to be an N-glycosylated protein capable of stimulating early follicle development. Growth of preantral follicles isolated from immature rats was enhanced by treatment with either GDF-9 or FSH whereas the combined treatment showed an additive effect. In addition, treatment with GDF-9, like forskolin, also stimulated inhibin-alpha content in explants of neonatal ovaries. In contrast, the stimulatory effects of GDF-9 were not mimicked by amino-terminal tagged GDF-9 that was apparently not bioactive. Thus, the present study demonstrates the important role of GDF-9 in early follicle growth and differentiation. The availability of recombinant bioactive GDF-9 allows future studies on the physiological role of GDF-9 in ovarian development in vivo.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Hayashi",
      "authorRank" : 1,
      "name" : "Hayashi M",
      "referenceId" : "RGD:A160469"
    }, {
      "firstName" : "EA",
      "lastName" : "McGee",
      "authorRank" : 2,
      "name" : "McGee EA",
      "referenceId" : "RGD:A9582"
    }, {
      "firstName" : "G",
      "lastName" : "Min",
      "authorRank" : 3,
      "name" : "Min G",
      "referenceId" : "RGD:A9583"
    }, {
      "firstName" : "C",
      "lastName" : "Klein",
      "authorRank" : 4,
      "name" : "Klein C",
      "referenceId" : "RGD:A9584"
    }, {
      "firstName" : "UM",
      "lastName" : "Rose",
      "authorRank" : 5,
      "name" : "Rose UM",
      "referenceId" : "RGD:A9585"
    }, {
      "firstName" : "M",
      "lastName" : "Van Duin",
      "authorRank" : 6,
      "name" : "Van Duin M",
      "referenceId" : "RGD:A9586"
    }, {
      "firstName" : "AJ",
      "lastName" : "Hsueh",
      "authorRank" : 7,
      "name" : "Hsueh AJ",
      "referenceId" : "RGD:A132316"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70645"
    } ]
  }, {
    "primaryId" : "PMID:10067850",
    "title" : "Gender differences in the responsiveness of the sex-dependent isoforms of hepatic P450 to the feminine plasma growth hormone profile.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Pampori NA and Shapiro BH, Endocrinology. 1999 Mar;140(3):1245-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-27T10:15:44.000-06:00",
    "volume" : "140",
    "pages" : "1245-54",
    "abstract" : "Most of the constitutive hepatic P450 isoforms expressed in the rat exhibit dramatic gender differences. Whereas only male hepatocytes contain CYP2A2, 2C11, and 3A2, only female hepatocytes express CYP2C12 and 3- to 4-fold greater levels of CYP2C7. This sexually dimorphic expression of hepatic P450 isoforms is regulated by the gender-dependent secretory GH profiles, i.e. episodic in males and continuous in females. In the case of the feminine GH profile, the continuous presence of the hormone in the circulation completely suppresses male-specific CYP2A2, 2C11, and 3A2, while stimulating full expression of female-dependent CYP2A1, 2C7, 2C12, and non-P450 testosterone 5alpha-reductase (type 1). The gender-dependent expression of the P450s can be reversed by exposing male rats to the continuous feminine plasma GH profile and females to the episodic masculine GH profile. Under these conditions, females will now express the male-specific isoforms and suppress the female-dependent forms, whereas the opposite will occur in the males. Nevertheless, it is not clear whether the levels of expression or suppression are comparable in male and female rats exposed to the same sex-dependent GH profiles. In the present study, we have renaturalized the circulating feminine GH profile in euthyroid-maintained, hypophysectomized female and male rats at six concentrations ranging from 3-100% of normal. Continuous monitoring of GH levels revealed indistinguishable plasma profiles in females and males at each dosage administered. In the case of females, restoration of the feminine-like plasma GH profile at a concentration that was 3% of the normal level restored expression levels (i.e. mRNA, protein, and/or catalytic activity) of female-dependent CYP2C12, 2A1, and 5alpha-reductase to 50% or greater of normal and fully suppressed expression of male-specific CYP2A2, 2C11, and 3A2. Twice the dosage of the hormone (6% of normal) was required to restore female-predominant CYP2C7 to 50% of normal in hypophysectomized female rats. In contrast, we found that all of the measured isoforms were significantly less responsive to the inductive and suppressive effects of the feminine-like GH profile when administered to male rats. While suppression of the male-specific isoforms (i.e. CYP2A2, 2C11, and 3A2) in male rats required concentrations of GH in the feminine profile 2-3 times greater than were effective in female rats, no dosage of the hormone was as effective in inducing female-dependent P450s (i.e. CYP2A1, 2C7, and 2C12) in males as in females. Clearly, the continuous feminine GH profile was more effective at inducing and suppressing gender-dependent isoforms of hepatic P450 when restored to female rats, where it is normally secreted, than in males. As GH profiles appear to be the sole factor responsible for regulating the sexually dimorphic expression of hepatic P450 isoforms in adult rats, the differential responsiveness of male and female rats to the feminine GH profile are likely to be inherently induced by irreversible imprinting during a critical developmental period.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NA",
      "lastName" : "Pampori",
      "authorRank" : 1,
      "name" : "Pampori NA",
      "referenceId" : "RGD:A134174"
    }, {
      "firstName" : "BH",
      "lastName" : "Shapiro",
      "authorRank" : 2,
      "name" : "Shapiro BH",
      "referenceId" : "RGD:A34110"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892008"
    } ]
  }, {
    "primaryId" : "PMID:10068207",
    "title" : "Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ono K, etal., Lab Invest. 1999 Feb;79(2):195-203.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-03-27T16:08:30.000-05:00",
    "volume" : "79",
    "pages" : "195-203",
    "abstract" : "MCAF (monocyte chemotactic and activating factor)/MCP-1 (monocyte chemoattractant protein-1) is an important mediator of monocyte recruitment to inflammatory sites. However, its pathophysiologic role in myocardial reperfusion injury remains unknown. Male Wistar rats were anesthetized, and the left anterior descending coronary artery was ligated for an hour, after which the ligature was  released. Northern blotting analysis revealed that MCAF/MCP-1 mRNA expression increased 16-fold in the reperfused region at 12 hours after reperfusion. MCAF/MCP-1 concentration in plasma and the heart was already elevated after hour  of ischemia in this model. Goat polyclonal antibodies were prepared by repeated immunization of animals with purified, recombinant rat MCAF/MCP-1, and the neutralizing activities of this antibody were confirmed by monocyte chemotaxis assay and administration to rats with crescentic glomerulonephritis. Intravenous  injection of anti-MCAF/MCP-1 antibody significantly reduced the infarct size at 24 hours after reperfusion compared with the injection of control IgG (33.9 +/- 5.1% vs 49.4 +/- 2.7% of ischemic area, mean +/- SEM). Administration of this antibody markedly decreased the intercellular adhesion molecule-1 mRNA expression and infiltration of macrophages, which suggested the pathophysiologic role of MCAF/MCP-1. Neutralization of MCAF/MCP-1 is beneficial by preventing reperfusion  injury in a rat model of myocardial ischemia and reperfusion.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Ono",
      "authorRank" : 1,
      "name" : "Ono",
      "referenceId" : "RGD:A356435"
    }, {
      "firstName" : "A",
      "lastName" : "Matsumori",
      "authorRank" : 2,
      "name" : "Matsumori A",
      "referenceId" : "RGD:A7324"
    }, {
      "firstName" : "Y",
      "lastName" : "Furukawa",
      "authorRank" : 3,
      "name" : "Furukawa Y",
      "referenceId" : "RGD:A7320"
    }, {
      "firstName" : "H",
      "lastName" : "Igata",
      "authorRank" : 4,
      "name" : "Igata",
      "referenceId" : "RGD:A181718"
    }, {
      "firstName" : "T",
      "lastName" : "Shioi",
      "authorRank" : 5,
      "name" : "Shioi T",
      "referenceId" : "RGD:A47081"
    }, {
      "firstName" : "K",
      "lastName" : "Matsushima",
      "authorRank" : 6,
      "name" : "Matsushima K",
      "referenceId" : "RGD:A15730"
    }, {
      "firstName" : "S",
      "lastName" : "Sasayama",
      "authorRank" : 7,
      "name" : "Sasayama S",
      "referenceId" : "RGD:A7325"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8549542"
    } ]
  }, {
    "primaryId" : "PMID:10068513",
    "title" : "Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS).",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Anikster Y, etal., Mol Genet Metab. 1999 Feb;66(2):111-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-06-27T16:09:20.000-05:00",
    "volume" : "66",
    "pages" : "111-6",
    "abstract" : "The most common mutation in the cystinosis gene, CTNS, is a 65-kb deletion thought to have originated in Germany. Although homozygotes for this deletion are detectable by the absence of the D17S829 polymorphic marker, no method exists to identify heterozygotes. We identified the 65-kb deletion breakpoints and used flanking PCR primers to amplify a 423-bp fragment present only in the deletion alleles. Using this method, we determined that 121 of 216 (56%) cystinosis alleles examined bore the 65-kb deletion. We found no non-Europeans with the deletion, and the deletion size and breakpoints appeared identical in all patients studied, supporting the concept of a founder effect. The addition of D17S829 primers (266 bp apart) to the PCR created a multiplex PCR system useful for diagnosing cystinosis patients homozygous and heterozygous for the 65-kb deletion.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Anikster",
      "authorRank" : 1,
      "name" : "Anikster Y",
      "referenceId" : "RGD:A74242"
    }, {
      "firstName" : "C",
      "lastName" : "Lucero",
      "authorRank" : 2,
      "name" : "Lucero C",
      "referenceId" : "RGD:A446160"
    }, {
      "firstName" : "J W",
      "lastName" : "Touchman",
      "authorRank" : 3,
      "name" : "Touchman JW",
      "referenceId" : "RGD:A446161"
    }, {
      "firstName" : "M",
      "lastName" : "Huizing",
      "authorRank" : 4,
      "name" : "Huizing M",
      "referenceId" : "RGD:A58852"
    }, {
      "firstName" : "G",
      "lastName" : "McDowell",
      "authorRank" : 5,
      "name" : "McDowell G",
      "referenceId" : "RGD:A446162"
    }, {
      "firstName" : "V",
      "lastName" : "Shotelersuk",
      "authorRank" : 6,
      "name" : "Shotelersuk V",
      "referenceId" : "RGD:A52454"
    }, {
      "firstName" : "E D",
      "lastName" : "Green",
      "authorRank" : 7,
      "name" : "Green ED",
      "referenceId" : "RGD:A446163"
    }, {
      "firstName" : "W A",
      "lastName" : "Gahl",
      "authorRank" : 8,
      "name" : "Gahl WA",
      "referenceId" : "RGD:A446164"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12910865"
    } ]
  }, {
    "primaryId" : "PMID:10068680",
    "title" : "Cyclin A1 expression in leukemia and normal hematopoietic cells.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Yang R, etal., Blood. 1999 Mar 15;93(6):2067-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-04T15:08:31.000-06:00",
    "volume" : "93",
    "pages" : "2067-74",
    "abstract" : "Human cyclin A1 is a newly cloned, tissue-specific cyclin that is prominently expressed in normal testis. In this study, we showed that cyclin A1 was highly expressed in a subset of leukemia samples from patients. The highest frequency of cyclin A1 overexpression was observed in acute myelocytic leukemias, especially those that were at the promyelocyte (M3) and myeloblast (M2) stages of development. Cyclin A1 expression was also detected in normal CD34(+) progenitor cells. The expression of cyclin A1 increased when these cells were stimulated to undergo myeloid differentiation in vitro. Taken together, our observations suggest that cyclin A1 may have a role in hematopoiesis. High levels of cyclin A1 expression are especially associated with certain leukemias blocked at the myeloblast and promyelocyte stages of differentiation.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang R",
      "referenceId" : "RGD:A6161"
    }, {
      "firstName" : "T",
      "lastName" : "Nakamaki",
      "authorRank" : 2,
      "name" : "Nakamaki T",
      "referenceId" : "RGD:A118904"
    }, {
      "firstName" : "M",
      "lastName" : "Lubbert",
      "authorRank" : 3,
      "name" : "Lubbert M",
      "referenceId" : "RGD:A118905"
    }, {
      "firstName" : "J",
      "lastName" : "Said",
      "authorRank" : 4,
      "name" : "Said J",
      "referenceId" : "RGD:A118906"
    }, {
      "firstName" : "A",
      "lastName" : "Sakashita",
      "authorRank" : 5,
      "name" : "Sakashita A",
      "referenceId" : "RGD:A118907"
    }, {
      "firstName" : "BS",
      "lastName" : "Freyaldenhoven",
      "authorRank" : 6,
      "name" : "Freyaldenhoven BS",
      "referenceId" : "RGD:A118908"
    }, {
      "firstName" : "S",
      "lastName" : "Spira",
      "authorRank" : 7,
      "name" : "Spira S",
      "referenceId" : "RGD:A118909"
    }, {
      "firstName" : "V",
      "lastName" : "Huynh",
      "authorRank" : 8,
      "name" : "Huynh V",
      "referenceId" : "RGD:A118910"
    }, {
      "firstName" : "C",
      "lastName" : "Muller",
      "authorRank" : 9,
      "name" : "Muller C",
      "referenceId" : "RGD:A49822"
    }, {
      "firstName" : "HP",
      "lastName" : "Koeffler",
      "authorRank" : 10,
      "name" : "Koeffler HP",
      "referenceId" : "RGD:A37080"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316304"
    } ]
  }, {
    "primaryId" : "PMID:10068684",
    "title" : "Missense mutations in the gp91-phox gene encoding cytochrome b558 in patients with cytochrome b positive and negative X-linked chronic granulomatous disease.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kaneda M, etal., Blood. 1999 Mar 15;93(6):2098-104.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-11T11:34:46.000-06:00",
    "volume" : "93",
    "pages" : "2098-104",
    "abstract" : "Chronic granulomatous disease (CGD) is a disorder of host defense due to genetic  defects of the superoxide (O2-) generating NADPH oxidase in phagocytes. A membrane-bound cytochrome b558, a heterodimer consisting of gp91-phox and p22-phox, is a critical component of the oxidase. The X-linked form of the disease is due to defects in the gp91-phox gene. We report here biochemical and genetic analyses of patients with typical and atypical X-linked CGD. Immunoblots  showed that neutrophils from one patient had small amounts of p22-phox and gp91-phox and a low level of O2- forming oxidase activity, in contrast to the complete absence of both subunits in two patients with typical CGD. Using polymerase chain reactions (PCR) on cDNA and genomic DNA, we found novel missense mutations of gp91-phox in the two typical patients and a point mutation in the variant CGD, a characteristic common to two other patients with similar variant CGD reported previously. Spectrophotometric analysis of the neutrophils from the  variant patient provided evidence for the presence of heme of cytochrome b558. Recently, we reported another variant CGD with similar amounts of both subunits,  but without oxidase activity or the heme spectrum. A predicted mutation at amino  acid 101 in gp91-phox was also confirmed in this variant CGD by PCR of the genomic DNA. These results on four patients, including those with two variant CGD, are discussed with respect to the missense mutated sites and the heme binding ligands in gp91-phox.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kaneda",
      "authorRank" : 1,
      "name" : "Kaneda M",
      "referenceId" : "RGD:A69969"
    }, {
      "firstName" : "H",
      "lastName" : "Sakuraba",
      "authorRank" : 2,
      "name" : "Sakuraba H",
      "referenceId" : "RGD:A72738"
    }, {
      "firstName" : "A",
      "lastName" : "Ohtake",
      "authorRank" : 3,
      "name" : "Ohtake A",
      "referenceId" : "RGD:A33508"
    }, {
      "firstName" : "A",
      "lastName" : "Nishida",
      "authorRank" : 4,
      "name" : "Nishida A",
      "referenceId" : "RGD:A104218"
    }, {
      "firstName" : "C",
      "lastName" : "Kiryu",
      "authorRank" : 5,
      "name" : "Kiryu",
      "referenceId" : "RGD:A213616"
    }, {
      "firstName" : "K",
      "lastName" : "Kakinuma",
      "authorRank" : 6,
      "name" : "Kakinuma",
      "referenceId" : "RGD:A213617"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11040560"
    } ]
  }, {
    "primaryId" : "PMID:10069391",
    "title" : "Overexpression of nucleoside diphosphate kinases induces neurite outgrowth and their substitution to inactive forms leads to suppression of nerve growth factor- and dibutyryl cyclic AMP-induced effects in PC12D cells.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Ishijima Y, etal., FEBS Lett. 1999 Feb 19;445(1):155-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-06-07T16:30:59.000-05:00",
    "volume" : "445",
    "pages" : "155-9",
    "abstract" : "Whether nucleoside diphosphate kinase (NDPK) is involved in neuronal differentiation was investigated with special reference to its enzyme activity. Neurite outgrowth of PC12D cells induced by nerve growth factor or a cyclic AMP analog was suppressed to some extent when inactive NDPKs (the active site histidine 118 was replaced with alanine), not active forms, were transiently overexpressed. This suppression was more definite in their stably expressed clones. NDPKbeta-transfected clones and, to a lesser extent, NDPKalpha-transfected clones, but not inactive NDPK-transfected clones, extended neurites without differentiation inducers. These results imply that NDPKs may play a role by exerting their enzyme activity during differentiation of PC12 cells.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Ishijima",
      "authorRank" : 1,
      "name" : "Ishijima Y",
      "referenceId" : "RGD:A140702"
    }, {
      "firstName" : "N",
      "lastName" : "Shimada",
      "authorRank" : 2,
      "name" : "Shimada N",
      "referenceId" : "RGD:A31311"
    }, {
      "firstName" : "M",
      "lastName" : "Fukuda",
      "authorRank" : 3,
      "name" : "Fukuda M",
      "referenceId" : "RGD:A11173"
    }, {
      "firstName" : "H",
      "lastName" : "Miyazaki",
      "authorRank" : 4,
      "name" : "Miyazaki H",
      "referenceId" : "RGD:A9395"
    }, {
      "firstName" : "NY",
      "lastName" : "Orlov",
      "authorRank" : 5,
      "name" : "Orlov NY",
      "referenceId" : "RGD:A140703"
    }, {
      "firstName" : "TG",
      "lastName" : "Orlova",
      "authorRank" : 6,
      "name" : "Orlova TG",
      "referenceId" : "RGD:A140704"
    }, {
      "firstName" : "T",
      "lastName" : "Yamada",
      "authorRank" : 7,
      "name" : "Yamada T",
      "referenceId" : "RGD:A159941"
    }, {
      "firstName" : "N",
      "lastName" : "Kimura",
      "authorRank" : 8,
      "name" : "Kimura N",
      "referenceId" : "RGD:A161499"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5132899"
    } ]
  }, {
    "primaryId" : "PMID:10069420",
    "title" : "Mechanisms of acute inflammatory lung injury induced by abdominal sepsis.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Neumann B, etal., Int Immunol. 1999 Feb;11(2):217-27.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-07-15T15:36:10.000-05:00",
    "volume" : "11",
    "pages" : "217-27",
    "abstract" : "Sequestration of neutrophils and release of histotoxic mediators are considered important for the development of pathologic alterations of the lung defined as adult respiratory distress syndrome. Mechanisms of inflammatory lung injury caused by abdominal sepsis were investigated using the colon ascendens stent peritonitis (CASP) model that closely mimics the human disease. In the CASP model, a continuous leakage of intraluminal bacteria into the peritoneal cavity is induced by implantation of a stent in the ascending colon, generating a septic focus. In contrast to the cecal ligation and puncture model of peritonitis, survival of mice following CASP surgery is dependent on IFN-gamma, but independent of tumor necrosis factor (TNF). Here we show that the systemic inflammation induced by CASP surgery results in a rapid and profound increase of lung vascular permeability that was associated with the activation and recruitment of neutrophils to the lung. Activation of circulating granulocytes was characterized by increased production of serine proteinases and reactive oxygen metabolites, as well as elevated expression of cell surface Mac-1. Expression of MIP-2, KC, MIP-1alpha and E-selectin mRNA in lung was strongly increased within 3 h following CASP surgery, whereas up-regulation of IP-10, MCP-1 and P-selectin was delayed. In contrast, induction of RANTES, LIX, ICAM-1 and VCAM-1 mRNA was weak or not detectable after CASP surgery. Importantly, recruitment of leukocytes to the lung was normal in lipopolysaccharide-resistant mice, and was not affected by antibody neutralization of TNF or the chemokines MIP-2 and KC.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Neumann",
      "authorRank" : 1,
      "name" : "Neumann B",
      "referenceId" : "RGD:A55909"
    }, {
      "firstName" : "N",
      "lastName" : "Zantl",
      "authorRank" : 2,
      "name" : "Zantl N",
      "referenceId" : "RGD:A97039"
    }, {
      "firstName" : "A",
      "lastName" : "Veihelmann",
      "authorRank" : 3,
      "name" : "Veihelmann A",
      "referenceId" : "RGD:A141569"
    }, {
      "firstName" : "K",
      "lastName" : "Emmanuilidis",
      "authorRank" : 4,
      "name" : "Emmanuilidis K",
      "referenceId" : "RGD:A141570"
    }, {
      "firstName" : "K",
      "lastName" : "Pfeffer",
      "authorRank" : 5,
      "name" : "Pfeffer K",
      "referenceId" : "RGD:A39053"
    }, {
      "firstName" : "CD",
      "lastName" : "Heidecke",
      "authorRank" : 6,
      "name" : "Heidecke CD",
      "referenceId" : "RGD:A141571"
    }, {
      "firstName" : "B",
      "lastName" : "Holzmann",
      "authorRank" : 7,
      "name" : "Holzmann B",
      "referenceId" : "RGD:A141572"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5135253"
    } ]
  }, {
    "primaryId" : "PMID:10069533",
    "title" : "Ischemia induces metallothionein III expression in neurons of rat brain.",
    "datePublished" : "1000-01-01T00:00:00.000-06:00",
    "citation" : "Yanagitani S, etal., Life Sci. 1999;64(8):707-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-27T15:01:53.000-06:00",
    "volume" : "64",
    "pages" : "707-15",
    "abstract" : "Metallothionein III (MT-III) is a brain-specific member of the metallothionein family and binds zinc in vivo. In order to confirm the precise localization of MT-III in normal rat brain and the change of MT-III expression after transient whole brain ischemia, we raised a high affinity phagemid-antibody specific for rat MT-III. Immunohistochemical analysis revealed that MT-III in normal brain is  localized abundantly in neuronal cell bodies in CA1-3 regions of hippocampus, dentate gyrus, cerebral cortex, olfactory bulb and Purkinje cells in cerebellum.  This expression pattern of MT-III was similar to that of MT-III mRNA observed by  in situ hybridization studies. ELISA and Northern blot analysis revealed that MT-III protein as well as mRNA levels were up-regulated in cerebrum soon after ischemic stress. Immunohistochemical analysis also demonstrated intense staining  in neurons in injured brain after ischemia, which distributed in the same regions as in normal brain. These results suggest that MT-III plays an important role in  protecting neurons from ischemic insult by reducing neurotoxic zinc levels and inhibits uncontrolled growth of neurites after ischemia.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Yanagitani",
      "authorRank" : 1,
      "name" : "Yanagitani",
      "referenceId" : "RGD:A198611"
    }, {
      "firstName" : "H",
      "lastName" : "Miyazaki",
      "authorRank" : 2,
      "name" : "Miyazaki H",
      "referenceId" : "RGD:A9395"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakahashi",
      "authorRank" : 3,
      "name" : "Nakahashi Y",
      "referenceId" : "RGD:A103465"
    }, {
      "firstName" : "K",
      "lastName" : "Kuno",
      "authorRank" : 4,
      "name" : "Kuno K",
      "referenceId" : "RGD:A15727"
    }, {
      "firstName" : "Y",
      "lastName" : "Ueno",
      "authorRank" : 5,
      "name" : "Ueno Y",
      "referenceId" : "RGD:A21547"
    }, {
      "firstName" : "M",
      "lastName" : "Matsushita",
      "authorRank" : 6,
      "name" : "Matsushita M",
      "referenceId" : "RGD:A5979"
    }, {
      "firstName" : "Y",
      "lastName" : "Naitoh",
      "authorRank" : 7,
      "name" : "Naitoh",
      "referenceId" : "RGD:A198612"
    }, {
      "firstName" : "S",
      "lastName" : "Taketani",
      "authorRank" : 8,
      "name" : "Taketani",
      "referenceId" : "RGD:A397028"
    }, {
      "firstName" : "K",
      "lastName" : "Inoue",
      "authorRank" : 9,
      "name" : "Inoue",
      "referenceId" : "RGD:A415387"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685804"
    } ]
  }, {
    "primaryId" : "PMID:10069662",
    "title" : "Serum IGF-binding protein-6 and prostate specific antigen in breast cancer.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Kaulsay KK, etal., Eur J Endocrinol. 1999 Feb;140(2):164-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-10-29T16:22:39.000-05:00",
    "volume" : "140",
    "pages" : "164-8",
    "abstract" : "OBJECTIVE: Recent studies have demonstrated the presence of the IGF-binding proteins (IGFBPs) and prostate specific antigen (PSA), an IGFBP protease. in human breast tissue. We sought to investigate the differences in serum IGFs, IGFBP-1, -3 and -6, and PSA between patients with surgically proven breast cancer and patients with benign breast disease. DESIGN AND METHODS: Concentrations of IGFs, IGFBP-1, -3 and -6, and PSA were determined in the sera from 57 patients with breast cancer (CA), and 46 women with benign breast disease (BBD) using immunoassays for IGFs and IGFBPs and an ultrasensitive ELISA for PSA. RESULTS: The mean (+/- S.E.M.) serum IGFBP-6 level in the CA group, 127 (16) ng/ml, was statistically significantly lower than in the BBD group, 157 (10) ng/ml (P = 0.016). Patients with CA had an elevated geometric mean serum PSA level of 0.018 (range: 0.0015-0.107) ng/ml, compared with 0.007 (range: 0.0015-0.019) ng/ml in women with BBD (P = 0.025). Mean serum IGFBP-1 concentrations were significantly lower in the CA group, 16 (2) ng/ml, versus 37 (4) ng/ml in the BBD group (P = 0.001). Mean serum IGFBP-3 concentrations were also lower in the CA group versus the BBD group, at 1981 (65) ng/ml, versus 2603 (140) ng/ml (P = 0.002) respectively. In the CA group, statistically significant correlations between PSA and IGFBP-6 (r = 0.413; P = 0.001), and between PSA and IGFBP-1 (r = -0.329; P = 0.021) were seen. Differences in IGF-I and -II between the two groups were not statistically significant. CONCLUSION: Lower serum concentrations of IGFBP-6, -3 and -1, but higher PSA concentrations were seen in the breast cancer group, and collectively these would suggest that there is an increase in bioavailable IGF-I in breast cancer.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KK",
      "lastName" : "Kaulsay",
      "authorRank" : 1,
      "name" : "Kaulsay KK",
      "referenceId" : "RGD:A101178"
    }, {
      "firstName" : "EH",
      "lastName" : "Ng",
      "authorRank" : 2,
      "name" : "Ng EH",
      "referenceId" : "RGD:A6472"
    }, {
      "firstName" : "CY",
      "lastName" : "Ji",
      "authorRank" : 3,
      "name" : "Ji CY",
      "referenceId" : "RGD:A101179"
    }, {
      "firstName" : "GH",
      "lastName" : "Ho",
      "authorRank" : 4,
      "name" : "Ho GH",
      "referenceId" : "RGD:A101180"
    }, {
      "firstName" : "TC",
      "lastName" : "Aw",
      "authorRank" : 5,
      "name" : "Aw TC",
      "referenceId" : "RGD:A101181"
    }, {
      "firstName" : "KO",
      "lastName" : "Lee",
      "authorRank" : 6,
      "name" : "Lee KO",
      "referenceId" : "RGD:A101182"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301715"
    } ]
  }, {
    "primaryId" : "PMID:10069712",
    "title" : "Congenital stapes ankylosis, broad thumbs, and hyperopia: report of a family and refinement of a syndrome.",
    "datePublished" : "1999-02-19T00:00:00.000-06:00",
    "citation" : "Milunsky J, etal., Am J Med Genet. 1999 Feb 19;82(5):404-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:25:56.000-05:00",
    "volume" : "82",
    "pages" : "404-8",
    "abstract" : "We report on a family with conductive hearing loss due to congenital stapes ankylosis, and with hyperopia, broad thumbs, and broad first toes. Neither of the studied relatives had symphalangism, possibly distinguishing this syndrome as an entity separate from the facio-audio-symphalangism and proximal symphalangism syndromes. An alternative possibility is that this family falls within the spectrum of the facioaudio-symphalangism and proximal symphalangism syndromes. Visualization of the ossicular chain, and ophthalmologic and radiologic studies are important in the evaluation of families with congenital conductive hearing loss. A characteristic physiognomy in our patients is present; this autosomal dominant syndrome was first described by Teunissen and Cremers [1990: Laryngoscope 100:380-384].",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Milunsky",
      "authorRank" : 1,
      "name" : "Milunsky J",
      "referenceId" : "RGD:A602428"
    }, {
      "firstName" : "C",
      "lastName" : "Suntra",
      "authorRank" : 2,
      "name" : "Suntra C",
      "referenceId" : "RGD:A602429"
    }, {
      "firstName" : "C B",
      "lastName" : "MacDonald",
      "authorRank" : 3,
      "name" : "MacDonald CB",
      "referenceId" : "RGD:A602430"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119858"
    } ]
  }, {
    "primaryId" : "PMID:10069810",
    "title" : "The DNA helicase activity of BLM is necessary for the correction of the genomic instability of bloom syndrome cells.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Neff NF, etal., Mol Biol Cell. 1999 Mar;10(3):665-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:46:04.000-05:00",
    "volume" : "10",
    "pages" : "665-76",
    "abstract" : "Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by growth deficiency, immunodeficiency, genomic instability, and the early development of cancers of many types. BLM, the protein encoded by BLM, the gene mutated in BS, is localized in nuclear foci and absent from BS cells. BLM encodes a DNA helicase, and proteins from three missense alleles lack displacement activity. BLM transfected into BS cells reduces the frequency of sister chromatid exchanges and restores BLM in the nucleus. Missense alleles fail to reduce the sister chromatid exchanges in transfected BS cells or restore the normal nuclear  pattern. BLM complements a phenotype of a Saccharomyces cerevisiae sgs1 top3 strain, and the missense alleles do not. This work demonstrates the importance of the enzymatic activity of BLM for its function and nuclear localization pattern.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NF",
      "lastName" : "Neff",
      "authorRank" : 1,
      "name" : "Neff NF",
      "referenceId" : "RGD:A60854"
    }, {
      "firstName" : "NA",
      "lastName" : "Ellis",
      "authorRank" : 2,
      "name" : "Ellis",
      "referenceId" : "RGD:A251888"
    }, {
      "firstName" : "TZ",
      "lastName" : "Ye",
      "authorRank" : 3,
      "name" : "Ye TZ",
      "referenceId" : "RGD:A56894"
    }, {
      "firstName" : "J",
      "lastName" : "Noonan",
      "authorRank" : 4,
      "name" : "Noonan",
      "referenceId" : "RGD:A261801"
    }, {
      "firstName" : "K",
      "lastName" : "Huang",
      "authorRank" : 5,
      "name" : "Huang K",
      "referenceId" : "RGD:A109580"
    }, {
      "firstName" : "M",
      "lastName" : "Sanz",
      "authorRank" : 6,
      "name" : "Sanz",
      "referenceId" : "RGD:A269470"
    }, {
      "firstName" : "M",
      "lastName" : "Proytcheva",
      "authorRank" : 7,
      "name" : "Proytcheva",
      "referenceId" : "RGD:A263711"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067887"
    } ]
  }, {
    "primaryId" : "PMID:10069978",
    "title" : "Genetic and biochemical determinants of abnormal monovalent ion transport in primary hypertension.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Orlov SN, etal., Am J Physiol 1999 Mar;276(3 Pt 1):C511-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-05T11:17:33.000-05:00",
    "volume" : "276",
    "pages" : "C511-36",
    "abstract" : "Data obtained during the last two decades show that spontaneously hypertensive rats, an acceptable experimental model of primary human hypertension, possess increased activity of both ubiquitous and renal cell-specific isoforms of the Na+/H+ exchanger (NHE) and Na+-K+-2Cl- cotransporter. Abnormalities of these ion transporters have been found in patients suffering from essential hypertension. Recent genetic studies demonstrate that genes encoding the beta- and gamma-subunits of ENaC, a renal cell-specific isoform of the Na+-K+-2Cl- cotransporter, and alpha3-, alpha1-, and beta2-subunits of the Na+-K+ pump are localized within quantitative trait loci (QTL) for elevated blood pressure as well as for enhanced heart-to-body weight ratio, proteinuria, phosphate excretion, and stroke latency. On the basis of the homology of genome maps, several other genes encoding these transporters, as well as the Na+/H+ exchanger and Na+-K+-2Cl- cotransporter, can be predicted in QTL related to the pathogenesis of hypertension. However, despite their location within QTL, analysis of cDNA structure did not reveal any mutation in the coding region of the above-listed transporters in primary hypertension, with the exception of G276L substitution in the alpha1-Na+-K+ pump from Dahl salt-sensitive rats and a higher occurrence of T594M mutation of beta-ENaC in the black population with essential hypertension. These results suggest that, in contrast to Mendelian forms of hypertension, the altered activity of monovalent ion transporters in primary hypertension is caused by abnormalities of systems involved in the regulation of their expression and/or function. Further analysis of QTL in F2 hybrids of normotensive and hypertensive rats and in affected sibling pairs will allow mapping of genes causing abnormalities of these regulatory pathways.",
    "issueName" : "3 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SN",
      "lastName" : "Orlov",
      "authorRank" : 1,
      "name" : "Orlov SN",
      "referenceId" : "RGD:A10882"
    }, {
      "firstName" : "NC",
      "lastName" : "Adragna",
      "authorRank" : 2,
      "name" : "Adragna NC",
      "referenceId" : "RGD:A10883"
    }, {
      "firstName" : "VA",
      "lastName" : "Adarichev",
      "authorRank" : 3,
      "name" : "Adarichev VA",
      "referenceId" : "RGD:A10884"
    }, {
      "firstName" : "P",
      "lastName" : "Hamet",
      "authorRank" : 4,
      "name" : "Hamet P",
      "referenceId" : "RGD:A84211"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619637"
    } ]
  }, {
    "primaryId" : "PMID:10069984",
    "title" : "Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC).",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Choi I, etal., Am J Physiol. 1999 Mar;276(3):C576-84. doi: 10.1152/ajpcell.1999.276.3.C576.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-12-20T13:04:08.000-06:00",
    "volume" : "276",
    "pages" : "C576-84",
    "abstract" : "Our group recently cloned the electrogenic Na+-HCO-3 cotransporter (NBC) from salamander kidney and later from mammalian kidney. Here we report cloning an NBC isoform (hhNBC) from a human heart cDNA library. hhNBC is identical to human renal NBC (hkNBC), except for the amino terminus, where the first 85 amino acids in hhNBC replace the first 41 amino acids of hkNBC. About 50% of the amino acid residues in this unique amino terminus are charged, compared with approximately 22% for the corresponding 41 residues in hkNBC. Northern blot analysis, with the use of the unique 5' fragment of hhNBC as a probe, shows strong expression in pancreas and expression in heart and brain, although at much lower levels. In Xenopus oocytes expressing hhNBC, adding 1.5% CO2/10 mM HCO-3 hyperpolarizes the membrane and causes a rapid fall in intracellular pH (pHi), followed by a pHi recovery. Subsequent removal of Na+ causes a depolarization and a reduced rate of pHi recovery. Removal of Cl- from the bath does not affect the pHi recovery. The stilbene derivative DIDS (200 microM) greatly reduces the hyperpolarization caused by adding CO2/HCO-3. In oocytes expressing hkNBC, the effects of adding CO2/HCO-3 and then removing Na+ were similar to those observed in oocytes expressing hhNBC. We conclude that hhNBC is an electrogenic Na+-HCO-3 cotransporter and that hkNBC is also electrogenic.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Choi",
      "authorRank" : 1,
      "name" : "Choi I",
      "referenceId" : "RGD:A23457"
    }, {
      "firstName" : "M F",
      "lastName" : "Romero",
      "authorRank" : 2,
      "name" : "Romero MF",
      "referenceId" : "RGD:A477768"
    }, {
      "firstName" : "N",
      "lastName" : "Khandoudi",
      "authorRank" : 3,
      "name" : "Khandoudi N",
      "referenceId" : "RGD:A477769"
    }, {
      "firstName" : "A",
      "lastName" : "Bril",
      "authorRank" : 4,
      "name" : "Bril A",
      "referenceId" : "RGD:A51333"
    }, {
      "firstName" : "W F",
      "lastName" : "Boron",
      "authorRank" : 5,
      "name" : "Boron WF",
      "referenceId" : "RGD:A468757"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:15090856"
    } ]
  }, {
    "primaryId" : "PMID:10069985",
    "title" : "Splicing of a retained intron within ROMK K+ channel RNA generates a novel set of isoforms in rat kidney.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Beesley AH, etal., Am J Physiol 1999 Mar;276(3 Pt 1):C585-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:54:28.000-06:00",
    "volume" : "276",
    "pages" : "C585-92",
    "abstract" : "The renal outer medulla K+ channel (ROMK) family of K+ channels may constitute a major pathway for K+ secretion in the distal nephron. To date, four main isoforms of this gene have been identified in the rat that differ only in their NH2-terminal amino acids and that share a common \"core exon\" that determines the remaining protein sequence. Using RT-PCR, we have identified a new set of ROMK isoforms in rat kidney that are generated by the deletion of a region within the ROMK core sequence that is identifiable as a typical mammalian intron. This splicing event was shown to be reproducible in vitro by detection of deleted ROMK mRNA in Madin-Darby canine kidney (MDCK) cells stably transfected with the gene for ROMK2. Translation of the deletion variant of ROMK2 was confirmed in vitro and visualized in MDCK cells following transient transfection with an enhanced green fluorescent protein tag. The deletion in this core region is predicted to generate hydrophilic proteins that are approximately one-third of the size of native ROMK and lack membrane-spanning domains.",
    "issueName" : "3 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AH",
      "lastName" : "Beesley",
      "authorRank" : 1,
      "name" : "Beesley AH",
      "referenceId" : "RGD:A27173"
    }, {
      "firstName" : "B",
      "lastName" : "Ortega",
      "authorRank" : 2,
      "name" : "Ortega B",
      "referenceId" : "RGD:A27174"
    }, {
      "firstName" : "SJ",
      "lastName" : "White",
      "authorRank" : 3,
      "name" : "White SJ",
      "referenceId" : "RGD:A27175"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727265"
    } ]
  }, {
    "primaryId" : "PMID:10070045",
    "title" : "Factors mediating the hemodynamic effects of tumor necrosis factor-alpha in portal hypertensive rats.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Muñoz J, etal., Am J Physiol. 1999 Mar;276(3):G687-93. doi: 10.1152/ajpgi.1999.276.3.G687.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-10-23T15:07:57.000-05:00",
    "volume" : "276",
    "pages" : "G687-93",
    "abstract" : "Nitric oxide, prostacyclin, and glucagon have been implicated in promoting the hyperdynamic circulatory state of portal hypertension. Recent evidence also indicates that increased tumor necrosis factor-alpha (TNF-alpha) production is involved in the pathogenesis of this hemodynamic abnormality. This study was aimed at investigating in rats with portal vein stenosis (PVS) the effects on splanchnic hemodynamics of blocking circulating TNF-alpha and the factors mediating the vascular action of this cytokine in this setting. Anti-TNF-alpha polyclonal antibodies or placebo was injected into rats (n = 96) before and 4 days after PVS (short-term inhibition) and at 24 h and 4, 7, 10 days after PVS (long-term inhibition). Short-term TNF-alpha inhibition reduced portal venous inflow and cardiac index and increased splanchnic and systemic resistance. Portal pressure was unchanged, but portal-systemic shunting was decreased. After long-term TNF-alpha inhibition, portal venous inflow and portal pressure were unchanged, but arterial pressure and systemic resistance rose significantly. Anti-TNF-alpha PVS rats exhibited lower increments of systemic resistance after Nomega-nitro-L-arginine methyl ester and indomethacin administration and lower serum levels of TNF-alpha, nitrates-nitrites, and 6-keto-PGF1alpha, both over the short and the long term. Serum glucagon levels rose after long-term inhibition. In conclusion, the specific role played by TNF-alpha in the development of the hyperdynamic state of portal hypertension appears to be mainly mediated through an increased release of nitric oxide and prostacyclin. Maintenance of the splanchnic hyperemia after long-term TNF-alpha inhibition could be due to a compensatory release of glucagon.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Muñoz",
      "authorRank" : 1,
      "name" : "Muñoz J",
      "referenceId" : "RGD:A475757"
    }, {
      "firstName" : "A",
      "lastName" : "Albillos",
      "authorRank" : 2,
      "name" : "Albillos A",
      "referenceId" : "RGD:A475758"
    }, {
      "firstName" : "M",
      "lastName" : "Pérez-Páramo",
      "authorRank" : 3,
      "name" : "Pérez-Páramo M",
      "referenceId" : "RGD:A475759"
    }, {
      "firstName" : "I",
      "lastName" : "Rossi",
      "authorRank" : 4,
      "name" : "Rossi I",
      "referenceId" : "RGD:A475760"
    }, {
      "firstName" : "M",
      "lastName" : "Alvarez-Mon",
      "authorRank" : 5,
      "name" : "Alvarez-Mon M",
      "referenceId" : "RGD:A55099"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14995425"
    } ]
  }, {
    "primaryId" : "PMID:10070062",
    "title" : "TAFII250, Egr-1, and D-type cyclin expression in mice and neonatal rat cardiomyocytes treated with doxorubicin.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Saadane N, etal., Am J Physiol. 1999 Mar;276(3 Pt 2):H803-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-04-21T14:01:17.000-05:00",
    "volume" : "276",
    "pages" : "H803-14",
    "abstract" : "Differential display identified that gene fragment HA220 homologous to the transcriptional activator factor II 250 (TAFII250) gene, or CCG1, was increased in hypertrophied rodent heart. To determine whether TAFII250 gene expression is modified after cardiac damage, we measured TAFII250 expression in vivo in mouse hearts after injection of the cardiotoxic agent doxorubicin (DXR) and in vitro in DXR-treated isolated rat neonatal cardiomyocytes. In vivo atrial natriuretic factor (ANF), beta-myosin heavy chain (beta-MHC), Egr-1, and TAFII250 expression increased with dose and time after a single DXR injection, but only ANF and beta-MHC expression were increased after multiple injections. After DXR treatment of neonatal cardiomyocytes we found decreased ANF, alpha-MHC, Egr-1, and TAFII250 expression. Expression of the TAFII250-regulated genes, the D-type cyclins, was increased after a single injection in adult mice and was decreased in DXR-treated cardiomyocytes. Thus expression of Erg-1, TAFII250, and the D-type cyclins is modulated after cardiotoxic damage in adult and neonatal heart.",
    "issueName" : "3 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Saadane",
      "authorRank" : 1,
      "name" : "Saadane N",
      "referenceId" : "RGD:A105677"
    }, {
      "firstName" : "L",
      "lastName" : "Alpert",
      "authorRank" : 2,
      "name" : "Alpert L",
      "referenceId" : "RGD:A5577"
    }, {
      "firstName" : "LE",
      "lastName" : "Chalifour",
      "authorRank" : 3,
      "name" : "Chalifour LE",
      "referenceId" : "RGD:A5575"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306531"
    } ]
  }, {
    "primaryId" : "PMID:10070140",
    "title" : "Role of renal medullary adenosine in the control of blood flow and sodium excretion.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Zou AP, etal., Am J Physiol 1999 Mar;276(3 Pt 2):R790-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-02-13T08:01:15.000-06:00",
    "volume" : "276",
    "pages" : "R790-8",
    "abstract" : "This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 +/- 5.2 nM, which was significantly higher than 55.6 +/- 5.3 nM in the renal cortex (n = 9). Renal medullary interstitial infusion of a selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol. kg-1. min-1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3, 7-dimethyl-1-propargylxanthine (DMPX; 150 pmol. kg-1. min-1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol. kg-1. min-1 (n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3 receptor agonist, N6-benzyl-5'-(N-ethylcarbonxamido)adenosine (300 pmol. kg-1. min-1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor-mediated antinatriuretic effects.",
    "issueName" : "3 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AP",
      "lastName" : "Zou",
      "authorRank" : 1,
      "name" : "Zou AP",
      "referenceId" : "RGD:A12502"
    }, {
      "firstName" : "K",
      "lastName" : "Nithipatikom",
      "authorRank" : 2,
      "name" : "Nithipatikom K",
      "referenceId" : "RGD:A14234"
    }, {
      "firstName" : "PL",
      "lastName" : "Li",
      "authorRank" : 3,
      "name" : "Li PL",
      "referenceId" : "RGD:A14217"
    }, {
      "firstName" : "JR",
      "lastName" : "Cowley AW",
      "authorRank" : 4,
      "name" : "Cowley AW JR",
      "referenceId" : "RGD:A6483"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:628573"
    } ]
  }, {
    "primaryId" : "PMID:10070148",
    "title" : "Altered renal hemodynamics and impaired myogenic responses in the fawn-hooded rat.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "van Dokkum RP, etal., Am J Physiol 1999 Mar;276(3 Pt 2):R855-63",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-02-12T10:41:04.000-06:00",
    "volume" : "276",
    "pages" : "R855-63",
    "abstract" : "The present study examined whether an abnormality in the myogenic response of renal arterioles that impairs autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) contributes to the development of renal damage in fawn-hooded hypertensive (FHH) rats. Autoregulation of whole kidney, cortical, and medullary blood flow and PGC were compared in young (12 wk old) FHH and fawn-hooded low blood pressure (FHL) rats in volume-replete and volume-expanded conditions. Baseline RBF, cortical and medullary blood flow, and PGC were significantly greater in FHH than in FHL rats. Autoregulation of renal and cortical blood flow was significantly impaired in FHH rats compared with results obtained in FHL rats. Myogenically mediated autoregulation of PGC was significantly greater in FHL than in FHH rats. PGC rose from 46 +/- 1 to 71 +/- 2 mmHg in response to an increase in renal perfusion pressure from 100 to 150 mmHg in FHH rats, whereas it only increased from 39 +/- 2 to 53 +/- 1 mmHg in FHL rats. Isolated perfused renal interlobular arteries from FHL rats constricted by 10% in response to elevations in transmural pressure from 70 to 120 mmHg. In contrast, the diameter of vessels from FHH rats increased by 15%. These results indicate that the myogenic response of small renal arteries is altered in FHH rats, and this contributes to an impaired autoregulation of renal blood flow and elevations in PGC in this strain.",
    "issueName" : "3 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RP",
      "lastName" : "Van Dokkum",
      "authorRank" : 1,
      "name" : "Van Dokkum RP",
      "referenceId" : "RGD:A100093"
    }, {
      "firstName" : "CW",
      "lastName" : "Sun",
      "authorRank" : 2,
      "name" : "Sun CW",
      "referenceId" : "RGD:A105"
    }, {
      "firstName" : "AP",
      "lastName" : "Provoost",
      "authorRank" : 3,
      "name" : "Provoost AP",
      "referenceId" : "RGD:A142035"
    }, {
      "firstName" : "HJ",
      "lastName" : "Jacob",
      "authorRank" : 4,
      "name" : "Jacob HJ",
      "referenceId" : "RGD:A160476"
    }, {
      "firstName" : "RJ",
      "lastName" : "Roman",
      "authorRank" : 5,
      "name" : "Roman RJ",
      "referenceId" : "RGD:A160477"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61023"
    } ]
  }, {
    "primaryId" : "PMID:10070364",
    "title" : "Matrilysin activity in the rat uterus during the oestrous cycle and implantation.",
    "datePublished" : "1998-01-01T00:00:00.000-06:00",
    "citation" : "Feng J, etal., J Reprod Fertil. 1998 Nov;114(2):347-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-05T11:58:27.000-06:00",
    "volume" : "114",
    "pages" : "347-50",
    "abstract" : "The objective of this study was to follow changes in the activity of the small matrix metalloproteinase matrilysin (MMP-7) in the rat uterus during the oestrous cycle and embryo implantation. Matrilysin was extracted from rat uteri, partially purified and separated into active and latent forms. The two forms of the enzyme  were quantified at all stages of the oestrous cycle and after oestradiol and progesterone treatment. The activity was also measured during the first 7 days of pregnancy. Both latent and active forms of MMP-7 reached a peak during the pro-oestrous stage of the cycle; the concentrations were three times higher than  at dioestrus and metoestrus. In rats treated with 0.1 mg oestradiol at metoestrus, both latent and active forms of the enzyme increased by more than two-fold after 24 h. In rats treated at pro-oestrus with 0.4 mg progesterone, there was a 70% increase in latent MMP-7, but no change in the active form. The highest concentrations of MMP-7 were observed on the first day of pregnancy. Between days 3 and 7 of pregnancy, the concentrations were relatively constant and comparable to the low concentrations at dioestrus. Enzyme activities were not different at implantation sites compared with remote sites.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Feng",
      "authorRank" : 1,
      "name" : "Feng J",
      "referenceId" : "RGD:A27539"
    }, {
      "firstName" : "JR",
      "lastName" : "Woessner JF",
      "authorRank" : 2,
      "name" : "Woessner JF JR",
      "referenceId" : "RGD:A31192"
    }, {
      "firstName" : "C",
      "lastName" : "Zhu",
      "authorRank" : 3,
      "name" : "Zhu C",
      "referenceId" : "RGD:A13319"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685349"
    } ]
  }, {
    "primaryId" : "PMID:10070498",
    "title" : "Identification of phospholipase C beta isoforms and their location in cultured vascular smooth muscle cells of pig, human and rat.",
    "datePublished" : "1998-02-01T00:00:00.000-06:00",
    "citation" : "Blayney L, etal., Cardiovasc Res. 1998 Dec;40(3):564-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-21T10:16:52.000-06:00",
    "volume" : "40",
    "pages" : "564-72",
    "abstract" : "OBJECTIVES: Four phospholipase C (PLC) beta isoforms have been described in pig aortic vascular smooth muscle. The aim was to determine if all four PLC beta isoforms are commonly expressed in vascular smooth muscle cells (VSMC) of three species, i.e. pig, human and rat, and if the individual isoforms had distinctive intracellular distributions. METHODS: Vascular smooth muscle cell cultures were derived from explants of porcine and rat aorta and a human renal artery cell line. PLC beta isoform content was resolved using Western blotting. Intracellular location was determined by immunocytochemistry and confocal microscopy. RESULTS: All three species expressed PLCs, beta 1, beta 2, beta 3 and beta 4. In all species, PLC beta 1 demonstrated foci of concentration throughout the cytoplasm; PLC beta 2 demonstrated a punctate pattern that was principally at the cell periphery or was in the Golgi, depending upon the antibody used; PLC beta 3 was also cytoplasmic but showed a different pattern from PLC beta 1 and PLC beta 4 was cytoplasmic, except in pig quiescent cells, where it was associated with filamentous structures at the intersection with the plasma membrane. CONCLUSIONS: VSMCs of three different species express all four PLC beta isoforms. Each isoform has a unique and consistent signature of distribution that is generally common to all species.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Blayney",
      "authorRank" : 1,
      "name" : "Blayney L",
      "referenceId" : "RGD:A17639"
    }, {
      "firstName" : "P",
      "lastName" : "Gapper",
      "authorRank" : 2,
      "name" : "Gapper P",
      "referenceId" : "RGD:A75530"
    }, {
      "firstName" : "C",
      "lastName" : "Rix",
      "authorRank" : 3,
      "name" : "Rix C",
      "referenceId" : "RGD:A75531"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599907"
    } ]
  }, {
    "primaryId" : "PMID:10070617",
    "title" : "Mutations in the glucose-6-phosphatase gene of 53 Italian patients with glycogen  storage disease type Ia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Stroppiano M, etal., J Inherit Metab Dis. 1999 Feb;22(1):43-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:47:48.000-05:00",
    "volume" : "22",
    "pages" : "43-9",
    "abstract" : "Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning of the G6Pase gene and the subsequent identification of several disease-causing mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 53 unrelated Italian patients. The two most common mutations, R83C and Q347X, accounted for 66.9% of the mutant alleles. Eight novel mutations and three rare mutations were identified in 15.7% of disease alleles. These results suggest that a DNA-based method can be used as an initial screening in Italian patients clinically suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In particular, a noninvasive diagnosis is a suitable method for the Italian subpopulation coming from Sicily, where the R83C mutation is present in 80% of mutant alleles. Molecular carrier detection and prenatal diagnosis can be provided to GSD1a families with identified mutation in the propositus.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Stroppiano",
      "authorRank" : 1,
      "name" : "Stroppiano",
      "referenceId" : "RGD:A259012"
    }, {
      "firstName" : "S",
      "lastName" : "Regis",
      "authorRank" : 2,
      "name" : "Regis S",
      "referenceId" : "RGD:A71689"
    }, {
      "firstName" : "M",
      "lastName" : "DiRocco",
      "authorRank" : 3,
      "name" : "DiRocco",
      "referenceId" : "RGD:A260168"
    }, {
      "firstName" : "F",
      "lastName" : "Caroli",
      "authorRank" : 4,
      "name" : "Caroli",
      "referenceId" : "RGD:A260169"
    }, {
      "firstName" : "P",
      "lastName" : "Gandullia",
      "authorRank" : 5,
      "name" : "Gandullia",
      "referenceId" : "RGD:A260170"
    }, {
      "firstName" : "R",
      "lastName" : "Gatti",
      "authorRank" : 6,
      "name" : "Gatti R",
      "referenceId" : "RGD:A72050"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064900"
    } ]
  }, {
    "primaryId" : "PMID:10070627",
    "title" : "Three novel and one recurrent ornithine carbamoyltransferase gene mutations in Polish patients.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Popowska E, etal., J Inherit Metab Dis. 1999 Feb;22(1):92-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:45:59.000-05:00",
    "volume" : "22",
    "pages" : "92-3",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Popowska",
      "authorRank" : 1,
      "name" : "Popowska",
      "referenceId" : "RGD:A251953"
    }, {
      "firstName" : "E",
      "lastName" : "Ciara",
      "authorRank" : 2,
      "name" : "Ciara",
      "referenceId" : "RGD:A251954"
    }, {
      "firstName" : "D",
      "lastName" : "Rokicki",
      "authorRank" : 3,
      "name" : "Rokicki",
      "referenceId" : "RGD:A251955"
    }, {
      "firstName" : "E",
      "lastName" : "Pronicka",
      "authorRank" : 4,
      "name" : "Pronicka",
      "referenceId" : "RGD:A251956"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062647"
    } ]
  }, {
    "primaryId" : "PMID:10071056",
    "title" : "The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is associated with a clinically distinct Charcot-Marie-Tooth phenotype.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "De Jonghe P, etal., Brain. 1999 Feb;122 ( Pt 2):281-90. doi: 10.1093/brain/122.2.281.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:46:34.000-05:00",
    "volume" : "122 ( Pt 2)",
    "pages" : "281-90",
    "abstract" : "We observed a missense mutation in the peripheral myelin protein zero gene (MPZ, Thr124Met) in seven Charcot-Marie-Tooth (CMT) families and in two isolated CMT patients of Belgian ancestry. Allele-sharing analysis of markers flanking the MPZ gene indicated that all patients with the Thr124Met mutation have one common ancestor. The mutation is associated with a clinically distinct phenotype characterized by late onset, marked sensory abnormalities and, in some families, deafness and pupillary abnormalities. Nerve conduction velocities of the motor median nerve vary from <38 m/s to normal values in these patients. Clusters of remyelinating axons in a sural nerve biopsy demonstrate an axonal involvement, with axonal regeneration. Phenotype-genotype correlations in 30 patients with the Thr124Met MPZ mutation indicate that, based on nerve conduction velocity criteria, these patients are difficult to classify as CMT1 or CMT2. We therefore conclude that CMT patients with slightly reduced or nearly normal nerve conduction velocity should be screened for MPZ mutations, particularly when additional clinical features such as marked sensory disturbances, pupillary abnormalities or deafness are also present.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "De Jonghe",
      "authorRank" : 1,
      "name" : "De Jonghe P",
      "referenceId" : "RGD:A43579"
    }, {
      "firstName" : "V",
      "lastName" : "Timmerman",
      "authorRank" : 2,
      "name" : "Timmerman V",
      "referenceId" : "RGD:A43578"
    }, {
      "firstName" : "C",
      "lastName" : "Ceuterick",
      "authorRank" : 3,
      "name" : "Ceuterick C",
      "referenceId" : "RGD:A53418"
    }, {
      "firstName" : "E",
      "lastName" : "Nelis",
      "authorRank" : 4,
      "name" : "Nelis E",
      "referenceId" : "RGD:A53414"
    }, {
      "firstName" : "E",
      "lastName" : "De Vriendt",
      "authorRank" : 5,
      "name" : "De Vriendt E",
      "referenceId" : "RGD:A73470"
    }, {
      "firstName" : "A",
      "lastName" : "Löfgren",
      "authorRank" : 6,
      "name" : "Löfgren A",
      "referenceId" : "RGD:A595821"
    }, {
      "firstName" : "A",
      "lastName" : "Vercruyssen",
      "authorRank" : 7,
      "name" : "Vercruyssen A",
      "referenceId" : "RGD:A595822"
    }, {
      "firstName" : "C",
      "lastName" : "Verellen",
      "authorRank" : 8,
      "name" : "Verellen C",
      "referenceId" : "RGD:A53423"
    }, {
      "firstName" : "L",
      "lastName" : "Van Maldergem",
      "authorRank" : 9,
      "name" : "Van Maldergem L",
      "referenceId" : "RGD:A9687"
    }, {
      "firstName" : "J J",
      "lastName" : "Martin",
      "authorRank" : 10,
      "name" : "Martin JJ",
      "referenceId" : "RGD:A587716"
    }, {
      "firstName" : "C",
      "lastName" : "Van Broeckhoven",
      "authorRank" : 11,
      "name" : "Van Broeckhoven C",
      "referenceId" : "RGD:A8488"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118701"
    } ]
  }, {
    "primaryId" : "PMID:10071185",
    "title" : "Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Van Kuilenburg AB, etal., Hum Genet. 1999 Jan;104(1):1-9. doi: 10.1007/pl00008711.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:37:19.000-05:00",
    "volume" : "104",
    "pages" : "1-9",
    "abstract" : "Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterised by thymine-uraciluria in homozygous deficient patients and has been associated with a variable clinical phenotype. In order to understand the genetic and phenotypic basis for DPD deficiency, we have reviewed 17 families presenting 22 patients with complete deficiency of DPD. In this group of patients, 7 different mutations have been identified, including 2 deletions [295-298delTCAT, 1897delC], 1 splice-site mutation [IVS14+1G>A)] and 4 missense mutations (85T>C, 703C>T, 2658G>A, 2983G>T). Analysis of the prevalence of the various mutations among DPD patients has shown that the G-->A point mutation in the invariant splice donor site is by far the most common (52%), whereas the other six mutations are less frequently observed. A large phenotypic variability has been observed, with convulsive disorders, motor retardation and mental retardation being the most abundant manifestations. A clear correlation between the genotype and phenotype has not been established. An altered beta-alanine, uracil and thymine homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A B",
      "lastName" : "Van Kuilenburg",
      "authorRank" : 1,
      "name" : "Van Kuilenburg AB",
      "referenceId" : "RGD:A594214"
    }, {
      "firstName" : "P",
      "lastName" : "Vreken",
      "authorRank" : 2,
      "name" : "Vreken P",
      "referenceId" : "RGD:A72111"
    }, {
      "firstName" : "N G",
      "lastName" : "Abeling",
      "authorRank" : 3,
      "name" : "Abeling NG",
      "referenceId" : "RGD:A594215"
    }, {
      "firstName" : "H D",
      "lastName" : "Bakker",
      "authorRank" : 4,
      "name" : "Bakker HD",
      "referenceId" : "RGD:A482366"
    }, {
      "firstName" : "R",
      "lastName" : "Meinsma",
      "authorRank" : 5,
      "name" : "Meinsma R",
      "referenceId" : "RGD:A594216"
    }, {
      "firstName" : "H",
      "lastName" : "Van Lenthe",
      "authorRank" : 6,
      "name" : "Van Lenthe H",
      "referenceId" : "RGD:A75140"
    }, {
      "firstName" : "R A",
      "lastName" : "De Abreu",
      "authorRank" : 7,
      "name" : "De Abreu RA",
      "referenceId" : "RGD:A592985"
    }, {
      "firstName" : "J A",
      "lastName" : "Smeitink",
      "authorRank" : 8,
      "name" : "Smeitink JA",
      "referenceId" : "RGD:A565875"
    }, {
      "firstName" : "H",
      "lastName" : "Kayserili",
      "authorRank" : 9,
      "name" : "Kayserili H",
      "referenceId" : "RGD:A35392"
    }, {
      "firstName" : "M Y",
      "lastName" : "Apak",
      "authorRank" : 10,
      "name" : "Apak MY",
      "referenceId" : "RGD:A594217"
    }, {
      "firstName" : "E",
      "lastName" : "Christensen",
      "authorRank" : 11,
      "name" : "Christensen E",
      "referenceId" : "RGD:A5297"
    }, {
      "firstName" : "I",
      "lastName" : "Holopainen",
      "authorRank" : 12,
      "name" : "Holopainen I",
      "referenceId" : "RGD:A594218"
    }, {
      "firstName" : "K",
      "lastName" : "Pulkki",
      "authorRank" : 13,
      "name" : "Pulkki K",
      "referenceId" : "RGD:A70130"
    }, {
      "firstName" : "D",
      "lastName" : "Riva",
      "authorRank" : 14,
      "name" : "Riva D",
      "referenceId" : "RGD:A297174"
    }, {
      "firstName" : "G",
      "lastName" : "Botteon",
      "authorRank" : 15,
      "name" : "Botteon G",
      "referenceId" : "RGD:A594219"
    }, {
      "firstName" : "E",
      "lastName" : "Holme",
      "authorRank" : 16,
      "name" : "Holme E",
      "referenceId" : "RGD:A575625"
    }, {
      "firstName" : "M",
      "lastName" : "Tulinius",
      "authorRank" : 17,
      "name" : "Tulinius M",
      "referenceId" : "RGD:A594220"
    }, {
      "firstName" : "W J",
      "lastName" : "Kleijer",
      "authorRank" : 18,
      "name" : "Kleijer WJ",
      "referenceId" : "RGD:A565681"
    }, {
      "firstName" : "F A",
      "lastName" : "Beemer",
      "authorRank" : 19,
      "name" : "Beemer FA",
      "referenceId" : "RGD:A573074"
    }, {
      "firstName" : "M",
      "lastName" : "Duran",
      "authorRank" : 20,
      "name" : "Duran M",
      "referenceId" : "RGD:A73786"
    }, {
      "firstName" : "K E",
      "lastName" : "Niezen-Koning",
      "authorRank" : 21,
      "name" : "Niezen-Koning KE",
      "referenceId" : "RGD:A575169"
    }, {
      "firstName" : "G P",
      "lastName" : "Smit",
      "authorRank" : 22,
      "name" : "Smit GP",
      "referenceId" : "RGD:A571475"
    }, {
      "firstName" : "C",
      "lastName" : "Jakobs",
      "authorRank" : 23,
      "name" : "Jakobs C",
      "referenceId" : "RGD:A16901"
    }, {
      "firstName" : "L M",
      "lastName" : "Smit",
      "authorRank" : 24,
      "name" : "Smit LM",
      "referenceId" : "RGD:A594221"
    }, {
      "firstName" : "A H",
      "lastName" : "Van Gennip",
      "authorRank" : 25,
      "name" : "Van Gennip AH",
      "referenceId" : "RGD:A594222"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118427"
    } ]
  }, {
    "primaryId" : "PMID:10071239",
    "title" : "Nutrient-dependent distribution of insulin and glucokinase immunoreactivities in rat pancreatic beta cells.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Jorns A, etal., Virchows Arch. 1999 Jan;434(1):75-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-11-11T16:13:18.000-06:00",
    "volume" : "434",
    "pages" : "75-82",
    "abstract" : "Functional heterogeneity among pancreatic beta cells is a characteristic feature of the islets of Langerhans. Under physiological conditions, beta cells in the pancreas of fed rats exhibited heterogeneous immunohistochemical staining for insulin and glucokinase. Intracellular beta cell glucokinase staining was either faint or dense. In the pericapillary space beta cell glucokinase immunoreactivity had a polar orientation, with the highest density in cytoplasmic regions close to the blood vessels. Starvation resulted in a loss of heterogeneity with homogeneous insulin staining in all beta cells of the islets, and this was accompanied by a loss of heterogeneous glucokinase staining. The intracellular polarity of glucokinase staining in contact to blood vessels also disappeared after starvation. Refeeding resulted in the reappearance of intercellular heterogeneity. In dependence on the functional demand, the endocrine pancreas recruited insulin from beta cells according to a well-defined hierarchy, with an initial preferential mobilization of medullary beta cells. In the course of this process intracellular polarity of glucokinase staining reappeared in areas of the beta cell with functional contact to the GLUT2 glucose transporter in the plasma membrane. This can be regarded as the morphological correlate of an activation of the glucose signal recognition apparatus. Interestingly, the study also provides evidence that the changes in glucokinase distribution apparently preceded those in insulin distribution, which is in keeping with the central role of glucokinase as the glucose sensor of the pancreatic beta cell.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Jorns",
      "authorRank" : 1,
      "name" : "Jorns A",
      "referenceId" : "RGD:A54745"
    }, {
      "firstName" : "M",
      "lastName" : "Tiedge",
      "authorRank" : 2,
      "name" : "Tiedge M",
      "referenceId" : "RGD:A54747"
    }, {
      "firstName" : "S",
      "lastName" : "Lenzen",
      "authorRank" : 3,
      "name" : "Lenzen S",
      "referenceId" : "RGD:A54746"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301948"
    } ]
  }, {
    "primaryId" : "PMID:10072077",
    "title" : "Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Moriggl R, etal., Immunity. 1999 Feb;10(2):249-59.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:40:09.000-05:00",
    "volume" : "10",
    "pages" : "249-59",
    "abstract" : "Many cytokines activate two highly homologous Stat proteins, 5a and 5b. Mice deficient in both genes lack all growth hormone and prolactin functions but retain functions associated with cytokines such as erythropoietin. Here, we demonstrate that, while lymphoid development is normal, Stat5a/b mutant peripheral T cells are profoundly deficient in proliferation and fail to undergo  cell cycle progression or to express genes controlling cell cycle progression. In addition, the mice lack NK cells, develop splenomegaly, and have T cells with an  activated phenotype, phenotypes seen in IL-2 receptor beta chain-deficient mice.  These phenotypes are not seen in mice lacking Stat5a or Stat5b alone. The results demonstrate that the Stat5 proteins, redundantly, are essential mediators of IL-2 signaling in T cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Moriggl",
      "authorRank" : 1,
      "name" : "Moriggl R",
      "referenceId" : "RGD:A94749"
    }, {
      "firstName" : "DJ",
      "lastName" : "Topham",
      "authorRank" : 2,
      "name" : "Topham DJ",
      "referenceId" : "RGD:A39536"
    }, {
      "firstName" : "S",
      "lastName" : "Teglund",
      "authorRank" : 3,
      "name" : "Teglund S",
      "referenceId" : "RGD:A25755"
    }, {
      "firstName" : "V",
      "lastName" : "Sexl",
      "authorRank" : 4,
      "name" : "Sexl",
      "referenceId" : "RGD:A292155"
    }, {
      "firstName" : "C",
      "lastName" : "McKay",
      "authorRank" : 5,
      "name" : "McKay C",
      "referenceId" : "RGD:A47064"
    }, {
      "firstName" : "D",
      "lastName" : "Wang",
      "authorRank" : 6,
      "name" : "Wang D",
      "referenceId" : "RGD:A18755"
    }, {
      "firstName" : "A",
      "lastName" : "Hoffmeyer",
      "authorRank" : 7,
      "name" : "Hoffmeyer A",
      "referenceId" : "RGD:A47076"
    }, {
      "firstName" : "J",
      "lastName" : "Van Deursen",
      "authorRank" : 8,
      "name" : "Van Deursen J",
      "referenceId" : "RGD:A36638"
    }, {
      "firstName" : "MY",
      "lastName" : "Sangster",
      "authorRank" : 9,
      "name" : "Sangster MY",
      "referenceId" : "RGD:A47075"
    }, {
      "firstName" : "KD",
      "lastName" : "Bunting",
      "authorRank" : 10,
      "name" : "Bunting",
      "referenceId" : "RGD:A331985"
    }, {
      "firstName" : "GC",
      "lastName" : "Grosveld",
      "authorRank" : 11,
      "name" : "Grosveld",
      "referenceId" : "RGD:A287646"
    }, {
      "firstName" : "JN",
      "lastName" : "Ihle",
      "authorRank" : 12,
      "name" : "Ihle JN",
      "referenceId" : "RGD:A39542"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340866"
    } ]
  }, {
    "primaryId" : "PMID:10072196",
    "title" : "Involvement of c-myc and max in CNS beta-endorphin modulation of hepatic ornithine decarboxylase responsiveness to insulin in rat pups.",
    "datePublished" : "1000-02-01T00:00:00.000-06:00",
    "citation" : "Bartolome JV, etal., Life Sci. 1999;64(5):PL87-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-26T14:40:42.000-06:00",
    "volume" : "64",
    "pages" : "PL87-91",
    "abstract" : "Previously, we have shown that subcutaneous administration of insulin stimulates ornithine decarboxylase (ODC) mRNA expression and enzymatic activity in the liver of infant control rats, but not in those pretreated intracerebroventricularly (i.c.v.) with beta-endorphin. This finding is consistent with the hypothesis that beta-endorphin synthesized in the brain plays a prime role in the control of postnatal development, in part, by modulating ODC gene transcription. We now report that insulin induced stimulation of hepatic ODC mRNA expression is accompanied by a concomitant increase in the expression of c-myc and max mRNAs, and that this effect is also inhibited by pretreatment with i.c.v. beta-endorphin. These results suggest that CNS beta-endorphin suppresses tissue ODC responsiveness to trophic hormones by downregulating the expression of c-myc and max mRNAs, the encoded proteins of which are known to act physiologically as transcriptional activators of the ODC gene.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JV",
      "lastName" : "Bartolome",
      "authorRank" : 1,
      "name" : "Bartolome JV",
      "referenceId" : "RGD:A119810"
    }, {
      "firstName" : "S",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang S",
      "referenceId" : "RGD:A162934"
    }, {
      "firstName" : "SM",
      "lastName" : "Schanberg",
      "authorRank" : 3,
      "name" : "Schanberg SM",
      "referenceId" : "RGD:A119811"
    }, {
      "firstName" : "MB",
      "lastName" : "Bartolome",
      "authorRank" : 4,
      "name" : "Bartolome MB",
      "referenceId" : "RGD:A119812"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316824"
    } ]
  }, {
    "primaryId" : "PMID:10072434",
    "title" : "Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Tang NL, etal., Hum Mol Genet. 1999 Apr;8(4):655-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:11:40.000-05:00",
    "volume" : "8",
    "pages" : "655-60",
    "abstract" : "Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of  carnitine. CDSP may present with acute metabolic derangement simulating Reye's syndrome within the first 2 years of life. After 3 years of age, patients with CDSP may present with cardiomyopathy and muscle weakness. A linkage with D5S436 in 5q was reported in a family. A recently cloned homologue of the organic cation transporter, OCTN2, which has sodium-dependent carnitine uptake properties, was also mapped to the same locus. We screened for mutation in OCTN2 in a confirmed CDSP family. One truncating mutation (Trp132Stop) and one missense mutation (Pro478Leu) of OCTN2 were identified together with two silent polymorphisms. Expression of the mutant cDNAs revealed virtually no uptake activity for both mutations. Our data indicate that mutations in OCTN2 are responsible for CDSP. Identification of the underlying gene in this disease will allow rapid detection  of carriers and postnatal diagnosis of affected patients.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NL",
      "lastName" : "Tang",
      "authorRank" : 1,
      "name" : "Tang NL",
      "referenceId" : "RGD:A130860"
    }, {
      "firstName" : "V",
      "lastName" : "Ganapathy",
      "authorRank" : 2,
      "name" : "Ganapathy V",
      "referenceId" : "RGD:A5011"
    }, {
      "firstName" : "X",
      "lastName" : "Wu",
      "authorRank" : 3,
      "name" : "Wu X",
      "referenceId" : "RGD:A8038"
    }, {
      "firstName" : "J",
      "lastName" : "Hui",
      "authorRank" : 4,
      "name" : "Hui J",
      "referenceId" : "RGD:A142439"
    }, {
      "firstName" : "P",
      "lastName" : "Seth",
      "authorRank" : 5,
      "name" : "Seth P",
      "referenceId" : "RGD:A5006"
    }, {
      "firstName" : "PM",
      "lastName" : "Yuen",
      "authorRank" : 6,
      "name" : "Yuen",
      "referenceId" : "RGD:A267638"
    }, {
      "firstName" : "RJ",
      "lastName" : "Wanders",
      "authorRank" : 7,
      "name" : "Wanders RJ",
      "referenceId" : "RGD:A5204"
    }, {
      "firstName" : "TF",
      "lastName" : "Fok",
      "authorRank" : 8,
      "name" : "Fok",
      "referenceId" : "RGD:A215549"
    }, {
      "firstName" : "NM",
      "lastName" : "Hjelm",
      "authorRank" : 9,
      "name" : "Hjelm",
      "referenceId" : "RGD:A281045"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072027"
    } ]
  }, {
    "primaryId" : "PMID:10072491",
    "title" : "Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Harriman GR, etal., J Immunol. 1999 Mar 1;162(5):2521-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:39:02.000-05:00",
    "volume" : "162",
    "pages" : "2521-9",
    "abstract" : "A murine model of IgA deficiency has been established by targeted deletion of the IgA switch and constant regions in embryonic stem cells. B cells from IgA-deficient mice were incapable of producing IgA in vitro in response to TGF-beta. IgA-deficient mice expressed higher levels of IgM and IgG in serum and  gastrointestinal secretions and decreased levels of IgE in serum and pulmonary secretions. Expression of IgG subclasses was complex, with the most consistent finding being an increase in IgG2b and a decrease in IgG3 in serum and secretions. No detectable IgA Abs were observed following mucosal immunization against influenza; however, compared with those in wild-type mice, increased levels of IgM Abs were seen in both serum and secretions. Development of lymphoid tissues as well as T and B lymphocyte function appeared normal otherwise. Peyer's patches in IgA-deficient mice were well developed with prominent germinal centers despite the absence of IgA in these germinal centers or intestinal lamina propria. Lymphocytes from IgA-deficient mice responded to T and B cell mitogens comparable to those of wild-type mice, while T cells from IgA-deficient mice produced comparable levels of IFN-gamma and IL-4 mRNA and protein. In conclusion, mice with targeted deletion of the IgA switch and constant regions are completely deficient in IgA and exhibit altered expression of other Ig isotypes, notably IgM, IgG2b, IgG3, and IgE, but otherwise have normal lymphocyte development, proliferative responses, and cytokine production.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GR",
      "lastName" : "Harriman",
      "authorRank" : 1,
      "name" : "Harriman",
      "referenceId" : "RGD:A330954"
    }, {
      "firstName" : "M",
      "lastName" : "Bogue",
      "authorRank" : 2,
      "name" : "Bogue",
      "referenceId" : "RGD:A331854"
    }, {
      "firstName" : "P",
      "lastName" : "Rogers",
      "authorRank" : 3,
      "name" : "Rogers",
      "referenceId" : "RGD:A265619"
    }, {
      "firstName" : "M",
      "lastName" : "Finegold",
      "authorRank" : 4,
      "name" : "Finegold M",
      "referenceId" : "RGD:A39187"
    }, {
      "firstName" : "S",
      "lastName" : "Pacheco",
      "authorRank" : 5,
      "name" : "Pacheco",
      "referenceId" : "RGD:A280853"
    }, {
      "firstName" : "A",
      "lastName" : "Bradley",
      "authorRank" : 6,
      "name" : "Bradley A",
      "referenceId" : "RGD:A39009"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhang",
      "authorRank" : 7,
      "name" : "Zhang Y",
      "referenceId" : "RGD:A5934"
    }, {
      "firstName" : "IN",
      "lastName" : "Mbawuike",
      "authorRank" : 8,
      "name" : "Mbawuike IN",
      "referenceId" : "RGD:A130156"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340814"
    } ]
  }, {
    "primaryId" : "PMID:10072492",
    "title" : "Mucosal immunity to influenza without IgA: an IgA knockout mouse model.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mbawuike IN, etal., J Immunol. 1999 Mar 1;162(5):2530-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T20:09:24.000-05:00",
    "volume" : "162",
    "pages" : "2530-7",
    "abstract" : "IgA knockout mice (IgA-/-) were generated by gene targeting and were used to determine the role of IgA in protection against mucosal infection by influenza and the value of immunization for preferential induction of secretory IgA. Aerosol challenge of naive IgA-/- mice and their wild-type IgA+/+ littermates with sublethal and lethal doses of influenza virus resulted in similar levels of  pulmonary virus infection and mortality. Intranasal and i.p. immunization with influenza vaccine plus cholera toxin/cholera toxin B induced significant mucosal  and serum influenza hemagglutinin-specific IgA Abs in IgA+/+ (but not IgA-/-) mice as well as IgG and IgM Abs in both IgA-/- and IgA+/+ mice; both exhibited similar levels of pulmonary and nasal virus replication and mortality following a lethal influenza virus challenge. Monoclonal anti-hemagglutinin IgG1, IgG2a, IgM, and polymeric IgA Abs were equally effective in preventing influenza virus infection in IgA-/- mice. These results indicate that IgA is not required for prevention of influenza virus infection and disease. Indeed, while mucosal immunization for selective induction of IgA against influenza may constitute a useful approach for control of influenza and other respiratory viral infections,  strategies that stimulate other Igs in addition may be more desirable.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "IN",
      "lastName" : "Mbawuike",
      "authorRank" : 1,
      "name" : "Mbawuike IN",
      "referenceId" : "RGD:A130156"
    }, {
      "firstName" : "S",
      "lastName" : "Pacheco",
      "authorRank" : 2,
      "name" : "Pacheco",
      "referenceId" : "RGD:A280853"
    }, {
      "firstName" : "CL",
      "lastName" : "Acuna",
      "authorRank" : 3,
      "name" : "Acuna",
      "referenceId" : "RGD:A332915"
    }, {
      "firstName" : "KC",
      "lastName" : "Switzer",
      "authorRank" : 4,
      "name" : "Switzer",
      "referenceId" : "RGD:A332916"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhang",
      "authorRank" : 5,
      "name" : "Zhang Y",
      "referenceId" : "RGD:A5934"
    }, {
      "firstName" : "GR",
      "lastName" : "Harriman",
      "authorRank" : 6,
      "name" : "Harriman",
      "referenceId" : "RGD:A330954"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11341628"
    } ]
  }, {
    "primaryId" : "PMID:10072499",
    "title" : "Genome-wide linkage analysis of chronic relapsing experimental autoimmune encephalomyelitis in the rat identifies a major susceptibility locus on chromosome 9.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Dahlman I, etal., J Immunol 1999 Mar 1;162(5):2581-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-12-20T15:50:25.000-06:00",
    "volume" : "162",
    "pages" : "2581-8",
    "abstract" : "The immunization of inbred Dark Agouti (DA) rats with an emulsion containing homogenized spinal cord and CFA induces chronic relapsing experimental autoimmune encephalomyelitis (EAE), a disease with many similarities to multiple sclerosis. We report here the first genome-wide search for quantitative trait loci regulating EAE in the rat using this model. We identified one quantitative trait locus on chromosome 9, Eae4, in a [DA(RT1av1) x BN(RT1n)]F2 intercross showing linkage to disease susceptibility and expression of mRNA for the proinflammatory cytokine IFN-gamma in the spinal cord. Eae4 had a larger influence on disease incidence among rats that were homozygous for the RT1av1 MHC haplotype (RT1av1 rats) compared with RT1n/av1 rats, suggesting an interaction between Eae4 and the MHC. Homozygosity for the DA allele at markers in Eae4 and in the MHC was sufficient for EAE. Thus, Eae4 is a major genetic factor determining susceptibility to EAE in this cross of DA rats. In addition, there was support for linkage to phenotypes of EAE on chromosomes 1, 2, 5, 7, 8, 12, and 15. The chromosome 12 region has been shown previously to predispose DA rats to arthritis, and the chromosome 2 region is syntenic to Eae3 in mice. We conclude that Eae4 and probably the other identified genome regions harbor genes regulating susceptibility to neuroinflammatory disease. The identification and functional characterization of these genes may disclose critical events in the pathogenesis of multiple sclerosis; understanding these events could be essential for the development of new therapies against the disease.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Dahlman",
      "authorRank" : 1,
      "name" : "Dahlman I",
      "referenceId" : "RGD:A114313"
    }, {
      "firstName" : "L",
      "lastName" : "Jacobsson",
      "authorRank" : 2,
      "name" : "Jacobsson L",
      "referenceId" : "RGD:A38938"
    }, {
      "firstName" : "A",
      "lastName" : "Glaser",
      "authorRank" : 3,
      "name" : "Glaser A",
      "referenceId" : "RGD:A147106"
    }, {
      "firstName" : "JC",
      "lastName" : "Lorentzen",
      "authorRank" : 4,
      "name" : "Lorentzen JC",
      "referenceId" : "RGD:A122872"
    }, {
      "firstName" : "M",
      "lastName" : "Andersson",
      "authorRank" : 5,
      "name" : "Andersson M",
      "referenceId" : "RGD:A165669"
    }, {
      "firstName" : "H",
      "lastName" : "Luthman",
      "authorRank" : 6,
      "name" : "Luthman H",
      "referenceId" : "RGD:A148950"
    }, {
      "firstName" : "T",
      "lastName" : "Olsson",
      "authorRank" : 7,
      "name" : "Olsson T",
      "referenceId" : "RGD:A157010"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69712"
    } ]
  }, {
    "primaryId" : "PMID:10072531",
    "title" : "gammadelta T cells contribute to control of chronic parasitemia in Plasmodium chabaudi infections in mice.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Seixas EM and Langhorne J, J Immunol. 1999 Mar 1;162(5):2837-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:49:14.000-05:00",
    "volume" : "162",
    "pages" : "2837-41",
    "abstract" : "During a primary infection of mice with Plasmodium chabaudi, gammadelta T cells are stimulated and their expansion coincides with recovery from the acute phase of infection in normal mice or with chronic infections in B cell-deficient mice (mu-MT). To determine whether the large gammadelta T cell pool observed in female B cell-deficient mice is responsible for controlling the chronic infection, studies were done using double-knockout mice deficient in both B and gammadelta cells (mu-MT x delta-/-TCR) and in gammadelta T cell-depleted mu-MT mice. In both types of gammadelta T cell-deficient mice, the early parasitemia following the peak of infection was exacerbated, and the chronic parasitemia was maintained at  significantly higher levels in the absence of gammadelta T cells. The majority of gammadelta T cells in C57BL/6 and mu-MT mice responding to infection belonged predominantly to a single family of gammadelta T cells with TCR composed of Vgamma2Vdelta4 chains and which produced IFN-gamma rather than IL-4.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EM",
      "lastName" : "Seixas",
      "authorRank" : 1,
      "name" : "Seixas",
      "referenceId" : "RGD:A332491"
    }, {
      "firstName" : "J",
      "lastName" : "Langhorne",
      "authorRank" : 2,
      "name" : "Langhorne",
      "referenceId" : "RGD:A331066"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11341041"
    } ]
  }, {
    "primaryId" : "PMID:10072578",
    "title" : "Assignment of the human endogenous retrovirus S71 (SSAV1) to chromosome 18 band q12.3 by radiation hybrid mapping.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Kim HS and Crow TJ, Cytogenet Cell Genet. 1998;83(3-4):207.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T15:06:25.000-05:00",
    "volume" : "83",
    "pages" : "207",
    "issueName" : "3-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HS",
      "lastName" : "Kim",
      "authorRank" : 1,
      "name" : "Kim HS",
      "referenceId" : "RGD:A17205"
    }, {
      "firstName" : "TJ",
      "lastName" : "Crow",
      "authorRank" : 2,
      "name" : "Crow",
      "referenceId" : "RGD:A240573"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11058148"
    } ]
  }, {
    "primaryId" : "PMID:10072583",
    "title" : "Assignment of the human skeletal muscle a-actin gene (ACTA1) to chromosome 1q42.13-->q42.2 by radiation hybrid mapping.",
    "datePublished" : "1998-06-01T00:00:00.000-05:00",
    "citation" : "Mogensen J, etal., Cytogenet Cell Genet 1998;83(3-4):224-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T16:05:21.000-05:00",
    "volume" : "83",
    "pages" : "224-5",
    "issueName" : "3-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Mogensen",
      "authorRank" : 1,
      "name" : "Mogensen J",
      "referenceId" : "RGD:A40784"
    }, {
      "firstName" : "TA",
      "lastName" : "Kruse",
      "authorRank" : 2,
      "name" : "Kruse TA",
      "referenceId" : "RGD:A40785"
    }, {
      "firstName" : "AD",
      "lastName" : "Borglum",
      "authorRank" : 3,
      "name" : "Borglum AD",
      "referenceId" : "RGD:A40786"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298659"
    } ]
  }, {
    "primaryId" : "PMID:10072602",
    "title" : "Organization and expression of rat Tspy.",
    "datePublished" : "1998-08-01T00:00:00.000-05:00",
    "citation" : "Dechend F, etal., Cytogenet Cell Genet 1998;83(3-4):270-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:32:38.000-05:00",
    "volume" : "83",
    "pages" : "270-4",
    "abstract" : "We have isolated both a full-length rat Tspy cDNA from testicular mRNA by rapid amplification of cDNA ends (RACE) and RT-PCR and a full-length rat Tspy gene from genomic DNA by PCR. In contrast to the mouse, where Tspy is present in a single copy and is apparently functionless, and to man and cattle, where TSPY is organized in a moderately repetitive cluster, the rat Tspy locus apparently consists of one complete functional and one truncated, probably nonfunctional, copy, coherently localized on Yp, as revealed by FISH analysis.",
    "issueName" : "3-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Dechend",
      "authorRank" : 1,
      "name" : "Dechend F",
      "referenceId" : "RGD:A23777"
    }, {
      "firstName" : "S",
      "lastName" : "Schubert",
      "authorRank" : 2,
      "name" : "Schubert S",
      "referenceId" : "RGD:A23778"
    }, {
      "firstName" : "I",
      "lastName" : "Nanda",
      "authorRank" : 3,
      "name" : "Nanda I",
      "referenceId" : "RGD:A23779"
    }, {
      "firstName" : "T",
      "lastName" : "Vogel",
      "authorRank" : 4,
      "name" : "Vogel T",
      "referenceId" : "RGD:A23780"
    }, {
      "firstName" : "M",
      "lastName" : "Schmid",
      "authorRank" : 5,
      "name" : "Schmid M",
      "referenceId" : "RGD:A23781"
    }, {
      "firstName" : "J",
      "lastName" : "Schmidtke",
      "authorRank" : 6,
      "name" : "Schmidtke J",
      "referenceId" : "RGD:A23782"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634384"
    } ]
  }, {
    "primaryId" : "PMID:10072717",
    "title" : "Expression of cardiac cytokines and inducible form of nitric oxide synthase (NOS2) in Trypanosoma cruzi-infected mice.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Huang H, etal., J Mol Cell Cardiol. 1999 Jan;31(1):75-88. doi: 10.1006/jmcc.1998.0848.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-11-10T14:50:51.000-06:00",
    "volume" : "31",
    "pages" : "75-88",
    "abstract" : "Expression of Cardiac Cytokines and Inducible Form of Nitric Oxide Synthase (NOS2) in Trypanosoma cruzi-infected Mice. Journal of Molecular and Cellular Cardiology (1999) 31, 75-88. Both cardiac cytokine and inducible nitric oxide synthase (NOS2) expression have been implicated in the cardiac dysfunction associated with myocarditis and cardiomyopathy. Chagas' disease, caused by Trypanosoma cruzi, is an important cause of cardiomyopathy. We examined the effect of T. cruzi (Brazil strain) infection with or without verapamil treatment on the expression of cytokines and NOS2 in the heart. Messenger RNA for NOS2, IL-1beta, and TNF-alpha was induced in the myocardium of infected mice, and Western blot analysis as well as immunohistochemistry demonstrated a significant increase in NOS2 protein. Verapamil treatment reduced the expression of cardiac NOS2 protein and the mRNAs for NOS2, TNF-alpha, and IL-1beta. Infection-associated increases in cardiac L-citrulline were also reduced by verapamil treatment. Verapamil-treated infected mice that survived for 80 days exhibited less inflammation and fibrosis compared to untreated mice. Gated MRI and echocardiography revealed an increased right ventricular inner diameter (RVID) in untreated but not in verapamil-treated infected CD1 mice. This suggests that the infection-associated expression of cytokines and NOS2 in the heart correlate with the severity of myocarditis and the effect of verapamil. The RVID was significantly increased in infected wild-type (WT) compared to infected syngeneic NOS2 knockout (NOS2-/-) mice. Fractional shortening was decreased and myocardial L-citrulline was increased in infected WT mice. These data suggest that NO generated from cardiac NOS2 may participate in the pathogenesis of murine chagasic heart disease.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Huang",
      "authorRank" : 1,
      "name" : "Huang H",
      "referenceId" : "RGD:A19951"
    }, {
      "firstName" : "J",
      "lastName" : "Chan",
      "authorRank" : 2,
      "name" : "Chan J",
      "referenceId" : "RGD:A43305"
    }, {
      "firstName" : "M",
      "lastName" : "Wittner",
      "authorRank" : 3,
      "name" : "Wittner M",
      "referenceId" : "RGD:A612160"
    }, {
      "firstName" : "L A",
      "lastName" : "Jelicks",
      "authorRank" : 4,
      "name" : "Jelicks LA",
      "referenceId" : "RGD:A612161"
    }, {
      "firstName" : "S A",
      "lastName" : "Morris",
      "authorRank" : 5,
      "name" : "Morris SA",
      "referenceId" : "RGD:A460786"
    }, {
      "firstName" : "S M",
      "lastName" : "Factor",
      "authorRank" : 6,
      "name" : "Factor SM",
      "referenceId" : "RGD:A612162"
    }, {
      "firstName" : "L M",
      "lastName" : "Weiss",
      "authorRank" : 7,
      "name" : "Weiss LM",
      "referenceId" : "RGD:A612163"
    }, {
      "firstName" : "V L",
      "lastName" : "Braunstein",
      "authorRank" : 8,
      "name" : "Braunstein VL",
      "referenceId" : "RGD:A612164"
    }, {
      "firstName" : "C J",
      "lastName" : "Bacchi",
      "authorRank" : 9,
      "name" : "Bacchi CJ",
      "referenceId" : "RGD:A612165"
    }, {
      "firstName" : "N",
      "lastName" : "Yarlett",
      "authorRank" : 10,
      "name" : "Yarlett N",
      "referenceId" : "RGD:A612166"
    }, {
      "firstName" : "M",
      "lastName" : "Chandra",
      "authorRank" : 11,
      "name" : "Chandra M",
      "referenceId" : "RGD:A62496"
    }, {
      "firstName" : "J",
      "lastName" : "Shirani",
      "authorRank" : 12,
      "name" : "Shirani J",
      "referenceId" : "RGD:A612167"
    }, {
      "firstName" : "H B",
      "lastName" : "Tanowitz",
      "authorRank" : 13,
      "name" : "Tanowitz HB",
      "referenceId" : "RGD:A612168"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:629006635"
    } ]
  }, {
    "primaryId" : "PMID:10072786",
    "title" : "Expression of growth/differentiation factor 11, a new member of the BMP/TGFbeta superfamily during mouse embryogenesis.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Nakashima M, etal., Mech Dev 1999 Feb;80(2):185-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:05.000-06:00",
    "volume" : "80",
    "pages" : "185-9",
    "abstract" : "We have cloned and characterized a new member of the bone morphogenetic protein/transforming growth factor beta (BMP/TGFbeta) superfamily, growth differentiation factor 11 (Gdf11), from rat incisor pulp RNA by reverse transcription-polymerase chain reaction using degenerate primers. The mature carboxyl-terminal domain encoded by Gdf11 is most closely related to Gdf8, being 90% identical to the mouse gene. Northern blot analysis revealed Gdf11 is expressed in adult dental pulp and brain. In situ hybridization of sections and whole-mount embryos demonstrated Gdf11 is first strongly expressed in restricted domains at 8.5 days post coitus (dpc) when it is highest in the tail bud. At 10.5 dpc, it is expressed in the branchial arches, limb bud, tail bud and posterior dorsal neural tube. Later, it is expressed in terminally-differentiated odontoblasts, the nasal epithelium, retina and specific regions of the brain.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Nakashima",
      "authorRank" : 1,
      "name" : "Nakashima M",
      "referenceId" : "RGD:A7381"
    }, {
      "firstName" : "T",
      "lastName" : "Toyono",
      "authorRank" : 2,
      "name" : "Toyono T",
      "referenceId" : "RGD:A7382"
    }, {
      "firstName" : "A",
      "lastName" : "Akamine",
      "authorRank" : 3,
      "name" : "Akamine A",
      "referenceId" : "RGD:A7383"
    }, {
      "firstName" : "A",
      "lastName" : "Joyner",
      "authorRank" : 4,
      "name" : "Joyner A",
      "referenceId" : "RGD:A7384"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69843"
    } ]
  }, {
    "primaryId" : "PMID:10072790",
    "title" : "Expression of the rat homologue of the Drosophila fat tumour suppressor gene.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Ponassi M, etal., Mech Dev 1999 Feb;80(2):207-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:47.000-05:00",
    "volume" : "80",
    "pages" : "207-12",
    "abstract" : "We have sequenced and defined the expression during rat embryogenesis of the protocadherin fat, the murine homologue of a Drosophila tumour suppressor gene. As previously described for human fat, the sequence encodes a large protocadherin with 34 cadherin repeats, five epidermal growth factor (EGF)-like repeats containing a single laminin A-G domain and a putative transmembrane portion followed by a cytoplasmic sequence. This cytoplasmic sequence shows homology to the b-catenin binding regions of classical cadherin cytoplasmic tails and also ends with a PDZ domain-binding motif. In situ hybridization studies at E15 show that fat is predominately expressed in fetal epithelial cell layers and in the CNS, although expression is also seen in tongue musculature and condensing cartilage. Within the CNS, expression is seen in the germinal regions and in areas of developing cortex, and this neural expression pattern is also seen at later embryonic (E18) and postnatal stages. No labelling was seen in adult tissues except in the CNS, where the remnant of the germinal zones, as well as the dentate gyrus, continue to express fat.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Ponassi",
      "authorRank" : 1,
      "name" : "Ponassi M",
      "referenceId" : "RGD:A18321"
    }, {
      "firstName" : "TS",
      "lastName" : "Jacques",
      "authorRank" : 2,
      "name" : "Jacques TS",
      "referenceId" : "RGD:A18322"
    }, {
      "firstName" : "L",
      "lastName" : "Ciani",
      "authorRank" : 3,
      "name" : "Ciani L",
      "referenceId" : "RGD:A18323"
    }, {
      "firstName" : "C",
      "lastName" : "Ffrench Constant",
      "authorRank" : 4,
      "name" : "Ffrench Constant C",
      "referenceId" : "RGD:A18324"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632716"
    } ]
  }, {
    "primaryId" : "PMID:10072897",
    "title" : "Inhibition of beta-myosin heavy chain gene expression in pressure overload rat heart by losartan and captopril.",
    "datePublished" : "1997-01-01T00:00:00.000-06:00",
    "citation" : "Ling Q, etal., Zhongguo Yao Li Xue Bao. 1997 Jan;18(1):63-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-05-01T12:47:59.000-05:00",
    "volume" : "18",
    "pages" : "63-6",
    "abstract" : "<br><b>AIM: </b>To study the effects of losartan and captopril on beta-myosin heavy chain (MHC), and alpha-MHC gene expression.<br><b>METHODS: </b>Pressure overload was produced by abdominal aortic coarctation (AAC) in rats. alpha- and beta-MHC mRNA were measured by Northern blot.<br><b>RESULTS: </b>In left ventricular myocardium of sham-operated rats, the alpha-MHC mRNA predominated, while the beta-MHC mRNA was only detectable. In response AAC, there was a 70-fold increase in the beta-MHC mRNA (P < 0.01), while alpha-MHC mRNA reduced to 26% (P < 0.01). Losartan (3 mg.kg-1.d-1, i.g. for 11 d) to AAC rats caused inhibitions of beta-MHC by 96% and alpha-MHC by 86% gene expression without lowering blood pressure. A reduction in beta-MHC mRNA was also seen in captopril-treated rats (30 mg.kg-1.d-1, i.g. for 11 d), but the inhibitory effect of captopril on alpha-MHC mRNA was less than that of losartan (44% vs 86%, P < 0.05).<br><b>CONCLUSIONS: </b>The shift of MHC isoform induced by pressure overload is due to up-regulation of beta-MHC and down-regulation of alpha-MHC gene expression. Inhibition of beta-MHC gene expression by losartan is achieved primarily by direct blockade of angiotensin II type I receptors in the myocardium, independent on hemodynamics.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Ling",
      "authorRank" : 1,
      "name" : "Ling Q",
      "referenceId" : "RGD:A44446"
    }, {
      "firstName" : "T H",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen TH",
      "referenceId" : "RGD:A442939"
    }, {
      "firstName" : "Z G",
      "lastName" : "Guo",
      "authorRank" : 3,
      "name" : "Guo ZG",
      "referenceId" : "RGD:A442940"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12880015"
    } ]
  }, {
    "primaryId" : "PMID:10073515",
    "title" : "Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Aithal GP, etal., Lancet. 1999 Feb 27;353(9154):717-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T20:20:39.000-05:00",
    "volume" : "353",
    "pages" : "717-9",
    "abstract" : "BACKGROUND: The cytochrome P450 CYP2C9 is responsible for the metabolism of S-warfarin. Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single aminoacid substitution in each case. The allelic variants are associated with impaired hydroxylation of S-warfarin in in-vitro expression systems. We have studied the effect of CYP2C9 polymorphism on the in-vivo warfarin dose requirement. METHODS: Patients with a daily warfarin dose requirement of 1.5 mg or less (low-dose group, n=36), randomly selected patients  with a wide range of dose requirements from an anticoagulant clinic in north-east England (clinic control group, n=52), and 100 healthy controls from the community in the same region were studied. Genotyping for the CYP2C9*2 and CYP2C9*3 alleles was done by PCR analysis. Case notes were reviewed to assess the difficulties encountered during the induction of warfarin therapy and bleeding complications in the low-dose and clinic control groups. FINDINGS: The odds ratio for individuals with a low warfarin dose requirement having one or more CYP2C9 variant alleles compared with the normal population was 6.21 (95% CI 2.48-15.6).  Patients in the low-dose group were more likely to have difficulties at the time  of induction of warfarin therapy (5.97 [2.26-15.82]) and have increased risk of major bleeding complications (rate ratio 3.68 [1.43-9.50]) when compared with randomly selected clinic controls. INTERPRETATION: We have shown that there is a  strong association between CYP2C9 variant alleles and low warfarin dose requirement. CYP2C9 genotyping may identify a subgroup of patients who have difficulty at induction of warfarin therapy and are potentially at a higher risk  of bleeding complications.",
    "issueName" : "9154",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GP",
      "lastName" : "Aithal",
      "authorRank" : 1,
      "name" : "Aithal",
      "referenceId" : "RGD:A321598"
    }, {
      "firstName" : "CP",
      "lastName" : "Day",
      "authorRank" : 2,
      "name" : "Day CP",
      "referenceId" : "RGD:A66048"
    }, {
      "firstName" : "PJ",
      "lastName" : "Kesteven",
      "authorRank" : 3,
      "name" : "Kesteven",
      "referenceId" : "RGD:A321599"
    }, {
      "firstName" : "AK",
      "lastName" : "Daly",
      "authorRank" : 4,
      "name" : "Daly AK",
      "referenceId" : "RGD:A66042"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11098587"
    } ]
  }, {
    "primaryId" : "PMID:10073573",
    "title" : "Characterization of the sequence and expression of a Ykt6 prenylated SNARE from rat.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Catchpoole DR and Wanjin H, DNA Cell Biol 1999 Feb;18(2):141-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:14:54.000-05:00",
    "volume" : "18",
    "pages" : "141-5",
    "abstract" : "The Ykt6 protein represents a novel soluble N-ethylmaleimide-sensitive fusion protein receptor (SNARE), as it is the only one known without a hydrophobic transmembrane region at the carboxy terminus. For this SNARE, however, membrane interaction is thought to be mediated through a cysteine/aliphatic/aliphatic/methionine or histidine (CAAX) C-terminal motif, a consensus sequence involved in prenylated membrane anchoring. To date, two full-length Ykt6 cDNAs have been reported, these being in yeast and human, with a further protein predicted from a Caenorhabditis elegans cosmid. Using a mouse EST clone identified as having 65% homology with the human Ykt6, we isolated a cDNA clone encoding the rat Ykt6 homolog (rYkt6). Sequence analysis of rYkt6 demonstrated that a high level of species conservation exists between the rat and human prenylated SNAREs, as both the nucleotide and amino acid sequences share >90% homology. Mammalian Ykt6 is shown here for the first time to be constitutively expressed in a variety of tissues. The species conservation and ubiquitous expression of prenylated SNAREs hence may be indicative of an important and central role for these proteins in cellular protein trafficking.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DR",
      "lastName" : "Catchpoole",
      "authorRank" : 1,
      "name" : "Catchpoole DR",
      "referenceId" : "RGD:A9409"
    }, {
      "firstName" : "H",
      "lastName" : "Wanjin",
      "authorRank" : 2,
      "name" : "Wanjin H",
      "referenceId" : "RGD:A9410"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70609"
    } ]
  }, {
    "primaryId" : "PMID:10073593",
    "title" : "Ganglioside GM2-activator protein and vesicular transport in collecting duct intercalated cells.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Mundel TM, etal., J Am Soc Nephrol. 1999 Mar;10(3):435-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-10T12:06:17.000-06:00",
    "volume" : "10",
    "pages" : "435-43",
    "abstract" : "This study describes the molecular characterization of an antigen defined by an autoantibody from a woman with habitual abortion as GM2-activator protein. The patient showed no disorder of renal function. Accidentally with routine serum screening for autoantibodies, an immunoreactivity was found in kidney collecting duct intercalated cells. Three distinct patterns of immunostaining of intercalated cells were observed: staining of the apical pole, basolateral pole, and diffuse cytoplasmic labeling. Ultrastructurally, the immunoreactivity was associated with \"studs,\" which represent the cytoplasmic domain of the vacuolar proton pump in intercalated cells. This pump is subjected to a shuttling mechanism from cytoplasmic stores to the cell membrane, which exclusively occurs in intercalated cells. Peptide sequences of a 23-kD protein purified from rat kidney cortex showed complete identity with corresponding sequences of GM2-activator protein. In the brain, GM2-activator protein is required for hexosaminidase A to split a sugar from ganglioside GM2. Because neither ganglioside GM2 nor GM1 (its precursor) is present in significant amounts in the kidney, the previous finding that this tissue contains the highest level of activator protein in the body was confusing. In this study, a novel role for GM2-activator protein in intercalated cells is proposed, and possible roles in the shuttling mechanism are discussed.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TM",
      "lastName" : "Mundel",
      "authorRank" : 1,
      "name" : "Mundel TM",
      "referenceId" : "RGD:A49407"
    }, {
      "firstName" : "HW",
      "lastName" : "Heid",
      "authorRank" : 2,
      "name" : "Heid HW",
      "referenceId" : "RGD:A56286"
    }, {
      "firstName" : "DJ",
      "lastName" : "Mahuran",
      "authorRank" : 3,
      "name" : "Mahuran DJ",
      "referenceId" : "RGD:A4916"
    }, {
      "firstName" : "W",
      "lastName" : "Kriz",
      "authorRank" : 4,
      "name" : "Kriz W",
      "referenceId" : "RGD:A45210"
    }, {
      "firstName" : "P",
      "lastName" : "Mundel",
      "authorRank" : 5,
      "name" : "Mundel P",
      "referenceId" : "RGD:A49411"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598994"
    } ]
  }, {
    "primaryId" : "PMID:10073607",
    "title" : "Intranephron distribution and regulation of endothelin-converting enzyme-1 in cyclosporin A-induced acute renal failure in rats.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Nakayama Y, etal., J Am Soc Nephrol. 1999 Mar;10(3):562-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-28T11:05:36.000-05:00",
    "volume" : "10",
    "pages" : "562-71",
    "abstract" : "Endothelin-1 (ET-1) is thought to play a significant role in acute renal failure  induced by cyclosporin A (CsA). The cDNA sequence encoding endothelin-converting  enzyme-1 (ECE-1), which produces the active form of ET-1 from big ET-1, was recently reported. To elicit the role of ECE-1 in the glomerular and tubular dysfunction induced by CsA, the effects of CsA on mRNA and protein expression of  ECE-1 in rat kidney and on mRNA expression of prepro-ET-1 and ET A- and B-type receptors in glomeruli were studied. ECE-1 mRNA was detected in glomeruli and in  whole nephron segments. ECE-1 mRNA expression was downregulated in all nephron segments at 24 h after CsA injection. Protein levels were also downregulated in glomeruli and in the outer and inner medulla. CsA rapidly increased prepro-ET-1 mRNA expression in glomeruli at 30 to 60 min after injection; this rapid increase was followed by an increase in plasma ET-1 levels. These increases were followed  by decreased expression of ECE-1, ET A-type receptor, and ET B-type receptor mRNA at 6 h after injection, and serum creatinine levels were increased at 24 h after  CsA injection. It is suggested that downregulation of glomerular and tubular ECE-1 expression may be caused by increased ET-1 synthesis in CsA-induced acute renal failure.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Nakayama",
      "authorRank" : 1,
      "name" : "Nakayama Y",
      "referenceId" : "RGD:A13628"
    }, {
      "firstName" : "H",
      "lastName" : "Nonoguchi",
      "authorRank" : 2,
      "name" : "Nonoguchi H",
      "referenceId" : "RGD:A12822"
    }, {
      "firstName" : "S",
      "lastName" : "Kiyama",
      "authorRank" : 3,
      "name" : "Kiyama",
      "referenceId" : "RGD:A170124"
    }, {
      "firstName" : "M",
      "lastName" : "Ikebe",
      "authorRank" : 4,
      "name" : "Ikebe M",
      "referenceId" : "RGD:A20606"
    }, {
      "firstName" : "Y",
      "lastName" : "Tashima",
      "authorRank" : 5,
      "name" : "Tashima Y",
      "referenceId" : "RGD:A48310"
    }, {
      "firstName" : "K",
      "lastName" : "Shimada",
      "authorRank" : 6,
      "name" : "Shimada",
      "referenceId" : "RGD:A403540"
    }, {
      "firstName" : "K",
      "lastName" : "Tanzawa",
      "authorRank" : 7,
      "name" : "Tanzawa K",
      "referenceId" : "RGD:A30060"
    }, {
      "firstName" : "K",
      "lastName" : "Tomita",
      "authorRank" : 8,
      "name" : "Tomita",
      "referenceId" : "RGD:A404608"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7244185"
    } ]
  }, {
    "primaryId" : "PMID:10073700",
    "title" : "Immune responses against human papillomavirus (HPV) type 16 virus-like particles in a cohort study of women with cervical intraepithelial neoplasia. I. Differential T-helper and IgG responses in relation to HPV infection and disease outcome.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "de Gruijl TD, etal., J Gen Virol. 1999 Feb;80 ( Pt 2):399-408.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-11-24T12:10:08.000-06:00",
    "volume" : "80 ( Pt 2)",
    "pages" : "399-408",
    "abstract" : "T-helper (Th) cell-dependent IL-2 production and plasma IgG responses to virus-like particles consisting of the human papillomavirus type 16 (HPV-16) major capsid protein L1 (L1-VLP) were determined in patients with cytological evidence of cervical intraepithelial neoplasia (CIN) participating in a non-intervention prospective cohort study. IgG responses were associated with HPV-16 persistence and high-grade CIN lesions, while high frequencies of Th responses were observed in patients with both virus clearance and virus persistence, irrespective of CIN grade. The IgG response was found in conjunction with an IL-2 response to L1-VLP in 87% of the patients. Recognition of the HPV-16 L1 Th epitope (amino acids 311-335) was found to be more closely associated than recognition of L1-VLP as a whole to HPV exposure and CIN development. Among the HPV-16+ patients included in this study, those showing a Th response to amino acids 311-335 were more likely to carry the HLA DRB1*11/DQB1*0301 haplotype, while those showing an IgG response to L1-VLP were more likely to carry DRB1*0101/DQB1*0501. However, neither cell-mediated nor humoral immune responses against HPV-16 L1 appear to be sufficient for the natural control of HPV infection and CIN development.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TD",
      "lastName" : "De Gruijl",
      "authorRank" : 1,
      "name" : "De Gruijl TD",
      "referenceId" : "RGD:A115783"
    }, {
      "firstName" : "HJ",
      "lastName" : "Bontkes",
      "authorRank" : 2,
      "name" : "Bontkes HJ",
      "referenceId" : "RGD:A115784"
    }, {
      "firstName" : "JM",
      "lastName" : "Walboomers",
      "authorRank" : 3,
      "name" : "Walboomers JM",
      "referenceId" : "RGD:A115785"
    }, {
      "firstName" : "P",
      "lastName" : "Coursaget",
      "authorRank" : 4,
      "name" : "Coursaget P",
      "referenceId" : "RGD:A115786"
    }, {
      "firstName" : "MJ",
      "lastName" : "Stukart",
      "authorRank" : 5,
      "name" : "Stukart MJ",
      "referenceId" : "RGD:A115787"
    }, {
      "firstName" : "C",
      "lastName" : "Dupuy",
      "authorRank" : 6,
      "name" : "Dupuy C",
      "referenceId" : "RGD:A17815"
    }, {
      "firstName" : "E",
      "lastName" : "Kueter",
      "authorRank" : 7,
      "name" : "Kueter E",
      "referenceId" : "RGD:A115788"
    }, {
      "firstName" : "RH",
      "lastName" : "Verheijen",
      "authorRank" : 8,
      "name" : "Verheijen RH",
      "referenceId" : "RGD:A99013"
    }, {
      "firstName" : "TJ",
      "lastName" : "Helmerhorst",
      "authorRank" : 9,
      "name" : "Helmerhorst TJ",
      "referenceId" : "RGD:A90858"
    }, {
      "firstName" : "MF",
      "lastName" : "Duggan-Keen",
      "authorRank" : 10,
      "name" : "Duggan-Keen MF",
      "referenceId" : "RGD:A115789"
    }, {
      "firstName" : "PL",
      "lastName" : "Stern",
      "authorRank" : 11,
      "name" : "Stern PL",
      "referenceId" : "RGD:A27024"
    }, {
      "firstName" : "CJ",
      "lastName" : "Meijer",
      "authorRank" : 12,
      "name" : "Meijer CJ",
      "referenceId" : "RGD:A96771"
    }, {
      "firstName" : "RJ",
      "lastName" : "Scheper",
      "authorRank" : 13,
      "name" : "Scheper RJ",
      "referenceId" : "RGD:A7249"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2314703"
    } ]
  }, {
    "primaryId" : "PMID:10073901",
    "title" : "Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Sawai H, etal., Prenat Diagn. 1999 Jan;19(1):21-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-02-15T14:47:15.000-06:00",
    "volume" : "19",
    "pages" : "21-4",
    "abstract" : "Thanatophoric dysplasia (TD) is the most frequent form of neonatal lethal skeletal dysplasia. Recently. mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that cause two subtypes of this disorder, type I (TDI) and type II (TDII), have been identified. This discovery has now made it possible to make a definite diagnosis of TD by molecular methods. To date, prenatal diagnosis of TD has been accomplished by ultrasonography in the second trimester. However, it is not always possible to distinguish TD fetuses it utero from the other osteochondrodysplasias by ultrasonography or radiography. We report on the prenatal diagnosis of a TD fetus, showing severe shortness of limbs and polyhydramnios, by identification of a mutation in the FGFR3 gene. Genomic DNA was isolated from the amniotic fluid and then subjected to PCR amplification. The common TDI mutation, C-->T transition at nucleotide 742 in the FGFR3 gene, was identified using restriction enzyme analysis. This information was critical in obstetric management decisions later in pregnancy. However, although the mutation responsible for TDI was detected previously, we noticed some inconsistencies in the published PCR results and have proposed a correction.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Sawai",
      "authorRank" : 1,
      "name" : "Sawai H",
      "referenceId" : "RGD:A22628"
    }, {
      "firstName" : "S",
      "lastName" : "Komori",
      "authorRank" : 2,
      "name" : "Komori S",
      "referenceId" : "RGD:A91929"
    }, {
      "firstName" : "A",
      "lastName" : "Ida",
      "authorRank" : 3,
      "name" : "Ida A",
      "referenceId" : "RGD:A91930"
    }, {
      "firstName" : "T",
      "lastName" : "Henmi",
      "authorRank" : 4,
      "name" : "Henmi T",
      "referenceId" : "RGD:A91931"
    }, {
      "firstName" : "T",
      "lastName" : "Bessho",
      "authorRank" : 5,
      "name" : "Bessho T",
      "referenceId" : "RGD:A91932"
    }, {
      "firstName" : "K",
      "lastName" : "Koyama",
      "authorRank" : 6,
      "name" : "Koyama K",
      "referenceId" : "RGD:A35964"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289863"
    } ]
  }, {
    "primaryId" : "PMID:10073946",
    "title" : "Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Jong MC, etal., Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):472-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-24T11:10:21.000-06:00",
    "volume" : "19",
    "pages" : "472-84",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MC",
      "lastName" : "Jong",
      "authorRank" : 1,
      "name" : "Jong MC",
      "referenceId" : "RGD:A59123"
    }, {
      "firstName" : "MH",
      "lastName" : "Hofker",
      "authorRank" : 2,
      "name" : "Hofker MH",
      "referenceId" : "RGD:A59124"
    }, {
      "firstName" : "LM",
      "lastName" : "Havekes",
      "authorRank" : 3,
      "name" : "Havekes LM",
      "referenceId" : "RGD:A13289"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578471"
    } ]
  }, {
    "primaryId" : "PMID:10073974",
    "title" : "Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Boot RG, etal., Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):687-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-02-25T10:52:35.000-06:00",
    "volume" : "19",
    "pages" : "687-94",
    "abstract" : "Atherosclerosis is initiated by the infiltration of monocytes into the subendothelial space of the vessel wall and subsequent lipid accumulation of the activated macrophages. The molecular mechanisms involved in the anomalous behavior of macrophages in atherogenesis have only partially been disclosed. Chitotriosidase and human cartilage gp-39 (HC gp-39) are members of the chitinase family of proteins and are expressed in lipid-laden macrophages accumulated in various organs during Gaucher disease. In addition, as shown in this study, chitotriosidase and HC gp-39 can be induced with distinct kinetics in cultured macrophages. We investigated the expression of these chitinase-like genes in the human atherosclerotic vessel wall by in situ hybridizations on atherosclerotic specimens derived from femoral artery (4 specimens), aorta (4 specimens), iliac artery (3 specimens), carotid artery (4 specimens), and coronary artery (1 specimen), as well as 5 specimens derived from apparently normal vascular tissue. We show for the first time that chitotriosidase and HC gp-39 expression was strongly upregulated in distinct subsets of macrophages in the atherosclerotic plaque. The expression patterns of chitotriosidase and HC gp-39 were compared and shown to be different from the patterns observed for the extracellular matrix protein osteopontin and the macrophage marker tartrate-resistant acid phosphatase. Our data emphasize the remarkable phenotypic variation among macrophages present in the atherosclerotic lesion. Furthermore, chitotriosidase enzyme activity was shown to be elevated up to 55-fold in extracts of atherosclerotic tissue. Although a function for chitotriosidase and HC gp-39 has not been identified, we hypothesize a role in cell migration and tissue remodeling during atherogenesis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RG",
      "lastName" : "Boot",
      "authorRank" : 1,
      "name" : "Boot RG",
      "referenceId" : "RGD:A135188"
    }, {
      "firstName" : "TA",
      "lastName" : "Van Achterberg",
      "authorRank" : 2,
      "name" : "Van Achterberg TA",
      "referenceId" : "RGD:A135189"
    }, {
      "firstName" : "BE",
      "lastName" : "Van Aken",
      "authorRank" : 3,
      "name" : "Van Aken BE",
      "referenceId" : "RGD:A135190"
    }, {
      "firstName" : "GH",
      "lastName" : "Renkema",
      "authorRank" : 4,
      "name" : "Renkema GH",
      "referenceId" : "RGD:A135191"
    }, {
      "firstName" : "MJ",
      "lastName" : "Jacobs",
      "authorRank" : 5,
      "name" : "Jacobs MJ",
      "referenceId" : "RGD:A135192"
    }, {
      "firstName" : "JM",
      "lastName" : "Aerts",
      "authorRank" : 6,
      "name" : "Aerts JM",
      "referenceId" : "RGD:A23182"
    }, {
      "firstName" : "CJ",
      "lastName" : "De Vries",
      "authorRank" : 7,
      "name" : "De Vries CJ",
      "referenceId" : "RGD:A129205"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892604"
    } ]
  }, {
    "primaryId" : "PMID:10073980",
    "title" : "Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Numaguchi Y, etal., Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):727-33. doi: 10.1161/01.atv.19.3.727.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-01-30T14:14:28.000-06:00",
    "volume" : "19",
    "pages" : "727-33",
    "abstract" : "Prostacyclin (PGI2), a metabolite of arachidonic acid, has the vasoprotective effects of vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation. We hypothesized that an overexpression of endogenous PGI2 may accelerate the recovery from endothelial damage and inhibit neointimal formation in the injured artery. To test this hypothesis, we investigated in vivo transfer of the PGI2 synthase (PCS) gene into balloon-injured rat carotid arteries by a nonviral lipotransfection method. Seven days after transfection, a significant regeneration of endothelium was observed in the arteries transfected with a plasmid carrying the rat PCS gene (pCMV-PCS), but little regeneration was seen in those with the control plasmid carrying the lacZ gene (pCMV-lacZ) (percent luminal circumference lined by newly regenerated endothelium: 87. 1+/-6.9% in pCMV-PCS-transfected vessels and 6.9+/-0.2% in pCMV-lacZ vessels, P<0.001). BrdU staining of arterial segments demonstrated a significantly lower incorporation in pCMV-PCS-transfected vessels (7. 5+/-0.3% positive nuclei in vessel cells) than in pCMV-lacZ (50. 7+/-9.6%, P<0.01). Moreover, 2 weeks after transfection, the PCS gene transfer resulted in a significant inhibition of neointimal formation (88% reduction in ratio of intima/media areas), whereas medial area was similar among the groups. Arterial segments transfected with pCMV-PCS produced significantly higher levels of 6-keto-PGF1alpha, the main metabolite of PGI2, compared with the segments transfected with pCMV-lacZ (10.2+/-0.55 and 2.1+/-0.32 ng/mg tissue for pCMV-PCS and pCMV-placZ, P<0.001). In conclusion, this study demonstrated that an in vivo PCS gene transfer increased the production of PGI2 and markedly inhibited neointimal formation with accelerated reendothelialization in rat carotid arteries after balloon injury.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Numaguchi",
      "authorRank" : 1,
      "name" : "Numaguchi Y",
      "referenceId" : "RGD:A63629"
    }, {
      "firstName" : "K",
      "lastName" : "Naruse",
      "authorRank" : 2,
      "name" : "Naruse K",
      "referenceId" : "RGD:A81581"
    }, {
      "firstName" : "M",
      "lastName" : "Harada",
      "authorRank" : 3,
      "name" : "Harada M",
      "referenceId" : "RGD:A314640"
    }, {
      "firstName" : "H",
      "lastName" : "Osanai",
      "authorRank" : 4,
      "name" : "Osanai H",
      "referenceId" : "RGD:A538085"
    }, {
      "firstName" : "S",
      "lastName" : "Mokuno",
      "authorRank" : 5,
      "name" : "Mokuno S",
      "referenceId" : "RGD:A538286"
    }, {
      "firstName" : "K",
      "lastName" : "Murase",
      "authorRank" : 6,
      "name" : "Murase K",
      "referenceId" : "RGD:A107047"
    }, {
      "firstName" : "H",
      "lastName" : "Matsui",
      "authorRank" : 7,
      "name" : "Matsui H",
      "referenceId" : "RGD:A11655"
    }, {
      "firstName" : "Y",
      "lastName" : "Toki",
      "authorRank" : 8,
      "name" : "Toki Y",
      "referenceId" : "RGD:A538084"
    }, {
      "firstName" : "T",
      "lastName" : "Ito",
      "authorRank" : 9,
      "name" : "Ito T",
      "referenceId" : "RGD:A151342"
    }, {
      "firstName" : "K",
      "lastName" : "Okumura",
      "authorRank" : 10,
      "name" : "Okumura K",
      "referenceId" : "RGD:A11657"
    }, {
      "firstName" : "T",
      "lastName" : "Hayakawa",
      "authorRank" : 11,
      "name" : "Hayakawa T",
      "referenceId" : "RGD:A4681"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401960092"
    } ]
  }, {
    "primaryId" : "PMID:10074303",
    "title" : "[Effects of chronic hypoxia on the expression of oncogene jun fos and myb mRNA in rat lung].",
    "datePublished" : "1997-02-01T00:00:00.000-06:00",
    "citation" : "Ran P, etal., Zhongguo Ying Yong Sheng Li Xue Za Zhi. 1997 Feb;13(1):21-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-01-03T13:13:42.000-06:00",
    "volume" : "13",
    "pages" : "21-4",
    "abstract" : "This paper is to investigate the expression of oncogene jun fos and myb mRNA in the lung of rats exposed to chronic hypoxia. 15 SD rats were put in low oxygen chamber (FiO2 = 0.1), 8 hrs daily for 1, 2 and 3 weeks. Five rats breathing room air served as control. Oncogene expression in lung tissue assessed by the use of in situ hybridization. The results showed that (1) there was a slight expression of jun mRNA but not fos and myb mRNA in the control normoxic rats' lung; (2) it was found that a less expression of jun mRNA in lung after 1 week hypoxia, but after 2 week hypoxia jun mRNA elevated again and significantly increased after 3 week hypoxia as compared with that in normoxia; (3) the oncogene myb mRNA expression showed significant increase in 1 and 2 week hypoxia and returned to normal status in 3 week hypoxia; (4) after 1 to 3 week hypoxia, a significant increased expression of fos mRNA was found as compared with that in normoxia. It is suggested hypoxia may induce increased expression of proto-oncogene jun myb and fos, which may be related to proliferation of pulmonary arterial smooth muscle cells and fibroblasts.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Ran",
      "authorRank" : 1,
      "name" : "Ran P",
      "referenceId" : "RGD:A131274"
    }, {
      "firstName" : "N",
      "lastName" : "Ouyang",
      "authorRank" : 2,
      "name" : "Ouyang N",
      "referenceId" : "RGD:A436749"
    }, {
      "firstName" : "N",
      "lastName" : "Zhong",
      "authorRank" : 3,
      "name" : "Zhong N",
      "referenceId" : "RGD:A55134"
    }, {
      "firstName" : "S",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen S",
      "referenceId" : "RGD:A157966"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11532745"
    } ]
  }, {
    "primaryId" : "PMID:10074491",
    "title" : "Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hou WS, etal., J Clin Invest. 1999 Mar;103(5):731-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:03:19.000-05:00",
    "volume" : "103",
    "pages" : "731-8",
    "abstract" : "Cathepsin K, a lysosomal cysteine protease critical for bone remodeling by osteoclasts, was recently identified as the deficient enzyme causing pycnodysostosis, an autosomal recessive osteosclerotic skeletal dysplasia. To investigate the nature of molecular lesions causing this disease, mutations in the cathepsin K gene from eight families were determined, identifying seven novel mutations (K52X, G79E, Q190X, Y212C, A277E, A277V, and R312G). Expression of the  first pro region missense mutation in a cysteine protease, G79E, in Pichia pastoris resulted in an unstable precursor protein, consistent with misfolding of the proenzyme. Expression of five mature region missense defects revealed that G146R, A277E, A277V, and R312G precursors were unstable, and no mature proteins or protease activity were detected. The Y212C precursor was activated to its mature form in a manner similar to that of the wild-type cathepsin K. The mature  Y212C enzyme retained its dipeptide substrate specificity and gelatinolytic activity, but it had markedly decreased activity toward type I collagen and a cathepsin K-specific tripeptide substrate, indicating that it was unable to bind  collagen triple helix. These studies demonstrated the molecular heterogeneity of  mutations causing pycnodysostosis, indicated that pro region conformation directs proper folding of the proenzyme, and suggested that the cathepsin K active site contains a critical collagen-binding domain.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WS",
      "lastName" : "Hou",
      "authorRank" : 1,
      "name" : "Hou",
      "referenceId" : "RGD:A273110"
    }, {
      "firstName" : "D",
      "lastName" : "Bromme",
      "authorRank" : 2,
      "name" : "Bromme D",
      "referenceId" : "RGD:A51706"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhao",
      "authorRank" : 3,
      "name" : "Zhao",
      "referenceId" : "RGD:A415939"
    }, {
      "firstName" : "E",
      "lastName" : "Mehler",
      "authorRank" : 4,
      "name" : "Mehler",
      "referenceId" : "RGD:A277696"
    }, {
      "firstName" : "C",
      "lastName" : "Dushey",
      "authorRank" : 5,
      "name" : "Dushey",
      "referenceId" : "RGD:A277697"
    }, {
      "firstName" : "H",
      "lastName" : "Weinstein",
      "authorRank" : 6,
      "name" : "Weinstein H",
      "referenceId" : "RGD:A79098"
    }, {
      "firstName" : "CS",
      "lastName" : "Miranda",
      "authorRank" : 7,
      "name" : "Miranda",
      "referenceId" : "RGD:A277698"
    }, {
      "firstName" : "C",
      "lastName" : "Fraga",
      "authorRank" : 8,
      "name" : "Fraga C",
      "referenceId" : "RGD:A63668"
    }, {
      "firstName" : "F",
      "lastName" : "Greig",
      "authorRank" : 9,
      "name" : "Greig",
      "referenceId" : "RGD:A277699"
    }, {
      "firstName" : "J",
      "lastName" : "Carey",
      "authorRank" : 10,
      "name" : "Carey",
      "referenceId" : "RGD:A277700"
    }, {
      "firstName" : "DL",
      "lastName" : "Rimoin",
      "authorRank" : 11,
      "name" : "Rimoin DL",
      "referenceId" : "RGD:A37393"
    }, {
      "firstName" : "RJ",
      "lastName" : "Desnick",
      "authorRank" : 12,
      "name" : "Desnick RJ",
      "referenceId" : "RGD:A15118"
    }, {
      "firstName" : "BD",
      "lastName" : "Gelb",
      "authorRank" : 13,
      "name" : "Gelb BD",
      "referenceId" : "RGD:A66206"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070750"
    } ]
  }, {
    "primaryId" : "PMID:10075146",
    "title" : "Postnatal changes of gene expression for tissue inhibitors of metalloproteinase-1 and -2 and cystatins S and C, in rat submandibular gland demonstrated by quantitative reverse transcription-polymerase chain reaction.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Nishiura T and Abe K, Arch Oral Biol. 1999 Jan;44(1):15-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-04-21T08:06:00.000-05:00",
    "volume" : "44",
    "pages" : "15-26",
    "abstract" : "The rat submandibular gland is not fully developed at birth and definitive differentiation takes place postnatally. The steady-state mRNA expression for the four proteinase inhibitor molecules, tissue inhibitors of metalloproteinase (TIMP)-1 and -2, and cystatins S and C, and for a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), in rat submandibular glands was measured by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR) at different stages of postnatal development. The gene-expression patterns of TIMP-1 and -2 relative to G3PDH were similar to each other. The TIMP-2 and cystatin C genes were more highly expressed than those of TIMP-1 and cystatin S at all stages. Moreover, the gene expressions of TIMP-1 and -2, and of cystatins S and C, were predominant between 1 and 7, and 7 and 12 weeks of age, respectively, and coincided developmentally with the regression of terminal tubule cells and the differentiation of granular convoluted tubule cells, respectively. Quantitative competitive RT-PCR allowed accurate measurement of small changes in the steady-state concentrations of these proteinase-inhibitor mRNA molecules.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Nishiura",
      "authorRank" : 1,
      "name" : "Nishiura T",
      "referenceId" : "RGD:A64309"
    }, {
      "firstName" : "K",
      "lastName" : "Abe",
      "authorRank" : 2,
      "name" : "Abe K",
      "referenceId" : "RGD:A9795"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306516"
    } ]
  }, {
    "primaryId" : "PMID:10075651",
    "title" : "Expression of the transcriptional repressor protein Kid-1 leads to the disintegration of the nucleolus.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Huang Z, etal., J Biol Chem 1999 Mar 19;274(12):7640-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:51:31.000-05:00",
    "volume" : "274",
    "pages" : "7640-8",
    "abstract" : "The rat Kid-1 gene codes for a 66-kDa protein with KRAB domains at the NH2 terminus and two Cys2His2-zinc finger clusters of four and nine zinc fingers at the COOH terminus. It was the first KRAB-zinc finger protein for which a transcriptional repressor activity was demonstrated. Subsequently, the KRAB-A domain was identified as a widespread transcriptional repressor motif. We now present a biochemical and functional analysis of the Kid-1 protein in transfected cells. The full-length Kid-1 protein is targeted to the nucleolus and adheres tightly to as yet undefined nucleolar structures, leading eventually to the disintegration of the nucleolus. The tight adherence and nucleolar distribution can be attributed to the larger zinc finger cluster, whereas the KRAB-A domain is responsible for the nucleolar fragmentation. Upon disintegration of the nucleolus, the nucleolar transcription factor upstream binding factor disappears from the nucleolar fragments. In the absence of Kid-1, the KRIP-1 protein, which represents the natural interacting partner of zinc finger proteins with a KRAB-A domain, is homogeneously distributed in the nucleus, whereas coexpression of Kid-1 leads to a shift of KRIP-1 into the nucleolus. Nucleolar run-ons demonstrate that rDNA transcription is shut off in the nucleolar fragments. Our data demonstrate the functional diversity of the KRAB and zinc finger domains of Kid-1 and provide new functional insights into the regulation of the nucleolar structure.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Huang",
      "authorRank" : 1,
      "name" : "Huang Z",
      "referenceId" : "RGD:A47921"
    }, {
      "firstName" : "B",
      "lastName" : "Philippin",
      "authorRank" : 2,
      "name" : "Philippin B",
      "referenceId" : "RGD:A47922"
    }, {
      "firstName" : "E",
      "lastName" : "O'Leary",
      "authorRank" : 3,
      "name" : "O'Leary E",
      "referenceId" : "RGD:A38871"
    }, {
      "firstName" : "JV",
      "lastName" : "Bonventre",
      "authorRank" : 4,
      "name" : "Bonventre JV",
      "referenceId" : "RGD:A28105"
    }, {
      "firstName" : "W",
      "lastName" : "Kriz",
      "authorRank" : 5,
      "name" : "Kriz W",
      "referenceId" : "RGD:A45210"
    }, {
      "firstName" : "R",
      "lastName" : "Witzgall",
      "authorRank" : 6,
      "name" : "Witzgall R",
      "referenceId" : "RGD:A38872"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1303369"
    } ]
  }, {
    "primaryId" : "PMID:10075692",
    "title" : "Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Sabo SL, etal., J Biol Chem. 1999 Mar 19;274(12):7952-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-09-30T16:56:54.000-05:00",
    "volume" : "274",
    "pages" : "7952-7",
    "abstract" : "The principal component of Alzheimer's amyloid plaques, Abeta, derives from proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65 is a brain-enriched protein that binds to APP. Although several laboratories have characterized the APP-FE65 interaction in vitro, the possible relevance of this interaction to Alzheimer's disease has remained unclear. We demonstrate here that APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as well as both alphaAPPs and Abeta secretion. The dramatic (4-fold) FE65-dependent increase in Abeta secretion suggests that agents which inhibit the interaction of FE65 with APP might reduce Abeta secretion in the brain and therefore be useful for preventing or slowing amyloid plaque formation.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SL",
      "lastName" : "Sabo",
      "authorRank" : 1,
      "name" : "Sabo SL",
      "referenceId" : "RGD:A85329"
    }, {
      "firstName" : "LM",
      "lastName" : "Lanier",
      "authorRank" : 2,
      "name" : "Lanier LM",
      "referenceId" : "RGD:A27319"
    }, {
      "firstName" : "AF",
      "lastName" : "Ikin",
      "authorRank" : 3,
      "name" : "Ikin AF",
      "referenceId" : "RGD:A100558"
    }, {
      "firstName" : "O",
      "lastName" : "Khorkova",
      "authorRank" : 4,
      "name" : "Khorkova O",
      "referenceId" : "RGD:A100559"
    }, {
      "firstName" : "S",
      "lastName" : "Sahasrabudhe",
      "authorRank" : 5,
      "name" : "Sahasrabudhe S",
      "referenceId" : "RGD:A100560"
    }, {
      "firstName" : "P",
      "lastName" : "Greengard",
      "authorRank" : 6,
      "name" : "Greengard P",
      "referenceId" : "RGD:A8299"
    }, {
      "firstName" : "JD",
      "lastName" : "Buxbaum",
      "authorRank" : 7,
      "name" : "Buxbaum JD",
      "referenceId" : "RGD:A53137"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301211"
    } ]
  }, {
    "primaryId" : "PMID:10075695",
    "title" : "The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Imaizumi K, etal., J Biol Chem 1999 Mar 19;274(12):7975-81.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-03-13T18:42:53.000-06:00",
    "volume" : "274",
    "pages" : "7975-81",
    "abstract" : "DP5, which contains a BH3 domain, was cloned as a neuronal apoptosis-inducing gene. To confirm that DP5 interacts with members of the Bcl-2 family, 293T cells were transiently co-transfected with DP5 and Bcl-xl cDNA constructs, and immunoprecipitation was carried out. The 30-kDa Bcl-xl was co-immunoprecipitated with Myc-tagged DP5, suggesting that DP5 physically interacts with Bcl-xl in mammalian cells. Previously, we reported that DP5 is induced during neuronal apoptosis in cultured sympathetic neurons. Here, we analyzed DP5 gene expression and the specific interaction of DP5 with Bcl-xl during neuronal death induced by amyloid-beta protein (A beta). DP5 mRNA was induced 6 h after treatment with A beta in cultured rat cortical neurons. The protein encoded by DP5 mRNA showed a specific interaction with Bcl-xl. Induction of DP5 gene expression was blocked by nifedipine, an inhibitor of L-type voltage-dependent calcium channels, and dantrolene, an inhibitor of calcium release from the endoplasmic reticulum. These results suggested that the induction of DP5 mRNA occurs downstream of the increase in cytosolic calcium concentration caused by A beta. Moreover, DP5 specifically interacts with Bcl-xl during neuronal apoptosis following exposure to A beta, and its binding could impair the survival-promoting activities of Bcl-xl. Thus, the induction of DP5 mRNA and the interaction of DP5 and Bcl-xl could play significant roles in neuronal degeneration following exposure to A beta.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Imaizumi",
      "authorRank" : 1,
      "name" : "Imaizumi K",
      "referenceId" : "RGD:A8702"
    }, {
      "firstName" : "T",
      "lastName" : "Morihara",
      "authorRank" : 2,
      "name" : "Morihara T",
      "referenceId" : "RGD:A8707"
    }, {
      "firstName" : "Y",
      "lastName" : "Mori",
      "authorRank" : 3,
      "name" : "Mori Y",
      "referenceId" : "RGD:A8708"
    }, {
      "firstName" : "T",
      "lastName" : "Katayama",
      "authorRank" : 4,
      "name" : "Katayama T",
      "referenceId" : "RGD:A8709"
    }, {
      "firstName" : "M",
      "lastName" : "Tsuda",
      "authorRank" : 5,
      "name" : "Tsuda M",
      "referenceId" : "RGD:A8703"
    }, {
      "firstName" : "T",
      "lastName" : "Furuyama",
      "authorRank" : 6,
      "name" : "Furuyama T",
      "referenceId" : "RGD:A8710"
    }, {
      "firstName" : "A",
      "lastName" : "Wanaka",
      "authorRank" : 7,
      "name" : "Wanaka A",
      "referenceId" : "RGD:A8705"
    }, {
      "firstName" : "M",
      "lastName" : "Takeda",
      "authorRank" : 8,
      "name" : "Takeda M",
      "referenceId" : "RGD:A8225"
    }, {
      "firstName" : "M",
      "lastName" : "Tohyama",
      "authorRank" : 9,
      "name" : "Tohyama M",
      "referenceId" : "RGD:A8619"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70327"
    } ]
  }, {
    "primaryId" : "PMID:10075701",
    "title" : "Multisite autophosphorylation of p21-activated protein kinase gamma-PAK as a function of activation.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Gatti A, etal., J Biol Chem. 1999 Mar 19;274(12):8022-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-20T17:56:48.000-05:00",
    "volume" : "274",
    "pages" : "8022-8",
    "abstract" : "p21-activated protein kinase (PAK) is a family of serine/threonine kinases whose  activity is stimulated by binding to small G-proteins such as Cdc42 and subsequent autophosphorylation. Focusing on the ubiquitous gamma-isoform of PAK in this study, baculovirus-infected insect cells were used to obtain recombinant  gamma-PAK, while native gamma-PAK was isolated from rabbit reticulocytes. Two-dimensional gel electrophoresis of gamma-PAK followed by immunoblot analysis  revealed a similar profile for native and recombinant gamma-PAK, both consisting  of multiple protein spots. Following Cdc42-stimulated autophosphorylation, the two-dimensional profiles of native and recombinant gamma-PAK were characterized by a similar acidic shift, suggesting a common response to Cdc42. To understand the effect of differential phosphorylation on its activation status, gamma-PAK autophosphorylation was conducted in the presence or absence of activators such as Cdc42 and histone II-AS, followed by tryptic digestion and comparative two-dimensional phosphopeptide mapping. The major phosphopeptides were subjected  to a combination of manual and automated amino acid sequencing. Overall, eight autophosphorylation sites were identified in Cdc42-activated gamma-PAK, six of which are in common with those previously reported in alpha-PAK, while Ser-19 and Ser-165 appear to be uniquely phosphorylated in the gamma-form. Further, the phosphorylation of Ser-141, Ser-165, and Thr-402 was found to correlate with gamma-PAK activation.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Gatti",
      "authorRank" : 1,
      "name" : "Gatti A",
      "referenceId" : "RGD:A32309"
    }, {
      "firstName" : "Z",
      "lastName" : "Huang",
      "authorRank" : 2,
      "name" : "Huang Z",
      "referenceId" : "RGD:A47921"
    }, {
      "firstName" : "PT",
      "lastName" : "Tuazon",
      "authorRank" : 3,
      "name" : "Tuazon PT",
      "referenceId" : "RGD:A88930"
    }, {
      "firstName" : "JA",
      "lastName" : "Traugh",
      "authorRank" : 4,
      "name" : "Traugh",
      "referenceId" : "RGD:A200107"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11061737"
    } ]
  }, {
    "primaryId" : "PMID:10075714",
    "title" : "RIN ZF, a novel zinc finger gene, encodes proteins that bind to the CACC element of the gastrin promoter.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Tillotson LG J Biol Chem 1999 Mar 19;274(12):8123-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:53.000-05:00",
    "volume" : "274",
    "pages" : "8123-8",
    "abstract" : "Expression of gastrin, a gut hormone and growth factor, has tissue-specific transcriptional regulation and can be induced in some tumors. Previous studies have shown that a CACC cis-regulatory element is important for transcriptional activation in pancreatic insulinoma cells. To identify CACC-binding proteins, a lambda phage cDNA library derived from a rat insulinoma cell line, RIN 38A, was screened by a Southwestern method. A novel member of the Cys2-His2 zinc finger gene family was cloned and designated RIN ZF, having a cDNA sequence of 3.8 kilobases. One full-length and a shorter splice variant were sequenced and had predicted protein masses of 91.6 and 88.7 kDa. Expression of both splice forms were ubiquitous in fetal and adult rat tissues. Recombinant RIN ZF protein exhibited sequence-specific binding to the gastrin CACC element in a gel mobility shift assay. In transient transfections, both splice variants appeared to have only weak activating effects on gastrin-luciferase reporter gene transcription. Furthermore, RIN ZF coexpression with Sp1 appeared to block the strongly activating effects of Sp1 mediated through the CACC element. These findings suggest that a novel set of zinc finger proteins may help regulate gastrin gene expression by interfering with Sp1 transactivation.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LG",
      "lastName" : "Tillotson",
      "authorRank" : 1,
      "name" : "Tillotson LG",
      "referenceId" : "RGD:A42989"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299407"
    } ]
  }, {
    "primaryId" : "PMID:10075722",
    "title" : "Identification of a glucose response element in the promoter of the rat glucagon receptor gene.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Portois L, etal., J Biol Chem 1999 Mar 19;274(12):8181-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-19T15:17:06.000-06:00",
    "volume" : "274",
    "pages" : "8181-90",
    "abstract" : "We cloned the 5' upstream region of the rat glucagon receptor gene, demonstrating that the 5' noncoding domain of the glucagon receptor mRNA contained two untranslated exons of 131 and 166 nucleotides (nt), respectively, separated by two introns of 0.6 and 3.2 kilobase pairs. We also observed an alternative splicing involving the 166-base pair exon. Cloning of up to 2 kilobase pairs of the newly identified genomic domain and transfection of various constructs driving a reporter gene, in pancreatic islet cell line INS-1, uncovered a strong glucose regulation of the promoter activity of plasmids containing up to nucleotide -868, or more, upstream from the transcriptional start point. This promoter activity displayed threshold-like behavior, with low activity of the promoter below 5 mM glucose, and maximal activation as of 10 mM glucose. This glucose regulation was mapped to a highly palindromic 19-nucleotide region between nt -545 and -527. Indeed, deletion or mutation of this sequence abolished the glucose regulation. This domain contained two palindromic \"E-boxes\" CACGTG and CAGCTG separated by 3 nt, a feature similar to the \"L4 box\" found in the pyruvate kinase L gene promoter. This is the first description of a G protein-coupled receptor gene promoter regulated by glucose.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Portois",
      "authorRank" : 1,
      "name" : "Portois L",
      "referenceId" : "RGD:A12254"
    }, {
      "firstName" : "B",
      "lastName" : "Maget",
      "authorRank" : 2,
      "name" : "Maget B",
      "referenceId" : "RGD:A1003"
    }, {
      "firstName" : "M",
      "lastName" : "Tastenoy",
      "authorRank" : 3,
      "name" : "Tastenoy M",
      "referenceId" : "RGD:A12255"
    }, {
      "firstName" : "J",
      "lastName" : "Perret",
      "authorRank" : 4,
      "name" : "Perret J",
      "referenceId" : "RGD:A30280"
    }, {
      "firstName" : "M",
      "lastName" : "Svoboda",
      "authorRank" : 5,
      "name" : "Svoboda M",
      "referenceId" : "RGD:A1004"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:728672"
    } ]
  }, {
    "primaryId" : "PMID:10075727",
    "title" : "Characterization of a novel rat brain glycosylphosphatidylinositol-anchored protein (Kilon), a member of the IgLON cell adhesion molecule family.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Funatsu N, etal., J Biol Chem 1999 Mar 19;274(12):8224-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T17:20:39.000-05:00",
    "volume" : "274",
    "pages" : "8224-30",
    "abstract" : "In the central nervous system, many cell adhesion molecules are known to participate in the establishment and remodeling of the neural circuit. Some of the cell adhesion molecules are known to be anchored to the membrane by the glycosylphosphatidylinositol (GPI) inserted to their C termini, and many GPI-anchored proteins are known to be localized in a Triton-insoluble membrane fraction of low density or so-called \"raft.\" In this study, we surveyed the GPI-anchored proteins in the Triton-insoluble low density fraction from 2-week-old rat brain by solubilization with phosphatidylinositol-specific phospholipase C. By Western blotting and partial peptide sequencing after the deglycosylation with peptide N-glycosidase F, the presence of Thy-1, F3/contactin, and T-cadherin was shown. In addition, one of the major proteins, having an apparent molecular mass of 36 kDa after the peptide N-glycosidase F digestion, was found to be a novel protein. The result of cDNA cloning showed that the protein is an immunoglobulin superfamily member with three C2 domains and has six putative glycosylation sites. Since this protein shows high sequence similarity to IgLON family members including LAMP, OBCAM, neurotrimin, CEPU-1, AvGP50, and GP55, we termed this protein Kilon (a kindred of IgLON). Kilon-specific monoclonal antibodies were produced, and Western blotting analysis showed that expression of Kilon is restricted to brain, and Kilon has an apparent molecular mass of 46 kDa in SDS-polyacrylamide gel electrophoresis in its expressed form. In brain, the expression of Kilon is already detected in E16 stage, and its level gradually increases during development. Kilon immunostaining was observed in the cerebral cortex and hippocampus, in which the strongly stained puncta were observed on dendrites and soma of pyramidal neurons.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Funatsu",
      "authorRank" : 1,
      "name" : "Funatsu N",
      "referenceId" : "RGD:A43027"
    }, {
      "firstName" : "S",
      "lastName" : "Miyata",
      "authorRank" : 2,
      "name" : "Miyata S",
      "referenceId" : "RGD:A43028"
    }, {
      "firstName" : "H",
      "lastName" : "Kumanogoh",
      "authorRank" : 3,
      "name" : "Kumanogoh H",
      "referenceId" : "RGD:A43029"
    }, {
      "firstName" : "M",
      "lastName" : "Shigeta",
      "authorRank" : 4,
      "name" : "Shigeta M",
      "referenceId" : "RGD:A43030"
    }, {
      "firstName" : "K",
      "lastName" : "Hamada",
      "authorRank" : 5,
      "name" : "Hamada K",
      "referenceId" : "RGD:A43031"
    }, {
      "firstName" : "Y",
      "lastName" : "Endo",
      "authorRank" : 6,
      "name" : "Endo Y",
      "referenceId" : "RGD:A20549"
    }, {
      "firstName" : "Y",
      "lastName" : "Sokawa",
      "authorRank" : 7,
      "name" : "Sokawa Y",
      "referenceId" : "RGD:A43032"
    }, {
      "firstName" : "S",
      "lastName" : "Maekawa",
      "authorRank" : 8,
      "name" : "Maekawa S",
      "referenceId" : "RGD:A16888"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299429"
    } ]
  }, {
    "primaryId" : "PMID:10075839",
    "title" : "Essential roles of retinoic acid signaling in interdigital apoptosis and control of BMP-7 expression in mouse autopods.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Dupe V, etal., Dev Biol 1999 Apr 1;208(1):30-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-31T15:20:07.000-05:00",
    "volume" : "208",
    "pages" : "30-43",
    "abstract" : "We previously reported that mice lacking the RARgamma gene and one or both alleles of the RARbeta gene (i.e., RARbeta+/-/RARgamma-/- and RARbeta-/-/RARgamma-/- mutants) display a severe and fully penetrant interdigital webbing (soft tissue syndactyly), caused by the persistence of the fetal interdigital mesenchyme (Ghyselinck et al., 1997, Int. J. Dev. Biol. 41, 425-447). In the present study, these compound mutants were used to investigate the cellular and molecular mechanisms involved in retinoic acid (RA)-dependent formation of the interdigital necrotic zones (INZs). The mutant INZs show a marked decrease in the number of apoptotic cells accompanied by an increase of cell proliferation. This marked decrease was not paralleled by a reduction of the number of macrophages, indicating that the chemotactic cues which normally attract these cells into the INZs were not affected. The expression of a number of genes known to be involved in the establishment of the INZs, the patterning of the autopod, and/or the initiation of apoptosis was also unaffected. These genes included BMP-2, BMP-4, Msx-1, Msx-2, 5' members of Hox complexes, Bcl2, Bax, and p53. In contrast, the mutant INZs displayed a specific, graded, down-regulation of tissue transglutaminase (tTG) promoter activity and of stromelysin-3 expression upon the removal of one or both alleles of the RARbeta gene from the RARgamma null genetic background. As retinoic acid response elements are present in the promoter regions of both tTG and stromelysin-3 genes, we propose that RA might increase the amount of cell death in the INZs through a direct modulation of tTG expression and that it also contributes to the process of tissue remodeling, which accompanies cell death, through an up-regulation of stromelysin-3 expression in the INZs. Approximately 10% of the RARbeta-/- /RARgamma-/- mutants displayed a supernumerary preaxial digit on hindfeet, which is also a feature of the BMP-7 null phenotype (Dudley et al., 1995, Genes Dev. 9, 2795-2807; Luo et al., 1995, Genes Dev. 9, 2808-2820). BMP-7 was globally down-regulated at an early stage in the autopods of these RAR double null mutants, prior to the appearance of the digital rays. Therefore, RA may exert some of its effects on anteroposterior autopod patterning through controlling BMP-7 expression.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Dupe",
      "authorRank" : 1,
      "name" : "Dupe V",
      "referenceId" : "RGD:A55168"
    }, {
      "firstName" : "NB",
      "lastName" : "Ghyselinck",
      "authorRank" : 2,
      "name" : "Ghyselinck NB",
      "referenceId" : "RGD:A55169"
    }, {
      "firstName" : "V",
      "lastName" : "Thomazy",
      "authorRank" : 3,
      "name" : "Thomazy V",
      "referenceId" : "RGD:A55170"
    }, {
      "firstName" : "L",
      "lastName" : "Nagy",
      "authorRank" : 4,
      "name" : "Nagy L",
      "referenceId" : "RGD:A55171"
    }, {
      "firstName" : "PJ",
      "lastName" : "Davies",
      "authorRank" : 5,
      "name" : "Davies PJ",
      "referenceId" : "RGD:A55172"
    }, {
      "firstName" : "P",
      "lastName" : "Chambon",
      "authorRank" : 6,
      "name" : "Chambon P",
      "referenceId" : "RGD:A25357"
    }, {
      "firstName" : "M",
      "lastName" : "Mark",
      "authorRank" : 7,
      "name" : "Mark M",
      "referenceId" : "RGD:A55173"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549486"
    } ]
  }, {
    "primaryId" : "PMID:10075978",
    "title" : "A novel gene coding for a Fas apoptosis inhibitory molecule (FAIM) isolated from inducibly Fas-resistant B lymphocytes.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Schneider TJ, etal., J Exp Med 1999 Mar 15;189(6):949-56.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:49:37.000-05:00",
    "volume" : "189",
    "pages" : "949-56",
    "abstract" : "The sensitivity of primary splenic B cells to Fas-mediated apoptosis is modulated in a receptor-specific fashion. Here we used a differential display strategy to detect cDNAs present in B cells rendered Fas resistant but absent in those rendered Fas sensitive. This led to the cloning and characterization of a novel 1.2-kb gene that encodes a Fas apoptosis inhibitory molecule (FAIM). faim-transfected BAL-17 B lymphoma cells were less sensitive by half or more to Fas-mediated apoptosis than were vector-transfected controls, using Fas ligand-bearing T cells or a cytotoxic anti-Fas antibody to trigger Fas, and this was associated with inhibition of Fas- induced poly-ADP ribose polymerase (PARP) cleavage. In primary B cells, the time course of faim mRNA and FAIM protein expression correlated with the induction of Fas resistance by surface (s)Ig engagement. Thus, FAIM is an inducible effector molecule that mediates Fas resistance produced by sIg engagement in B cells. However, faim is broadly expressed in various tissues and the faim sequence is highly conserved evolutionarily, suggesting that its role extends beyond lymphocyte homeostasis. As FAIM has no significant regions of homology to other gene products that modulate Fas killing, it appears to represent a distinct, new class of antiapoptotic protein.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TJ",
      "lastName" : "Schneider",
      "authorRank" : 1,
      "name" : "Schneider TJ",
      "referenceId" : "RGD:A45465"
    }, {
      "firstName" : "GM",
      "lastName" : "Fischer",
      "authorRank" : 2,
      "name" : "Fischer GM",
      "referenceId" : "RGD:A45466"
    }, {
      "firstName" : "TJ",
      "lastName" : "Donohoe",
      "authorRank" : 3,
      "name" : "Donohoe TJ",
      "referenceId" : "RGD:A45467"
    }, {
      "firstName" : "TP",
      "lastName" : "Colarusso",
      "authorRank" : 4,
      "name" : "Colarusso TP",
      "referenceId" : "RGD:A45468"
    }, {
      "firstName" : "TL",
      "lastName" : "Rothstein",
      "authorRank" : 5,
      "name" : "Rothstein TL",
      "referenceId" : "RGD:A45469"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302210"
    } ]
  }, {
    "primaryId" : "PMID:10076558",
    "title" : "Two germline missense mutations at codons 804 and 806 of the RET proto-oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without codon 918 mutation.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Miyauchi A, etal., Jpn J Cancer Res. 1999 Jan;90(1):1-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:47:17.000-05:00",
    "volume" : "90",
    "pages" : "1-5",
    "abstract" : "Multiple endocrine neoplasia (MEN) type 2B is a clinically distinct entity among  the autosomal dominant MEN 2 syndromes. Most patients with MEN 2B carry a germline mutation (M918T) of the RET proto-oncogene, while a few carry A883F. We  examined a patient with MEN 2B, but without M918T or A883F, and her relatives. Here, we report the presence in this patient of 2 germline mutations, V804M and Y806C in the same allele. While the novel Y806C was inherited from her father, its carriers (her father and brother) was not affected by MEN 2. In contrast, V804M was a de novo mutation, that has been reported in patients with familial medullary thyroid carcinoma. Combinations of mutations of the RET proto-oncogene  may cause oncogenic activities different from those of single mutations.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Miyauchi",
      "authorRank" : 1,
      "name" : "Miyauchi A",
      "referenceId" : "RGD:A68979"
    }, {
      "firstName" : "H",
      "lastName" : "Futami",
      "authorRank" : 2,
      "name" : "Futami",
      "referenceId" : "RGD:A243172"
    }, {
      "firstName" : "N",
      "lastName" : "Hai",
      "authorRank" : 3,
      "name" : "Hai",
      "referenceId" : "RGD:A269554"
    }, {
      "firstName" : "T",
      "lastName" : "Yokozawa",
      "authorRank" : 4,
      "name" : "Yokozawa T",
      "referenceId" : "RGD:A60868"
    }, {
      "firstName" : "K",
      "lastName" : "Kuma",
      "authorRank" : 5,
      "name" : "Kuma",
      "referenceId" : "RGD:A269555"
    }, {
      "firstName" : "N",
      "lastName" : "Aoki",
      "authorRank" : 6,
      "name" : "Aoki N",
      "referenceId" : "RGD:A55684"
    }, {
      "firstName" : "S",
      "lastName" : "Kosugi",
      "authorRank" : 7,
      "name" : "Kosugi S",
      "referenceId" : "RGD:A34156"
    }, {
      "firstName" : "K",
      "lastName" : "Sugano",
      "authorRank" : 8,
      "name" : "Sugano K",
      "referenceId" : "RGD:A81535"
    }, {
      "firstName" : "K",
      "lastName" : "Yamaguchi",
      "authorRank" : 9,
      "name" : "Yamaguchi",
      "referenceId" : "RGD:A408426"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067922"
    } ]
  }, {
    "primaryId" : "PMID:10076889",
    "title" : "Expression of gicerin, a novel cell adhesion molecule, is upregulated in the astrocytes after hypoglossal nerve injury in rats.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Li BS, etal., Neurosci Lett. 1999 Feb 5;260(3):149-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-09-27T15:23:41.000-05:00",
    "volume" : "260",
    "pages" : "149-52",
    "abstract" : "Gicerin is an integral membrane glycoprotein which mediates cell-cell and cell-extracellular matrix (ECM) interactions in the nervous system. We studied gicerin expression in the hypoglossal nucleus post transection using in situ hybridization and immunocytochemistry. We found that hypoglossal nerve injury resulted in a significant increase in gicerin expression. Its expression levels reached peak values in reactive astrocytes surrounding axotomized motoneurons of  the ipsilateral hypoglossal nucleus 14 days after hypoglossal nerve injury. The results indicate that gicerin is up-regulated during nerve regeneration, suggesting that gicerin expressed in the reactive astrocytes might be involved in the processes of nerve regeneration.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BS",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li BS",
      "referenceId" : "RGD:A6690"
    }, {
      "firstName" : "QN",
      "lastName" : "Su",
      "authorRank" : 2,
      "name" : "Su",
      "referenceId" : "RGD:A173482"
    }, {
      "firstName" : "H",
      "lastName" : "Kiyama",
      "authorRank" : 3,
      "name" : "Kiyama",
      "referenceId" : "RGD:A413872"
    }, {
      "firstName" : "N",
      "lastName" : "Miki",
      "authorRank" : 4,
      "name" : "Miki N",
      "referenceId" : "RGD:A5707"
    }, {
      "firstName" : "DR",
      "lastName" : "Robinow",
      "authorRank" : 5,
      "name" : "Robinow",
      "referenceId" : "RGD:A173484"
    }, {
      "firstName" : "L",
      "lastName" : "Zhang",
      "authorRank" : 6,
      "name" : "Zhang",
      "referenceId" : "RGD:A416991"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7364787"
    } ]
  }, {
    "primaryId" : "PMID:10077047",
    "title" : "Combined molecular and clinical approaches for the identification of families with familial adenomatous polyposis coli.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Gebert JF, etal., Ann Surg. 1999 Mar;229(3):350-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:48:51.000-05:00",
    "volume" : "229",
    "pages" : "350-61",
    "abstract" : "OBJECTIVE: Using an interdisciplinary clinical and molecular approach, the authors identified APC germline mutations in families with familial adenomatous polyposis (FAP). Correlation of mutation site with disease manifestation and the  impact of molecular data on clinical proceedings were examined. SUMMARY BACKGROUND DATA: Germline mutations in the APC gene predispose to FAP. Established and proposed genotype-phenotype correlations as well as the influence of mutation site on surgical procedures have been reported. The predictive value  of APC mutation analysis for disease manifestation and therapeutic decision making needs to be investigated further. METHODS: One hundred twenty-three kindreds of the local FAP registry were included in this study. CHRPE phenotype was defined as at least one large characteristic lesion or a total of four lesions in both eyes. APC mutations were identified by protein truncation test and automated DNA sequencing from patient lymphocyte DNA and RNA. RESULTS: APC germline mutations were identified in 85/123 families with FAP. They were located between codons 213 and 1581 of the APC gene and displayed distinct genotype-phenotype correlations. CHRPE status facilitated mutation analysis by discriminating regions of interest within the APC coding region. Severe manifestations of desmoids were restricted to mutations between codons 1444 through 1581. Whereas 91% (75/82) of at-risk persons were excluded as mutation carriers, APC germline mutations were detected before clinical examination in 9%  (7/82) of at-risk persons. One patient agreed to endoscopy only after mutation detection. CONCLUSIONS: This study supports the feasibility of combined molecular and clinical screening of families with FAP and may provide a guideline for routine presymptomatic molecular diagnostics in a clinical laboratory.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JF",
      "lastName" : "Gebert",
      "authorRank" : 1,
      "name" : "Gebert",
      "referenceId" : "RGD:A265065"
    }, {
      "firstName" : "C",
      "lastName" : "Dupon",
      "authorRank" : 2,
      "name" : "Dupon",
      "referenceId" : "RGD:A265066"
    }, {
      "firstName" : "M",
      "lastName" : "Kadmon",
      "authorRank" : 3,
      "name" : "Kadmon",
      "referenceId" : "RGD:A251602"
    }, {
      "firstName" : "M",
      "lastName" : "Hahn",
      "authorRank" : 4,
      "name" : "Hahn",
      "referenceId" : "RGD:A265067"
    }, {
      "firstName" : "C",
      "lastName" : "Herfarth",
      "authorRank" : 5,
      "name" : "Herfarth",
      "referenceId" : "RGD:A264961"
    }, {
      "firstName" : "M",
      "lastName" : "Von Knebel Doeberitz",
      "authorRank" : 6,
      "name" : "Von Knebel Doeberitz M",
      "referenceId" : "RGD:A93649"
    }, {
      "firstName" : "HK",
      "lastName" : "Schackert",
      "authorRank" : 7,
      "name" : "Schackert HK",
      "referenceId" : "RGD:A61383"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066484"
    } ]
  }, {
    "primaryId" : "PMID:10077326",
    "title" : "Persistent phosphorylation of cyclic AMP responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Hu BR, etal., Neuroscience. 1999 Mar;89(2):437-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-07-13T14:30:46.000-05:00",
    "volume" : "89",
    "pages" : "437-52",
    "abstract" : "The transcription factors cyclic AMP responsive element-binding protein (CREB) and activating transcription factor-2 were studied in rat brains subjected to 15  min ischemia followed by varied periods of reperfusion using western blot and immunocytochemical analyses. The total amounts of both CREB and activating transcription factor-2 were not altered in the hippocampus after ischemia. In contrast, levels of the phosphorylated forms of both transcription factors decreased during ischemia but rebounded following reperfusion. The phospho-forms  of CREB and activating transcription factor-2 showed regional and temporal differences in their expression. Phospho-CREB was increased relative to control levels at 30 min, and continued to increase for at least three days postischemia, mainly in dentate granule cells. The level of phospho-activating transcription factor-2 appeared to be higher in CAI pyramidal cells than in dentate granule cells after ischemia. The present findings suggest that the signaling pathways for phosphorylation of CREB may be neuroprotective for dentate cells, which are relatively resistant to ischemic insults. The increased phospho-activating transcription factor-2 may reflect increased stresses in these neurons. The more  modest activation of CREB pathways in CA1 neurons may not be enough to overcome the increased stresses in these neurons, contributing to delayed neuronal death.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BR",
      "lastName" : "Hu",
      "authorRank" : 1,
      "name" : "Hu BR",
      "referenceId" : "RGD:A100579"
    }, {
      "firstName" : "CM",
      "lastName" : "Fux",
      "authorRank" : 2,
      "name" : "Fux",
      "referenceId" : "RGD:A204381"
    }, {
      "firstName" : "ME",
      "lastName" : "Martone",
      "authorRank" : 3,
      "name" : "Martone ME",
      "referenceId" : "RGD:A67526"
    }, {
      "firstName" : "JA",
      "lastName" : "Zivin",
      "authorRank" : 4,
      "name" : "Zivin",
      "referenceId" : "RGD:A204382"
    }, {
      "firstName" : "MH",
      "lastName" : "Ellisman",
      "authorRank" : 5,
      "name" : "Ellisman MH",
      "referenceId" : "RGD:A6388"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10047405"
    } ]
  }, {
    "primaryId" : "PMID:10077454",
    "title" : "Circulating thrombomodulin and hematological alterations in type 2 diabetic patients with retinopathy.",
    "datePublished" : "1998-08-01T00:00:00.000-05:00",
    "citation" : "Fujiwara Y, etal., J Atheroscler Thromb. 1998;5(1):21-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-18T14:20:54.000-05:00",
    "volume" : "5",
    "pages" : "21-8",
    "abstract" : "To clarify the relationship between circulating thrombomodulin (TM) and endothelial cell damage in diabetes mellitus, plasma levels of TM were quantitated by an enzyme linked immunoabsorbant assay (ELISA) in 164 type 2 diabetes mellitus and 72 normal control subjects, and these levels were compared with those of von Willebrand factor antigen (vWf: Ag), thrombin antithrombin III complexes (TAT), plasmin-alpha2-plasmin inhibitor complexes (PIC), fibrinogen, D-dimer, urinary albumin excretion rate (AER), intima-media thickness (IMT) and plaque score of the common carotid artery assessed with high resolution B-mode ultrasonography. Plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and plaque score were significantly increased in the diabetic patients compared to the normal control subjects. Plasma TM levels showed significant correlation with vWf: Ag (r=0.350, p<0.0001), TAT (r = 0.334, p < 0.0001), PIC (r = 0.450, p < 0.0001), AER (r = 0.334, p < 0.0001), IMT (r = 0.181, P<0.01), plaque score (r=0.385, p<0.0001). Among four groups of diabetic patients, divided based on their severity of diabetic retinopathy, there were no significant differences in age, sex, systolic and diastolic blood pressure levels, HbA,1c, or plasma lipid levels, although the plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and the plaque score in the patients with proliferative retinopathy were significantly higher than those of the healthy controls and patients with simple retinopathy. Among the 43 normoalbuminuric patients without intima-media thickness or thickened plaque (AER<30 mg/g Creatinine, IMT<1.0 mm, plaque score = 0), plasma levels of TM, vWf: Ag, TAT, PIC were significantly higher in those patients with retinopathy than in those without retinopathy. Multivariate analysis showed TM, TAT and PIC levels to be independent predictors of diabetic retinopathy. In conclusion, circulating TM reflects endothelial cell damage in patients with diabetic retinopathy, and hypercoagulability might play an important role in endothelial cell damage.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Fujiwara",
      "authorRank" : 1,
      "name" : "Fujiwara Y",
      "referenceId" : "RGD:A22247"
    }, {
      "firstName" : "S",
      "lastName" : "Tagami",
      "authorRank" : 2,
      "name" : "Tagami S",
      "referenceId" : "RGD:A63453"
    }, {
      "firstName" : "Y",
      "lastName" : "Kawakami",
      "authorRank" : 3,
      "name" : "Kawakami Y",
      "referenceId" : "RGD:A39103"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580648"
    } ]
  }, {
    "primaryId" : "PMID:10077518",
    "title" : "Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Mathur A, etal., Circulation. 1999 Mar 16;99(10):1337-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:09:02.000-05:00",
    "volume" : "99",
    "pages" : "1337-43",
    "abstract" : "BACKGROUND: Genetic defects are being increasingly recognized in the etiology of  primary cardiomyopathy (CM). Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first step in the beta-oxidation spiral of fatty acid metabolism, the crucial pathway for cardiac energy production. METHODS AND RESULTS: We studied 37 patients with CM, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis, features suggestive of fatty acid oxidation disorders. Single-stranded conformational variance was used to screen genomic DNA. DNA sequencing and mutational analysis revealed 21 different mutations on the VLCAD gene in 18 patients. Of the mutations, 80% were associated with CM. Severe CM in infancy was recognized in most patients (67%) at presentation. Hepatic dysfunction was common (33%). RNA blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD mRNA in  patients with frame-shift or splice-site mutations and absent or severe reduction in enzyme activity in all. CONCLUSIONS: Infantile CM is the most common clinical  phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are heterogeneous. Although mortality at presentation is high, both the metabolic disorder and cardiomyopathy are reversible.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Mathur",
      "authorRank" : 1,
      "name" : "Mathur A",
      "referenceId" : "RGD:A105765"
    }, {
      "firstName" : "HF",
      "lastName" : "Sims",
      "authorRank" : 2,
      "name" : "Sims HF",
      "referenceId" : "RGD:A29320"
    }, {
      "firstName" : "D",
      "lastName" : "Gopalakrishnan",
      "authorRank" : 3,
      "name" : "Gopalakrishnan",
      "referenceId" : "RGD:A255473"
    }, {
      "firstName" : "B",
      "lastName" : "Gibson",
      "authorRank" : 4,
      "name" : "Gibson B",
      "referenceId" : "RGD:A75441"
    }, {
      "firstName" : "P",
      "lastName" : "Rinaldo",
      "authorRank" : 5,
      "name" : "Rinaldo P",
      "referenceId" : "RGD:A78454"
    }, {
      "firstName" : "J",
      "lastName" : "Vockley",
      "authorRank" : 6,
      "name" : "Vockley J",
      "referenceId" : "RGD:A15054"
    }, {
      "firstName" : "G",
      "lastName" : "Hug",
      "authorRank" : 7,
      "name" : "Hug G",
      "referenceId" : "RGD:A58692"
    }, {
      "firstName" : "AW",
      "lastName" : "Strauss",
      "authorRank" : 8,
      "name" : "Strauss",
      "referenceId" : "RGD:A412707"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063537"
    } ]
  }, {
    "primaryId" : "PMID:10077576",
    "title" : "Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1 is a Src substrate during mitosis.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Di Fruscio M, etal., Proc Natl Acad Sci U S A 1999 Mar 16;96(6):2710-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-26T07:13:33.000-06:00",
    "volume" : "96",
    "pages" : "2710-5",
    "abstract" : "Sam68, the 68-kDa Src substrate associated during mitosis, is an RNA-binding protein with signaling properties that contains a GSG (GRP33, Sam68, GLD-1) domain. Here we report the cloning of two Sam68-like-mammalian proteins, SLM-1 and SLM-2. These proteins have an approximately 70% sequence identity with Sam68 in their GSG domain. SLM-1 and SLM-2 have the characteristic Sam68 SH2 and SH3 domain binding sites. SLM-1 is an RNA-binding protein that is tyrosine phosphorylated by Src during mitosis. SLM-1 bound the SH2 and SH3 domains of p59(fyn), Grb-2, phospholipase Cgamma-1 (PLCgamma-1), and/or p120(rasGAP), suggesting it may function as a multifunctional adapter protein for Src during mitosis. SLM-2 is an RNA-binding protein that is not tyrosine phosphorylated by Src or p59(fyn). Moreover, SLM-2 did not associate with the SH3 domains of p59(fyn), Grb-2, PLCgamma-1, or p120(rasGAP), suggesting that SLM-2 may not function as an adapter protein for these proteins. The identification of SLM-1 and SLM-2 demonstrates the presence of a Sam68/SLM family whose members have the potential to link signaling pathways with RNA metabolism.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Di Fruscio",
      "authorRank" : 1,
      "name" : "Di Fruscio M",
      "referenceId" : "RGD:A27032"
    }, {
      "firstName" : "T",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen T",
      "referenceId" : "RGD:A19396"
    }, {
      "firstName" : "S",
      "lastName" : "Richard",
      "authorRank" : 3,
      "name" : "Richard S",
      "referenceId" : "RGD:A18855"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727209"
    } ]
  }, {
    "primaryId" : "PMID:10077612",
    "title" : "Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.",
    "datePublished" : "1999-03-16T00:00:00.000-06:00",
    "citation" : "Basson CT, etal., Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2919-24. doi: 10.1073/pnas.96.6.2919.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:16:10.000-05:00",
    "volume" : "96",
    "pages" : "2919-24",
    "abstract" : "To better understand the role of TBX5, a T-box containing transcription factor in forelimb and heart development, we have studied the clinical features of Holt-Oram syndrome caused by 10 different TBX5 mutations. Defects predicted to create null alleles caused substantial abnormalities both in limb and heart. In contrast, missense mutations produced distinct phenotypes: Gly80Arg caused significant cardiac malformations but only minor skeletal abnormalities; and Arg237Gln and Arg237Trp caused extensive upper limb malformations but less significant cardiac abnormalities. Amino acids altered by missense mutations were located on the three-dimensional structure of a related T-box transcription factor, Xbra, bound to DNA. Residue 80 is highly conserved within T-box sequences that interact with the major groove of target DNA; residue 237 is located in the T-box domain that selectively binds to the minor groove of DNA. These structural data, taken together with the predominant cardiac or skeletal phenotype produced by each missense mutation, suggest that organ-specific gene activation by TBX5 is predicated on biophysical interactions with different target DNA sequences.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C T",
      "lastName" : "Basson",
      "authorRank" : 1,
      "name" : "Basson CT",
      "referenceId" : "RGD:A590264"
    }, {
      "firstName" : "T",
      "lastName" : "Huang",
      "authorRank" : 2,
      "name" : "Huang T",
      "referenceId" : "RGD:A58343"
    }, {
      "firstName" : "R C",
      "lastName" : "Lin",
      "authorRank" : 3,
      "name" : "Lin RC",
      "referenceId" : "RGD:A590265"
    }, {
      "firstName" : "D R",
      "lastName" : "Bachinsky",
      "authorRank" : 4,
      "name" : "Bachinsky DR",
      "referenceId" : "RGD:A590266"
    }, {
      "firstName" : "S",
      "lastName" : "Weremowicz",
      "authorRank" : 5,
      "name" : "Weremowicz S",
      "referenceId" : "RGD:A25723"
    }, {
      "firstName" : "A",
      "lastName" : "Vaglio",
      "authorRank" : 6,
      "name" : "Vaglio A",
      "referenceId" : "RGD:A35659"
    }, {
      "firstName" : "R",
      "lastName" : "Bruzzone",
      "authorRank" : 7,
      "name" : "Bruzzone R",
      "referenceId" : "RGD:A7400"
    }, {
      "firstName" : "R",
      "lastName" : "Quadrelli",
      "authorRank" : 8,
      "name" : "Quadrelli R",
      "referenceId" : "RGD:A35656"
    }, {
      "firstName" : "M",
      "lastName" : "Lerone",
      "authorRank" : 9,
      "name" : "Lerone M",
      "referenceId" : "RGD:A590267"
    }, {
      "firstName" : "G",
      "lastName" : "Romeo",
      "authorRank" : 10,
      "name" : "Romeo G",
      "referenceId" : "RGD:A10755"
    }, {
      "firstName" : "M",
      "lastName" : "Silengo",
      "authorRank" : 11,
      "name" : "Silengo M",
      "referenceId" : "RGD:A297188"
    }, {
      "firstName" : "A",
      "lastName" : "Pereira",
      "authorRank" : 12,
      "name" : "Pereira A",
      "referenceId" : "RGD:A590268"
    }, {
      "firstName" : "J",
      "lastName" : "Krieger",
      "authorRank" : 13,
      "name" : "Krieger J",
      "referenceId" : "RGD:A20741"
    }, {
      "firstName" : "S F",
      "lastName" : "Mesquita",
      "authorRank" : 14,
      "name" : "Mesquita SF",
      "referenceId" : "RGD:A590269"
    }, {
      "firstName" : "M",
      "lastName" : "Kamisago",
      "authorRank" : 15,
      "name" : "Kamisago M",
      "referenceId" : "RGD:A56223"
    }, {
      "firstName" : "C C",
      "lastName" : "Morton",
      "authorRank" : 16,
      "name" : "Morton CC",
      "referenceId" : "RGD:A590270"
    }, {
      "firstName" : "M E",
      "lastName" : "Pierpont",
      "authorRank" : 17,
      "name" : "Pierpont ME",
      "referenceId" : "RGD:A590271"
    }, {
      "firstName" : "C W",
      "lastName" : "Müller",
      "authorRank" : 18,
      "name" : "Müller CW",
      "referenceId" : "RGD:A590272"
    }, {
      "firstName" : "J G",
      "lastName" : "Seidman",
      "authorRank" : 19,
      "name" : "Seidman JG",
      "referenceId" : "RGD:A447165"
    }, {
      "firstName" : "C E",
      "lastName" : "Seidman",
      "authorRank" : 20,
      "name" : "Seidman CE",
      "referenceId" : "RGD:A563495"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598117795"
    } ]
  }, {
    "primaryId" : "PMID:10077617",
    "title" : "Abnormalities at 14q32.1 in T cell malignancies involve two oncogenes.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Pekarsky Y, etal., Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2949-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-31T13:28:22.000-06:00",
    "volume" : "96",
    "pages" : "2949-51",
    "abstract" : "The TCL1 oncogene on human chromosome 14q32.1 is involved in the development of T cell leukemia in humans. Its expression in these leukemias is activated by chromosomal translocations and inversions at 14q32.1. Here we report the isolation and characterization of a new member of the TCL1 gene family, TCL1b, located approximately 16 kb centromeric of TCL1. The 1.2-kb TCL1b cDNA encodes a 14-kDa protein of 128 aa and shows 60% similarity to Tcl1. Expression profiles of TCL1 and TCL1b genes are very similar: both genes are expressed at very low levels in normal bone marrow and peripheral lymphocytes but are activated in T cell leukemia by rearrangements of the 14q32.1 region. Thus, translocations and inversions at 14q32. 1 in T cell malignancies involve two oncogenes.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Pekarsky",
      "authorRank" : 1,
      "name" : "Pekarsky Y",
      "referenceId" : "RGD:A46527"
    }, {
      "firstName" : "C",
      "lastName" : "Hallas",
      "authorRank" : 2,
      "name" : "Hallas C",
      "referenceId" : "RGD:A73524"
    }, {
      "firstName" : "M",
      "lastName" : "Isobe",
      "authorRank" : 3,
      "name" : "Isobe M",
      "referenceId" : "RGD:A36921"
    }, {
      "firstName" : "G",
      "lastName" : "Russo",
      "authorRank" : 4,
      "name" : "Russo G",
      "referenceId" : "RGD:A64875"
    }, {
      "firstName" : "CM",
      "lastName" : "Croce",
      "authorRank" : 5,
      "name" : "Croce CM",
      "referenceId" : "RGD:A35770"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599360"
    } ]
  }, {
    "primaryId" : "PMID:10077636",
    "title" : "Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Pieper AA, etal., Proc Natl Acad Sci U S A 1999 Mar 16;96(6):3059-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T12:09:15.000-05:00",
    "volume" : "96",
    "pages" : "3059-64",
    "abstract" : "Streptozotocin (STZ) selectively destroys insulin-producing beta islet cells of the pancreas providing a model of type I diabetes. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme whose overactivation by DNA strand breaks depletes its substrate NAD+ and then ATP, leading to cellular death from energy depletion. We demonstrate DNA damage and a major activation of PARP in pancreatic islets of STZ-treated mice. These mice display a 500% increase in blood glucose and major pancreatic islet damage. In mice with homozygous targeted deletion of PARP (PARP -/-), blood glucose and pancreatic islet structure are normal, indicating virtually total protection from STZ diabetes. Partial protection occurs in PARP +/- animals. Thus, PARP activation may participate in the pathophysiology of type I diabetes, for which PARP inhibitors might afford therapeutic benefit.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AA",
      "lastName" : "Pieper",
      "authorRank" : 1,
      "name" : "Pieper AA",
      "referenceId" : "RGD:A44302"
    }, {
      "firstName" : "DJ",
      "lastName" : "Brat",
      "authorRank" : 2,
      "name" : "Brat DJ",
      "referenceId" : "RGD:A44303"
    }, {
      "firstName" : "DK",
      "lastName" : "Krug",
      "authorRank" : 3,
      "name" : "Krug DK",
      "referenceId" : "RGD:A44304"
    }, {
      "firstName" : "CC",
      "lastName" : "Watkins",
      "authorRank" : 4,
      "name" : "Watkins CC",
      "referenceId" : "RGD:A44305"
    }, {
      "firstName" : "A",
      "lastName" : "Gupta",
      "authorRank" : 5,
      "name" : "Gupta A",
      "referenceId" : "RGD:A12147"
    }, {
      "firstName" : "S",
      "lastName" : "Blackshaw",
      "authorRank" : 6,
      "name" : "Blackshaw S",
      "referenceId" : "RGD:A10307"
    }, {
      "firstName" : "A",
      "lastName" : "Verma",
      "authorRank" : 7,
      "name" : "Verma A",
      "referenceId" : "RGD:A44306"
    }, {
      "firstName" : "ZQ",
      "lastName" : "Wang",
      "authorRank" : 8,
      "name" : "Wang ZQ",
      "referenceId" : "RGD:A44307"
    }, {
      "firstName" : "SH",
      "lastName" : "Snyder",
      "authorRank" : 9,
      "name" : "Snyder SH",
      "referenceId" : "RGD:A149337"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300264"
    } ]
  }, {
    "primaryId" : "PMID:10077649",
    "title" : "Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ihara K, etal., Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3132-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-09T08:57:01.000-06:00",
    "volume" : "96",
    "pages" : "3132-6",
    "abstract" : "Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies. Our previous hematological analysis indicated similarities between human CAMT and murine c-mpl (thrombopoietin receptor) deficiency. Because the c-mpl gene was considered as one of the candidate genes for this disorder, we analyzed the genomic sequence of the c-mpl gene of a 10-year-old Japanese girl with CAMT. We detected two heterozygous point mutations: a C-to-T transition at the cDNA nucleotide position 556 (Q186X) in exon 4 and a single nucleotide deletion of thymine at position 1,499 (1,499 delT) in exon 10. Both mutations were predicted to result in a prematurely terminated c-Mpl protein, which, if translated, lacks all intracellular domains essential for signal transduction. Each of the mutations was segregated from the patient's parents. Accordingly, the patient was a compound heterozygote for two mutations of the c-mpl gene, each derived from one of the parents. The present study suggests that at least a certain type of CAMT is caused by the c-mpl mutation, which disrupts the function of thrombopoietin receptor.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Ihara",
      "authorRank" : 1,
      "name" : "Ihara K",
      "referenceId" : "RGD:A46122"
    }, {
      "firstName" : "E",
      "lastName" : "Ishii",
      "authorRank" : 2,
      "name" : "Ishii E",
      "referenceId" : "RGD:A77231"
    }, {
      "firstName" : "M",
      "lastName" : "Eguchi",
      "authorRank" : 3,
      "name" : "Eguchi M",
      "referenceId" : "RGD:A67027"
    }, {
      "firstName" : "H",
      "lastName" : "Takada",
      "authorRank" : 4,
      "name" : "Takada H",
      "referenceId" : "RGD:A24759"
    }, {
      "firstName" : "A",
      "lastName" : "Suminoe",
      "authorRank" : 5,
      "name" : "Suminoe A",
      "referenceId" : "RGD:A77232"
    }, {
      "firstName" : "RA",
      "lastName" : "Good",
      "authorRank" : 6,
      "name" : "Good RA",
      "referenceId" : "RGD:A76509"
    }, {
      "firstName" : "T",
      "lastName" : "Hara",
      "authorRank" : 7,
      "name" : "Hara T",
      "referenceId" : "RGD:A158023"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600454"
    } ]
  }, {
    "primaryId" : "PMID:10077664",
    "title" : "Cortical bitufted, horizontal, and Martinotti cells preferentially express and secrete reelin into perineuronal nets, nonsynaptically modulating gene expression.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Pesold C, etal., Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3217-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-05-03T12:53:31.000-05:00",
    "volume" : "96",
    "pages" : "3217-22",
    "abstract" : "Reelin (Reln) is a protein with some structural analogies with other extracellular matrix proteins that functions in the regulation of neuronal migration during the development of cortical laminated structures. In the cortex of adult animals, Reln is expressed primarily in gamma-aminobutyric acid (GABA)ergic neurons and is secreted into perineuronal nets. However, only 50-60% of GABAergic interneurons express Reln. We have characterized this subpopulation of cortical GABAergic neurons that expresses Reln by using two strategies: (i) a double immunolabeling procedure to determine the colocalization of Reln with neuropeptides and Ca2+-binding proteins and (ii) a combination of Golgi staining and Reln immunolabeling to determine the morphology of the rat cortical cells that store Reln. Many interneurons that express Neuropeptide Y (NPY) or somatostatin (but none of those that express parvalbumin) are Reln-immunopositive. A small population of calbindin-positive interneurons and very few calretinin-positive cells express Reln immunopositivity. Golgi staining revealed that layer I horizontal cells, layer II-V bitufted neurons, and some deep cortical layer Martinotti cells express Reln. Basket and chandelier cells are often immunopositive to parvalbumin, but never to Reln. Although Reln is secreted by GABAergic neurons, its target are not the GABA receptors, but rather may be extrasynaptically located in perineuronal nets and concerned with the modulation of neuronal plasticity. Dab1, the target adapter protein that presumably mediates transcription regulation via the extrasynaptic actions of Reln, is expressed predominantly in pyramidal neurons, but it can also be detected in a small population of GABAergic neurons that are neither horizontal nor bitufted neurons.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Pesold",
      "authorRank" : 1,
      "name" : "Pesold C",
      "referenceId" : "RGD:A122730"
    }, {
      "firstName" : "WS",
      "lastName" : "Liu",
      "authorRank" : 2,
      "name" : "Liu WS",
      "referenceId" : "RGD:A30208"
    }, {
      "firstName" : "A",
      "lastName" : "Guidotti",
      "authorRank" : 3,
      "name" : "Guidotti A",
      "referenceId" : "RGD:A24680"
    }, {
      "firstName" : "E",
      "lastName" : "Costa",
      "authorRank" : 4,
      "name" : "Costa E",
      "referenceId" : "RGD:A16285"
    }, {
      "firstName" : "HJ",
      "lastName" : "Caruncho",
      "authorRank" : 5,
      "name" : "Caruncho HJ",
      "referenceId" : "RGD:A122360"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317955"
    } ]
  }, {
    "primaryId" : "PMID:10078570",
    "title" : "The quantitative trait locus on chromosome 2 for serum leptin levels is confirmed in African-Americans.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Rotimi CN, etal., Diabetes. 1999 Mar;48(3):643-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-11-12T09:48:05.000-06:00",
    "volume" : "48",
    "pages" : "643-4",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CN",
      "lastName" : "Rotimi",
      "authorRank" : 1,
      "name" : "Rotimi CN",
      "referenceId" : "RGD:A89178"
    }, {
      "firstName" : "AG",
      "lastName" : "Comuzzie",
      "authorRank" : 2,
      "name" : "Comuzzie AG",
      "referenceId" : "RGD:A40006"
    }, {
      "firstName" : "WL",
      "lastName" : "Lowe",
      "authorRank" : 3,
      "name" : "Lowe WL",
      "referenceId" : "RGD:A89179"
    }, {
      "firstName" : "A",
      "lastName" : "Luke",
      "authorRank" : 4,
      "name" : "Luke A",
      "referenceId" : "RGD:A39812"
    }, {
      "firstName" : "J",
      "lastName" : "Blangero",
      "authorRank" : 5,
      "name" : "Blangero J",
      "referenceId" : "RGD:A162628"
    }, {
      "firstName" : "RS",
      "lastName" : "Cooper",
      "authorRank" : 6,
      "name" : "Cooper RS",
      "referenceId" : "RGD:A39811"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642927"
    } ]
  }, {
    "primaryId" : "PMID:10078579",
    "title" : "Hemostatic variables as independent predictors for fetal growth retardation in preeclampsia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Schjetlein R, etal., Acta Obstet Gynecol Scand. 1999 Mar;78(3):191-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-19T13:48:38.000-05:00",
    "volume" : "78",
    "pages" : "191-7",
    "abstract" : "BACKGROUND: Preeclampsia is a major contributor to perinatal disease and fetal growth retardation (FGR). It has been suggested that increased intravascular coagulation, fibrin deposition in spiral arteries and hypoperfusion of the placenta are involved in these pregnancy complications. METHODS: Multiple variables of the hemostatic system and lipid metabolism, as well as clinical features, were entered into univariate and multivariate models in order to examine the association with preeclampsia and FGR. RESULTS: Two hundred women with preeclampsia and 97 normotensive pregnant women were examined. Plasma levels of the thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor free  antigen (TFPI-Fag), protein S free antigen, plasminogen activator inhibitor type-1 (PAI-1) activity and serum levels of triglycerides were significantly increased, whereas plasma levels of antithrombin (AT), fibrinogen, C4b-binding protein (C4b-BP), PAI-2 antigen and serum HDL-cholesterol levels were decreased in the presence of preeclampsia. In the multivariate regression analysis, high TFPI-Fag plasma levels were associated with the presence of preeclampsia. The presence of FGR was in the univariate analysis associated with decreased PAI-1 activity and lower concentrations of fibrin, fibrinogen, factor VII antigen and PAI-2 antigen, as well as with evidence of macroscopic placental infarction. In a multivariate regression model, low maternal weight, placental infarction and low  PAI-2 levels were predictors for low birth weight. In a logistic regression model, with the presence or absence of FGR as the dependent variable, male sex of the infant, placental infarction, low PAI-1 activity and factor VII antigen or PAI-2 antigen levels were independent predictors. CONCLUSIONS: Our results are consistent with activated coagulation in the placental vessels in preeclampsia. A low concentration of PAI-2 antigen in plasma emerged as the most consistent risk  factor for preeclampsia and FGR.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Schjetlein",
      "authorRank" : 1,
      "name" : "Schjetlein",
      "referenceId" : "RGD:A243425"
    }, {
      "firstName" : "M",
      "lastName" : "Abdelnoor",
      "authorRank" : 2,
      "name" : "Abdelnoor",
      "referenceId" : "RGD:A243426"
    }, {
      "firstName" : "G",
      "lastName" : "Haugen",
      "authorRank" : 3,
      "name" : "Haugen",
      "referenceId" : "RGD:A243427"
    }, {
      "firstName" : "H",
      "lastName" : "Husby",
      "authorRank" : 4,
      "name" : "Husby",
      "referenceId" : "RGD:A243428"
    }, {
      "firstName" : "PM",
      "lastName" : "Sandset",
      "authorRank" : 5,
      "name" : "Sandset",
      "referenceId" : "RGD:A209360"
    }, {
      "firstName" : "F",
      "lastName" : "Wisloff",
      "authorRank" : 6,
      "name" : "Wisloff",
      "referenceId" : "RGD:A243429"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11060132"
    } ]
  }, {
    "primaryId" : "PMID:10078851",
    "title" : "Absence of genetic variation in some obesity candidate genes (GLP1R, ASIP, MC4R, MC5R) among Pima indians.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Norman RA, etal., Int J Obes Relat Metab Disord. 1999 Feb;23(2):163-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-10-30T12:13:07.000-05:00",
    "volume" : "23",
    "pages" : "163-5",
    "abstract" : "OBJECTIVE: To examine the obesity candidate genes glucagon-like-peptide receptor (GLP1R), agouti signaling protein (ASIP) and the melanocortin receptors 4 and 5 (MC4R and MC5R) for DNA polymorphisms in their coding regions. SUBJECTS: Unrelated, non-diabetic Pima Indians (8 to 12 from each extreme of body fat). MEASUREMENTS: DNA sequencing within the coding regions of each gene. RESULT: Only one variant was detected, a silent substitution in exon 6 of GLP1R. CONCLUSION: The exclusion of any common amino-acid polymorphisms (allele frequency > or = 0.20). implies that structural variants of these genes do not contribute to variation in the high level of obesity observed among the Pima Indians.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RA",
      "lastName" : "Norman",
      "authorRank" : 1,
      "name" : "Norman RA",
      "referenceId" : "RGD:A84379"
    }, {
      "firstName" : "P",
      "lastName" : "Permana",
      "authorRank" : 2,
      "name" : "Permana P",
      "referenceId" : "RGD:A114328"
    }, {
      "firstName" : "Y",
      "lastName" : "Tanizawa",
      "authorRank" : 3,
      "name" : "Tanizawa Y",
      "referenceId" : "RGD:A4195"
    }, {
      "firstName" : "E",
      "lastName" : "Ravussin",
      "authorRank" : 4,
      "name" : "Ravussin E",
      "referenceId" : "RGD:A84175"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2314007"
    } ]
  }, {
    "primaryId" : "PMID:10078962",
    "title" : "Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-gamma, interleukin-7, or B7-1-transfected tumor cells.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Visse E, etal., Cancer Gene Ther 1999 Jan-Feb;6(1):37-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:54:30.000-06:00",
    "volume" : "6",
    "pages" : "37-44",
    "abstract" : "Progress in the definition of the roles of various costimulators and cytokines in determining the type and height of immune responses has made it important to explore genetically altered tumor cells expressing such molecules for therapeutic immunizations. We have studied the effect of therapeutic subcutaneous (s.c.) immunizations on the growth of preexisting intracerebral brain tumor isografts in the rat. Transfectant glioma cell clones expressing either rat interferon-gamma (IFN-gamma), rat interleukin-7 (IL-7), or rat B7-1 were selected. After irradiation (80 Gy) the clones were used for immunization (administered in up to four s.c. doses in a hind leg over 14-day intervals starting 1 day after the intracranial isografting of the parental tumor). Significant growth inhibition of the intracerebral parental tumors was induced by transfectants expressing IFN-gamma and IL-7, respectively. The strongest effect was observed with IFN-gamma-expressing cells, resulting in cures in 37% of the males and in 100% of the females. Immunization with IL-7 had a similar, strong initial effect, with significantly prolonged survival in the majority of the rats but a lower final cure rate (survival for >150 days). The B7-1-expressing tumor clones induced cures in seven of eight female rats; however, no cures were seen in the male rats. It was also shown that the B7-1-expressing cells were themselves strongly immunogenic in female rats, requiring high cell numbers to result in a progressively growing tumor upon s.c. isografting; this was not the case in male rats. As a whole, the results imply that despite the unfavorable location of intracerebral tumors, therapeutic s.c. immunizations with certain types of genetically altered tumor cells can induce complete regressions with permanent survival and without gross neurological or other apparent signs of brain damage. The present results demonstrate complete regressions when immunizations are initiated shortly after intracranial isografting, when the intracerebral tumor is small.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Visse",
      "authorRank" : 1,
      "name" : "Visse E",
      "referenceId" : "RGD:A27176"
    }, {
      "firstName" : "P",
      "lastName" : "Siesjo",
      "authorRank" : 2,
      "name" : "Siesjo P",
      "referenceId" : "RGD:A27177"
    }, {
      "firstName" : "B",
      "lastName" : "Widegren",
      "authorRank" : 3,
      "name" : "Widegren B",
      "referenceId" : "RGD:A27178"
    }, {
      "firstName" : "HO",
      "lastName" : "Sjogren",
      "authorRank" : 4,
      "name" : "Sjogren HO",
      "referenceId" : "RGD:A27179"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727266"
    } ]
  }, {
    "primaryId" : "PMID:10079066",
    "title" : "N-acylglycine amidation: implications for the biosynthesis of fatty acid primary amides.",
    "datePublished" : "1999-03-16T00:00:00.000-06:00",
    "citation" : "Wilcox BJ, etal., Biochemistry. 1999 Mar 16;38(11):3235-45. doi: 10.1021/bi982255j.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-02-16T06:50:44.000-06:00",
    "volume" : "38",
    "pages" : "3235-45",
    "abstract" : "Bifunctional peptidylglycine alpha-amidating enzyme (alpha-AE) catalyzes the O2-dependent conversion of C-terminal glycine-extended prohormones to the active, C-terminal alpha-amidated peptide and glyoxylate. We show that alpha-AE will also catalyze the oxidative cleavage of N-acylglycines, from N-formylglycine to N-arachidonoylglycine. N-Formylglycine is the smallest amide substrate yet reported for alpha-AE. The (V/K)app for N-acylglycine amidation varies approximately 1000-fold, with the (V/K)app increasing as the acyl chain length increases. This effect is largely an effect on the KM,app; the KM,app for N-formylglycine is 23 +/- 0.88 mM, while the KM,app for N-lauroylglycine and longer chain N-acylglycines is in the range of 60-90 microM. For the amidation of N-acetylglycine, N-(tert-butoxycarbonyl)glycine, N-hexanoylglycine, and N-oleoylglycine, the rate of O2 consumption is faster than the rate of glyoxylate production. These results indicate that there must be the initial formation of an oxidized intermediate from the N-acylglycine before glyoxylate is produced. The intermediate is shown to be N-acyl-alpha-hydroxyglycine by two-dimensional 1H-13C heteronuclear multiple quantum coherence (HMQC) NMR.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B J",
      "lastName" : "Wilcox",
      "authorRank" : 1,
      "name" : "Wilcox BJ",
      "referenceId" : "RGD:A467922"
    }, {
      "firstName" : "K J",
      "lastName" : "Ritenour-Rodgers",
      "authorRank" : 2,
      "name" : "Ritenour-Rodgers KJ",
      "referenceId" : "RGD:A467923"
    }, {
      "firstName" : "A S",
      "lastName" : "Asser",
      "authorRank" : 3,
      "name" : "Asser AS",
      "referenceId" : "RGD:A467924"
    }, {
      "firstName" : "L E",
      "lastName" : "Baumgart",
      "authorRank" : 4,
      "name" : "Baumgart LE",
      "referenceId" : "RGD:A467925"
    }, {
      "firstName" : "M A",
      "lastName" : "Baumgart",
      "authorRank" : 5,
      "name" : "Baumgart MA",
      "referenceId" : "RGD:A467926"
    }, {
      "firstName" : "D L",
      "lastName" : "Boger",
      "authorRank" : 6,
      "name" : "Boger DL",
      "referenceId" : "RGD:A467927"
    }, {
      "firstName" : "J L",
      "lastName" : "DeBlassio",
      "authorRank" : 7,
      "name" : "DeBlassio JL",
      "referenceId" : "RGD:A467928"
    }, {
      "firstName" : "M A",
      "lastName" : "deLong",
      "authorRank" : 8,
      "name" : "deLong MA",
      "referenceId" : "RGD:A467929"
    }, {
      "firstName" : "U",
      "lastName" : "Glufke",
      "authorRank" : 9,
      "name" : "Glufke U",
      "referenceId" : "RGD:A467930"
    }, {
      "firstName" : "M E",
      "lastName" : "Henz",
      "authorRank" : 10,
      "name" : "Henz ME",
      "referenceId" : "RGD:A467931"
    }, {
      "firstName" : "L",
      "lastName" : "King",
      "authorRank" : 11,
      "name" : "King L",
      "referenceId" : "RGD:A467932"
    }, {
      "firstName" : "K A",
      "lastName" : "Merkler",
      "authorRank" : 12,
      "name" : "Merkler KA",
      "referenceId" : "RGD:A467933"
    }, {
      "firstName" : "J E",
      "lastName" : "Patterson",
      "authorRank" : 13,
      "name" : "Patterson JE",
      "referenceId" : "RGD:A467934"
    }, {
      "firstName" : "J J",
      "lastName" : "Robleski",
      "authorRank" : 14,
      "name" : "Robleski JJ",
      "referenceId" : "RGD:A467935"
    }, {
      "firstName" : "J C",
      "lastName" : "Vederas",
      "authorRank" : 15,
      "name" : "Vederas JC",
      "referenceId" : "RGD:A467936"
    }, {
      "firstName" : "D J",
      "lastName" : "Merkler",
      "authorRank" : 16,
      "name" : "Merkler DJ",
      "referenceId" : "RGD:A467937"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14390048"
    } ]
  }, {
    "primaryId" : "PMID:10079200",
    "title" : "Bone morphogenetic protein-3b (BMP-3b) gene expression is correlated with differentiation in rat calvarial osteoblasts.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hino J, etal., Biochem Biophys Res Commun. 1999 Mar 16;256(2):419-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-10T16:41:54.000-06:00",
    "volume" : "256",
    "pages" : "419-24",
    "abstract" : "BMP-3b (also called GDF-10) is a novel BMP-3-related protein recently discovered in rat femur tissue. Gene expression of BMP-3b in osteoblastic cells and its regulation by prolonged culture, BMP-2 and transforming growth factor beta1 (TGF-beta1) were examined. The BMP-3b gene was highly expressed in rat osteoblasts obtained from calvarial bones but not in the osteoblastic cell lines (MC3T3-E1 and U2-OS). BMP-3b mRNA increased during osteoblastic differentiation in prolonged culture and was associated with increased alkaline phosphatase (ALPase) activity. When BMP-2, an enhancer of ALPase activity, was added to the primary osteoblast culture, BMP-3b mRNA increased 6.9-fold after 24 h. In contrast, TGF-beta1 treatment, which suppresses ALPase activity, rapidly and completely inhibited gene expression of BMP-3b. The regulation of BMP-3 mRNA differed from that of BMP-3b, even though both proteins share 81% identity. These findings indicate that BMP-3b gene expression is regulated by osteoblastic differentiation and BMP-3b functions in highly differentiated osteoblasts.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Hino",
      "authorRank" : 1,
      "name" : "Hino J",
      "referenceId" : "RGD:A15342"
    }, {
      "firstName" : "H",
      "lastName" : "Matsuo",
      "authorRank" : 2,
      "name" : "Matsuo H",
      "referenceId" : "RGD:A5292"
    }, {
      "firstName" : "K",
      "lastName" : "Kangawa",
      "authorRank" : 3,
      "name" : "Kangawa K",
      "referenceId" : "RGD:A5511"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316373"
    } ]
  }, {
    "primaryId" : "PMID:10079256",
    "title" : "Human ligands of the Notch receptor.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Gray GE, etal., Am J Pathol 1999 Mar;154(3):785-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-12-29T16:23:20.000-06:00",
    "volume" : "154",
    "pages" : "785-94",
    "abstract" : "During development, the Notch signaling pathway is essential for the appropriate differentiation of many cell types in organisms across the phylogenetic scale, including humans. Notch signaling is also implicated in human diseases, including a leukemia and two hereditary syndromes known as Alagille and CADASIL. To generate tools for pursuing the role of the Notch pathway in human disease and development, we have cloned and analyzed the expression of three human homologues of the Notch ligands Delta and Serrate, human Jagged1 (HJ1), human Jagged2 (HJ2), and human Delta1 (H-Delta-1), and determined their chromosomal localizations. We have also raised antibodies to HJ1, and used these antibodies in conjunction with in situ hybridization to examine the expression of these ligands in normal and cancerous cervical tissue. We find that, as reported previously for Notch, the ligands are up-regulated in certain neoplastic tissues. This observation is consistent with the notion that Notch signaling is an important element in these pathogenic conditions, raising the possibility that modulation of Notch activity could be used to influence the fate of the cells and offering a conceivable therapeutic avenue.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GE",
      "lastName" : "Gray",
      "authorRank" : 1,
      "name" : "Gray GE",
      "referenceId" : "RGD:A49903"
    }, {
      "firstName" : "RS",
      "lastName" : "Mann",
      "authorRank" : 2,
      "name" : "Mann RS",
      "referenceId" : "RGD:A49904"
    }, {
      "firstName" : "E",
      "lastName" : "Mitsiadis",
      "authorRank" : 3,
      "name" : "Mitsiadis E",
      "referenceId" : "RGD:A49905"
    }, {
      "firstName" : "D",
      "lastName" : "Henrique",
      "authorRank" : 4,
      "name" : "Henrique D",
      "referenceId" : "RGD:A49906"
    }, {
      "firstName" : "ML",
      "lastName" : "Carcangiu",
      "authorRank" : 5,
      "name" : "Carcangiu ML",
      "referenceId" : "RGD:A49907"
    }, {
      "firstName" : "A",
      "lastName" : "Banks",
      "authorRank" : 6,
      "name" : "Banks A",
      "referenceId" : "RGD:A49908"
    }, {
      "firstName" : "J",
      "lastName" : "Leiman",
      "authorRank" : 7,
      "name" : "Leiman J",
      "referenceId" : "RGD:A49909"
    }, {
      "firstName" : "D",
      "lastName" : "Ward",
      "authorRank" : 8,
      "name" : "Ward D",
      "referenceId" : "RGD:A161317"
    }, {
      "firstName" : "D",
      "lastName" : "Ish-Horowitz",
      "authorRank" : 9,
      "name" : "Ish-Horowitz D",
      "referenceId" : "RGD:A49910"
    }, {
      "firstName" : "S",
      "lastName" : "Artavanis-Tsakonas",
      "authorRank" : 10,
      "name" : "Artavanis-Tsakonas S",
      "referenceId" : "RGD:A49911"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1304492"
    } ]
  }, {
    "primaryId" : "PMID:10079261",
    "title" : "IL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the rat.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Yu XQ, etal., Am J Pathol. 1999 Mar;154(3):833-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-11-08T09:58:48.000-06:00",
    "volume" : "154",
    "pages" : "833-41",
    "abstract" : "Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule that acts to  promote macrophage infiltration in rat anti-glomerular basement membrane (GBM) glomerulonephritis. The present study investigated the role of interleukin-1 (IL-1) in the up-regulation of renal OPN expression in this disease model. Accelerated anti-GBM glomerulonephritis was induced in groups of six rats. Animals were treated by a constant infusion of the IL-1 receptor antagonist or saline (control) over days -1 to 14 (induction phase) or days 7 to 21 (established disease). In normal rat kidney, OPN was expressed in a few tubules (<5%) and absent from glomeruli. During the development of rat anti-GBM disease (days 7 to 21), there was substantial up-regulation of OPN mRNA and protein expression in glomeruli (>5 cells per glomerular cross-section) and tubular epithelial cells (50-75% OPN-positive). Up-regulation of OPN expression was associated with macrophage accumulation within the kidney, severe proteinuria, loss of renal function, and severe histological damage including glomerular crescentic formation and tubulointerstitial fibrosis. In contrast, IL-1 receptor  antagonist treatment of either the induction phase of disease or established disease significantly reduced OPN mRNA and protein expression in glomeruli (/75-85%, P < 0.001) and tubules (/45-60%, P < 0.001). The reduction in OPN expression was associated with significant inhibition of macrophage accumulation  and progressive renal injury. In vitro, the addition of IL-1 to the normal rat tubular epithelial cell line NRK52E up-regulated OPN mRNA and protein levels, an  effect that was dose-dependent and inhibited by the addition of IL-1 receptor antagonist, thus demonstrating that IL-1 can act directly to up-regulate renal OPN expression. In conclusion, this study provides in vivo and in vitro evidence  that IL-1 up-regulates OPN expression in experimental kidney disease and support  for the argument that inhibition of OPN expression is one mechanism by which IL-1 receptor antagonist treatment suppresses macrophage-mediated renal injury.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "XQ",
      "lastName" : "Yu",
      "authorRank" : 1,
      "name" : "Yu XQ",
      "referenceId" : "RGD:A145257"
    }, {
      "firstName" : "JM",
      "lastName" : "Fan",
      "authorRank" : 2,
      "name" : "Fan JM",
      "referenceId" : "RGD:A59511"
    }, {
      "firstName" : "DJ",
      "lastName" : "Nikolic-Paterson",
      "authorRank" : 3,
      "name" : "Nikolic-Paterson DJ",
      "referenceId" : "RGD:A28569"
    }, {
      "firstName" : "N",
      "lastName" : "Yang",
      "authorRank" : 4,
      "name" : "Yang N",
      "referenceId" : "RGD:A26492"
    }, {
      "firstName" : "W",
      "lastName" : "Mu",
      "authorRank" : 5,
      "name" : "Mu W",
      "referenceId" : "RGD:A59514"
    }, {
      "firstName" : "R",
      "lastName" : "Pichler",
      "authorRank" : 6,
      "name" : "Pichler R",
      "referenceId" : "RGD:A159481"
    }, {
      "firstName" : "RJ",
      "lastName" : "Johnson",
      "authorRank" : 7,
      "name" : "Johnson RJ",
      "referenceId" : "RGD:A77382"
    }, {
      "firstName" : "RC",
      "lastName" : "Atkins",
      "authorRank" : 8,
      "name" : "Atkins RC",
      "referenceId" : "RGD:A19944"
    }, {
      "firstName" : "HY",
      "lastName" : "Lan",
      "authorRank" : 9,
      "name" : "Lan HY",
      "referenceId" : "RGD:A59515"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6909131"
    } ]
  }, {
    "primaryId" : "PMID:10079270",
    "title" : "Bone marrow-derived cells are required for the induction of a pulmonary inflammatory response mediated by CD40 ligation.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Wiley JA and Harmsen AG, Am J Pathol. 1999 Mar;154(3):919-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:42:27.000-05:00",
    "volume" : "154",
    "pages" : "919-26",
    "abstract" : "The expression of inflammatory mediators by various cells following in vitro CD40 ligation is well known. However, knowledge of the role and interaction with these cells in the establishment and maintenance of in vivo immune-mediated inflammation is limited. In this report, a chimeric mouse model based on CD40 knockout and wild-type mice was used to assess the role of bone marrow (BM)-derived and non-BM-derived cells in a CD40-mediated pulmonary inflammation response. CD40+ BM-derived cells were required for initial cell recruitment, pulmonary edema, and weight loss associated with this response. The structural CD40+ non-BM-derived cells of the lung, such as fibroblasts, epithelial cells, and endothelial cells, could not by themselves establish any level of pulmonary inflammation. However, both the CD40+ BM-derived cells and the structural CD40+ non-BM-derived cells of the lung were required to maximize the level of pulmonary inflammation. Both B cells and T cells played a contributing role in macrophage recruitment and pulmonary edema but neither contributed to the inflammation-associated weight loss. These experiments indicate that CD40+ BM-derived cells were critical to the induction of pulmonary inflammation and that alveolar macrophages, B cells, and T cells contributed to selective aspects  of the response.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Wiley",
      "authorRank" : 1,
      "name" : "Wiley",
      "referenceId" : "RGD:A332109"
    }, {
      "firstName" : "AG",
      "lastName" : "Harmsen",
      "authorRank" : 2,
      "name" : "Harmsen",
      "referenceId" : "RGD:A332110"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340915"
    } ]
  }, {
    "primaryId" : "PMID:10079938",
    "title" : "Study of structure of secretory 28 kDa protein from the rat olfactory epithelium",
    "datePublished" : "1998-08-01T00:00:00.000-05:00",
    "citation" : "Andreeva SG, etal., Bioorg Khim 1998 Nov;24(11):816-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-08-20T09:45:03.000-05:00",
    "volume" : "24",
    "pages" : "816-21",
    "abstract" : "Clone lambda a26.1 isolated from rat olfactory epithelium contains a full-length 28-kDa protein cDNA (1414 b.p.). The reconstructed protein sequence comprises 223 aa with a calculated molecular mass of 24,630 Da. A substantial homology was revealed between the amino acid sequence of the 28-kDa protein and those of thiol-specific antioxidants (peroxiredoxines). The 28-kDa protein belongs to the 1 Cys-subfamily of peroxiredoxines and is the first member of peroxiredoxines identified in the olfactory epithelium.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SG",
      "lastName" : "Andreeva",
      "authorRank" : 1,
      "name" : "Andreeva SG",
      "referenceId" : "RGD:A9459"
    }, {
      "firstName" : "MI",
      "lastName" : "Merkulova",
      "authorRank" : 2,
      "name" : "Merkulova MI",
      "referenceId" : "RGD:A9460"
    }, {
      "firstName" : "TM",
      "lastName" : "Shuvaeva",
      "authorRank" : 3,
      "name" : "Shuvaeva TM",
      "referenceId" : "RGD:A9461"
    }, {
      "firstName" : "VI",
      "lastName" : "Novoselov",
      "authorRank" : 4,
      "name" : "Novoselov VI",
      "referenceId" : "RGD:A9462"
    }, {
      "firstName" : "IV",
      "lastName" : "Peshenko",
      "authorRank" : 5,
      "name" : "Peshenko IV",
      "referenceId" : "RGD:A9463"
    }, {
      "firstName" : "SV",
      "lastName" : "Novoselov",
      "authorRank" : 6,
      "name" : "Novoselov SV",
      "referenceId" : "RGD:A8984"
    }, {
      "firstName" : "EE",
      "lastName" : "Fesenko",
      "authorRank" : 7,
      "name" : "Fesenko EE",
      "referenceId" : "RGD:A9464"
    }, {
      "firstName" : "VM",
      "lastName" : "Lipkin",
      "authorRank" : 8,
      "name" : "Lipkin VM",
      "referenceId" : "RGD:A9465"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70621"
    } ]
  }, {
    "primaryId" : "PMID:10080172",
    "title" : "An almost-intact human endogenous retrovirus K on human chromosome 7.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Mayer J, etal., Nat Genet. 1999 Mar;21(3):257-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:52:44.000-05:00",
    "volume" : "21",
    "pages" : "257-8",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Mayer",
      "authorRank" : 1,
      "name" : "Mayer J",
      "referenceId" : "RGD:A58785"
    }, {
      "firstName" : "M",
      "lastName" : "Sauter",
      "authorRank" : 2,
      "name" : "Sauter",
      "referenceId" : "RGD:A168242"
    }, {
      "firstName" : "A",
      "lastName" : "Racz",
      "authorRank" : 3,
      "name" : "Racz",
      "referenceId" : "RGD:A237811"
    }, {
      "firstName" : "D",
      "lastName" : "Scherer",
      "authorRank" : 4,
      "name" : "Scherer",
      "referenceId" : "RGD:A227881"
    }, {
      "firstName" : "N",
      "lastName" : "Mueller-Lantzsch",
      "authorRank" : 5,
      "name" : "Mueller-Lantzsch",
      "referenceId" : "RGD:A223678"
    }, {
      "firstName" : "E",
      "lastName" : "Meese",
      "authorRank" : 6,
      "name" : "Meese E",
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    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11057416"
    } ]
  }, {
    "primaryId" : "PMID:10080174",
    "title" : "Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Schuelke M, etal., Nat Genet. 1999 Mar;21(3):260-1. doi: 10.1038/6772.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:24:54.000-05:00",
    "volume" : "21",
    "pages" : "260-1",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Schuelke",
      "authorRank" : 1,
      "name" : "Schuelke M",
      "referenceId" : "RGD:A39230"
    }, {
      "firstName" : "J",
      "lastName" : "Smeitink",
      "authorRank" : 2,
      "name" : "Smeitink J",
      "referenceId" : "RGD:A77673"
    }, {
      "firstName" : "E",
      "lastName" : "Mariman",
      "authorRank" : 3,
      "name" : "Mariman E",
      "referenceId" : "RGD:A602276"
    }, {
      "firstName" : "J",
      "lastName" : "Loeffen",
      "authorRank" : 4,
      "name" : "Loeffen J",
      "referenceId" : "RGD:A77671"
    }, {
      "firstName" : "B",
      "lastName" : "Plecko",
      "authorRank" : 5,
      "name" : "Plecko B",
      "referenceId" : "RGD:A448948"
    }, {
      "firstName" : "F",
      "lastName" : "Trijbels",
      "authorRank" : 6,
      "name" : "Trijbels F",
      "referenceId" : "RGD:A77677"
    }, {
      "firstName" : "S",
      "lastName" : "Stöckler-Ipsiroglu",
      "authorRank" : 7,
      "name" : "Stöckler-Ipsiroglu S",
      "referenceId" : "RGD:A602277"
    }, {
      "firstName" : "L",
      "lastName" : "van den Heuvel",
      "authorRank" : 8,
      "name" : "van den Heuvel L",
      "referenceId" : "RGD:A566903"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119825"
    } ]
  }, {
    "primaryId" : "PMID:10080178",
    "title" : "Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Sakuntabhai A, etal., Nat Genet 1999 Mar;21(3):271-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:43:51.000-06:00",
    "volume" : "21",
    "pages" : "271-7",
    "abstract" : "Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2(+)-ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca(2+)-signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Sakuntabhai",
      "authorRank" : 1,
      "name" : "Sakuntabhai A",
      "referenceId" : "RGD:A36201"
    }, {
      "firstName" : "V",
      "lastName" : "Ruiz-Perez",
      "authorRank" : 2,
      "name" : "Ruiz-Perez V",
      "referenceId" : "RGD:A36202"
    }, {
      "firstName" : "S",
      "lastName" : "Carter",
      "authorRank" : 3,
      "name" : "Carter S",
      "referenceId" : "RGD:A36203"
    }, {
      "firstName" : "N",
      "lastName" : "Jacobsen",
      "authorRank" : 4,
      "name" : "Jacobsen N",
      "referenceId" : "RGD:A36204"
    }, {
      "firstName" : "S",
      "lastName" : "Burge",
      "authorRank" : 5,
      "name" : "Burge S",
      "referenceId" : "RGD:A36205"
    }, {
      "firstName" : "S",
      "lastName" : "Monk",
      "authorRank" : 6,
      "name" : "Monk S",
      "referenceId" : "RGD:A36206"
    }, {
      "firstName" : "M",
      "lastName" : "Smith",
      "authorRank" : 7,
      "name" : "Smith M",
      "referenceId" : "RGD:A161330"
    }, {
      "firstName" : "CS",
      "lastName" : "Munro",
      "authorRank" : 8,
      "name" : "Munro CS",
      "referenceId" : "RGD:A36207"
    }, {
      "firstName" : "M",
      "lastName" : "O'Donovan",
      "authorRank" : 9,
      "name" : "O'Donovan M",
      "referenceId" : "RGD:A36208"
    }, {
      "firstName" : "N",
      "lastName" : "Craddock",
      "authorRank" : 10,
      "name" : "Craddock N",
      "referenceId" : "RGD:A36209"
    }, {
      "firstName" : "R",
      "lastName" : "Kucherlapati",
      "authorRank" : 11,
      "name" : "Kucherlapati R",
      "referenceId" : "RGD:A36210"
    }, {
      "firstName" : "JL",
      "lastName" : "Rees",
      "authorRank" : 12,
      "name" : "Rees JL",
      "referenceId" : "RGD:A6259"
    }, {
      "firstName" : "M",
      "lastName" : "Owen",
      "authorRank" : 13,
      "name" : "Owen M",
      "referenceId" : "RGD:A36211"
    }, {
      "firstName" : "GM",
      "lastName" : "Lathrop",
      "authorRank" : 14,
      "name" : "Lathrop GM",
      "referenceId" : "RGD:A134841"
    }, {
      "firstName" : "AP",
      "lastName" : "Monaco",
      "authorRank" : 15,
      "name" : "Monaco AP",
      "referenceId" : "RGD:A36213"
    }, {
      "firstName" : "T",
      "lastName" : "Strachan",
      "authorRank" : 16,
      "name" : "Strachan T",
      "referenceId" : "RGD:A26710"
    }, {
      "firstName" : "A",
      "lastName" : "Hovnanian",
      "authorRank" : 17,
      "name" : "Hovnanian A",
      "referenceId" : "RGD:A36214"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734619"
    } ]
  }, {
    "primaryId" : "PMID:10080180",
    "title" : "Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Bonne G, etal., Nat Genet. 1999 Mar;21(3):285-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-02-27T15:22:14.000-06:00",
    "volume" : "21",
    "pages" : "285-8",
    "abstract" : "Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD; OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the disease. Mutations in EMD, the gene encoding emerin, are responsible for the X-linked form. We have mapped the locus for EDMD-AD to an 8-cM interval on chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype in four other small families was potentially linked to this locus. This region contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the nuclear lamina, lamins A and C, produced by alternative splicing. We identified four mutations in LMNA that co-segregate with the disease phenotype in the five families: one nonsense mutation and three missense mutations. These results are the first identification of mutations in a component of the nuclear lamina as a cause of inherited muscle disorder. Together with mutations in EMD (refs 5,6), they underscore the potential importance of the nuclear envelope components in the pathogenesis of neuromuscular disorders.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Bonne",
      "authorRank" : 1,
      "name" : "Bonne G",
      "referenceId" : "RGD:A61719"
    }, {
      "firstName" : "M R",
      "lastName" : "Di Barletta",
      "authorRank" : 2,
      "name" : "Di Barletta MR",
      "referenceId" : "RGD:A439652"
    }, {
      "firstName" : "S",
      "lastName" : "Varnous",
      "authorRank" : 3,
      "name" : "Varnous S",
      "referenceId" : "RGD:A439653"
    }, {
      "firstName" : "H M",
      "lastName" : "Bécane",
      "authorRank" : 4,
      "name" : "Bécane HM",
      "referenceId" : "RGD:A439654"
    }, {
      "firstName" : "E H",
      "lastName" : "Hammouda",
      "authorRank" : 5,
      "name" : "Hammouda EH",
      "referenceId" : "RGD:A439655"
    }, {
      "firstName" : "L",
      "lastName" : "Merlini",
      "authorRank" : 6,
      "name" : "Merlini L",
      "referenceId" : "RGD:A35393"
    }, {
      "firstName" : "F",
      "lastName" : "Muntoni",
      "authorRank" : 7,
      "name" : "Muntoni F",
      "referenceId" : "RGD:A39236"
    }, {
      "firstName" : "C R",
      "lastName" : "Greenberg",
      "authorRank" : 8,
      "name" : "Greenberg CR",
      "referenceId" : "RGD:A439656"
    }, {
      "firstName" : "F",
      "lastName" : "Gary",
      "authorRank" : 9,
      "name" : "Gary F",
      "referenceId" : "RGD:A61723"
    }, {
      "firstName" : "J A",
      "lastName" : "Urtizberea",
      "authorRank" : 10,
      "name" : "Urtizberea JA",
      "referenceId" : "RGD:A439657"
    }, {
      "firstName" : "D",
      "lastName" : "Duboc",
      "authorRank" : 11,
      "name" : "Duboc D",
      "referenceId" : "RGD:A62862"
    }, {
      "firstName" : "M",
      "lastName" : "Fardeau",
      "authorRank" : 12,
      "name" : "Fardeau M",
      "referenceId" : "RGD:A37513"
    }, {
      "firstName" : "D",
      "lastName" : "Toniolo",
      "authorRank" : 13,
      "name" : "Toniolo D",
      "referenceId" : "RGD:A55549"
    }, {
      "firstName" : "K",
      "lastName" : "Schwartz",
      "authorRank" : 14,
      "name" : "Schwartz K",
      "referenceId" : "RGD:A7050"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12791020"
    } ]
  }, {
    "primaryId" : "PMID:10080181",
    "title" : "Notch signalling pathway mediates hair cell development in mammalian cochlea.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Lanford PJ, etal., Nat Genet. 1999 Mar;21(3):289-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:36:02.000-05:00",
    "volume" : "21",
    "pages" : "289-92",
    "abstract" : "The mammalian cochlea contains an invariant mosaic of sensory hair cells and non-sensory supporting cells reminiscent of invertebrate structures such as the compound eye in Drosophila melanogaster. The sensory epithelium in the mammalian  cochlea (the organ of Corti) contains four rows of mechanosensory hair cells: a single row of inner hair cells and three rows of outer hair cells. Each hair cell is separated from the next by an interceding supporting cell, forming an invariant and alternating mosaic that extends the length of the cochlear duct. Previous results suggest that determination of cell fates in the cochlear mosaic  occurs via inhibitory interactions between adjacent progenitor cells (lateral inhibition). Cells populating the cochlear epithelium appear to constitute a developmental equivalence group in which developing hair cells suppress differentiation in their immediate neighbours through lateral inhibition. These interactions may be mediated through the Notch signalling pathway, a molecular mechanism that is involved in the determination of a variety of cell fates. Here  we show that genes encoding the receptor protein Notch1 and its ligand, Jagged 2, are expressed in alternating cell types in the developing sensory epithelium. In  addition, genetic deletion of Jag2 results in a significant increase in sensory hair cells, presumably as a result of a decrease in Notch activation. These results provide direct evidence for Notch-mediated lateral inhibition in a mammalian system and support a role for Notch in the development of the cochlear  mosaic.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PJ",
      "lastName" : "Lanford",
      "authorRank" : 1,
      "name" : "Lanford",
      "referenceId" : "RGD:A184707"
    }, {
      "firstName" : "Y",
      "lastName" : "Lan",
      "authorRank" : 2,
      "name" : "Lan Y",
      "referenceId" : "RGD:A109922"
    }, {
      "firstName" : "R",
      "lastName" : "Jiang",
      "authorRank" : 3,
      "name" : "Jiang R",
      "referenceId" : "RGD:A131479"
    }, {
      "firstName" : "C",
      "lastName" : "Lindsell",
      "authorRank" : 4,
      "name" : "Lindsell",
      "referenceId" : "RGD:A184708"
    }, {
      "firstName" : "G",
      "lastName" : "Weinmaster",
      "authorRank" : 5,
      "name" : "Weinmaster G",
      "referenceId" : "RGD:A7453"
    }, {
      "firstName" : "T",
      "lastName" : "Gridley",
      "authorRank" : 6,
      "name" : "Gridley T",
      "referenceId" : "RGD:A26252"
    }, {
      "firstName" : "MW",
      "lastName" : "Kelley",
      "authorRank" : 7,
      "name" : "Kelley MW",
      "referenceId" : "RGD:A137802"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553713"
    } ]
  }, {
    "primaryId" : "PMID:10080182",
    "title" : "Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Torrents D, etal., Nat Genet. 1999 Mar;21(3):293-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-05-08T09:08:42.000-05:00",
    "volume" : "21",
    "pages" : "293-6",
    "abstract" : "Lysinuric protein intolerance (LPI; OMIM 222700) is a rare, recessive disorder with a worldwide distribution, but with a high prevalence in the Finnish population; symptoms include failure to thrive, growth retardation, muscle hypotonia and hepatosplenomegaly. A defect in the plasma membrane transport of dibasic amino acids has been demonstrated at the baso-lateral membrane of epithelial cells in small intestine and in renal tubules and in plasma membrane of cultured skin fibroblasts from LPI patients. The gene causing LPI has been assigned by linkage analysis to 14q11-13. Here we report mutations in SLC7A7 cDNA (encoding y+L amino acid transporter-1, y+LAT-1), which expresses dibasic amino-acid transport activity and is located in the LPI region, in 31 Finnish LPI patients and 1 Spanish patient. The Finnish patients are homozygous for a founder missense mutation leading to a premature stop codon. The Spanish patient is a compound heterozygote with a missense mutation in one allele and a frameshift mutation in the other. The frameshift mutation generates a premature stop codon, eliminating the last one-third of the protein. The missense mutation abolishes y+LAT-1 amino-acid transport activity when co-expressed with the heavy chain of the cell-surface antigen 4F2 (4F2hc, also known as CD98) in Xenopus laevis oocytes. Our data establish that mutations in SLC7A7 cause LPI.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Torrents",
      "authorRank" : 1,
      "name" : "Torrents D",
      "referenceId" : "RGD:A82313"
    }, {
      "firstName" : "J",
      "lastName" : "Mykkanen",
      "authorRank" : 2,
      "name" : "Mykkanen J",
      "referenceId" : "RGD:A82314"
    }, {
      "firstName" : "M",
      "lastName" : "Pineda",
      "authorRank" : 3,
      "name" : "Pineda M",
      "referenceId" : "RGD:A77074"
    }, {
      "firstName" : "L",
      "lastName" : "Feliubadalo",
      "authorRank" : 4,
      "name" : "Feliubadalo L",
      "referenceId" : "RGD:A39374"
    }, {
      "firstName" : "R",
      "lastName" : "Estevez",
      "authorRank" : 5,
      "name" : "Estevez R",
      "referenceId" : "RGD:A82315"
    }, {
      "firstName" : "R",
      "lastName" : "De Cid",
      "authorRank" : 6,
      "name" : "De Cid R",
      "referenceId" : "RGD:A82316"
    }, {
      "firstName" : "P",
      "lastName" : "Sanjurjo",
      "authorRank" : 7,
      "name" : "Sanjurjo P",
      "referenceId" : "RGD:A82317"
    }, {
      "firstName" : "A",
      "lastName" : "Zorzano",
      "authorRank" : 8,
      "name" : "Zorzano A",
      "referenceId" : "RGD:A295520"
    }, {
      "firstName" : "V",
      "lastName" : "Nunes",
      "authorRank" : 9,
      "name" : "Nunes V",
      "referenceId" : "RGD:A295508"
    }, {
      "firstName" : "K",
      "lastName" : "Huoponen",
      "authorRank" : 10,
      "name" : "Huoponen K",
      "referenceId" : "RGD:A82318"
    }, {
      "firstName" : "A",
      "lastName" : "Reinikainen",
      "authorRank" : 11,
      "name" : "Reinikainen A",
      "referenceId" : "RGD:A82319"
    }, {
      "firstName" : "O",
      "lastName" : "Simell",
      "authorRank" : 12,
      "name" : "Simell O",
      "referenceId" : "RGD:A82320"
    }, {
      "firstName" : "ML",
      "lastName" : "Savontaus",
      "authorRank" : 13,
      "name" : "Savontaus ML",
      "referenceId" : "RGD:A63935"
    }, {
      "firstName" : "P",
      "lastName" : "Aula",
      "authorRank" : 14,
      "name" : "Aula P",
      "referenceId" : "RGD:A71476"
    }, {
      "firstName" : "M",
      "lastName" : "Palacin",
      "authorRank" : 15,
      "name" : "Palacin M",
      "referenceId" : "RGD:A39395"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1624296"
    } ]
  }, {
    "primaryId" : "PMID:10080183",
    "title" : "SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Borsani G, etal., Nat Genet. 1999 Mar;21(3):297-301.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:20:14.000-05:00",
    "volume" : "21",
    "pages" : "297-301",
    "abstract" : "Lysinuric protein intolerance (LPI, MIM 222700) is an autosomal recessive multisystem disorder found mainly in Finland and Italy. On a normal diet, LPI patients present poor feeding, vomiting, diarrhoea, episodes of hyperammoniaemic  coma and failure to thrive. Hepatosplenomegaly, osteoporosis and a life-threatening pulmonary involvement (alveolar proteinosis) are also seen. LPI  is caused by defective cationic amino acid (CAA) transport at the basolateral membrane of epithelial cells in kidney and intestine. Metabolic derangement is characterized by increased renal excretion of CAA, reduced CAA absorption from intestine and orotic aciduria. The gene causing LPI was assigned using linkage analysis to chromosome 14q11.2 near the T-cell receptor alpha/delta chains locus, and a critical region has been defined. We have identified two new transcripts (SLC7A8 and SLC7A7) homologous to amino acid transporters, highly expressed in kidney and mapping in the LPI critical region. Mutational analysis of both transcripts revealed that SLC7A7 (for solute carrier family 7, member 7) is mutated in LPI. In five Italian patients, we found either an insertion or deletion in the coding sequence, which provides evidence of a causative role of SLC7A7 in LPI. Furthermore, we detected a splice acceptor change resulting in a frameshift and premature translation termination in four unrelated Finnish patients. This mutation may represent the founder LPI allele in Finland.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Borsani",
      "authorRank" : 1,
      "name" : "Borsani",
      "referenceId" : "RGD:A331058"
    }, {
      "firstName" : "MT",
      "lastName" : "Bassi",
      "authorRank" : 2,
      "name" : "Bassi MT",
      "referenceId" : "RGD:A28952"
    }, {
      "firstName" : "MP",
      "lastName" : "Sperandeo",
      "authorRank" : 3,
      "name" : "Sperandeo",
      "referenceId" : "RGD:A229506"
    }, {
      "firstName" : "A",
      "lastName" : "De Grandi",
      "authorRank" : 4,
      "name" : "De Grandi A",
      "referenceId" : "RGD:A161858"
    }, {
      "firstName" : "A",
      "lastName" : "Buoninconti",
      "authorRank" : 5,
      "name" : "Buoninconti",
      "referenceId" : "RGD:A264085"
    }, {
      "firstName" : "M",
      "lastName" : "Riboni",
      "authorRank" : 6,
      "name" : "Riboni M",
      "referenceId" : "RGD:A161859"
    }, {
      "firstName" : "M",
      "lastName" : "Manzoni",
      "authorRank" : 7,
      "name" : "Manzoni M",
      "referenceId" : "RGD:A161857"
    }, {
      "firstName" : "B",
      "lastName" : "Incerti",
      "authorRank" : 8,
      "name" : "Incerti B",
      "referenceId" : "RGD:A28953"
    }, {
      "firstName" : "A",
      "lastName" : "Pepe",
      "authorRank" : 9,
      "name" : "Pepe",
      "referenceId" : "RGD:A255198"
    }, {
      "firstName" : "G",
      "lastName" : "Andria",
      "authorRank" : 10,
      "name" : "Andria G",
      "referenceId" : "RGD:A73040"
    }, {
      "firstName" : "A",
      "lastName" : "Ballabio",
      "authorRank" : 11,
      "name" : "Ballabio",
      "referenceId" : "RGD:A313536"
    }, {
      "firstName" : "G",
      "lastName" : "Sebastio",
      "authorRank" : 12,
      "name" : "Sebastio",
      "referenceId" : "RGD:A253532"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072189"
    } ]
  }, {
    "primaryId" : "PMID:10080184",
    "title" : "Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Gong Y, etal., Nat Genet. 1999 Mar;21(3):302-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-05T16:12:36.000-06:00",
    "volume" : "21",
    "pages" : "302-4",
    "abstract" : "The secreted polypeptide noggin (encoded by the Nog gene) binds and inactivates members of the transforming growth factor beta superfamily of signalling proteins (TGFbeta-FMs), such as BMP4 (ref. 1). By diffusing through extracellular matrices more efficiently than TGFbeta-FMs, noggin may have a principal role in creating morphogenic gradients. During mouse embryogenesis, Nog is expressed at multiple sites, including developing bones. Nog-/- mice die at birth from multiple defects that include bony fusion of the appendicular skeleton. We have identified five dominant human NOG mutations in unrelated families segregating proximal symphalangism (SYM1; OMIM 185800) and a de novo mutation in a patient with unaffected parents. We also found a dominant NOG mutation in a family segregating multiple synostoses syndrome (SYNS1; OMIM 186500); both SYM1 and SYNS1 have multiple joint fusion as their principal feature. All seven NOG mutations alter evolutionarily conserved amino acid residues. The findings reported here confirm that NOG is essential for joint formation and suggest that NOG requirements during skeletogenesis differ between species and between specific skeletal elements within species.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Gong",
      "authorRank" : 1,
      "name" : "Gong Y",
      "referenceId" : "RGD:A1105"
    }, {
      "firstName" : "D",
      "lastName" : "Krakow",
      "authorRank" : 2,
      "name" : "Krakow D",
      "referenceId" : "RGD:A71362"
    }, {
      "firstName" : "J",
      "lastName" : "Marcelino",
      "authorRank" : 3,
      "name" : "Marcelino J",
      "referenceId" : "RGD:A76666"
    }, {
      "firstName" : "D",
      "lastName" : "Wilkin",
      "authorRank" : 4,
      "name" : "Wilkin D",
      "referenceId" : "RGD:A76667"
    }, {
      "firstName" : "D",
      "lastName" : "Chitayat",
      "authorRank" : 5,
      "name" : "Chitayat D",
      "referenceId" : "RGD:A35394"
    }, {
      "firstName" : "R",
      "lastName" : "Babul-Hirji",
      "authorRank" : 6,
      "name" : "Babul-Hirji R",
      "referenceId" : "RGD:A76487"
    }, {
      "firstName" : "L",
      "lastName" : "Hudgins",
      "authorRank" : 7,
      "name" : "Hudgins L",
      "referenceId" : "RGD:A76668"
    }, {
      "firstName" : "CW",
      "lastName" : "Cremers",
      "authorRank" : 8,
      "name" : "Cremers CW",
      "referenceId" : "RGD:A72706"
    }, {
      "firstName" : "FP",
      "lastName" : "Cremers",
      "authorRank" : 9,
      "name" : "Cremers FP",
      "referenceId" : "RGD:A25619"
    }, {
      "firstName" : "HG",
      "lastName" : "Brunner",
      "authorRank" : 10,
      "name" : "Brunner HG",
      "referenceId" : "RGD:A35400"
    }, {
      "firstName" : "K",
      "lastName" : "Reinker",
      "authorRank" : 11,
      "name" : "Reinker K",
      "referenceId" : "RGD:A71520"
    }, {
      "firstName" : "DL",
      "lastName" : "Rimoin",
      "authorRank" : 12,
      "name" : "Rimoin DL",
      "referenceId" : "RGD:A37393"
    }, {
      "firstName" : "DH",
      "lastName" : "Cohn",
      "authorRank" : 13,
      "name" : "Cohn DH",
      "referenceId" : "RGD:A37395"
    }, {
      "firstName" : "FR",
      "lastName" : "Goodman",
      "authorRank" : 14,
      "name" : "Goodman FR",
      "referenceId" : "RGD:A76669"
    }, {
      "firstName" : "W",
      "lastName" : "Reardon",
      "authorRank" : 15,
      "name" : "Reardon W",
      "referenceId" : "RGD:A40773"
    }, {
      "firstName" : "M",
      "lastName" : "Patton",
      "authorRank" : 16,
      "name" : "Patton M",
      "referenceId" : "RGD:A76670"
    }, {
      "firstName" : "CA",
      "lastName" : "Francomano",
      "authorRank" : 17,
      "name" : "Francomano CA",
      "referenceId" : "RGD:A39144"
    }, {
      "firstName" : "ML",
      "lastName" : "Warman",
      "authorRank" : 18,
      "name" : "Warman ML",
      "referenceId" : "RGD:A59365"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600234"
    } ]
  }, {
    "primaryId" : "PMID:10080186",
    "title" : "Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Aminoff M, etal., Nat Genet 1999 Mar;21(3):309-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-10T16:55:22.000-05:00",
    "volume" : "21",
    "pages" : "309-13",
    "abstract" : "Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Aminoff",
      "authorRank" : 1,
      "name" : "Aminoff M",
      "referenceId" : "RGD:A4141"
    }, {
      "firstName" : "JE",
      "lastName" : "Carter",
      "authorRank" : 2,
      "name" : "Carter JE",
      "referenceId" : "RGD:A4142"
    }, {
      "firstName" : "RB",
      "lastName" : "Chadwick",
      "authorRank" : 3,
      "name" : "Chadwick RB",
      "referenceId" : "RGD:A4143"
    }, {
      "firstName" : "C",
      "lastName" : "Johnson",
      "authorRank" : 4,
      "name" : "Johnson C",
      "referenceId" : "RGD:A4144"
    }, {
      "firstName" : "R",
      "lastName" : "Grasbeck",
      "authorRank" : 5,
      "name" : "Grasbeck R",
      "referenceId" : "RGD:A4145"
    }, {
      "firstName" : "MA",
      "lastName" : "Abdelaal",
      "authorRank" : 6,
      "name" : "Abdelaal MA",
      "referenceId" : "RGD:A4146"
    }, {
      "firstName" : "H",
      "lastName" : "Broch",
      "authorRank" : 7,
      "name" : "Broch H",
      "referenceId" : "RGD:A4147"
    }, {
      "firstName" : "LB",
      "lastName" : "Jenner",
      "authorRank" : 8,
      "name" : "Jenner LB",
      "referenceId" : "RGD:A4148"
    }, {
      "firstName" : "PJ",
      "lastName" : "Verroust",
      "authorRank" : 9,
      "name" : "Verroust PJ",
      "referenceId" : "RGD:A122488"
    }, {
      "firstName" : "SK",
      "lastName" : "Moestrup",
      "authorRank" : 10,
      "name" : "Moestrup SK",
      "referenceId" : "RGD:A122490"
    }, {
      "firstName" : "A",
      "lastName" : "De la Chapelle",
      "authorRank" : 11,
      "name" : "De la Chapelle A",
      "referenceId" : "RGD:A4151"
    }, {
      "firstName" : "R",
      "lastName" : "Krahe",
      "authorRank" : 12,
      "name" : "Krahe R",
      "referenceId" : "RGD:A4152"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61796"
    } ]
  }, {
    "primaryId" : "PMID:10080919",
    "title" : "Interaction of S-SCAM with neural plakophilin-related Armadillo-repeat protein/delta-catenin.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ide N, etal., Biochem Biophys Res Commun. 1999 Mar 24;256(3):456-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:17:45.000-05:00",
    "volume" : "256",
    "pages" : "456-61",
    "abstract" : "Synaptic scaffolding molecule (S-SCAM) is a multiple PDZ domain-containing protein, which interacts with neuroligin, a cell adhesion molecule, and the NMDA  receptor. In this study, we searched for S-SCAM-interacting proteins and obtained a neuralplakophilin-related armadillo-repeat protein (NPRAP)/delta-catenin. NPRAP/delta-catenin bound to the last PDZ domain of S-SCAM via its carboxyl-terminus in three different cell-free assay systems, was coimmunoprecipitated with S-SCAM from rat crude synaptosomes, and was localized at the excitatory synapses in rat hippocampal neurons. NPRAP/delta-catenin may be implicated in the molecular organization of synaptic junctions through the interaction with S-SCAM.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Ide",
      "authorRank" : 1,
      "name" : "Ide N",
      "referenceId" : "RGD:A15957"
    }, {
      "firstName" : "Y",
      "lastName" : "Hata",
      "authorRank" : 2,
      "name" : "Hata",
      "referenceId" : "RGD:A397673"
    }, {
      "firstName" : "M",
      "lastName" : "Deguchi",
      "authorRank" : 3,
      "name" : "Deguchi M",
      "referenceId" : "RGD:A16949"
    }, {
      "firstName" : "K",
      "lastName" : "Hirao",
      "authorRank" : 4,
      "name" : "Hirao K",
      "referenceId" : "RGD:A4762"
    }, {
      "firstName" : "I",
      "lastName" : "Yao",
      "authorRank" : 5,
      "name" : "Yao I",
      "referenceId" : "RGD:A8910"
    }, {
      "firstName" : "Y",
      "lastName" : "Takai",
      "authorRank" : 6,
      "name" : "Takai",
      "referenceId" : "RGD:A403509"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041005"
    } ]
  }, {
    "primaryId" : "PMID:10081",
    "title" : "L-Asparagine synthetase in serum as a marker for neoplasia.",
    "datePublished" : "1976-01-01T00:00:00.000-06:00",
    "citation" : "Cooney DA, etal., Cancer Res. 1976 Sep;36(9 pt.1):3238-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-01-21T13:47:21.000-06:00",
    "volume" : "36",
    "pages" : "3238-45",
    "abstract" : "L-Asparagine synthetase appears in serum approximately 7 days after the s.c. implantation of 1 X 10(5) cells of Leukemia 5178Y/AR (resistant to L-asparaginase) and increases in activity as the neoplasm grows and metastasizes. The principal source of the enzyme is the primary tumor. After intravranial inoculation of tumor, the rate of leakage of the enzyme is more pronounced than when the subcutaneous, intramuscular, or intraperitoneal routes are used. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037), a nitro-sourea effective in the palliation of L5178Y/AR, temporarily halts the influx of enzyme into the blood stream, as does surgical excision of the s.c. tumor nodules. Treatment of mice with L-asparaginase within 24 hr of inoculation of the tumor markedly augments both tumor growth and the rate of penetration of L-asparagine synthetase into the circulation. Several other L-asparagine synthetase into the circulation. Several other L-asparaginase-resistant tumors also were found to spill L-asparagine synthetase into the serum, but the correlation between this phenomenon and the specific activity of the enzyme in homogenates of the tumor was imperfect.",
    "issueName" : "9 pt.1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DA",
      "lastName" : "Cooney",
      "authorRank" : 1,
      "name" : "Cooney DA",
      "referenceId" : "RGD:A118109"
    }, {
      "firstName" : "VD",
      "lastName" : "King",
      "authorRank" : 2,
      "name" : "King VD",
      "referenceId" : "RGD:A118110"
    }, {
      "firstName" : "RG",
      "lastName" : "Cable",
      "authorRank" : 3,
      "name" : "Cable RG",
      "referenceId" : "RGD:A118111"
    }, {
      "firstName" : "JR",
      "lastName" : "Taylor B",
      "authorRank" : 4,
      "name" : "Taylor B JR",
      "referenceId" : "RGD:A118112"
    }, {
      "firstName" : "I",
      "lastName" : "Wodinsky",
      "authorRank" : 5,
      "name" : "Wodinsky I",
      "referenceId" : "RGD:A118113"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316006"
    } ]
  }, {
    "primaryId" : "PMID:10081919",
    "title" : "Both protein kinase G dependent and independent mechanisms are involved in the modulation of glutamate release by nitric oxide in rat hippocampal nerve terminals.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Sequeira SM, etal., Neurosci Lett. 1999 Feb 12;261(1-2):29-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-02T18:48:10.000-06:00",
    "volume" : "261",
    "pages" : "29-32",
    "abstract" : "We compared the effects of sodium nitroprusside (SNP), and of 8-bromo guanosine 3',5'-cyclic monophosphate (8-BrcGMP), on the 4-aminopyridine (4-AP)-evoked Ca2+-dependent release of glutamate from hippocampal nerve terminals and further  investigated the role of protein kinase G (PKG) in this mechanism. SNP and 8-BrcGMP dose-dependently inhibited glutamate release, however SNP concentrations ([SNP]) > 500 microM abolished the 4-AP evoked release, whereas 8-BrcGMP maximally inhibited the release by about 30%. The inhibition of glutamate release at low concentrations of SNP (< or = 5 microM) was of about 20%, and was reversed by Rp-8(4-chlorophenylthio)guanosine-3',5'-cyclic-monophosphorotioate ) (RpCPTcGMP, 50 nM), but the inhibition at higher concentrations (5 < SNP < or = 50 microM) was insensitive to the PKG inhibitor, but sensitive to [1 H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one] (ODQ), which partially prevented the  inhibition. [SNP] > 50 microM strongly inhibited glutamate release, and this was  not reversed by either inhibitor. Furthermore, [SNP] < or = 50 microM enhanced cGMP formation, and the observed effects were not related to either decreased Ca2+ entry or ATP/ADP levels. Our results indicate that NO/PKG is the signaling pathway underlying the inhibition of glutamate release at low concentrations of NO, and imply that other NO-dependent, but PKG-independent, mechanisms are activated and have complementary roles at higher NO concentrations.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SM",
      "lastName" : "Sequeira",
      "authorRank" : 1,
      "name" : "Sequeira SM",
      "referenceId" : "RGD:A160910"
    }, {
      "firstName" : "AP",
      "lastName" : "Carvalho",
      "authorRank" : 2,
      "name" : "Carvalho AP",
      "referenceId" : "RGD:A84196"
    }, {
      "firstName" : "CM",
      "lastName" : "Carvalho",
      "authorRank" : 3,
      "name" : "Carvalho CM",
      "referenceId" : "RGD:A84197"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7777119"
    } ]
  }, {
    "primaryId" : "PMID:10081937",
    "title" : "Molecular cloning of the cone-rod homeobox gene (Crx) from the rat and its temporal expression pattern in the retina under a daily light-dark cycle.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Sakamoto K, etal., Neurosci Lett 1999 Feb 12;261(1-2):101-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T14:11:54.000-05:00",
    "volume" : "261",
    "pages" : "101-4",
    "abstract" : "The primary structure of the cone-rod homeobox protein (CRX), a member of the OTX-like homeobox protein family, in the rat was deduced from the cDNA nucleotide sequence. The deduced protein consisted of 299 amino acid residues with motifs conserved in mammalian CRXs, and was 98% identical to mouse CRX. Northern blot analysis showed that Crx mRNA levels in the rat retina were constant under a daily light-dark cycle. These findings suggest that the expression mechanism of rat Crx in the retina was different from that in the pineal, where Crx mRNA exhibits a daily expression rhythm.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Sakamoto",
      "authorRank" : 1,
      "name" : "Sakamoto K",
      "referenceId" : "RGD:A156713"
    }, {
      "firstName" : "K",
      "lastName" : "Oishi",
      "authorRank" : 2,
      "name" : "Oishi K",
      "referenceId" : "RGD:A17741"
    }, {
      "firstName" : "T",
      "lastName" : "Okada",
      "authorRank" : 3,
      "name" : "Okada T",
      "referenceId" : "RGD:A161261"
    }, {
      "firstName" : "Y",
      "lastName" : "Onuma",
      "authorRank" : 4,
      "name" : "Onuma Y",
      "referenceId" : "RGD:A17743"
    }, {
      "firstName" : "K",
      "lastName" : "Yokoyama",
      "authorRank" : 5,
      "name" : "Yokoyama K",
      "referenceId" : "RGD:A17744"
    }, {
      "firstName" : "K",
      "lastName" : "Sugimoto",
      "authorRank" : 6,
      "name" : "Sugimoto K",
      "referenceId" : "RGD:A5821"
    }, {
      "firstName" : "N",
      "lastName" : "Ishida",
      "authorRank" : 7,
      "name" : "Ishida N",
      "referenceId" : "RGD:A149267"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632541"
    } ]
  }, {
    "primaryId" : "PMID:10081980",
    "title" : "Genetic polymorphism in the persyn (gamma-synuclein) gene and the risk of Alzheimer's disease.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Luedecking EK, etal., Neurosci Lett. 1999 Feb 19;261(3):186-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-03-13T13:58:28.000-05:00",
    "volume" : "261",
    "pages" : "186-8",
    "abstract" : "Alzheimer's disease (AD) is a complex disease with the possible involvement of several genes. Genetic studies on sporadic late-onset AD have determined APOE*4 to be the major risk factor. Members of the synuclein gene family are potential candidates for the risk of AD. The persyn gene (gamma-synuclein) has recently been characterized and a common polymorphism (Glu110Val) has been identified. In  this study we investigated the association of this polymorphism with sporadic late-onset AD patients. We screened DNA samples of 313 late-onset cases and 352 controls. No significant association was observed between the missense mutation and AD. When the data were stratified by APOE*4 carriers and non-APOE*4 carriers, no difference was seen for the Glu110Val polymorphism. There was also no difference in genotype or allele frequency when stratified by the ACT*A allele. Although our data show no effect of this persyn polymorphism in AD, characterization of additional polymorphisms in this gene may provide more conclusive answers.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EK",
      "lastName" : "Luedecking",
      "authorRank" : 1,
      "name" : "Luedecking EK",
      "referenceId" : "RGD:A152276"
    }, {
      "firstName" : "M",
      "lastName" : "Ganguli",
      "authorRank" : 2,
      "name" : "Ganguli M",
      "referenceId" : "RGD:A152277"
    }, {
      "firstName" : "ST",
      "lastName" : "DeKosky",
      "authorRank" : 3,
      "name" : "DeKosky ST",
      "referenceId" : "RGD:A28021"
    }, {
      "firstName" : "MI",
      "lastName" : "Kamboh",
      "authorRank" : 4,
      "name" : "Kamboh MI",
      "referenceId" : "RGD:A59036"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6480088"
    } ]
  }, {
    "primaryId" : "PMID:10082128",
    "title" : "Identification of a heparin binding site and the biological activities of the laminin alpha1 chain carboxy-terminal globular domain.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Yoshida I, etal., J Cell Physiol. 1999 Apr;179(1):18-28.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-06-01T14:54:57.000-05:00",
    "volume" : "179",
    "pages" : "18-28",
    "abstract" : "The carboxy-terminal globular domain (G-domain) of the laminin alpha1 chain has been shown to promote heparin binding, cell adhesion, and neurite outgrowth. In this study, we defined the potential sequences originating from the G-domain of laminin alpha1 chain which possess these functional activities. A series of peptides were synthesized from the G-domain, termed LG peptides (LG-1 to LG-6) and were tested for their various biological activities. In the direct [3H] heparin binding assays, LG-6 (residues 2,335-2,348: KDFLSIELVRGRVK) mediated high levels of [3H]heparin binding, and this peptide also directly promoted cell adhesion and spreading, including B16F10, M2, HT1080, and PC12 cells. The peptide LG-6 also promoted the neurite outgrowth of PC12 cells, mouse granule cells, and chick telencephalic cells. An anti-peptide LG-6 antibody inhibited laminin-1 and peptide LG-6-mediated cell adhesion and neurite outgrowth. Furthermore, an anti-integrin alpha2 antibody also inhibited the cell adhesion activity. These results suggest that peptide LG-6 plays a functional role as a heparin binding site in the G-domain of the laminin alpha1 chain, and this sequence was thus concluded to play a crucial role in regulating cell adhesion and spreading and neurite out-growth which is related to integrin alpha2.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Yoshida",
      "authorRank" : 1,
      "name" : "Yoshida I",
      "referenceId" : "RGD:A36161"
    }, {
      "firstName" : "K",
      "lastName" : "Tashiro",
      "authorRank" : 2,
      "name" : "Tashiro K",
      "referenceId" : "RGD:A4602"
    }, {
      "firstName" : "A",
      "lastName" : "Monji",
      "authorRank" : 3,
      "name" : "Monji A",
      "referenceId" : "RGD:A107836"
    }, {
      "firstName" : "I",
      "lastName" : "Nagata",
      "authorRank" : 4,
      "name" : "Nagata I",
      "referenceId" : "RGD:A107837"
    }, {
      "firstName" : "Y",
      "lastName" : "Hayashi",
      "authorRank" : 5,
      "name" : "Hayashi Y",
      "referenceId" : "RGD:A299696"
    }, {
      "firstName" : "Y",
      "lastName" : "Mitsuyama",
      "authorRank" : 6,
      "name" : "Mitsuyama Y",
      "referenceId" : "RGD:A107839"
    }, {
      "firstName" : "N",
      "lastName" : "Tashiro",
      "authorRank" : 7,
      "name" : "Tashiro N",
      "referenceId" : "RGD:A53473"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2307408"
    } ]
  }, {
    "primaryId" : "PMID:10082437",
    "title" : "CTLA4 promoter and exon 1 dimorphisms in multiple sclerosis.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Harbo HF, etal., Tissue Antigens 1999 Jan;53(1):106-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-15T14:37:15.000-05:00",
    "volume" : "53",
    "pages" : "106-10",
    "abstract" : "The human cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene may be a candidate susceptibility gene in multiple sclerosis (MS). In this study the distribution of the dimorphisms of exon 1 (+49 A/G) and promoter (-318 C/T) regions of the CTLA4 gene was analysed in 296 unrelated Norwegian MS patients and 271 matched controls by polymerase chain reaction and restriction fragment length polymorphism. The frequency of the exon 1 (+49) A-G genotype was increased in patients (57%) compared with controls (44%) (Pcorrected=0.01), and even more increased in patients with relapsing remitting MS (59%) (Pcorrected=0.006). No other significant differences were found between clinical subgroups of patients or between HLA-DRB1*1501, DQB1*0602-positive and negative patients and controls.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HF",
      "lastName" : "Harbo",
      "authorRank" : 1,
      "name" : "Harbo HF",
      "referenceId" : "RGD:A52942"
    }, {
      "firstName" : "EG",
      "lastName" : "Celius",
      "authorRank" : 2,
      "name" : "Celius EG",
      "referenceId" : "RGD:A52943"
    }, {
      "firstName" : "F",
      "lastName" : "Vartdal",
      "authorRank" : 3,
      "name" : "Vartdal F",
      "referenceId" : "RGD:A52944"
    }, {
      "firstName" : "A",
      "lastName" : "Spurkland",
      "authorRank" : 4,
      "name" : "Spurkland A",
      "referenceId" : "RGD:A48469"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358538"
    } ]
  }, {
    "primaryId" : "PMID:10082471",
    "title" : "TIMP-4 is regulated by vascular injury in rats.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Dollery CM, etal., Circ Res. 1999 Mar 19;84(5):498-504.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-03-13T14:50:15.000-05:00",
    "volume" : "84",
    "pages" : "498-504",
    "abstract" : "The role of basement membrane-degrading matrix metalloproteinases (MMPs) in enabling vascular smooth muscle cell migration after vascular injury has been established in several animal models. In contrast, the role of their native inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), has remained unproven despite frequent coregulation of MMPs and TIMPs in other disease states. We have investigated the time course of expression and localization of TIMP-4 in rat carotid arteries 6 hours, 24 hours, 3 days, 7 days, and 14 days after balloon injury by in situ hybridization, immunohistochemistry, and Western blot analysis. TIMP-4 protein was present in the adventitia of injured carotid arteries from 24 hours after injury. At 7 and 14 days after injury, widespread immunostaining for TIMP-4 was observed throughout the neointima, media, and adventitia of injured arteries. Western blot analysis confirmed the quantitative increase in TIMP-4 protein at 7 and 14 days. In situ hybridization detected increased expression of TIMP-4 as early as 24 hours after injury and a marked induction in neointimal cells 7 days after injury. We then studied the effect of TIMP-4 protein on the migration of smooth muscle cells through a matrix-coated membrane in vitro and demonstrated a 53% reduction in invasion of rat vascular smooth muscle cells. These data and the temporal relationship between the upregulation of TIMP-4, its accumulation, and the onset of collagen deposition suggest an important role for TIMP-4 in the proteolytic balance of the vasculature controlling both smooth muscle migration and collagen accumulation in the injured arterial wall.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CM",
      "lastName" : "Dollery",
      "authorRank" : 1,
      "name" : "Dollery CM",
      "referenceId" : "RGD:A93109"
    }, {
      "firstName" : "JR",
      "lastName" : "McEwan",
      "authorRank" : 2,
      "name" : "McEwan JR",
      "referenceId" : "RGD:A93110"
    }, {
      "firstName" : "M",
      "lastName" : "Wang",
      "authorRank" : 3,
      "name" : "Wang M",
      "referenceId" : "RGD:A9187"
    }, {
      "firstName" : "QA",
      "lastName" : "Sang",
      "authorRank" : 4,
      "name" : "Sang QA",
      "referenceId" : "RGD:A93111"
    }, {
      "firstName" : "YE",
      "lastName" : "Liu",
      "authorRank" : 5,
      "name" : "Liu YE",
      "referenceId" : "RGD:A93043"
    }, {
      "firstName" : "YE",
      "lastName" : "Shi",
      "authorRank" : 6,
      "name" : "Shi YE",
      "referenceId" : "RGD:A93046"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2290470"
    } ]
  }, {
    "primaryId" : "PMID:10082481",
    "title" : "Structure of the type B human natriuretic peptide receptor gene and association of a novel microsatellite polymorphism with essential hypertension.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Rehemudula D, etal., Circ Res. 1999 Mar 19;84(5):605-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-24T14:37:52.000-05:00",
    "volume" : "84",
    "pages" : "605-10",
    "abstract" : "The natriuretic peptide (NP) system may play a crucial role in development of essential hypertension (EH). C-type NP dilates arteries and lowers blood pressure and inhibits proliferation of vascular smooth muscle cells via the type B NP receptor (NPR-B). However, the association of the human NPR-B gene with EH has not been studied, because little is known about the genomic organization of this gene. We designed oligonucleotide primers based on the cDNA sequence of the human NPR-B gene, and long-range polymerase chain reaction (PCR) was performed. The amplified fragments were sequenced directly, and the exon/intron organization of the human NPR-B gene was determined. The gene, which spans approximately 16.5 kbp, is composed of 22 exons, and the intron-exon junctions follow the GT-AG rule. Seven hundred fifty base pairs of the 5'-flanking region were sequenced using a thermal asymmetric interlaced-PCR (TAIL-PCR) method. This region contains 10 potential Sp1 binding sites and lacks a TATA box. Rapid amplification of cDNA ends (RACE) revealed the transcriptional start site at -14 bp. A CA/GT microsatellite repeat was identified with a hybridization-based method and was converted to a sequence-tagged site (STS). The GT microsatellite repeat was localized to intron 2 approximately 150 bp downstream of the exon-intron junction. Two alleles, (GT)10 and (GT)11, were detected in both EH patients and age-matched normotensive (NT) controls. Multiple logistic linear regression analysis indicated that the NPR-B genotype is associated significantly with EH (odds ratio 1.55; 95% confidence interval, 1.02 to 2.35). The (GT)11 frequency was 0.316 (65/206) for the EH group and 0.218 (44/202) for the NT group and differed significantly between the EH and NT groups (chi2=4.97, P=0.026). The structural organization of the human NPR-B gene was determined, and a novel GT repeat polymorphism, which associated with EH, was identified. These results suggest that one cause of EH is a mutation in this gene or a closely related gene or region.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Rehemudula",
      "authorRank" : 1,
      "name" : "Rehemudula D",
      "referenceId" : "RGD:A63981"
    }, {
      "firstName" : "T",
      "lastName" : "Nakayama",
      "authorRank" : 2,
      "name" : "Nakayama T",
      "referenceId" : "RGD:A140893"
    }, {
      "firstName" : "M",
      "lastName" : "Soma",
      "authorRank" : 3,
      "name" : "Soma M",
      "referenceId" : "RGD:A40156"
    }, {
      "firstName" : "Y",
      "lastName" : "Takahashi",
      "authorRank" : 4,
      "name" : "Takahashi Y",
      "referenceId" : "RGD:A158326"
    }, {
      "firstName" : "J",
      "lastName" : "Uwabo",
      "authorRank" : 5,
      "name" : "Uwabo J",
      "referenceId" : "RGD:A63984"
    }, {
      "firstName" : "M",
      "lastName" : "Sato",
      "authorRank" : 6,
      "name" : "Sato M",
      "referenceId" : "RGD:A154914"
    }, {
      "firstName" : "Y",
      "lastName" : "Izumi",
      "authorRank" : 7,
      "name" : "Izumi Y",
      "referenceId" : "RGD:A21571"
    }, {
      "firstName" : "K",
      "lastName" : "Kanmatsuse",
      "authorRank" : 8,
      "name" : "Kanmatsuse K",
      "referenceId" : "RGD:A9394"
    }, {
      "firstName" : "Y",
      "lastName" : "Ozawa",
      "authorRank" : 9,
      "name" : "Ozawa Y",
      "referenceId" : "RGD:A20769"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580772"
    } ]
  }, {
    "primaryId" : "PMID:10082497",
    "title" : "Evidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kainulainen K, etal., Hypertension 1999 Mar;33(3):844-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:50.000-05:00",
    "volume" : "33",
    "pages" : "844-9",
    "abstract" : "Components of the renin-angiotensin system play an important role in the normal regulation of blood pressure. We carried out a comprehensive genetic linkage study of the genes involved in the renin-angiotensin cascade in Finnish hypertensive twins and their affected siblings. We found no evidence for linkage between essential hypertension and the genes coding for renin, angiotensinogen, angiotensin-converting enzyme, or kallikrein 1 in the 329 hypertensive individuals of 142 families studied. In contrast, two intragenic markers for the type 1 angiotensin II receptor (AT1) showed some evidence for linkage in the total sample. A closer examination of this gene locus was carried out using subgroups of nonobese sibpairs with early onset of hypertension and uniform geographical origin. These stratifications yielded suggestive evidence for linkage of hypertension to the genetic area containing the AT1 gene, with a maximal multipoint logarithm of the odds (LOD) score of 2.9. A genetic association study carried out in an independent series of 50 hypertensive cases and 122 normotensive controls showed an increase in the frequency of the A1166-->C allele of the AT1 gene in the hypertensive individuals. In a novel variant of model-free multipoint linkage analysis allowing linkage disequilibrium in the calculations, an LOD score of 5.13 was obtained. Sequence analyses of the entire coding region and 848 bp of promoter region in the DNA sample on 8 index samples did not reveal previously unpublished sequence variations. The data provide evidence that a common genetic variant of the AT1 gene locus influences the risk of essential hypertension in the Finnish population.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Kainulainen",
      "authorRank" : 1,
      "name" : "Kainulainen K",
      "referenceId" : "RGD:A40131"
    }, {
      "firstName" : "M",
      "lastName" : "Perola",
      "authorRank" : 2,
      "name" : "Perola M",
      "referenceId" : "RGD:A166401"
    }, {
      "firstName" : "J",
      "lastName" : "Terwilliger",
      "authorRank" : 3,
      "name" : "Terwilliger J",
      "referenceId" : "RGD:A40133"
    }, {
      "firstName" : "J",
      "lastName" : "Kaprio",
      "authorRank" : 4,
      "name" : "Kaprio J",
      "referenceId" : "RGD:A39894"
    }, {
      "firstName" : "M",
      "lastName" : "Koskenvuo",
      "authorRank" : 5,
      "name" : "Koskenvuo M",
      "referenceId" : "RGD:A40134"
    }, {
      "firstName" : "AC",
      "lastName" : "Syvanen",
      "authorRank" : 6,
      "name" : "Syvanen AC",
      "referenceId" : "RGD:A40135"
    }, {
      "firstName" : "E",
      "lastName" : "Vartiainen",
      "authorRank" : 7,
      "name" : "Vartiainen E",
      "referenceId" : "RGD:A40136"
    }, {
      "firstName" : "L",
      "lastName" : "Peltonen",
      "authorRank" : 8,
      "name" : "Peltonen L",
      "referenceId" : "RGD:A37206"
    }, {
      "firstName" : "K",
      "lastName" : "Kontula",
      "authorRank" : 9,
      "name" : "Kontula K",
      "referenceId" : "RGD:A40137"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298037"
    } ]
  }, {
    "primaryId" : "PMID:10082529",
    "title" : "Synergism with germ line transcription factor Oct-4: viral oncoproteins share the ability to mimic a stem cell-specific activity.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Brehm A, etal., Mol Cell Biol. 1999 Apr;19(4):2635-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T13:41:28.000-05:00",
    "volume" : "19",
    "pages" : "2635-43",
    "abstract" : "Activation of transcription by Oct-4 from remote binding sites requires a cofactor that is restricted to embryonal stem cells. The adenovirus E1A protein can mimic the activity of this stem cell-specific factor and stimulates Oct-4 activity in differentiated cells. Here we characterize the Oct-4-E1A interaction  and show that the E1A 289R protein harbors two independent Oct-4 binding sites, both of which specifically interact with the POU domain of Oct-4. Furthermore, we demonstrate that, like E1A, the human papillomavirus E7 oncoprotein also specifically binds to the Oct-4 POU domain. E7 and Oct-4 can form a complex both  in vitro and in vivo. Expression of E7 in differentiated cells stimulates Oct-4-mediated transactivation from distal binding sites. Moreover, Oct-4, but not other Oct factors, is active when expressed in cells transformed by human papillomavirus. Our results suggest that different viruses have evolved oncoproteins that share the ability to target Oct-4 and to mimic a stem cell-specific activity.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Brehm",
      "authorRank" : 1,
      "name" : "Brehm A",
      "referenceId" : "RGD:A95054"
    }, {
      "firstName" : "K",
      "lastName" : "Ohbo",
      "authorRank" : 2,
      "name" : "Ohbo K",
      "referenceId" : "RGD:A15622"
    }, {
      "firstName" : "W",
      "lastName" : "Zwerschke",
      "authorRank" : 3,
      "name" : "Zwerschke",
      "referenceId" : "RGD:A222921"
    }, {
      "firstName" : "V",
      "lastName" : "Botquin",
      "authorRank" : 4,
      "name" : "Botquin",
      "referenceId" : "RGD:A222922"
    }, {
      "firstName" : "P",
      "lastName" : "Jansen-Durr",
      "authorRank" : 5,
      "name" : "Jansen-Durr",
      "referenceId" : "RGD:A203346"
    }, {
      "firstName" : "HR",
      "lastName" : "Scholer",
      "authorRank" : 6,
      "name" : "Scholer HR",
      "referenceId" : "RGD:A55370"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11053644"
    } ]
  }, {
    "primaryId" : "PMID:10082570",
    "title" : "A novel ubiquitin-specific protease, UBP43, cloned from leukemia fusion protein AML1-ETO-expressing mice, functions in hematopoietic cell differentiation.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Liu LQ, etal., Mol Cell Biol 1999 Apr;19(4):3029-38.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-01T15:11:56.000-05:00",
    "volume" : "19",
    "pages" : "3029-38",
    "abstract" : "Using PCR-coupled subtractive screening-representational difference analysis, we have cloned a novel gene from AML1-ETO knockin mice. This gene is highly expressed in the yolk sac and fetal liver of the knockin mice. Nucleotide sequence analysis indicates that its cDNA contains an 1,107-bp open reading frame encoding a 368-amino-acid polypeptide. Further protein sequence and protein translation analysis shows that it belongs to a family of ubiquitin-specific proteases (UBP), and its molecular mass is 43 kDa. Therefore, we have named this gene UBP43. Like other ubiquitin proteases, the UBP43 protein has deubiquitinating enzyme activity. Protein ubiquitination has been implicated in many important cellular events. In wild-type adult mice, UBP43 is highly expressed in the thymus and in peritoneal macrophages. Among nine different murine hematopoietic cell lines analyzed, UBP43 expression is detectable only in cell lines related to the monocytic lineage. Furthermore, its expression is regulated during cytokine-induced monocytic cell differentiation. We have investigated its function in the hematopoietic myeloid cell line M1. UBP43 was introduced into M1 cells by retroviral gene transfer, and several high-expressing UBP43 clones were obtained for further study. Morphologic and cell surface marker examination of UBP43/M1 cells reveals that overexpression of UBP43 blocks cytokine-induced terminal differentiation of monocytic cells. These data suggest that UBP43 plays an important role in hematopoiesis by modulating either the ubiquitin-dependent proteolytic pathway or the ubiquitination state of another regulatory factor(s) during myeloid cell differentiation.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LQ",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu LQ",
      "referenceId" : "RGD:A55306"
    }, {
      "firstName" : "JR",
      "lastName" : "Ilaria R",
      "authorRank" : 2,
      "name" : "Ilaria R JR",
      "referenceId" : "RGD:A55307"
    }, {
      "firstName" : "PD",
      "lastName" : "Kingsley",
      "authorRank" : 3,
      "name" : "Kingsley PD",
      "referenceId" : "RGD:A5456"
    }, {
      "firstName" : "A",
      "lastName" : "Iwama",
      "authorRank" : 4,
      "name" : "Iwama A",
      "referenceId" : "RGD:A10602"
    }, {
      "firstName" : "RA",
      "lastName" : "Van Etten",
      "authorRank" : 5,
      "name" : "Van Etten RA",
      "referenceId" : "RGD:A55308"
    }, {
      "firstName" : "J",
      "lastName" : "Palis",
      "authorRank" : 6,
      "name" : "Palis J",
      "referenceId" : "RGD:A55309"
    }, {
      "firstName" : "DE",
      "lastName" : "Zhang",
      "authorRank" : 7,
      "name" : "Zhang DE",
      "referenceId" : "RGD:A55310"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549528"
    } ]
  }, {
    "primaryId" : "PMID:10082676",
    "title" : "Molecular cloning and expression of a second glucuronyltransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Seiki T, etal., Biochem Biophys Res Commun 1999 Feb 5;255(1):182-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-28T15:16:00.000-05:00",
    "volume" : "255",
    "pages" : "182-7",
    "abstract" : "A cDNA encoding a novel glucuronyltransferase was cloned from a rat brain cDNA library. The cDNA sequence contained an open reading frame encoding 324 amino acids, with type II transmembrane topology. The amino acid sequence revealed 49% homology to rat GlcAT-P, a glucuronyltransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope of glycoproteins, [Terayama et al. (1997) Proc. Natl. Acad. Sci. USA 94, 6093-6098] and the highest sequence homology was found in the catalytic region. Northern blot analysis indicated that this newly cloned glucuronyltransferase is expressed in the nervous system, consistent with the selective localization of the HNK-1 carbohydrate epitope in the nervous system. Transfection of this cDNA into COS-1 cells induced the expression of the HNK-1 carbohydrate epitope on cell surfaces, and induced the morphological changes in these cells. These results indicated that this newly cloned cDNA is a second glucuronyltransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Seiki",
      "authorRank" : 1,
      "name" : "Seiki T",
      "referenceId" : "RGD:A10335"
    }, {
      "firstName" : "S",
      "lastName" : "Oka",
      "authorRank" : 2,
      "name" : "Oka S",
      "referenceId" : "RGD:A10334"
    }, {
      "firstName" : "K",
      "lastName" : "Terayama",
      "authorRank" : 3,
      "name" : "Terayama K",
      "referenceId" : "RGD:A10333"
    }, {
      "firstName" : "K",
      "lastName" : "Imiya",
      "authorRank" : 4,
      "name" : "Imiya K",
      "referenceId" : "RGD:A16785"
    }, {
      "firstName" : "T",
      "lastName" : "Kawasaki",
      "authorRank" : 5,
      "name" : "Kawasaki T",
      "referenceId" : "RGD:A10339"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632232"
    } ]
  }, {
    "primaryId" : "PMID:10082755",
    "title" : "Differential expression of thrombospondin and cellular fibronectin during remodeling in proliferative glomerulonephritis.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Barnes JL, etal., J Histochem Cytochem. 1999 Apr;47(4):533-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-01-15T14:36:04.000-06:00",
    "volume" : "47",
    "pages" : "533-44",
    "abstract" : "Thrombospondin-1 (TSP-1) and an alternatively spliced fibronectin (Fn)-EIIIA isoform are adhesive proteins associated with embryogenesis and tissue remodeling. We compared, by immunohistochemistry and in situ hybridization, the course of TSP-1 and Fn-EIIIA expression in a model of glomerulonephritis induced  by Habu snake venom (HV) and characterized by mesangial cell migration, proliferation, and extracellular matrix (ECM) synthesis. At 24 hr after HV, TSP-1 and Fn-EIIIA proteins localized in the central aspects of lesions associated with platelets and macrophages and at the margins of lesions coinciding with mesangial cell migration (determined by Thy-1 staining). Mesangial cells at this time expressed TSP-1 but not Fn-EIIIA mRNA. TSP-1 protein and mRNA peaked in lesions at 48 hr and were associated with cell proliferation (determined by PCNA, alpha-smooth muscle actin phenotype, and expression of beta-PDGF receptor mRNA).  TSP-1 expression declined at 72 hr when expression of ECM synthesis peaked, as determined by increased expression of collagen Type IV, laminin, and TGF-beta1 protein and mRNA. Mesangial cell expression of Fn-EIIIA was first observed at 48  hr and was most abundant at 72 hr after HV. Therefore, platelet- and macrophage-derived Fn-EIIIA and TSP-1 in early lesions are associated with mesangial cell migration. Mesangial cell upregulation of TSP-1 is associated with migration and proliferation but not maximal ECM accumulation, whereas mesangial cell expression of Fn-EIIIA is associated with proliferation and ECM accumulation. These results suggest distinctive temporal and spatial roles for TSP-1 and Fn-EIIIA in remodeling during glomerular disease. (J Histochem Cytochem 47:533-543, 1999)",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JL",
      "lastName" : "Barnes",
      "authorRank" : 1,
      "name" : "Barnes JL",
      "referenceId" : "RGD:A14197"
    }, {
      "firstName" : "RJ",
      "lastName" : "Mitchell",
      "authorRank" : 2,
      "name" : "Mitchell RJ",
      "referenceId" : "RGD:A161057"
    }, {
      "firstName" : "JJ",
      "lastName" : "Kanalas",
      "authorRank" : 3,
      "name" : "Kanalas JJ",
      "referenceId" : "RGD:A31206"
    }, {
      "firstName" : "VL",
      "lastName" : "Barnes",
      "authorRank" : 4,
      "name" : "Barnes VL",
      "referenceId" : "RGD:A161058"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7206847"
    } ]
  }, {
    "primaryId" : "PMID:10083731",
    "title" : "Novel mutations, including the second most common in Japan, in the beta-hexosaminidase alpha subunit gene, and a simple screening of Japanese patients with Tay-Sachs disease.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Tanaka A, etal., J Hum Genet. 1999;44(2):91-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:01:13.000-05:00",
    "volume" : "44",
    "pages" : "91-5",
    "abstract" : "Two novel mutations of the beta-hexosaminidase alpha subunit gene were identified in Japanese patients with the infantile form of Tay-Sachs disease. One mutation was a one-base deletion at nt613C, which generated a stop codon at two codons downstream, in three unrelated patients. The other mutation was a one-base substitution of G-to-A at IVS 5, +1, which caused a splicing abnormality, in one  patient. A missense mutation of R170W, which has already been reported in other ethnic groups, was also newly identified in one patient. In 1993, the most common mutation (IVS 5, -1G-->T) in Japanese patients with Tay-Sachs disease was reported as the major mutation in Japan accounting for 80% of 56 mutant alleles from 28 unrelated patients. The deletion of nt613C was the second most common mutation, accounting for 5% of the mutant alleles. The previously reported mutation IVS 5, -1G-->T and the nt613C deletion found in this study together accounted for 85% of the mutations causing Tay-Sachs disease among Japanese. Since these two mutations were located in or close to exon 6 and since they abolish Fok I (IVS 5, -1G-->T) and Sfa NI (nt613C deletion) restriction sites, respectively, they were screened rapidly by single polymerase chain reaction followed by digestion with these enzymes.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Tanaka",
      "authorRank" : 1,
      "name" : "Tanaka A",
      "referenceId" : "RGD:A9438"
    }, {
      "firstName" : "M",
      "lastName" : "Fujimaru",
      "authorRank" : 2,
      "name" : "Fujimaru",
      "referenceId" : "RGD:A270626"
    }, {
      "firstName" : "K",
      "lastName" : "Choeh",
      "authorRank" : 3,
      "name" : "Choeh",
      "referenceId" : "RGD:A270627"
    }, {
      "firstName" : "G",
      "lastName" : "Isshiki",
      "authorRank" : 4,
      "name" : "Isshiki",
      "referenceId" : "RGD:A256700"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068295"
    } ]
  }, {
    "primaryId" : "PMID:10083733",
    "title" : "Germline mutations of the APC gene in Korean familial adenomatous polyposis patients.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Won YJ, etal., J Hum Genet. 1999;44(2):103-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:14:34.000-05:00",
    "volume" : "44",
    "pages" : "103-8",
    "abstract" : "We extensively analyzed genomic DNA and messenger RNA (mRNA) from 62 unrelated Korean patients with familial adenomatous polyposis (FAP) for identification of germline adenomatous polyposis coli (APC) gene mutations. We adopted both single-strand conformation polymorphism (SSCP) analysis and a method of analysis  involving the reverse transcription-polymerase chain reaction (RT-PCR) followed by a protein truncation test (PTT). DNA sequencing confirmed all alterations represented by aberrant bands. Germline mutations were identified in 38 patients  (61%). Nineteen of the detected mutations were presumed to be novel, thus emphasizing the heterogeneity of the mutational spectrum in Korean FAP patients.  In the initial 48 patients, SSCP analysis was followed by PTT for those patients  for whom no detectable mutations were found by SSCP. Using this combined approach, we identified germline APC gene mutations in 29 of the 48 FAP patients  (60%), including 6 patients in whom SSCP analysis failed to distinguish the mutant allele. In the 14 later patients, we identified truncating mutations in 9  patients (64%) using PTT only. Our results confirm that the mutation detection rate with PTT was superior to that with SSCP, and suggest that PTT would be a more practical screening method to detect germline mutations of the APC gene in FAP patients.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YJ",
      "lastName" : "Won",
      "authorRank" : 1,
      "name" : "Won",
      "referenceId" : "RGD:A214701"
    }, {
      "firstName" : "KJ",
      "lastName" : "Park",
      "authorRank" : 2,
      "name" : "Park KJ",
      "referenceId" : "RGD:A101300"
    }, {
      "firstName" : "HJ",
      "lastName" : "Kwon",
      "authorRank" : 3,
      "name" : "Kwon HJ",
      "referenceId" : "RGD:A123327"
    }, {
      "firstName" : "JH",
      "lastName" : "Lee",
      "authorRank" : 4,
      "name" : "Lee JH",
      "referenceId" : "RGD:A5688"
    }, {
      "firstName" : "JH",
      "lastName" : "Kim",
      "authorRank" : 5,
      "name" : "Kim",
      "referenceId" : "RGD:A416999"
    }, {
      "firstName" : "YJ",
      "lastName" : "Kim",
      "authorRank" : 6,
      "name" : "Kim YJ",
      "referenceId" : "RGD:A23953"
    }, {
      "firstName" : "SH",
      "lastName" : "Chun",
      "authorRank" : 7,
      "name" : "Chun",
      "referenceId" : "RGD:A275274"
    }, {
      "firstName" : "HJ",
      "lastName" : "Han",
      "authorRank" : 8,
      "name" : "Han HJ",
      "referenceId" : "RGD:A83187"
    }, {
      "firstName" : "JG",
      "lastName" : "Park",
      "authorRank" : 9,
      "name" : "Park JG",
      "referenceId" : "RGD:A122589"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069916"
    } ]
  }, {
    "primaryId" : "PMID:10084306",
    "title" : "Induction of selected lipid metabolic enzymes and differentiation-linked structural proteins by air exposure in fetal rat skin explants.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Komuves LG, etal., J Invest Dermatol. 1999 Mar;112(3):303-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-05T08:59:09.000-06:00",
    "volume" : "112",
    "pages" : "303-9",
    "abstract" : "The epidermal permeability barrier of premature infants matures rapidly following birth. Previous studies suggest that air exposure could contribute to this acceleration, because: (i) development of a structurally and functionally mature barrier accelerates when fetal rat skin explants are incubated at an air-medium interface, and (ii) occlusion with a water-impermeable membrane prevents this acceleration. To investigate further the effects of air exposure on epidermal barrier ontogenesis, we compared the activities of several key enzymes of lipid metabolism and gene expression of protein markers of epidermal differentiation in fetal rat skin explants grown immersed versus air exposed. The rate-limiting enzymes of cholesterol (HMG CoA reductase) and ceramide (serine palmitoyl transferase) synthesis were not affected. In contrast, the normal developmental increases in activities of glucosylceramide synthase and cholesterol sulfotransferase, responsible for the synthesis of glucosylceramides and cholesterol sulfate, respectively, were accelerated further by air exposure. Additionally, two enzymes required for the final stages of barrier maturation and essential for normal stratum corneum function, beta-glucocerebrosidase, which converts glucosylceramide to ceramide, and steroid sulfatase, which desulfates cholesterol sulfate, also increased with air exposure. Furthermore, filaggrin and loricrin mRNA levels, and filaggrin, loricrin, and involucrin protein levels all increased with air exposure. Finally, occlusion with a water-impermeable membrane prevented both the air-exposure-induced increase in lipid enzyme activity, and the expression of loricrin, filaggrin, and involucrin. Thus, air exposure stimulates selected lipid metabolic enzymes and the gene expression of key structural proteins in fetal epidermis, providing a biochemical basis for air-induced acceleration of permeability barrier maturation in premature infants.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LG",
      "lastName" : "Komuves",
      "authorRank" : 1,
      "name" : "Komuves LG",
      "referenceId" : "RGD:A71906"
    }, {
      "firstName" : "K",
      "lastName" : "Hanley",
      "authorRank" : 2,
      "name" : "Hanley K",
      "referenceId" : "RGD:A71907"
    }, {
      "firstName" : "Y",
      "lastName" : "Jiang",
      "authorRank" : 3,
      "name" : "Jiang Y",
      "referenceId" : "RGD:A8248"
    }, {
      "firstName" : "C",
      "lastName" : "Katagiri",
      "authorRank" : 4,
      "name" : "Katagiri C",
      "referenceId" : "RGD:A71908"
    }, {
      "firstName" : "PM",
      "lastName" : "Elias",
      "authorRank" : 5,
      "name" : "Elias PM",
      "referenceId" : "RGD:A71515"
    }, {
      "firstName" : "ML",
      "lastName" : "Williams",
      "authorRank" : 6,
      "name" : "Williams ML",
      "referenceId" : "RGD:A71909"
    }, {
      "firstName" : "KR",
      "lastName" : "Feingold",
      "authorRank" : 7,
      "name" : "Feingold KR",
      "referenceId" : "RGD:A71516"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598949"
    } ]
  }, {
    "primaryId" : "PMID:10084951",
    "title" : "Fas and Fas ligand messenger ribonucleic acid and protein expression in the rat corpus luteum during apoptosis-mediated luteolysis.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Roughton SA, etal., Biol Reprod. 1999 Apr;60(4):797-804.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-25T15:01:43.000-05:00",
    "volume" : "60",
    "pages" : "797-804",
    "abstract" : "Apoptosis has been found to occur during regression of the corpus luteum (CL) in  many species. The Fas (APO-1/CD95) receptor, a transmembrane protein that induces apoptosis in the cell when bound to Fas ligand (FasL), may be involved. This study established and quantitated the presence and regulation of Fas receptor and FasL in the rat CL during pregnancy and postpartum. Using immunohistochemistry, FasL was localized in CL during pregnancy and postpartum. Fas was localized at Day 1 of pregnancy and at the time of luteolysis. Both Fas and FasL mRNA were found to be expressed throughout pregnancy and postpartum using reverse transcription-polymerase chain reaction (RT-PCR). Relative quantitative RT-PCR established that expression of FasL mRNA increased significantly at Day 22 of pregnancy and decreased by Day 3 postpartum. Spontaneous apoptosis of rat CL placed in an in vitro culture model with serum-free medium was examined by analysis of extracted DNA using 3' end-labeling. Treatment with an anti-rat Fas monoclonal antibody demonstrated a reduction in the occurrence of spontaneous apoptosis. These data support a role for Fas receptor and FasL in rat CL apoptosis during luteolysis.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SA",
      "lastName" : "Roughton",
      "authorRank" : 1,
      "name" : "Roughton",
      "referenceId" : "RGD:A190561"
    }, {
      "firstName" : "RR",
      "lastName" : "Lareu",
      "authorRank" : 2,
      "name" : "Lareu RR",
      "referenceId" : "RGD:A15918"
    }, {
      "firstName" : "AH",
      "lastName" : "Bittles",
      "authorRank" : 3,
      "name" : "Bittles",
      "referenceId" : "RGD:A190562"
    }, {
      "firstName" : "AM",
      "lastName" : "Dharmarajan",
      "authorRank" : 4,
      "name" : "Dharmarajan AM",
      "referenceId" : "RGD:A15923"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662857"
    } ]
  }, {
    "primaryId" : "PMID:10085034",
    "title" : "Effects of interleukin-1 receptor antagonist overexpression on infection by Listeria monocytogenes.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Irikura VM, etal., Infect Immun. 1999 Apr;67(4):1901-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-08T13:10:43.000-05:00",
    "volume" : "67",
    "pages" : "1901-9",
    "abstract" : "Interleukin-1 receptor antagonist (IL-1ra) is a naturally occurring cytokine whose only known function is the inhibition of interleukin-1 (IL-1). Using a reverse genetic approach in mice, we previously showed that increasing IL-1ra gene dosage leads to reduced survival of a primary listerial infection. In this study, we characterize further the role of endogenously produced IL-1ra and, by inference, IL-1 in murine listeriosis. IL-1ra overexpression inhibits, but does not eliminate, primary immune responses, reducing survival and increasing bacterial loads in the target organs. We demonstrate that IL-1ra functions in the innate immune response to regulate the peak leukocyte levels in the blood, the accumulation of leukocytes at sites of infection, and the activation of macrophages during a primary infection. Reduced macrophage class II major histocompatibility complex expression was observed despite increased gamma interferon (IFN-gamma) levels, suggesting that IL-1 activity is essential along with IFN-gamma for macrophage activation in vivo. We also show that IL-1ra plays  a more limited role during secondary listeriosis, blunting the strength of the delayed-type hypersensitivity response to listerial antigen while not significantly altering cellular immunity to a second infectious challenge. When these results are compared to those for other mutant mice, IL-1ra appears to be unique among the cytokines studied to date in its regulation of leukocyte migration during primary listeriosis.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "VM",
      "lastName" : "Irikura",
      "authorRank" : 1,
      "name" : "Irikura",
      "referenceId" : "RGD:A359625"
    }, {
      "firstName" : "E",
      "lastName" : "Hirsch",
      "authorRank" : 2,
      "name" : "Hirsch E",
      "referenceId" : "RGD:A37171"
    }, {
      "firstName" : "D",
      "lastName" : "Hirsh",
      "authorRank" : 3,
      "name" : "Hirsh",
      "referenceId" : "RGD:A359626"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11522759"
    } ]
  }, {
    "primaryId" : "PMID:10085035",
    "title" : "Characterization of a novel trypanosome lytic factor from human serum.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Raper J, etal., Infect Immun. 1999 Apr;67(4):1910-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T15:05:31.000-05:00",
    "volume" : "67",
    "pages" : "1910-6",
    "abstract" : "Natural resistance of humans to the cattle pathogen Trypanosoma brucei brucei has been attributed to the presence in human serum of nonimmune factors that lyse the parasite. Normal human serum contains two trypanosome lytic factors (TLFs). TLF1  is a 500-kDa lipoprotein, which is reported to contain apolipoprotein A-I (apoA-I), haptoglobin-related protein (Hpr), hemoglobin, paraoxonase, and apoA-II, whereas TLF2 is a larger, poorly characterized particle. We report here  a new immunoaffinity-based purification procedure for TLF2 and TLF1, as well as further characterization of the components of each purified TLF. Immunoaffinity-purified TLF1 has a specific activity 10-fold higher than that of  TLF1 purified by previously described methods. Moreover, we find that TLF1 is a lipoprotein particle that contains mainly apoA-I and Hpr, trace amounts of paraoxonase, apoA-II, and haptoglobin, but no detectable hemoglobin. Characterization of TLF2 reveals that it is a 1,000-kDa protein complex containing mainly immunoglobulin M, apoA-I, and Hpr but less than 1% detectable lipid.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Raper",
      "authorRank" : 1,
      "name" : "Raper",
      "referenceId" : "RGD:A240432"
    }, {
      "firstName" : "R",
      "lastName" : "Fung",
      "authorRank" : 2,
      "name" : "Fung",
      "referenceId" : "RGD:A240433"
    }, {
      "firstName" : "J",
      "lastName" : "Ghiso",
      "authorRank" : 3,
      "name" : "Ghiso J",
      "referenceId" : "RGD:A44350"
    }, {
      "firstName" : "V",
      "lastName" : "Nussenzweig",
      "authorRank" : 4,
      "name" : "Nussenzweig",
      "referenceId" : "RGD:A240434"
    }, {
      "firstName" : "S",
      "lastName" : "Tomlinson",
      "authorRank" : 5,
      "name" : "Tomlinson S",
      "referenceId" : "RGD:A11791"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11058107"
    } ]
  }, {
    "primaryId" : "PMID:10085040",
    "title" : "Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Sato K, etal., Infect Immun. 1999 Apr;67(4):1943-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-17T14:26:44.000-05:00",
    "volume" : "67",
    "pages" : "1943-6",
    "abstract" : "Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models,  and interleukin (IL)-1beta, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-alpha) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1beta, IL-6, IL-8, and TNF-alpha were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1beta showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8,  and TNF-alpha concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-alpha but not IL-1beta concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Sato",
      "authorRank" : 1,
      "name" : "Sato",
      "referenceId" : "RGD:A415987"
    }, {
      "firstName" : "CL",
      "lastName" : "Liebeler",
      "authorRank" : 2,
      "name" : "Liebeler",
      "referenceId" : "RGD:A397812"
    }, {
      "firstName" : "MK",
      "lastName" : "Quartey",
      "authorRank" : 3,
      "name" : "Quartey",
      "referenceId" : "RGD:A397813"
    }, {
      "firstName" : "CT",
      "lastName" : "Le",
      "authorRank" : 4,
      "name" : "Le",
      "referenceId" : "RGD:A315317"
    }, {
      "firstName" : "GS",
      "lastName" : "Giebink",
      "authorRank" : 5,
      "name" : "Giebink GS",
      "referenceId" : "RGD:A123857"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11553900"
    } ]
  }, {
    "primaryId" : "PMID:10085097",
    "title" : "Identification of multiple phosphoinositide-specific phospholipases D as new regulatory enzymes for phosphatidylinositol 3,4, 5-trisphosphate.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Ching TT, etal., J Biol Chem. 1999 Mar 26;274(13):8611-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-11-19T11:17:18.000-06:00",
    "volume" : "274",
    "pages" : "8611-7",
    "abstract" : "In the course of delineating the regulatory mechanism underlying phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) metabolism, we have discovered three distinct phosphoinositide-specific phospholipase D (PI-PLD) isozymes from rat brain, tentatively designated as PI-PLDa, PI-PLDb, and PI-PLDc. These enzymes convert [3H]PI(3,4,5)P3 to generate a novel inositol phosphate, D-myo-[3H]inositol 3,4,5-trisphosphate ([3H]Ins(3,4,5)P3) and phosphatidic acid. These isozymes are predominantly associated with the cytosol, a notable difference from phosphatidylcholine PLDs. They are partially purified by a three-step procedure consisting of DEAE, heparin, and Sephacryl S-200 chromatography. PI-PLDa and PI-PLDb display a high degree of substrate specificity for PI(3,4, 5)P3, with a relative potency of PI(3,4,5)P3 >> phosphatidylinositol 3-phosphate (PI(3)P) or phosphatidylinositol 4-phosphate (PI(4)P) > phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) > phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). In contrast, PI-PLDc preferentially utilizes PI(3)P as substrate, followed by, in sequence, PI(3,4,5)P3, PI(4)P, PI(3,4)P2, and PI(4,5)P2. Both PI(3, 4)P2 and PI(4,5)P2 are poor substrates for all three isozymes, indicating that the regulatory mechanisms underlying these phosphoinositides are different from that of PI(3,4,5)P3. None of these enzymes reacts with phosphatidylcholine, phosphatidylserine, or phosphatidylethanolamine. All three PI-PLDs are Ca2+-dependent. Among them, PI-PLDb and PI-PLDc show maximum activities within a sub-microM range (0.3 and 0.9 microM Ca2+, respectively), whereas PI-PLDa exhibits an optimal [Ca2+] at 20 microM. In contrast to PC-PLD, Mg2+ has no significant effect on the enzyme activity. All three enzymes require sodium deoxycholate for optimal activities; other detergents examined including Triton X-100 and Nonidet P-40 are, however, inhibitory. In addition, PI(4,5)P2 stimulates these isozymes in a dose-dependent manner. Enhancement in the enzyme activity is noted only when the molar ratio of PI(4,5)P2 to PI(3,4, 5)P3 is between 1:1 and 2:1.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TT",
      "lastName" : "Ching",
      "authorRank" : 1,
      "name" : "Ching TT",
      "referenceId" : "RGD:A115411"
    }, {
      "firstName" : "DS",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang DS",
      "referenceId" : "RGD:A50358"
    }, {
      "firstName" : "AL",
      "lastName" : "Hsu",
      "authorRank" : 3,
      "name" : "Hsu AL",
      "referenceId" : "RGD:A115412"
    }, {
      "firstName" : "PJ",
      "lastName" : "Lu",
      "authorRank" : 4,
      "name" : "Lu PJ",
      "referenceId" : "RGD:A115413"
    }, {
      "firstName" : "CS",
      "lastName" : "Chen",
      "authorRank" : 5,
      "name" : "Chen CS",
      "referenceId" : "RGD:A74331"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2314534"
    } ]
  }, {
    "primaryId" : "PMID:10085103",
    "title" : "Purification and characterization from rat kidney membranes of a novel platelet-activating factor (PAF)-dependent transacetylase that catalyzes the hydrolysis of PAF, formation of PAF analogs, and C2-ceramide.",
    "datePublished" : "1999-03-26T00:00:00.000-06:00",
    "citation" : "Karasawa K, etal., J Biol Chem. 1999 Mar 26;274(13):8655-61. doi: 10.1074/jbc.274.13.8655.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-10-10T08:05:58.000-05:00",
    "volume" : "274",
    "pages" : "8655-61",
    "abstract" : "We have previously identified two enzyme activities that transfer the acetyl group from platelet-activating factor (PAF) in a CoA-independent manner to lysoplasmalogen or sphingosine in HL-60 cells, endothelial cells, and a variety of rat tissues. These were termed as PAF:lysoplasmalogen (lysophospholipid) transacetylase and PAF:sphingosine transacetylase, respectively. In the present study, we have solubilized and purified this PAF-dependent transacetylase 13,700-fold from rat kidney membranes (mitochondrial plus microsomal membranes) based on the PAF:lysoplasmalogen transacetylase activity. The mitochondria and microsomes were prepared and washed three times, then solubilized with 0.04% Tween 20 at a detergent/protein (w/w) ratio of 0.1. The solubilized fractions from mitochondria and microsomes were combined and subjected to sequential column chromatographies on DEAE-Sepharose, hydroxyapatite, phenyl-Sepharose, and chromatofocusing. The enzyme was further purified by native-polyacrylamide gel electrophoresis (PAGE) and affinity gel matrix in which the competitive inhibitor of the enzyme, 1-O-hexadecyl-2-N-methylcarbamyl-sn-glycero-3-phosphoethanolamine was covalently attached to the CH-Sepharose. On SDS-PAGE, the purified enzyme showed a single homogeneous band with an apparent molecular mass of 40 kDa. The purified enzyme catalyzed transacetylation of the acetyl group not only from PAF to lysoplasmalogen forming plasmalogen analogs of PAF, but also to sphingosine producing N-acetylsphingosine (C2-ceramide). In addition, this enzyme acted as a PAF-acetylhydrolase in the absence of lipid acceptor molecules. These results suggest that PAF-dependent transacetylase is an enzyme that modifies the cellular functions of PAF through generation of other diverse lipid mediators.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Karasawa",
      "authorRank" : 1,
      "name" : "Karasawa K",
      "referenceId" : "RGD:A489121"
    }, {
      "firstName" : "X",
      "lastName" : "Qiu",
      "authorRank" : 2,
      "name" : "Qiu X",
      "referenceId" : "RGD:A49448"
    }, {
      "firstName" : "T",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee T",
      "referenceId" : "RGD:A72574"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:39458031"
    } ]
  }, {
    "primaryId" : "PMID:10085122",
    "title" : "Ca2+ sensitization and potentiation of the maximum level of myofibrillar ATPase activity caused by mutations of troponin T found in familial hypertrophic cardiomyopathy.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Yanaga F, etal., J Biol Chem. 1999 Mar 26;274(13):8806-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:54:30.000-05:00",
    "volume" : "274",
    "pages" : "8806-12",
    "abstract" : "Human wild-type cardiac troponin T, I, C and five troponin T mutants (I79N, R92Q, F110I, E244D, and R278C) causing familial hypertrophic cardiomyopathy were expressed in Escherichia coli, and then were purified and incorporated into rabbit cardiac myofibrils using a troponin exchange technique. The Ca2+-sensitive ATPase activity of these myofibrillar preparations was measured in order to examine the functional consequences of these troponin mutations. An I79N troponin T mutation was found to cause a definite increase in Ca2+ sensitivity of the myofibrillar ATPase activity without inducing any significant change in the maximum level of ATPase activity. A detailed analysis indicated the inhibitory action of troponin I to be impaired by the I79N troponin T mutation. Two more troponin T mutations (R92Q and R278C) were also found to have a Ca2+-sensitizing  effect without inducing any change in maximum ATPase activity. Two other troponin T mutations (F110I and E244D) had no Ca2+-sensitizing effects on the ATPase activity, but remarkably potentiated the maximum level of ATPase activity. These  findings indicate that hypertrophic cardiomyopathy-linked troponin T mutations have at least two different effects on the Ca2+-sensitive ATPase activity, Ca2+-sensitization and potentiation of the maximum level of the ATPase activity.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Yanaga",
      "authorRank" : 1,
      "name" : "Yanaga",
      "referenceId" : "RGD:A270110"
    }, {
      "firstName" : "S",
      "lastName" : "Morimoto",
      "authorRank" : 2,
      "name" : "Morimoto S",
      "referenceId" : "RGD:A13993"
    }, {
      "firstName" : "I",
      "lastName" : "Ohtsuki",
      "authorRank" : 3,
      "name" : "Ohtsuki I",
      "referenceId" : "RGD:A62476"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068117"
    } ]
  }, {
    "primaryId" : "PMID:10085132",
    "title" : "Requirements of protein kinase cdelta for catalytic function. Role of glutamic acid 500 and autophosphorylation on serine 643.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Stempka L, etal., J Biol Chem. 1999 Mar 26;274(13):8886-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-09-28T16:58:10.000-05:00",
    "volume" : "274",
    "pages" : "8886-92",
    "abstract" : "Recently, we reported that, in contrast to protein kinase C (PKC)alpha and betaII, PKCdelta does not require phosphorylation of a specific threonine (Thr505) in the activation loop for catalytic competence (Stempka et al. (1997) J. Biol. Chem. 272, 6805-6811). Here, we show that the acidic residue glutamic acid 500 (Glu500) in the activation loop is important for the catalytic function of PKCdelta. A Glu500 to valine mutant shows 76 and 73% reduced kinase activity toward autophosphorylation and substrate phosphorylation, respectively. With regard to thermal stability and inhibition by the inhibitors Go6976 and Go6983 the mutant does not differ from the wild type, indicating that the general conformation of the molecule is not altered by the site-directed mutagenesis. Thus, Glu500 in the activation loop of PKCdelta might take over at least part of the role of the phosphate groups on Thr497 and Thr500 of PKCalpha and betaII, respectively. Accordingly, PKCdelta exhibits kinase activity and is able to autophosphorylate probably without posttranslational modification. Autophosphorylation of PKCdelta in vitro occurs on Ser643, as demonstrated by matrix-assisted laser desorption ionization mass spectrometry of tryptic peptides of autophosphorylated PKCdelta wild type and mutants. A peptide containing this site is phosphorylated also in vivo, i.e. in recombinant PKCdelta purified from baculovirus-infected insect cells. A Ser643 to alanine mutation indicates that autophosphorylation of Ser643 is not essential for the kinase activity of PKCdelta. Probably additional (auto)phosphorylation site(s) exist that have not yet been identified.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Stempka",
      "authorRank" : 1,
      "name" : "Stempka L",
      "referenceId" : "RGD:A88371"
    }, {
      "firstName" : "M",
      "lastName" : "Schnolzer",
      "authorRank" : 2,
      "name" : "Schnolzer M",
      "referenceId" : "RGD:A86936"
    }, {
      "firstName" : "S",
      "lastName" : "Radke",
      "authorRank" : 3,
      "name" : "Radke S",
      "referenceId" : "RGD:A88372"
    }, {
      "firstName" : "G",
      "lastName" : "Rincke",
      "authorRank" : 4,
      "name" : "Rincke G",
      "referenceId" : "RGD:A88373"
    }, {
      "firstName" : "F",
      "lastName" : "Marks",
      "authorRank" : 5,
      "name" : "Marks F",
      "referenceId" : "RGD:A24289"
    }, {
      "firstName" : "M",
      "lastName" : "Gschwendt",
      "authorRank" : 6,
      "name" : "Gschwendt M",
      "referenceId" : "RGD:A88374"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642552"
    } ]
  }, {
    "primaryId" : "PMID:10085137",
    "title" : "Identification and characterization of the fifth membrane-type matrix metalloproteinase MT5-MMP.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Pei D J Biol Chem 1999 Mar 26;274(13):8925-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-08T18:56:56.000-06:00",
    "volume" : "274",
    "pages" : "8925-32",
    "abstract" : "A new member of the membrane-type matrix metalloproteinase (MT-MMP) subfamily tentatively named MT5-MMP was isolated from mouse brain cDNA library. It is predicted to contain (i) a candidate signal sequence, (ii) a propeptide region with the highly conserved PRCGVPD sequence, (iii) a potential furin recognition motif RRRRNKR, (iv) a zinc-binding catalytic domain, (v) a hemopexin-like domain, (vi) a 24-residue hydrophobic domain as a potential transmembrane domain, and (vii) a short cytosolic domain. Reverse transcriptase-polymerase chain reaction analysis of its transcripts indicates that MT5-MMP is expressed in a brain-specific manner consistent with the origin of its EST clone from cerebellum. It is also highly expressed during embryonic development at stages day 11 and 15. Like other MT-MMPs, MT5-MMP specifically activates progelatinase A when co-expressed in Madin-Darby canine kidney cells. Its ability to activate progelatinase A is dependent on its proteolytic activity since a mutation converting Glu to Ala in the zinc binding motif HE255LGH renders MT5-MMP inactive against progelatinase A. In contrast to other MT-MMPs, MT5-MMP tends to shed from cell surface as soluble proteinases, thus offering flexibility as both a cell bound and soluble proteinase for extracellular matrix remodeling processes. Taken together, these properties serve to distinguish MT5-MMP as a versatile MT-MMP playing an important role in extracellular matrix remodeling events in the brain and during embryonic development.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Pei",
      "authorRank" : 1,
      "name" : "Pei D",
      "referenceId" : "RGD:A38675"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:737631"
    } ]
  }, {
    "primaryId" : "PMID:10085150",
    "title" : "The hereditary hemochromatosis protein, HFE, specifically regulates transferrin-mediated iron uptake in HeLa cells.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Roy CN, etal., J Biol Chem 1999 Mar 26;274(13):9022-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-23T10:46:09.000-05:00",
    "volume" : "274",
    "pages" : "9022-8",
    "abstract" : "HFE is the protein product of the gene mutated in the autosomal recessive disease hereditary hemochromatosis (Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R. J., Ellis, M. C., Fullan, A., Hinton, L. M., Jones, N. L., Kimmel, B. E., Kronmal, G. S., Lauer, P., Lee, V. K., Loeb, D. B., Mapa, F. A., McClelland, E., Meyer, N. C., Mintier, G. A., Moeller, N., Moore, T., Morikang, E., Prasss, C. E., Quintana, L., Starnes, S. M., Schatzman, R. C., Brunke, K. J., Drayna, D. T., Risch, N. J., Bacon, B. R., and Wolff, R. R. (1996) Nat. Genet. 13, 399-408). At the cell surface, HFE complexes with transferrin receptor (TfR), increasing the dissociation constant of transferrin (Tf) for its receptor 10-fold (Gross, C. N., Irrinki, A., Feder, J. N., and Enns, C. A. (1998) J. Biol. Chem. 273, 22068-22074; Feder, J. N., Penny, D. M., Irrinki, A., Lee, V. K., Lebron, J. A., Watson, N. , Tsuchihashi, Z., Sigal, E., Bjorkman, P. J., and Schatzman, R. C. (1998) Proc. Natl. Acad. Sci. U S A 95, 1472-1477). HFE does not remain at the cell surface, but traffics with TfR to Tf-positive internal compartments (Gross et al., 1998). Using a HeLa cell line in which the expression of HFE is controlled by tetracycline, we show that the expression of HFE reduces 55Fe uptake from Tf by 33% but does not affect the endocytic or exocytic rates of TfR cycling. Therefore, HFE appears to reduce cellular acquisition of iron from Tf within endocytic compartments. HFE specifically reduces iron uptake from Tf, as non-Tf-mediated iron uptake from Fe-nitrilotriacetic acid is not altered. These results explain the decreased ferritin levels seen in our HeLa cell system and demonstrate the specific control of HFE over the Tf-mediated pathway of iron uptake. These results also have implications for the understanding of cellular iron homeostasis in organs such as the liver, pancreas, heart, and spleen that are iron loaded in hereditary hemochromatotic individuals lacking functional HFE.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CN",
      "lastName" : "Roy",
      "authorRank" : 1,
      "name" : "Roy CN",
      "referenceId" : "RGD:A53552"
    }, {
      "firstName" : "DM",
      "lastName" : "Penny",
      "authorRank" : 2,
      "name" : "Penny DM",
      "referenceId" : "RGD:A53553"
    }, {
      "firstName" : "JN",
      "lastName" : "Feder",
      "authorRank" : 3,
      "name" : "Feder JN",
      "referenceId" : "RGD:A30510"
    }, {
      "firstName" : "CA",
      "lastName" : "Enns",
      "authorRank" : 4,
      "name" : "Enns CA",
      "referenceId" : "RGD:A49744"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358656"
    } ]
  }, {
    "primaryId" : "PMID:10085160",
    "title" : "PU.1 and USF are required for macrophage-specific mannose receptor promoter activity.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Egan BS, etal., J Biol Chem. 1999 Mar 26;274(13):9098-107.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-10-01T15:55:43.000-05:00",
    "volume" : "274",
    "pages" : "9098-107",
    "abstract" : "In the current study we report the isolation of 854 base pairs of the rat mannose receptor promoter. Analysis of the sequence revealed one Sp1 site, three PU.1 sites, and a potential TATA box (TTTAAA) 33 base pairs 5' of the transcriptional  start site. The tissue specificity of the promoter was determined using transient transfections. The promoter was most active in the mature macrophage cell line NR8383 although the promoter also showed activity in the monocytic cell line RAW. No activity was observed in pre-monocytic cell lines or epithelial cell lines. Mutation of the TTTAAA sequence to TTGGAA resulted in a 50% decrease in activity  in transient transfection assays suggesting that the promoter contains a functional TATA box. Using electrophoretic mobility shift assays and mutagenesis  we established that the transcription factors Sp1, PU.1, and USF bound to the mannose receptor promoter, but only PU.1 and USF contributed to activation. Transient transfections using a dominant negative construct of USF resulted in a  50% decrease in mannose receptor promoter activity, further establishing the role of USF in activating the rat mannose receptor promoter. Comparison of the rat, mouse, and human sequence demonstrated that some binding sites are not conserved. Gel shifts were performed to investigate differences in protein binding between species. USF bound to the rat and human promoter but not to the mouse promoter, suggesting that different mechanisms are involved in regulation of mannose receptor expression in these species. From these results we conclude that, similar to other myeloid promoters, transcription of the rat mannose receptor is  regulated by binding of PU.1 and a ubiquitous factor at an adjacent site. However, unlike other myeloid promoters, we have identified USF as the ubiquitous factor, and demonstrated that the promoter contains a functional TATA box.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BS",
      "lastName" : "Egan",
      "authorRank" : 1,
      "name" : "Egan",
      "referenceId" : "RGD:A194821"
    }, {
      "firstName" : "KB",
      "lastName" : "Lane",
      "authorRank" : 2,
      "name" : "Lane KB",
      "referenceId" : "RGD:A36428"
    }, {
      "firstName" : "VL",
      "lastName" : "Shepherd",
      "authorRank" : 3,
      "name" : "Shepherd",
      "referenceId" : "RGD:A194822"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9586452"
    } ]
  }, {
    "primaryId" : "PMID:10085220",
    "title" : "The protein disulphide-isomerase family: unravelling a string of folds.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Ferrari DM and Soling HD, Biochem J 1999 Apr 1;339 ( Pt 1):1-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-08T09:00:58.000-06:00",
    "volume" : "339 ( Pt 1)",
    "pages" : "1-10",
    "abstract" : "The mammalian protein disulphide-isomerase (PDI) family encompasses several highly divergent proteins that are involved in the processing and maturation of secretory proteins in the endoplasmic reticulum. These proteins are characterized by the presence of one or more domains of roughly 95-110 amino acids related to the cytoplasmic protein thioredoxin. All but the PDI-D subfamily are composed entirely of repeats of such domains, with at least one domain containing and one domain lacking a redox-active -Cys-Xaa-Xaa-Cys- tetrapeptide. In addition to their known roles as redox catalysts and isomerases, the last few years have revealed additional functions of the PDI proteins, including peptide binding, cell adhesion and perhaps chaperone activities. Attention is now turning to the non-redox-active domains of the PDIs, which may play an important role in all of the known activities of these proteins. Thus the presence of both redox-active and -inactive domains within these proteins portends a complexity of functions differentially accommodated by the various family members.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DM",
      "lastName" : "Ferrari",
      "authorRank" : 1,
      "name" : "Ferrari DM",
      "referenceId" : "RGD:A57004"
    }, {
      "firstName" : "HD",
      "lastName" : "Soling",
      "authorRank" : 2,
      "name" : "Soling HD",
      "referenceId" : "RGD:A18184"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556678"
    } ]
  }, {
    "primaryId" : "PMID:10085234",
    "title" : "cDNA cloning and expression of rat homeobox gene, Hex, and functional characterization of the protein.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Tanaka T, etal., Biochem J 1999 Apr 1;339 ( Pt 1):111-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-08T13:41:17.000-05:00",
    "volume" : "339 ( Pt 1)",
    "pages" : "111-7",
    "abstract" : "We isolated two cDNA clones of rat Hex, a homeobox protein, studied its expression in rat liver and various cells, and characterized the protein. The levels of Hex mRNA were only slightly increased in liver of rats refed with a high-carbohydrate diet or after partial hepatectomy. Whereas the expression of Hex mRNA was detected in hepatocytes isolated from adult rat liver and also in highly differentiated hepatoma cells, no Hex mRNA was detected in poorly differentiated hepatoma cells. Hex mRNA was also detected in liver from embryo aged 15 days. Expression of Hex was increased in F9 cells during differentiation into visceral endoderm cells by treatment with retinoic acid. This stimulation occurred prior to an increase in the level of alpha-fetoprotein mRNA. When fusion-protein expression vectors of GAL4 DNA-binding domain and Hex were co-transfected with luciferase reporter plasmid, with or without five copies of the GAL4-binding site, into HepG2 cells, the luciferase activities were decreased in concentration- and GAL4-binding site-dependent manners. This repression did not require the presence of the homeodomain, which is located between the amino acid residues 137 and 196. Its repression domain was mapped between the residues 45 and 136 in the proline-rich N-terminal region. In addition, the homeodomain was responsible for DNA-binding of Hex. These results indicate that Hex functions as a transcriptional repressor and may be involved in the differentiation and/or maintenance of the differentiated state in hepatocytes.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Tanaka",
      "authorRank" : 1,
      "name" : "Tanaka T",
      "referenceId" : "RGD:A404001"
    }, {
      "firstName" : "T",
      "lastName" : "Inazu",
      "authorRank" : 2,
      "name" : "Inazu T",
      "referenceId" : "RGD:A11262"
    }, {
      "firstName" : "K",
      "lastName" : "Yamada",
      "authorRank" : 3,
      "name" : "Yamada K",
      "referenceId" : "RGD:A11181"
    }, {
      "firstName" : "Z",
      "lastName" : "Myint",
      "authorRank" : 4,
      "name" : "Myint Z",
      "referenceId" : "RGD:A11263"
    }, {
      "firstName" : "VW",
      "lastName" : "Keng",
      "authorRank" : 5,
      "name" : "Keng VW",
      "referenceId" : "RGD:A11264"
    }, {
      "firstName" : "Y",
      "lastName" : "Inoue",
      "authorRank" : 6,
      "name" : "Inoue Y",
      "referenceId" : "RGD:A161343"
    }, {
      "firstName" : "N",
      "lastName" : "Taniguchi",
      "authorRank" : 7,
      "name" : "Taniguchi N",
      "referenceId" : "RGD:A4634"
    }, {
      "firstName" : "T",
      "lastName" : "Noguchi",
      "authorRank" : 8,
      "name" : "Noguchi T",
      "referenceId" : "RGD:A11266"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:625370"
    } ]
  }, {
    "primaryId" : "PMID:10085239",
    "title" : "Transcriptional regulation of the human asparagine synthetase gene by carbohydrate availability.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Barbosa-Tessmann IP, etal., Biochem J. 1999 Apr 1;339 ( Pt 1):151-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-01-21T12:40:56.000-06:00",
    "volume" : "339 ( Pt 1)",
    "pages" : "151-8",
    "abstract" : "Transcription of the asparagine synthetase (AS) gene is induced by amino acid deprivation. The present data illustrate that this gene is also under transcriptional control by carbohydrate availability. Incubation of human HepG2 hepatoma cells in glucose-free medium resulted in an increased AS mRNA content, reaching a maximum of about 14-fold over control cells after approx. 12 h. Extracellular glucose caused the repression of the content of AS mRNA in a concentration-dependent manner, with a k1/2 (concentration causing a half-maximal repression) of 1 mM. Fructose, galactose, mannose, 2-deoxyglucose and xylitol were found to maintain the mRNA content of both AS and the glucose-regulated protein GRP78 in a state of repression, whereas 3-O-methylglucose did not. Incubation in either histidine-free or glucose-free medium also resulted in adaptive regulation of the AS gene in BNL-CL.2 mouse hepatocytes, rat C6 glioma cells and human MOLT4 lymphocytes, in addition to HepG2 cells. In contrast, the steady-state mRNA content of GRP78 was unaffected by amino acid availability. Transient transfection assays using a reporter gene construct documented that glucose deprivation increases AS gene transcription via elements within the proximal 3 kbp of the AS promoter. These results illustrate that human AS gene transcription is induced following glucose limitation of the cells.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "IP",
      "lastName" : "Barbosa-Tessmann",
      "authorRank" : 1,
      "name" : "Barbosa-Tessmann IP",
      "referenceId" : "RGD:A118093"
    }, {
      "firstName" : "VL",
      "lastName" : "Pineda",
      "authorRank" : 2,
      "name" : "Pineda VL",
      "referenceId" : "RGD:A118094"
    }, {
      "firstName" : "HS",
      "lastName" : "Nick",
      "authorRank" : 3,
      "name" : "Nick HS",
      "referenceId" : "RGD:A48185"
    }, {
      "firstName" : "SM",
      "lastName" : "Schuster",
      "authorRank" : 4,
      "name" : "Schuster SM",
      "referenceId" : "RGD:A107397"
    }, {
      "firstName" : "MS",
      "lastName" : "Kilberg",
      "authorRank" : 5,
      "name" : "Kilberg MS",
      "referenceId" : "RGD:A40446"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2315999"
    } ]
  }, {
    "primaryId" : "PMID:10085243",
    "title" : "Mammalian PIG-L and its yeast homologue Gpi12p are N-acetylglucosaminylphosphatidylinositol de-N-acetylases essential in glycosylphosphatidylinositol biosynthesis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Watanabe R, etal., Biochem J. 1999 Apr 1;339 ( Pt 1)(Pt 1):185-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-12-06T01:55:57.000-06:00",
    "volume" : "339 ( Pt 1)",
    "pages" : "185-92",
    "abstract" : "Glycosylphosphatidylinositol (GPI) is used as a membrane anchor by many eukaryotic cell-surface proteins. The second step of GPI biosynthesis is de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). We have previously cloned the rat PIG-L gene by expression cloning that complemented a mutant Chinese hamster ovary cell line defective in this step. Here we show that recombinant rat PIG-L protein purified from Escherichia coli as a complex with GroEL has GlcNAc-PI de-N-acetylase activity in vitro. The activity was not enhanced by GTP, which is known to enhance the de-N-acetylase activity of mammalian cell microsomes. As with other de-N-acetylases that act on the GlcNAc moiety, metal ions, in particular Mn2+ and Ni2+, enhanced the enzyme activity of PIG-L. The Saccharomyces cerevisiae YMR281W open reading frame encodes a protein (termed Gpi12p) with 24% amino acid identity with rat PIG-L. On transfection into mammalian PIG-L-deficient cells, this gene, GPI12, restored the cell-surface expression of GPI-anchored proteins and GlcNAc-PI de-N-acetylase activity. The disruption of the gene caused lethality in S. cerevisiae. These results indicate that GlcNAc-PI de-N-acetylase is conserved between mammals and yeasts and that the de-N-acetylation step is also indispensable in yeasts.",
    "issueName" : "Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Watanabe",
      "authorRank" : 1,
      "name" : "Watanabe R",
      "referenceId" : "RGD:A7309"
    }, {
      "firstName" : "K",
      "lastName" : "Ohishi",
      "authorRank" : 2,
      "name" : "Ohishi K",
      "referenceId" : "RGD:A7310"
    }, {
      "firstName" : "Y",
      "lastName" : "Maeda",
      "authorRank" : 3,
      "name" : "Maeda Y",
      "referenceId" : "RGD:A7307"
    }, {
      "firstName" : "N",
      "lastName" : "Nakamura",
      "authorRank" : 4,
      "name" : "Nakamura N",
      "referenceId" : "RGD:A5185"
    }, {
      "firstName" : "T",
      "lastName" : "Kinoshita",
      "authorRank" : 5,
      "name" : "Kinoshita T",
      "referenceId" : "RGD:A7311"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401901217"
    } ]
  }, {
    "primaryId" : "PMID:10086067",
    "title" : "Glucose transporter (Glut1, Glut3) mRNA in human placenta of diabetic and non-diabetic pregnancies.",
    "datePublished" : "1997-10-01T00:00:00.000-05:00",
    "citation" : "Sciullo E, etal., Early Pregnancy. 1997 Sep;3(3):172-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-10-05T16:55:59.000-05:00",
    "volume" : "3",
    "pages" : "172-82",
    "abstract" : "Transport of glucose into the cell is catalyzed by glucose transporters (Glut). Glut1 and Glut3 are expressed at various levels in many human tissues, including the placenta. It has been reported that ambient glucose can affect both glucose transport activity and expression of the Glut genes, and protein. To date, very few studies concerning Glut in the placenta have been published, and studies in vivo in human diabetic pregnancy are lacking. We therefore investigated placental Glut1 and Glut3 mRNA by Northern blot analysis in ten diabetic (five insulin dependent diabetes mellitus (IDDM), two non-insulin dependent diabetes mellitus (NIDDM) and three gestational diabetes mellitus (GDM)) and nine non-diabetic women. The quantitative results of specific mRNA/beta-actin ratios were expressed as arbitrary units. The results were evaluated according to metabolic and clinical findings. Glut1 and Glut3 mRNA values in diabetic and non-diabetic pregnant women were similar. The metabolic environment seems to affect the Glut3 mRNA levels in IDDM pregnant women but not the control women. In addition, Glut3 mRNA decreased in late pregnancy in the diabetic but not in the control women. Moreover, Glut1 mRNA levels were correlated with maternal age in the diabetic as well as in the control women (significantly). Finally, an inverse correlation was found between Glut1 mRNA levels and placental weight (in both diabetic and non-diabetic women). These results, although preliminary, shed some light on the function of these glucose transporters in normal as well as in diabetic pregnancies and prompt us to carry out a further investigation to better elucidate fetomaternal metabolic correlation at the placental level.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Sciullo",
      "authorRank" : 1,
      "name" : "Sciullo E",
      "referenceId" : "RGD:A113124"
    }, {
      "firstName" : "G",
      "lastName" : "Cardellini",
      "authorRank" : 2,
      "name" : "Cardellini G",
      "referenceId" : "RGD:A113125"
    }, {
      "firstName" : "MG",
      "lastName" : "Baroni",
      "authorRank" : 3,
      "name" : "Baroni MG",
      "referenceId" : "RGD:A62161"
    }, {
      "firstName" : "P",
      "lastName" : "Torresi",
      "authorRank" : 4,
      "name" : "Torresi P",
      "referenceId" : "RGD:A113126"
    }, {
      "firstName" : "A",
      "lastName" : "Buongiorno",
      "authorRank" : 5,
      "name" : "Buongiorno A",
      "referenceId" : "RGD:A113127"
    }, {
      "firstName" : "P",
      "lastName" : "Pozzilli",
      "authorRank" : 6,
      "name" : "Pozzilli P",
      "referenceId" : "RGD:A161949"
    }, {
      "firstName" : "F",
      "lastName" : "Fallucca",
      "authorRank" : 7,
      "name" : "Fallucca F",
      "referenceId" : "RGD:A112334"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313619"
    } ]
  }, {
    "primaryId" : "PMID:10086355",
    "title" : "The mahogany protein is a receptor involved in suppression of obesity.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Nagle DL, etal., Nature 1999 Mar 11;398(6723):148-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:43:58.000-06:00",
    "volume" : "398",
    "pages" : "148-52",
    "abstract" : "Genetic studies have shown that mutations within the mahogany locus suppress the pleiotropic phenotypes, including obesity, of the agouti-lethal-yellow mutant. Here we identify the mahogany gene and its product; this study, to our knowledge, represents the first positional cloning of a suppressor gene in the mouse. Expression of the mahogany gene is broad; however, in situ hybridization analysis emphasizes the importance of its expression in the ventromedial hypothalamic nucleus, a region that is intimately involved in the regulation of body weight and feeding. We present new genetic studies that indicate that the mahogany locus does not suppress the obese phenotype of the melanocortin-4-receptor null allele or those of the monogenic obese models (Lep(db), tub and Cpe(fat)). However, mahogany can suppress diet-induced obesity, the mechanism of which is likely to have implications for therapeutic intervention in common human obesity. The amino-acid sequence of the mahogany protein suggests that it is a large, single-transmembrane-domain receptor-like molecule, with a short cytoplasmic tail containing a site that is conserved between Caenorhabditis elegans and mammals. We propose two potential, alternative modes of action for mahogany: one draws parallels with the mechanism of action of low-affinity proteoglycan receptors such as fibroblast growth factor and transforming growth factor-beta, and the other suggests that mahogany itself is a signalling receptor.",
    "issueName" : "6723",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DL",
      "lastName" : "Nagle",
      "authorRank" : 1,
      "name" : "Nagle DL",
      "referenceId" : "RGD:A36235"
    }, {
      "firstName" : "SH",
      "lastName" : "McGrail",
      "authorRank" : 2,
      "name" : "McGrail SH",
      "referenceId" : "RGD:A36236"
    }, {
      "firstName" : "J",
      "lastName" : "Vitale",
      "authorRank" : 3,
      "name" : "Vitale J",
      "referenceId" : "RGD:A36237"
    }, {
      "firstName" : "EA",
      "lastName" : "Woolf",
      "authorRank" : 4,
      "name" : "Woolf EA",
      "referenceId" : "RGD:A36238"
    }, {
      "firstName" : "JR",
      "lastName" : "Dussault BJ",
      "authorRank" : 5,
      "name" : "Dussault BJ JR",
      "referenceId" : "RGD:A36239"
    }, {
      "firstName" : "L",
      "lastName" : "DiRocco",
      "authorRank" : 6,
      "name" : "DiRocco L",
      "referenceId" : "RGD:A36240"
    }, {
      "firstName" : "L",
      "lastName" : "Holmgren",
      "authorRank" : 7,
      "name" : "Holmgren L",
      "referenceId" : "RGD:A24298"
    }, {
      "firstName" : "J",
      "lastName" : "Montagno",
      "authorRank" : 8,
      "name" : "Montagno J",
      "referenceId" : "RGD:A36241"
    }, {
      "firstName" : "P",
      "lastName" : "Bork",
      "authorRank" : 9,
      "name" : "Bork P",
      "referenceId" : "RGD:A36242"
    }, {
      "firstName" : "D",
      "lastName" : "Huszar",
      "authorRank" : 10,
      "name" : "Huszar D",
      "referenceId" : "RGD:A36243"
    }, {
      "firstName" : "V",
      "lastName" : "Fairchild-Huntress",
      "authorRank" : 11,
      "name" : "Fairchild-Huntress V",
      "referenceId" : "RGD:A36244"
    }, {
      "firstName" : "P",
      "lastName" : "Ge",
      "authorRank" : 12,
      "name" : "Ge P",
      "referenceId" : "RGD:A22770"
    }, {
      "firstName" : "J",
      "lastName" : "Keilty",
      "authorRank" : 13,
      "name" : "Keilty J",
      "referenceId" : "RGD:A36245"
    }, {
      "firstName" : "C",
      "lastName" : "Ebeling",
      "authorRank" : 14,
      "name" : "Ebeling C",
      "referenceId" : "RGD:A27325"
    }, {
      "firstName" : "L",
      "lastName" : "Baldini",
      "authorRank" : 15,
      "name" : "Baldini L",
      "referenceId" : "RGD:A36246"
    }, {
      "firstName" : "J",
      "lastName" : "Gilchrist",
      "authorRank" : 16,
      "name" : "Gilchrist J",
      "referenceId" : "RGD:A36247"
    }, {
      "firstName" : "P",
      "lastName" : "Burn",
      "authorRank" : 17,
      "name" : "Burn P",
      "referenceId" : "RGD:A36248"
    }, {
      "firstName" : "GA",
      "lastName" : "Carlson",
      "authorRank" : 18,
      "name" : "Carlson GA",
      "referenceId" : "RGD:A36249"
    }, {
      "firstName" : "KJ",
      "lastName" : "Moore",
      "authorRank" : 19,
      "name" : "Moore KJ",
      "referenceId" : "RGD:A36250"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734623"
    } ]
  }, {
    "primaryId" : "PMID:10086383",
    "title" : "Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic beta tumor cells.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Perl AK, etal., Nat Med. 1999 Mar;5(3):286-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-21T10:51:54.000-05:00",
    "volume" : "5",
    "pages" : "286-91",
    "abstract" : "As in the development of many human cancers, in a transgenic mouse model of beta-cell carcinogenesis (Rip1Tag2), expression of neural cell adhesion molecule (NCAM) changes from the 120-kDa isoform in normal tissue to the 140/180-kDa isoforms in tumors. NCAM-deficient RiplTag2 mice, generated by crossing Rip1Tag2 mice with NCAM knockout mice, develop metastases, a tumor stage that is not seen in normal Rip1Tag2 mice. In contrast, overexpression of NCAM 120 in NCAM-deficient Rip1Tag2 mice prevents tumor metastasis. The results indicate that the loss of NCAM-mediated cell adhesion is one rate-limiting step in the actual metastatic dissemination of beta tumor cells.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AK",
      "lastName" : "Perl",
      "authorRank" : 1,
      "name" : "Perl AK",
      "referenceId" : "RGD:A125274"
    }, {
      "firstName" : "U",
      "lastName" : "Dahl",
      "authorRank" : 2,
      "name" : "Dahl U",
      "referenceId" : "RGD:A125275"
    }, {
      "firstName" : "P",
      "lastName" : "Wilgenbus",
      "authorRank" : 3,
      "name" : "Wilgenbus P",
      "referenceId" : "RGD:A125276"
    }, {
      "firstName" : "H",
      "lastName" : "Cremer",
      "authorRank" : 4,
      "name" : "Cremer H",
      "referenceId" : "RGD:A125121"
    }, {
      "firstName" : "H",
      "lastName" : "Semb",
      "authorRank" : 5,
      "name" : "Semb H",
      "referenceId" : "RGD:A125277"
    }, {
      "firstName" : "G",
      "lastName" : "Christofori",
      "authorRank" : 6,
      "name" : "Christofori G",
      "referenceId" : "RGD:A125278"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2326067"
    } ]
  }, {
    "primaryId" : "PMID:10086390",
    "title" : "The pathogenesis of familial hypertrophic cardiomyopathy: early and evolving effects from an alpha-cardiac myosin heavy chain missense mutation.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Georgakopoulos D, etal., Nat Med. 1999 Mar;5(3):327-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:18:37.000-05:00",
    "volume" : "5",
    "pages" : "327-30",
    "abstract" : "Familial hypertrophic cardiomyopathy (FHC) is a genetic disorder resulting from mutations in genes encoding sarcomeric proteins. This typically induces hyperdynamic ejection, impaired relaxation, delayed early filling, myocyte disarray and fibrosis, and increased chamber end-systolic stiffness. To better understand the disease pathogenesis, early (primary) abnormalities must be distinguished from evolving responses to the genetic defect. We did in vivo analysis using a mouse model of FHC with an Arg403Gln alpha-cardiac myosin heavy  chain missense mutation, and used newly developed methods for assessing in situ pressure-volume relations. Hearts of young mutant mice (6 weeks old), which show  no chamber morphologic or gross histologic abnormalities, had altered contraction kinetics, with considerably delayed pressure relaxation and chamber filling, yet  accelerated systolic pressure rise. Older mutant mice (20 weeks old), which develop fiber disarray and fibrosis, had diastolic and systolic kinetic changes similar to if not slightly less than those of younger mice. However, the hearts of older mutant mice also showed hyperdynamic contraction, with increased end-systolic chamber stiffness, outflow tract pressure gradients and a lower cardiac index due to reduced chamber filling; all 'hallmarks' of human disease. These data provide new insights into the temporal evolution of FHC. Such data may help direct new therapeutic strategies to diminish disease progression.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Georgakopoulos",
      "authorRank" : 1,
      "name" : "Georgakopoulos D",
      "referenceId" : "RGD:A46903"
    }, {
      "firstName" : "ME",
      "lastName" : "Christe",
      "authorRank" : 2,
      "name" : "Christe ME",
      "referenceId" : "RGD:A83141"
    }, {
      "firstName" : "M",
      "lastName" : "Giewat",
      "authorRank" : 3,
      "name" : "Giewat",
      "referenceId" : "RGD:A269104"
    }, {
      "firstName" : "CM",
      "lastName" : "Seidman",
      "authorRank" : 4,
      "name" : "Seidman",
      "referenceId" : "RGD:A278435"
    }, {
      "firstName" : "JG",
      "lastName" : "Seidman",
      "authorRank" : 5,
      "name" : "Seidman JG",
      "referenceId" : "RGD:A32536"
    }, {
      "firstName" : "DA",
      "lastName" : "Kass",
      "authorRank" : 6,
      "name" : "Kass DA",
      "referenceId" : "RGD:A46910"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071014"
    } ]
  }, {
    "primaryId" : "PMID:10086961",
    "title" : "Genome-wide linkage analyses of systolic blood pressure using highly discordant siblings.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Krushkal J, etal., Circulation 1999 Mar 23;99(11):1407-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-04-23T16:42:02.000-05:00",
    "volume" : "99",
    "pages" : "1407-10",
    "abstract" : "BACKGROUND: Elevated blood pressure is a risk factor for cardiovascular, cerebrovascular, and renal diseases. Complex mechanisms of blood pressure regulation pose a challenge to identifying genetic factors that influence interindividual blood pressure variation in the population at large. METHODS AND RESULTS: We performed a genome-wide linkage analysis of systolic blood pressure in humans using an efficient, highly discordant, full-sibling design. We identified 4 regions of the human genome that show statistical significant linkage to genes that influence interindividual systolic blood pressure variation (2p22.1 to 2p21, 5q33.3 to 5q34, 6q23.1 to 6q24.1, and 15q25.1 to 15q26.1). These regions contain a number of candidate genes that are involved in physiological mechanisms of blood pressure regulation. CONCLUSIONS: These results provide both novel information about genome regions in humans that influence interindividual blood pressure variation and a basis for identifying the contributing genes. Identification of the functional mutations in these genes may uncover novel mechanisms for blood pressure regulation and suggest new therapies and prevention strategies.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Krushkal",
      "authorRank" : 1,
      "name" : "Krushkal J",
      "referenceId" : "RGD:A38894"
    }, {
      "firstName" : "R",
      "lastName" : "Ferrell",
      "authorRank" : 2,
      "name" : "Ferrell R",
      "referenceId" : "RGD:A40128"
    }, {
      "firstName" : "SC",
      "lastName" : "Mockrin",
      "authorRank" : 3,
      "name" : "Mockrin SC",
      "referenceId" : "RGD:A40129"
    }, {
      "firstName" : "ST",
      "lastName" : "Turner",
      "authorRank" : 4,
      "name" : "Turner ST",
      "referenceId" : "RGD:A39790"
    }, {
      "firstName" : "CF",
      "lastName" : "Sing",
      "authorRank" : 5,
      "name" : "Sing CF",
      "referenceId" : "RGD:A40130"
    }, {
      "firstName" : "E",
      "lastName" : "Boerwinkle",
      "authorRank" : 6,
      "name" : "Boerwinkle E",
      "referenceId" : "RGD:A12911"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298036"
    } ]
  }, {
    "primaryId" : "PMID:10086964",
    "title" : "Common variant in AMPD1 gene predicts improved clinical outcome in patients with heart failure.",
    "datePublished" : "1999-03-23T00:00:00.000-06:00",
    "citation" : "Loh E, etal., Circulation. 1999 Mar 23;99(11):1422-5. doi: 10.1161/01.cir.99.11.1422.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-05-09T14:31:30.000-05:00",
    "volume" : "99",
    "pages" : "1422-5",
    "abstract" : "<br><b>BACKGROUND: </b>This study was undertaken to identify gene(s) that may be associated with improved clinical outcome in patients with congestive heart failure (CHF). The adenosine monophosphate deaminase locus (AMPD1) was selected for study. We hypothesized that inheritance of the mutant AMPD1 allele is associated with increased probability of survival without cardiac transplantation in patients with CHF.<br><b>METHODS AND RESULTS: </b>AMPD1 genotype was determined in 132 patients with advanced CHF and 91 control reference subjects by use of a polymerase chain reaction-based, allele-specific oligonucleotide detection assay. In patients with CHF, those heterozygous (n=20) or homozygous (n=1) for the mutant AMPD1 allele (AMPD1 +/- or -/-, respectively) experienced a significantly longer duration of heart failure symptoms before referral for transplantation evaluation than CHF patients homozygous for the wild-type allele (AMPD1 +/+; n=111; 7.6+/-6.5 versus 3.2+/-3.6 years; P<0.001). The OR of surviving without cardiac transplantation >/=5 years after initial hospitalization for CHF symptoms was 8.6 times greater (95% CI: 3.05, 23.87) in those patients carrying >/=1 mutant AMPD1 allele than in those carrying 2 wild-type AMPD1 +/+ alleles.<br><b>CONCLUSIONS: </b>After the onset of CHF symptoms, the mutant AMPD1 allele is associated with prolonged probability of survival without cardiac transplantation. The mechanism by which the presence of the mutant AMPD1 allele may modify the clinical phenotype of heart failure remains to be determined.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Loh",
      "authorRank" : 1,
      "name" : "Loh E",
      "referenceId" : "RGD:A113104"
    }, {
      "firstName" : "T R",
      "lastName" : "Rebbeck",
      "authorRank" : 2,
      "name" : "Rebbeck TR",
      "referenceId" : "RGD:A440326"
    }, {
      "firstName" : "P D",
      "lastName" : "Mahoney",
      "authorRank" : 3,
      "name" : "Mahoney PD",
      "referenceId" : "RGD:A527287"
    }, {
      "firstName" : "D",
      "lastName" : "DeNofrio",
      "authorRank" : 4,
      "name" : "DeNofrio D",
      "referenceId" : "RGD:A527288"
    }, {
      "firstName" : "J L",
      "lastName" : "Swain",
      "authorRank" : 5,
      "name" : "Swain JL",
      "referenceId" : "RGD:A527289"
    }, {
      "firstName" : "E W",
      "lastName" : "Holmes",
      "authorRank" : 6,
      "name" : "Holmes EW",
      "referenceId" : "RGD:A527290"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:329349359"
    } ]
  }, {
    "primaryId" : "PMID:10086971",
    "title" : "C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Berthet M, etal., Circulation. 1999 Mar 23;99(11):1464-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:08:36.000-05:00",
    "volume" : "99",
    "pages" : "1464-70",
    "abstract" : "BACKGROUND: The long-QT syndrome (LQTS) is a genetically heterogeneous disease in which 4 genes encoding ion-channel subunits have been identified. Most of the mutations have been determined in the transmembrane domains of the cardiac potassium channel genes KCNQ1 and HERG. In this study, we investigated the 3' part of HERG for mutations. METHODS AND RESULTS: New specific primers allowed the amplification of the 3' part of HERG, the identification of 2 missense mutations, S818L and V822 M, in the putative cyclic nucleotide binding domain, and a 1-bp insertion, 3108+1G. Hypokalemia was a triggering factor for torsade de pointes in 2 of the probands of these families. Lastly, in a large family, a maternally inherited G to A transition was found in the splicing donor consensus site of HERG, 2592+1G-A, and a paternally inherited mutation, A341E, was identified in KCNQ1. The 2 more severely affected sisters bore both mutations. CONCLUSIONS: The discovery of mutations in the C-terminal part of HERG emphasizes that this region plays a significant role in cardiac repolarization. Clinical data suggests that these mutations may be less malignant than mutations occurring in the pore region, but they can become clinically significant in cases of hypokalemia. The first description of 2 patients with double heterozygosity associated with a dramatic malignant phenotype implies that genetic analysis of severely affected young patients should include an investigation for >1 mutation in the LQT genes.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Berthet",
      "authorRank" : 1,
      "name" : "Berthet",
      "referenceId" : "RGD:A250666"
    }, {
      "firstName" : "I",
      "lastName" : "Denjoy",
      "authorRank" : 2,
      "name" : "Denjoy",
      "referenceId" : "RGD:A172939"
    }, {
      "firstName" : "C",
      "lastName" : "Donger",
      "authorRank" : 3,
      "name" : "Donger",
      "referenceId" : "RGD:A260376"
    }, {
      "firstName" : "L",
      "lastName" : "Demay",
      "authorRank" : 4,
      "name" : "Demay L",
      "referenceId" : "RGD:A62864"
    }, {
      "firstName" : "H",
      "lastName" : "Hammoude",
      "authorRank" : 5,
      "name" : "Hammoude",
      "referenceId" : "RGD:A266407"
    }, {
      "firstName" : "D",
      "lastName" : "Klug",
      "authorRank" : 6,
      "name" : "Klug",
      "referenceId" : "RGD:A251653"
    }, {
      "firstName" : "E",
      "lastName" : "Schulze-Bahr",
      "authorRank" : 7,
      "name" : "Schulze-Bahr E",
      "referenceId" : "RGD:A64464"
    }, {
      "firstName" : "P",
      "lastName" : "Richard",
      "authorRank" : 8,
      "name" : "Richard P",
      "referenceId" : "RGD:A53382"
    }, {
      "firstName" : "H",
      "lastName" : "Funke",
      "authorRank" : 9,
      "name" : "Funke H",
      "referenceId" : "RGD:A57712"
    }, {
      "firstName" : "K",
      "lastName" : "Schwartz",
      "authorRank" : 10,
      "name" : "Schwartz K",
      "referenceId" : "RGD:A7050"
    }, {
      "firstName" : "P",
      "lastName" : "Coumel",
      "authorRank" : 11,
      "name" : "Coumel",
      "referenceId" : "RGD:A253160"
    }, {
      "firstName" : "B",
      "lastName" : "Hainque",
      "authorRank" : 12,
      "name" : "Hainque B",
      "referenceId" : "RGD:A61722"
    }, {
      "firstName" : "P",
      "lastName" : "Guicheney",
      "authorRank" : 13,
      "name" : "Guicheney P",
      "referenceId" : "RGD:A37505"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066892"
    } ]
  }, {
    "primaryId" : "PMID:10087188",
    "title" : "Facilitated antigen presentation by B cells expressing IgD when responding T cells express IgD-receptors.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Wu Y, etal., Cell Immunol. 1999 Mar 15;192(2):194-202.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:34:23.000-05:00",
    "volume" : "192",
    "pages" : "194-202",
    "abstract" : "In vitro studies have confirmed that cognate interactions between T and B cells are required to demonstrate enhanced helper activity using T cells with upregulated IgD-receptors (IgD-Rs). We studied the mechanism by which IgD-R+ T cells facilitate antibody responses by examining whether T cells also benefit from their expression of IgD-R. Experiments were designed to determine whether upregulation of IgD-R on T cells facilitates antigen presentation by IgD+ B cells. Goat Ig-primed splenic T cells from BALB/c mice were tested for their ability to respond to antigen-presenting B cells treated with goat anti-mouse (GAM) IgM or GAM IgD. T cell responses to GAM IgM and GAM IgD presented by B cells were significantly higher when goat Ig-primed cells were induced to express IgD-R by exposure to oligomeric IgD compared with goat Ig-primed control T cells. This effect was inhibited when monomeric IgD was added to the cultures. No differences in T and IgD-R+ T cell responses were seen using adherent cells as APCs. B cells from IgD-/- mice were also tested. Such B cells present antigen to  IgD-R+ T cells without promoting enhanced responses compared with B cells from heterozygous IgD+/- mice. These studies suggest that IgD may play a costimulatory role during antigen presentation. We conclude that when T cells are induced to express IgD-R, these lectin-like receptors can ligate B cell membrane IgD during  antigen presentation to facilitate responses of each of the cells engaged in cognate interaction, yielding enhanced antigen-specific T cell and B cell responses.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Wu",
      "authorRank" : 1,
      "name" : "Wu Y",
      "referenceId" : "RGD:A17025"
    }, {
      "firstName" : "SM",
      "lastName" : "Lakshmi Tamma",
      "authorRank" : 2,
      "name" : "Lakshmi Tamma",
      "referenceId" : "RGD:A331161"
    }, {
      "firstName" : "V",
      "lastName" : "Lima",
      "authorRank" : 3,
      "name" : "Lima",
      "referenceId" : "RGD:A331162"
    }, {
      "firstName" : "R",
      "lastName" : "Coico",
      "authorRank" : 4,
      "name" : "Coico",
      "referenceId" : "RGD:A331163"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340542"
    } ]
  }, {
    "primaryId" : "PMID:10087197",
    "title" : "The genomic organization of type I keratin genes in mice.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Sato H, etal., Genomics 1999 Mar 15;56(3):303-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-08T09:00:54.000-06:00",
    "volume" : "56",
    "pages" : "303-9",
    "abstract" : "We isolated two new keratin cDNAs by screening a cDNA library constructed from poly(A)+ RNA of the dorsal and abdominal skin of C57BL/10J mice with a probe of human KRT14. Due to its high sequence homology to human keratin 17 cDNA, one full-length cDNA is most likely to be mouse keratin 17 (Krt1-17) cDNA. The other is the putative full-length cDNA of a novel type I keratin gene, designated Krt1-c29. These two keratin genes were mapped to the distal portion of Chromosome 11, where the mouse keratin gene complex-1 (Krt1) is localized. To elucidate the genomic organization of Krt1 in mice, we carried out genetic and physical analyses of Krt1. A large-scale linkage analysis using intersubspecific backcrosses suggested that there are two major clusters in Krt1, one containing Krt1-c29, Krt1-10, and Krt1-12 and the other containing Krt1-14, -15, -17, and -19. Truncation experiments with two yeast artificial chromosome clones containing the two clusters above have revealed that the gene order of Krt1 is centromere-Krt1-c29-Krt1-10-Krt1-12-Krt1-13-K rt1-15-Krt1-19-Krt1-14-K rt1-17-telomere. Finally, we analyzed sequence divergence between the genes belonging to the Krt1 complex. The results clearly indicated that genes are classified into two major groups with respect to phylogenetic relationship. Each group consists of the respective gene cluster demonstrated by genetic and physical analyses in this study, suggesting that the physical organization of the Krt1 complex reflects the evolutionary process of gene duplication of this complex.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Sato",
      "authorRank" : 1,
      "name" : "Sato H",
      "referenceId" : "RGD:A6517"
    }, {
      "firstName" : "T",
      "lastName" : "Koide",
      "authorRank" : 2,
      "name" : "Koide T",
      "referenceId" : "RGD:A17344"
    }, {
      "firstName" : "T",
      "lastName" : "Sagai",
      "authorRank" : 3,
      "name" : "Sagai T",
      "referenceId" : "RGD:A56988"
    }, {
      "firstName" : "SI",
      "lastName" : "Ishiguro",
      "authorRank" : 4,
      "name" : "Ishiguro SI",
      "referenceId" : "RGD:A56989"
    }, {
      "firstName" : "M",
      "lastName" : "Tamai",
      "authorRank" : 5,
      "name" : "Tamai M",
      "referenceId" : "RGD:A25202"
    }, {
      "firstName" : "N",
      "lastName" : "Saitou",
      "authorRank" : 6,
      "name" : "Saitou N",
      "referenceId" : "RGD:A56990"
    }, {
      "firstName" : "T",
      "lastName" : "Shiroishi",
      "authorRank" : 7,
      "name" : "Shiroishi T",
      "referenceId" : "RGD:A56991"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556673"
    } ]
  }, {
    "primaryId" : "PMID:10087202",
    "title" : "Cloning and characterization of UXT, a novel gene in human Xp11, which is widely and abundantly expressed in tumor tissue.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Schroer A, etal., Genomics 1999 Mar 15;56(3):340-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-01T15:11:52.000-05:00",
    "volume" : "56",
    "pages" : "340-3",
    "abstract" : "Several different disease loci with unknown genetic background map to human Xp11. In a systematic search for novel genes, we identified a novel transcript, UXT (HGMW-approved symbol), close to the ELK1 locus in Xp11.23-p11.22. The gene is composed of seven exons and encodes a protein of 157 amino acids, which is highly conserved in mouse. We showed that UXT is ubiquitously expressed and subject to X-inactivation. No homology to any known genes was found. Database surveys indicate an abundant expression in tumor tissues.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Schroer",
      "authorRank" : 1,
      "name" : "Schroer A",
      "referenceId" : "RGD:A55289"
    }, {
      "firstName" : "S",
      "lastName" : "Schneider",
      "authorRank" : 2,
      "name" : "Schneider S",
      "referenceId" : "RGD:A55290"
    }, {
      "firstName" : "H",
      "lastName" : "Ropers",
      "authorRank" : 3,
      "name" : "Ropers H",
      "referenceId" : "RGD:A55291"
    }, {
      "firstName" : "H",
      "lastName" : "Nothwang",
      "authorRank" : 4,
      "name" : "Nothwang H",
      "referenceId" : "RGD:A55292"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549523"
    } ]
  }, {
    "primaryId" : "PMID:10087204",
    "title" : "Mapping of the KHSRP gene to a region of conserved synteny on human chromosome 19p13.3 and mouse chromosome 17.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Ring HZ, etal., Genomics 1999 Mar 15;56(3):350-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-08T09:00:51.000-06:00",
    "volume" : "56",
    "pages" : "350-2",
    "abstract" : "The K homology-type splicing regulatory protein, KSRP, activates splicing through intronic splicing enhancer sequences. It is highly expressed in neural cells and is required for the neural-specific splicing of the c-src N1 exon. In this study, we mapped the gene (gene symbols KHSRP and Khsrp) to human chromosome 19 by using radiation hybrid panels and to mouse chromosome 17 by studying an interspecific backcross panel. Human KHSRP is a positional candidate gene for familial febrile convulsion and Cayman type cerebellar ataxia. Comparative analysis of the human and mouse genomes indicates that the KHSRP gene is located in regions of conserved synteny between the two species.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HZ",
      "lastName" : "Ring",
      "authorRank" : 1,
      "name" : "Ring HZ",
      "referenceId" : "RGD:A56975"
    }, {
      "firstName" : "V",
      "lastName" : "Vameghi-Meyers",
      "authorRank" : 2,
      "name" : "Vameghi-Meyers V",
      "referenceId" : "RGD:A56976"
    }, {
      "firstName" : "JM",
      "lastName" : "Nikolic",
      "authorRank" : 3,
      "name" : "Nikolic JM",
      "referenceId" : "RGD:A56977"
    }, {
      "firstName" : "H",
      "lastName" : "Min",
      "authorRank" : 4,
      "name" : "Min H",
      "referenceId" : "RGD:A56978"
    }, {
      "firstName" : "DL",
      "lastName" : "Black",
      "authorRank" : 5,
      "name" : "Black DL",
      "referenceId" : "RGD:A56979"
    }, {
      "firstName" : "U",
      "lastName" : "Francke",
      "authorRank" : 6,
      "name" : "Francke U",
      "referenceId" : "RGD:A15635"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556669"
    } ]
  }, {
    "primaryId" : "PMID:10087256",
    "title" : "A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Fontoura BM, etal., J Cell Biol. 1999 Mar 22;144(6):1097-112.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-12-01T14:55:53.000-06:00",
    "volume" : "144",
    "pages" : "1097-112",
    "abstract" : "The mammalian nuclear pore complex (NPC) is comprised of approximately 50 unique  proteins, collectively known as nucleoporins. Through fractionation of rat liver  nuclei, we have isolated >30 potentially novel nucleoporins and have begun a systematic characterization of these proteins. Here, we present the characterization of Nup96, a novel nucleoporin with a predicted molecular mass of 96 kD. Nup96 is generated through an unusual biogenesis pathway that involves synthesis of a 186-kD precursor protein. Proteolytic cleavage of the precursor yields two nucleoporins: Nup98, a previously characterized GLFG-repeat containing nucleoporin, and Nup96. Mutational and functional analyses demonstrate that both  the Nup98-Nup96 precursor and the previously characterized Nup98 (synthesized independently from an alternatively spliced mRNA) are proteolytically cleaved in  vivo. This biogenesis pathway for Nup98 and Nup96 is evolutionarily conserved, as the putative Saccharomyces cerevisiae homologues, N-Nup145p and C-Nup145p, are also produced through proteolytic cleavage of a precursor protein. Using immunoelectron microscopy, Nup96 was localized to the nucleoplasmic side of the NPC, at or near the nucleoplasmic basket. The correct targeting of both Nup96 and Nup98 to the nucleoplasmic side of the NPC was found to be dependent on proteolytic cleavage, suggesting that the cleavage process may regulate NPC assembly. Finally, by biochemical fractionation, a complex containing Nup96, Nup107, and at least two Sec13- related proteins was identified, revealing that a major sub-complex of the NPC is conserved between yeast and mammals.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BM",
      "lastName" : "Fontoura",
      "authorRank" : 1,
      "name" : "Fontoura BM",
      "referenceId" : "RGD:A56418"
    }, {
      "firstName" : "G",
      "lastName" : "Blobel",
      "authorRank" : 2,
      "name" : "Blobel G",
      "referenceId" : "RGD:A6045"
    }, {
      "firstName" : "MJ",
      "lastName" : "Matunis",
      "authorRank" : 3,
      "name" : "Matunis MJ",
      "referenceId" : "RGD:A45830"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10413910"
    } ]
  }, {
    "primaryId" : "PMID:10087275",
    "title" : "Genetic analysis of collagen Q: roles in acetylcholinesterase and butyrylcholinesterase assembly and in synaptic structure and function.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Feng G, etal., J Cell Biol 1999 Mar 22;144(6):1349-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T12:10:02.000-05:00",
    "volume" : "144",
    "pages" : "1349-60",
    "abstract" : "Acetylcholinesterase (AChE) occurs in both asymmetric forms, covalently associated with a collagenous subunit called Q (ColQ), and globular forms that may be either soluble or membrane associated. At the skeletal neuromuscular junction, asymmetric AChE is anchored to the basal lamina of the synaptic cleft, where it hydrolyzes acetylcholine to terminate synaptic transmission. AChE has also been hypothesized to play developmental roles in the nervous system, and ColQ is also expressed in some AChE-poor tissues. To seek roles of ColQ and AChE at synapses and elsewhere, we generated ColQ-deficient mutant mice. ColQ-/- mice completely lacked asymmetric AChE in skeletal and cardiac muscles and brain; they also lacked asymmetric forms of the AChE homologue, butyrylcholinesterase. Thus, products of the ColQ gene are required for assembly of all detectable asymmetric AChE and butyrylcholinesterase. Surprisingly, globular AChE tetramers were also absent from neonatal ColQ-/- muscles, suggesting a role for the ColQ gene in assembly or stabilization of AChE forms that do not themselves contain a collagenous subunit. Histochemical, immunohistochemical, toxicological, and electrophysiological assays all indicated absence of AChE at ColQ-/- neuromuscular junctions. Nonetheless, neuromuscular function was initially robust, demonstrating that AChE and ColQ do not play obligatory roles in early phases of synaptogenesis. Moreover, because acute inhibition of synaptic AChE is fatal to normal animals, there must be compensatory mechanisms in the mutant that allow the synapse to function in the chronic absence of AChE. One structural mechanism appears to be a partial ensheathment of nerve terminals by Schwann cells. Compensation was incomplete, however, as animals lacking ColQ and synaptic AChE failed to thrive and most died before they reached maturity.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Feng",
      "authorRank" : 1,
      "name" : "Feng G",
      "referenceId" : "RGD:A44520"
    }, {
      "firstName" : "E",
      "lastName" : "Krejci",
      "authorRank" : 2,
      "name" : "Krejci E",
      "referenceId" : "RGD:A7252"
    }, {
      "firstName" : "J",
      "lastName" : "Molgo",
      "authorRank" : 3,
      "name" : "Molgo J",
      "referenceId" : "RGD:A44521"
    }, {
      "firstName" : "JM",
      "lastName" : "Cunningham",
      "authorRank" : 4,
      "name" : "Cunningham JM",
      "referenceId" : "RGD:A8971"
    }, {
      "firstName" : "J",
      "lastName" : "Massoulie",
      "authorRank" : 5,
      "name" : "Massoulie J",
      "referenceId" : "RGD:A7257"
    }, {
      "firstName" : "JR",
      "lastName" : "Sanes",
      "authorRank" : 6,
      "name" : "Sanes JR",
      "referenceId" : "RGD:A31075"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300297"
    } ]
  }, {
    "primaryId" : "PMID:10087293",
    "title" : "Identification of a novel inflammation-protective locus in the Fischer rat.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Listwak S, etal., Mamm Genome 1999 Apr;10(4):362-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-12-20T15:50:24.000-06:00",
    "volume" : "10",
    "pages" : "362-5",
    "abstract" : "Inbred LEW/N rats are relatively susceptible, while histocompatible inbred F344/N rats are relatively resistant to development of a wide variety of inflammatory diseases in response to a range of pro-inflammatory stimuli. In a LEW/N vs. F344/N F2 intercross, we identified a quantitative trait locus (QTL) on Chr 10 that protects in a dominant fashion against the exudate volume component of innate inflammation in the F344/N rat, as well as a suggestive QTL on Chr 2 near the Fibrinogen cluster region. The exudate volume linkage region on Chr 10 may be similar to one of the multiple regions found to link to inflammatory arthritis phenotypes in other crosses. The suggestive linkage on Chr 2 has not been previously reported and does not seem to contribute to this phenotype in the same manner as the QTL on Chr 10. These findings are consistent with the hypothesis that the innate exudate volume trait is a sub-phenotype of more complex inflammatory phenotypes, such as arthritis, and genes within the Chr 10 linkage region could account for differences in this non-specific acute phase component of the inflammatory response. Since the rat Chr 10 exudate volume linkage region we have identified is syntenic with a region of human Chr 17 that has been shown to link to a variety of autoimmune/inflammatory diseases, including insulin-dependent diabetes mellitus, multiple sclerosis, and psoriasis, identification of genes within this linkage region will shed light on genes relevant to the earliest inflammatory component and to susceptibility and resistance to such human autoimmune/inflammatory diseases.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Listwak",
      "authorRank" : 1,
      "name" : "Listwak S",
      "referenceId" : "RGD:A6882"
    }, {
      "firstName" : "RM",
      "lastName" : "Barrientos",
      "authorRank" : 2,
      "name" : "Barrientos RM",
      "referenceId" : "RGD:A6883"
    }, {
      "firstName" : "G",
      "lastName" : "Koike",
      "authorRank" : 3,
      "name" : "Koike G",
      "referenceId" : "RGD:A51179"
    }, {
      "firstName" : "S",
      "lastName" : "Ghosh",
      "authorRank" : 4,
      "name" : "Ghosh S",
      "referenceId" : "RGD:A6884"
    }, {
      "firstName" : "M",
      "lastName" : "Gomez",
      "authorRank" : 5,
      "name" : "Gomez M",
      "referenceId" : "RGD:A6885"
    }, {
      "firstName" : "B",
      "lastName" : "Misiewicz",
      "authorRank" : 6,
      "name" : "Misiewicz B",
      "referenceId" : "RGD:A6886"
    }, {
      "firstName" : "EM",
      "lastName" : "Sternberg",
      "authorRank" : 7,
      "name" : "Sternberg EM",
      "referenceId" : "RGD:A6887"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69693"
    } ]
  }, {
    "primaryId" : "PMID:10087294",
    "title" : "Rat osteotesticular phosphatase gene (Esp): genomic structure and chromosome location.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Lathrop W, etal., Mamm Genome 1999 Apr;10(4):366-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T14:52:04.000-05:00",
    "volume" : "10",
    "pages" : "366-70",
    "abstract" : "Osteotesticular phosphatase (OST-PTPase) is a class III receptor-type tyrosine phosphatase (RPTPase). It has 10 tandem fibronectin III-like (FN-III) repeats in the extracellular region and two phosphatase domains in the intracellular region. The expression of the rat OST-PTPase gene, Esp, is restricted to osteoblasts and Sertoli cells, and the transcript level in osteoblasts is highly up-regulated by parathyroid hormone and cAMP treatment. We report here the cloning and characterization of the rat Esp gene, including a 2.9-kb 5' flanking region sequence. Two potential binding sites for Osf2/Cbfa1, an osteoblast-specific transcription factor, are present in the promoter. Esp is composed of 35 exons, but spans merely 20 kb, making it the most compact RPTPase gene identified. Each FN-III repeat is encoded by a single exon flanked with phase 1 introns. Two phosphatase domains are encoded by 16 exons in a genomic organization similar to those in RPRPalpha, RPTPgamma, and Ptprc genes. Esp was mapped by fluorescence in situ hybridization to rat chromosome 13q1. These results represent the first genomic structure of a mammalian class III RPTPase gene.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Lathrop",
      "authorRank" : 1,
      "name" : "Lathrop W",
      "referenceId" : "RGD:A18572"
    }, {
      "firstName" : "J",
      "lastName" : "Jordan",
      "authorRank" : 2,
      "name" : "Jordan J",
      "referenceId" : "RGD:A18573"
    }, {
      "firstName" : "D",
      "lastName" : "Eustice",
      "authorRank" : 3,
      "name" : "Eustice D",
      "referenceId" : "RGD:A18574"
    }, {
      "firstName" : "D",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen D",
      "referenceId" : "RGD:A5571"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632780"
    } ]
  }, {
    "primaryId" : "PMID:10087454",
    "title" : "Prohormone convertases 1 and 2 process ProPACAP and generate matured, bioactive PACAP38 and PACAP27 in transfected rat pituitary GH4C1 cells.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Li M, etal., Neuroendocrinology. 1999 Mar;69(3):217-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-06-18T08:55:44.000-05:00",
    "volume" : "69",
    "pages" : "217-26",
    "abstract" : "Pituitary adenylate cyclase-activating polypetide (PACAP) exists in two amidated forms, PACAP38 and PACAP27, which are expressed in the magnocellular and parvocellular neurons of the paraventricular nucleus (PVN) and the magnocellular neurons of the supraoptic nucleus (SON) of the hypothalamus. The prohormone convertases PC1 and PC2, subtilisin-like PCs of the Kex2 family, are expressed in neuroendocrine cells. Immunocytochemistry and in situ hybridization of PC1 and PC2 in the hypothalamus have shown that PC1 and PC2 are also present in the PVN and SON. Therefore, it is possible that the precursor of PACAP is processed by PC1 and/or PC2 in the hypothalamic nuclei and then converted to its mature forms. To test this hypothesis, rat pituitary GH4C1 cells were supertransfected with human PACAP cDNA and either rat PC1 or PC2 cDNA. The acid extracts of these cells were analyzed by reversed-phase HPLC for proPACAP, PACAP38 and/or PACAP27 radioimmunoassays using three antibodies with different recognition sites, and then bioassayed for the ability to stimulate adenylate cyclase. The cells transfected with PACAP cDNA alone yielded PACAP-like immunoreactivity (PACAP-li) corresponding to molecular weights between 15 and 20 kDa without PACAP bioactivity. Cotransfection of these cells with PC1 or PC2 generated PACAP-li, which coeluted with synthetic PACAP38 and PACAP27, respectively. Western blot also revealed 4.5- and 3.0-kDa PACAP-li bands, which correspond to the molecular weights of PACAP38 and PACAP27, respectively. The HPLC fractions containing PACAP-li, which were coeluted with synthetic PACAP38 and PACAP27, showed marked bioactivities. These findings suggest that the precursor of PACAP expressed in the PVN and SON of the hypothalamus could be efficiently processed by PC1 and PC2, and then converted to mature, bioactive PACAP38 and PACAP27.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li M",
      "referenceId" : "RGD:A5679"
    }, {
      "firstName" : "Y",
      "lastName" : "Shuto",
      "authorRank" : 2,
      "name" : "Shuto Y",
      "referenceId" : "RGD:A12860"
    }, {
      "firstName" : "A",
      "lastName" : "Somogyvari-Vigh",
      "authorRank" : 3,
      "name" : "Somogyvari-Vigh A",
      "referenceId" : "RGD:A108296"
    }, {
      "firstName" : "A",
      "lastName" : "Arimura",
      "authorRank" : 4,
      "name" : "Arimura A",
      "referenceId" : "RGD:A43977"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2308913"
    } ]
  }, {
    "primaryId" : "PMID:10088047",
    "title" : "Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Manuck SB, etal., Biol Psychiatry 1999 Mar 1;45(5):603-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-07-05T16:11:57.000-05:00",
    "volume" : "45",
    "pages" : "603-14",
    "abstract" : "BACKGROUND: Central nervous system (CNS) serotonergic activity correlates inversely with human aggressive behavior, and individual differences in aggressive disposition are at least partially heritable. This study was conducted to evaluate the possible association between measures of antagonistic behavior and an intronic polymorphism of the gene coding for tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis. METHODS: Locally recruited men and women (n = 251) were genotyped for the A218C polymorphism located in intron 7 of the TPH gene. All subjects were administered standard interview and questionnaire indices of aggression and anger-related traits of personality; in a portion of subjects, CNS serotonergic activity was assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). RESULTS: Persons having any TPH U allele scored significantly higher on measures of aggression and tendency to experience unprovoked anger and were more likely to report expressing their anger outwardly than individuals homozygous for the alternate L allele. In men, but not women, peak prolactin response to fenfluramine was also attenuated among subjects having any U allele, relative to LL homozygotes. CONCLUSIONS: Individual differences in aggressive disposition are associated with an intronic polymorphism of the TPH gene in a nonpatient sample of community-derived volunteers.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SB",
      "lastName" : "Manuck",
      "authorRank" : 1,
      "name" : "Manuck SB",
      "referenceId" : "RGD:A54065"
    }, {
      "firstName" : "JD",
      "lastName" : "Flory",
      "authorRank" : 2,
      "name" : "Flory JD",
      "referenceId" : "RGD:A54066"
    }, {
      "firstName" : "RE",
      "lastName" : "Ferrell",
      "authorRank" : 3,
      "name" : "Ferrell RE",
      "referenceId" : "RGD:A39359"
    }, {
      "firstName" : "KM",
      "lastName" : "Dent",
      "authorRank" : 4,
      "name" : "Dent KM",
      "referenceId" : "RGD:A54067"
    }, {
      "firstName" : "JJ",
      "lastName" : "Mann",
      "authorRank" : 5,
      "name" : "Mann JJ",
      "referenceId" : "RGD:A38951"
    }, {
      "firstName" : "MF",
      "lastName" : "Muldoon",
      "authorRank" : 6,
      "name" : "Muldoon MF",
      "referenceId" : "RGD:A54068"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358789"
    } ]
  }, {
    "primaryId" : "PMID:1008825",
    "title" : "Characterization of the glucose 6-phosphate dehydrogenase activity in rat liver mitochondria.",
    "datePublished" : "1976-08-01T00:00:00.000-05:00",
    "citation" : "Grunwald M and Hill HZ, Biochem J. 1976 Dec 1;159(3):683-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-08-01T15:16:54.000-05:00",
    "volume" : "159",
    "pages" : "683-7",
    "abstract" : "Glucose 6-phosphate dehydrogenase activity in rat liver mitochondria can be released by detergent. The released activity is separated by chromatography into  two peaks. One peak has the kinetic behaviour and mobility similar to the soluble sex-linked enzyme, whereas the other peak is similar to the microsomal hexose 6-phosphate dehydrogenase. There is no evidence for the existence of a new glucose 6-phosphate dehydrogenase activity in rat liver mitochondria.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Grunwald",
      "authorRank" : 1,
      "name" : "Grunwald M",
      "referenceId" : "RGD:A156914"
    }, {
      "firstName" : "HZ",
      "lastName" : "Hill",
      "authorRank" : 2,
      "name" : "Hill HZ",
      "referenceId" : "RGD:A156915"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6784512"
    } ]
  }, {
    "primaryId" : "PMID:10088816",
    "title" : "Clinical characteristics of ocular angiomatosis in von Hippel-Lindau disease and  correlation with germline mutation.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Webster AR, etal., Arch Ophthalmol. 1999 Mar;117(3):371-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:43:15.000-05:00",
    "volume" : "117",
    "pages" : "371-8",
    "abstract" : "OBJECTIVES: To examine the epidemiologic and clinical characteristics of the ocular manifestations of von Hippel-Lindau (VHL) disease and to detect phenotype-genotype relationships of disease severity. DESIGN: A cross-sectional clinical and molecular genetic study. PATIENTS AND METHODS: One hundred eighty-three affected VHL gene carriers from 81 unrelated pedigrees were interviewed and examined; clinical data were also obtained from 12 living and 39  deceased affected relatives. DNA extracted from venous blood was used to identify mutations in the VHL gene. RESULTS: The prevalence of ocular angiomatosis (hemangioblastomas) in von Hippel-Lindau disease was 67.8% (124/183), and the mean number of angiomas in gene carriers was 1.85 (range, 0-15). Neither prevalence nor angioma count increased with age. Severe vision loss in 1 or both  eyes was associated with presentation at a young age. The cumulative probability  of incurring vision loss by age 50 years was 35% in all gene carriers, 55% in those with angiomatosis, and significantly worse in those coming to us with symptoms. Angiomas were nonrandomly distributed in the fundus, occurring rarely at the posterior pole (1% of retinal tumors) and commonly on the optic disc (8% of eyes) and supratemporal retina. Complications of ocular angiomatosis included  disc and retinal neovascularization; secondary angioma formation; retinal detachment, exudation, and membrane; and retinal and vitreous hemorrhage. Germ-line VHL mutations were detected in 161 of 183 patients and 69 (85%) of 81 pedigrees and included deletions (n= 16), missense (mutations causing amino acid  substitutions; n = 24), nonsense (premature stop codons; n = 15), frameshift (n = 13), and splice-site (n = 1) mutations. There was no association between the type or position of mutation and the severity of ocular angiomatosis. CONCLUSIONS: A systematic clinical description of a large cohort of VHL gene carriers further defines the ocular phenotype. There is no general influence of germline mutation  on severity of ocular disease in VHL. CLINICAL RELEVANCE: The ophthalmic and molecular genetic description of patients with VHL disease.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AR",
      "lastName" : "Webster",
      "authorRank" : 1,
      "name" : "Webster AR",
      "referenceId" : "RGD:A74231"
    }, {
      "firstName" : "ER",
      "lastName" : "Maher",
      "authorRank" : 2,
      "name" : "Maher ER",
      "referenceId" : "RGD:A75031"
    }, {
      "firstName" : "AT",
      "lastName" : "Moore",
      "authorRank" : 3,
      "name" : "Moore AT",
      "referenceId" : "RGD:A74230"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067817"
    } ]
  }, {
    "primaryId" : "PMID:10089464",
    "title" : "Crystallization and preliminary X-ray diffraction studies of perchloric acid soluble protein (PSP) from rat liver.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Djinovic Carugo K, etal., Acta Crystallogr D Biol Crystallogr. 1999 Mar;55(Pt 3):667-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-20T10:36:18.000-06:00",
    "volume" : "55",
    "pages" : "667-8",
    "abstract" : "Perchloric acid soluble protein purified from the cytosol fraction of rat liver has been crystallized in a form suitable for high-resolution X-ray diffraction studies. Octahedral crystals reaching 0.5 mm in cross-sectional diameter were produced by the hanging-drop method using polyethylene glycol (Mr = 8 kDa) as precipitant. These crystals diffract to 2.44 A on an in-house X-ray source and to 1.8 A using a bending-magnet beamline at ESRF Grenoble. The crystals belong to the cubic space group P213 with a = 89.90 A and two molecules per asymmetric unit, as indicated from a Vm value of 2.12 A3 Da-1 and self-rotation function computation. Screening for heavy-atom derivatives identified a platinum compound  and xenon that bind to the protein.",
    "issueName" : "Pt 3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Djinovic Carugo",
      "authorRank" : 1,
      "name" : "Djinovic Carugo",
      "referenceId" : "RGD:A198463"
    }, {
      "firstName" : "M",
      "lastName" : "Saraste",
      "authorRank" : 2,
      "name" : "Saraste",
      "referenceId" : "RGD:A198464"
    }, {
      "firstName" : "T",
      "lastName" : "Oka",
      "authorRank" : 3,
      "name" : "Oka T",
      "referenceId" : "RGD:A9885"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685566"
    } ]
  }, {
    "primaryId" : "PMID:10089893",
    "title" : "Molecular characterization of two mutations in platelet glycoprotein (GP) Ib alpha in two Finnish Bernard-Soulier syndrome families.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Koskela S, etal., Eur J Haematol. 1999 Mar;62(3):160-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-21T15:31:22.000-06:00",
    "volume" : "62",
    "pages" : "160-8",
    "abstract" : "Bernard-Soulier syndrome (BSS) is a rare hereditary bleeding disorder and macrothrombocytopenia which is caused by a defect in the platelet glycoprotein Ib/IX/V (GP Ib/IX/V) complex, the receptor for von Willebrand factor and thrombin. Here we report the molecular basis of the classical form of BSS in two  unrelated Finnish patients, both with a life-long history of severe bleeding. Flow cytometry and immunoblotting showed no expression of GP Ib/IX, GP Ib alpha,  GP Ib beta or GP IX (less than 10%) in the patients' platelets. No expression of  GP V (< 10%) was observed in propositus 1, but a residual amount was found in propositus 2 (24%). DNA sequencing analysis revealed that propositus 1 was compound heterozygous for a two-base-pair deletion at Tyr505(TAT) and a point mutation Leu129(CTC)Pro(CCC) in the GP Ib alpha gene. Propositus 2 was homozygous for the Tyr505(TAT) deletion. The nine relatives who were heterozygous for either of the mutations also had low levels of GP Ib alpha (74-90%). Hence, Bernard-Soulier patients homozygous or compound heterozygous for Tyr505(TAT) are  severely affected. Interestingly, both mutations have independently been found in three other families in previous reports, suggesting their ancient age or mutational 'hot spot'.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Koskela",
      "authorRank" : 1,
      "name" : "Koskela",
      "referenceId" : "RGD:A210680"
    }, {
      "firstName" : "J",
      "lastName" : "Partanen",
      "authorRank" : 2,
      "name" : "Partanen J",
      "referenceId" : "RGD:A39898"
    }, {
      "firstName" : "TT",
      "lastName" : "Salmi",
      "authorRank" : 3,
      "name" : "Salmi",
      "referenceId" : "RGD:A210681"
    }, {
      "firstName" : "R",
      "lastName" : "Kekomaki",
      "authorRank" : 4,
      "name" : "Kekomaki",
      "referenceId" : "RGD:A210682"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10450819"
    } ]
  }, {
    "primaryId" : "PMID:10089913",
    "title" : "Uncommon missense and splice mutations and resulting biochemical phenotypes in German patients with X-linked chronic granulomatous disease.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Roesler J, etal., Exp Hematol. 1999 Mar;27(3):505-11.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:20:10.000-05:00",
    "volume" : "27",
    "pages" : "505-11",
    "abstract" : "Chronic granulomatous disease is an inherited disease characterized by the inability of phagocytes to generate normal amounts of superoxide, leaving patients susceptible to opportunistic, life-threatening infections. In the majority of cases, cytochrome b558 is absent in the X-chromosomal form of CGD. However, the neutrophils from six of nine X-linked CGD patients, reported here, expressed normal or decreased amounts of this cytochrome and are referred to as \"variant\" forms. In three of these six variant patients, a roughly proportional decrease in cytochrome b558 expression and production of H2O2 were found. In two  cases this phenotype could be well explained by special splice mutations, whereas in the third case it was caused by a missense mutation, predicting Ser 193-->Phe. In the other three variant patients, cytochrome b558 expression and H2O2 production were clearly disproportionate as the generation of H2O2 was much more  decreased than cytochrome expression. Missense mutations also were found in these cases. One of these mutations, predicting Leu 546-->Pro and affecting the putative nicotinamide adenine dinucleotide phosphate binding site, led to normal  levels of cytochrome b558 expression and reduced H2O2 production. In the other two mutations, predicting Pro 339-->His and His 338-->Tyr, the putative flavin adenine dinucleotide binding site was affected. This could explain the corresponding uncommon phenotypes, characterized by zero or trace amounts of H2O2 production and the expression of relatively high amounts of nonfunctional or low  functional cytochrome b558, respectively. The only missense mutation found that prevented the expression of any cytochrome b558 was caused by a predicted His 222-->Arg exchange in one of the three classic cases. The two other classic phenotypes were caused by splice mutations.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Roesler",
      "authorRank" : 1,
      "name" : "Roesler J",
      "referenceId" : "RGD:A152552"
    }, {
      "firstName" : "S",
      "lastName" : "Heyden",
      "authorRank" : 2,
      "name" : "Heyden",
      "referenceId" : "RGD:A263342"
    }, {
      "firstName" : "M",
      "lastName" : "Burdelski",
      "authorRank" : 3,
      "name" : "Burdelski M",
      "referenceId" : "RGD:A44664"
    }, {
      "firstName" : "H",
      "lastName" : "Schafer",
      "authorRank" : 4,
      "name" : "Schafer H",
      "referenceId" : "RGD:A85762"
    }, {
      "firstName" : "HW",
      "lastName" : "Kreth",
      "authorRank" : 5,
      "name" : "Kreth HW",
      "referenceId" : "RGD:A80825"
    }, {
      "firstName" : "R",
      "lastName" : "Lehmann",
      "authorRank" : 6,
      "name" : "Lehmann",
      "referenceId" : "RGD:A335851"
    }, {
      "firstName" : "D",
      "lastName" : "Paul",
      "authorRank" : 7,
      "name" : "Paul",
      "referenceId" : "RGD:A263343"
    }, {
      "firstName" : "J",
      "lastName" : "Marzahn",
      "authorRank" : 8,
      "name" : "Marzahn",
      "referenceId" : "RGD:A263344"
    }, {
      "firstName" : "M",
      "lastName" : "Gahr",
      "authorRank" : 9,
      "name" : "Gahr",
      "referenceId" : "RGD:A263345"
    }, {
      "firstName" : "A",
      "lastName" : "Rosen-Wolff",
      "authorRank" : 10,
      "name" : "Rosen-Wolff",
      "referenceId" : "RGD:A219105"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065917"
    } ]
  }, {
    "primaryId" : "PMID:10089940",
    "title" : "Familial hypercholesterolemia kindred in Utah with novel C54S mutations of the LDL receptor gene.",
    "datePublished" : "1998-08-01T00:00:00.000-05:00",
    "citation" : "Emi M, etal., Jpn Heart J. 1998 Nov;39(6):785-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:19:04.000-05:00",
    "volume" : "39",
    "pages" : "785-9",
    "abstract" : "In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To determine the genetic etiology of the lipoprotein abnormalities, we screened DNA  samples for mutations in all 18 exons and the exon- intron boundaries of the low-density lipoprotein (LDL) receptor gene. Novel point mutations were identified in the proband: a T-to-A transversion at nucleotide position 223, causing substitution of Ser for Cys at codon 54 in exon 3 of the receptor gene. This amino acid replacement would disrupt one of the disulfide bonds necessary for maintenance of the secondary structure of the repeat at the N-terminal of the receptor, prevent correct folding of the receptor, and result in defective intracellular transport of the receptor.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Emi",
      "authorRank" : 1,
      "name" : "Emi",
      "referenceId" : "RGD:A391019"
    }, {
      "firstName" : "E",
      "lastName" : "Yamaki",
      "authorRank" : 2,
      "name" : "Yamaki",
      "referenceId" : "RGD:A361106"
    }, {
      "firstName" : "T",
      "lastName" : "Hirayama",
      "authorRank" : 3,
      "name" : "Hirayama",
      "referenceId" : "RGD:A402813"
    }, {
      "firstName" : "H",
      "lastName" : "Katsumata",
      "authorRank" : 4,
      "name" : "Katsumata",
      "referenceId" : "RGD:A361213"
    }, {
      "firstName" : "V",
      "lastName" : "Pozharov",
      "authorRank" : 5,
      "name" : "Pozharov",
      "referenceId" : "RGD:A361214"
    }, {
      "firstName" : "LL",
      "lastName" : "Wu",
      "authorRank" : 6,
      "name" : "Wu LL",
      "referenceId" : "RGD:A21269"
    }, {
      "firstName" : "PN",
      "lastName" : "Hopkins",
      "authorRank" : 7,
      "name" : "Hopkins PN",
      "referenceId" : "RGD:A45035"
    }, {
      "firstName" : "RR",
      "lastName" : "Williams",
      "authorRank" : 8,
      "name" : "Williams RR",
      "referenceId" : "RGD:A45036"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11526593"
    } ]
  }, {
    "primaryId" : "PMID:10090127",
    "title" : "Altered bladder function in transgenic mice expressing rat elastin.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Lemack GE, etal., Neurourol Urodyn 1999;18(1):55-68.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-08-23T09:13:59.000-05:00",
    "volume" : "18",
    "pages" : "55-68",
    "abstract" : "The elasticity of tissues subjected to repeated deformation is provided by the presence of elastic fibers in the extracellular matrix (ECM). The most abundant component of elastic fibers is elastin, whose soluble precursor is tropoelastin. To establish the role elastin plays in the bladder, this study describes the biosynthetic, histologic, and physiologic consequences of expression of an isoform of rat tropoelastin in transgenic mouse bladder. The polymerase chain reaction (PCR) was used to determine expression of a rat tropoelastin minigene in transgenic mice. Histochemical methods were used to demonstrate changes in elastic fibers in frozen sections of bladder. Cystometric analysis was carried out in transgenic and non-transgenic mice, prior to and after 3 weeks of partial outlet obstruction. The PCR assay demonstrated that bladder tissue of transgenic mice expressed rat tropoelastin mRNA, whereas non-transgenes did not. Increased deposition of elastic fibers was demonstrated with the Verhoeff-van Gieson stain. Bladders of transgenic animals were more compliant than bladders of their non-transgenic littermates. Partial outlet obstruction resulted in increased bladder volume and more compliant bladders in non-transgenic mice. In contrast, the bladder volume and compliance in transgenes was almost unchanged by obstruction. This study demonstrates that normal elastic fiber assembly is prerequisite for the compliant properties of the bladder wall. Moreover, the response of the bladder to obstruction is critically influenced by elastin synthesis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GE",
      "lastName" : "Lemack",
      "authorRank" : 1,
      "name" : "Lemack GE",
      "referenceId" : "RGD:A35263"
    }, {
      "firstName" : "Z",
      "lastName" : "Szabo",
      "authorRank" : 2,
      "name" : "Szabo Z",
      "referenceId" : "RGD:A35264"
    }, {
      "firstName" : "Z",
      "lastName" : "Urban",
      "authorRank" : 3,
      "name" : "Urban Z",
      "referenceId" : "RGD:A35265"
    }, {
      "firstName" : "CD",
      "lastName" : "Boyd",
      "authorRank" : 4,
      "name" : "Boyd CD",
      "referenceId" : "RGD:A29481"
    }, {
      "firstName" : "K",
      "lastName" : "Csiszar",
      "authorRank" : 5,
      "name" : "Csiszar K",
      "referenceId" : "RGD:A35266"
    }, {
      "firstName" : "JR",
      "lastName" : "Vaughan ED",
      "authorRank" : 6,
      "name" : "Vaughan ED JR",
      "referenceId" : "RGD:A35267"
    }, {
      "firstName" : "D",
      "lastName" : "Felsen",
      "authorRank" : 7,
      "name" : "Felsen D",
      "referenceId" : "RGD:A35268"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:731206"
    } ]
  }, {
    "primaryId" : "PMID:10090169",
    "title" : "Systemic lupus erythematosus, a disease associated with low levels of clusterin/apoJ, an antiinflammatory protein.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Newkirk MM, etal., J Rheumatol. 1999 Mar;26(3):597-603.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-08-08T17:52:58.000-05:00",
    "volume" : "26",
    "pages" : "597-603",
    "abstract" : "OBJECTIVE: To measure the serum levels of clusterin, an antiinflammatory protein, which binds and inactivates complement, in patients with systemic lupus erythematosus (SLE) to determine whether the levels correlate with disease. METHODS: The levels of serum clusterin were measured by ELISA in 80 patients with SLE (76 female, 4 male). Clinical and serological information was gathered on 115 visits. Overall disease activity scores were determined using the Systemic Lupus  Activity Measure-Revised. RESULTS: Serum clusterin levels were significantly decreased in patients with SLE and correlated inversely with disease activity (p  < 0.00001). Low clusterin levels were significantly associated with skin ulcers (p < 0.0001), loss of hair (p = 0.002), proteinuria (p = 0.018), low platelet count (p = 0.03), and arthritis (p < 0.0001). The clusterin levels did not correlate with either systemic complement consumption, as measured by C3 or C4, or with prednisone use. CONCLUSION: A highly significant correlation was observed between low levels of serum clusterin and a number of SLE disease features. This  deficiency of clusterin could directly or indirectly affect the disease process.  Individuals lacking sufficient amounts of clusterin systemically likely have poor control of antibody mediated inflammation at sites of apoptosis where autoantigens are exposed.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Newkirk",
      "authorRank" : 1,
      "name" : "Newkirk",
      "referenceId" : "RGD:A192716"
    }, {
      "firstName" : "P",
      "lastName" : "Apostolakos",
      "authorRank" : 2,
      "name" : "Apostolakos",
      "referenceId" : "RGD:A192717"
    }, {
      "firstName" : "C",
      "lastName" : "Neville",
      "authorRank" : 3,
      "name" : "Neville",
      "referenceId" : "RGD:A192718"
    }, {
      "firstName" : "PR",
      "lastName" : "Fortin",
      "authorRank" : 4,
      "name" : "Fortin PR",
      "referenceId" : "RGD:A151359"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8696021"
    } ]
  }, {
    "primaryId" : "PMID:10090325",
    "title" : "Interaction between the renin-angiotensin system and insulin-like growth factor I in aorto-caval fistula-induced cardiac hypertrophy in rats.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Wåhlander H, etal., Acta Physiol Scand. 1999 Feb;165(2):143-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-05-25T13:50:49.000-05:00",
    "volume" : "165",
    "pages" : "143-54",
    "abstract" : "The effects of angiotensin converting enzyme inhibition and angiotensin II receptor blockade on the development of cardiac hypertrophy and myocardial insulin-like growth factor I (IGF-I) in volume overload were studied in male Wistar rats with aorto-caval fistulas (ACF). Rats were treated with ramipril (RAM, 3 mg kg(-1) day(-1)) for 4-20 days or losartan (LOS, 10 mg kg(-1) day(-1)) for 2-7 days. Myocardial IGF-I and IGF-I receptor (IGF-I-R) mRNA were determined by solution hybridization. ACF caused hypertrophy of left (LV) and right ventricles (RV). Hypertrophy appeared on day 2 and reached maximal values of +60% in LV and +75% in RV at day 12. Systolic blood pressure was initially reduced 15% but recovered by day 12. RAM abolished the recovery of blood pressure. Furthermore, RAM attenuated RV hypertrophy by 17% on day 7 and on day 20, RV weights were close to values found in controls. Beginning on day 9, RAM reduced LV weight back to control levels in parallel to blood pressure. In contrast, LOS affected neither RV nor LV hypertrophy. RV IGF-I mRNA increased 60-100% on day 7 alone in RV in ACF. RAM potentiated the increase in RV IGF-I to +400% and induced an increase in RV IGF-I-R mRNA on day 7 (+90%) in ACF. LOS did not affect RV IGF-I. Development of cardiac hypertrophy in ACF seemed independent of angiotensin II. RV hypertrophy was associated with activation of IGF-I independent of the renin-angiotensin system. IGF-I was further potentiated when development of hypertrophy was attenuated, possibly indicative of a greater urge for compensational growth in a relatively thinner and more volume-distended chamber.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Wåhlander",
      "authorRank" : 1,
      "name" : "Wåhlander H",
      "referenceId" : "RGD:A444568"
    }, {
      "firstName" : "A",
      "lastName" : "Wickman",
      "authorRank" : 2,
      "name" : "Wickman A",
      "referenceId" : "RGD:A444569"
    }, {
      "firstName" : "J",
      "lastName" : "Isgaard",
      "authorRank" : 3,
      "name" : "Isgaard J",
      "referenceId" : "RGD:A123733"
    }, {
      "firstName" : "P",
      "lastName" : "Friberg",
      "authorRank" : 4,
      "name" : "Friberg P",
      "referenceId" : "RGD:A444570"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12904918"
    } ]
  }, {
    "primaryId" : "PMID:10090473",
    "title" : "Mutant transcripts of the LDL receptor gene: mRNA structure and quantity.",
    "datePublished" : "1000-06-01T00:00:00.000-06:00",
    "citation" : "Rodningen OK, etal., Hum Mutat. 1999;13(3):186-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T20:20:39.000-05:00",
    "volume" : "13",
    "pages" : "186-96",
    "abstract" : "mRNA of the low-density lipoprotein receptor (LDLR) gene from 22 heterozygous familial hypercholesterolemic subjects possessing different mutations in this gene was analyzed by Northern blot analysis and reverse transcription-polymerase  chain reaction (RT-PCR) in order to detect abnormally spliced transcripts. These  analyses revealed abnormally spliced transcripts for the two splice-site mutations 1359-1G-->A and 1705 + 1G-->T. The abnormally spliced transcript for mutation 1359-1G-->A was caused by activation of a cryptic acceptor splice site in exon 10. As a result, seven nucleotides of exon 10 were deleted. For mutation  1705 + 1G-->T, two mutant transcripts were observed. In the first transcript, exon 10 was spliced to exon 13, and in the second transcript intron 11 was retained. The relative amount of mutant transcripts from 14 of the 22 subjects was determined by use of an RT-PCR-based method. Quantitation of the relative amounts of mutant transcripts for five missense mutations resulted in a mean value (+/-SD) of 52.8% (+/-4.55). In comparison, quantitation of the relative amounts of mutant transcripts for five nonsense mutations resulted in a mean value of 31.8% (+/-6.91). This value was significantly lower than the value of 54.2% (+/-2.38) obtained for nine healthy subjects (P < 0.0001). The relative amount of mutant transcripts for the 1705 + 1G-->T mutation was 36%. Thus, transcripts from alleles containing premature stop codons are present in reduced  amounts, whereas transcripts from alleles containing missense mutations are present in normal amounts. These findings underscore the importance of determining how mutations affect mRNA structure and quantity in order to understand how mutations cause disease.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "OK",
      "lastName" : "Rodningen",
      "authorRank" : 1,
      "name" : "Rodningen",
      "referenceId" : "RGD:A234800"
    }, {
      "firstName" : "S",
      "lastName" : "Tonstad",
      "authorRank" : 2,
      "name" : "Tonstad S",
      "referenceId" : "RGD:A87838"
    }, {
      "firstName" : "OD",
      "lastName" : "Saugstad",
      "authorRank" : 3,
      "name" : "Saugstad",
      "referenceId" : "RGD:A270468"
    }, {
      "firstName" : "L",
      "lastName" : "Ose",
      "authorRank" : 4,
      "name" : "Ose L",
      "referenceId" : "RGD:A15946"
    }, {
      "firstName" : "TP",
      "lastName" : "Leren",
      "authorRank" : 5,
      "name" : "Leren TP",
      "referenceId" : "RGD:A137172"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11098585"
    } ]
  }, {
    "primaryId" : "PMID:10090476",
    "title" : "Novel mutations associated with carnitine palmitoyltransferase II deficiency.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Taggart RT, etal., Hum Mutat. 1999;13(3):210-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:10:27.000-05:00",
    "volume" : "13",
    "pages" : "210-20",
    "abstract" : "The most common form of carnitine palmitoyltransferase II (CPT II) deficiency occurs in adults and is characterized by muscle pain, stiffness, and myoglobinuria, triggered by exercise, fasting, or other metabolic stress. This study reports the molecular heterogeneity of CPT2 mutations and their biochemical consequences among a series of 59 individuals who were suspected of having CPT II deficiency based on the decreased CPT activity observed in muscle or leukocytes samples, clinical findings, or referral for mutation analysis from other laboratories. Only 19 subjects were considered to be at particularly high risk of CPT II deficiency based on review of their clinical symptoms and residual CPT activity. The samples were initially screened for 11 mutations with allele-specific oligonucleotides (ASO). Extensive sequence analysis was subsequently performed on 14 samples which either had a CPT2 mutation detected by ASO screening or the residual CPT activity was below that observed in ASO positive samples. Three known (P50H, S113L, and F448L) and three novel mutations  were identified among 13 individuals in this study. A single nucleotide polymorphism was also identified 11 bp distal to the CPT2 polyadenylation site that will be useful for linkage analysis. Two of the new mutations were single nucleotide missense mutations, R503C and G549D, that occurred in highly conserved regions of the CPT isoforms, and the third was a frameshift mutation, 413 delAG,  caused by a 2-bp deletion upstream of a previously identified missense mutation,  F448L. The 413 delAG mutation was the second most common mutation identified in our study (20% of mutant alleles) and all individuals with the mutation were of Ashkenazi Jewish ancestry suggesting a defined ethnic origin for the mutation. Despite rigorous mutation analysis, six of 13 individuals identified with CPT2 mutations remained as heterozygotes. We propose that heterozygosity for certain CPT2 mutations, S113L and R503C, is sufficient to render individuals at risk of clinical symptoms.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RT",
      "lastName" : "Taggart",
      "authorRank" : 1,
      "name" : "Taggart RT",
      "referenceId" : "RGD:A37425"
    }, {
      "firstName" : "D",
      "lastName" : "Smail",
      "authorRank" : 2,
      "name" : "Smail D",
      "referenceId" : "RGD:A37423"
    }, {
      "firstName" : "C",
      "lastName" : "Apolito",
      "authorRank" : 3,
      "name" : "Apolito",
      "referenceId" : "RGD:A274919"
    }, {
      "firstName" : "GD",
      "lastName" : "Vladutiu",
      "authorRank" : 4,
      "name" : "Vladutiu GD",
      "referenceId" : "RGD:A37421"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069804"
    } ]
  }, {
    "primaryId" : "PMID:10090482",
    "title" : "Mutation analysis of the BRCA1 and BRCA2 genes results in the identification of novel and recurrent mutations in 6/16 flemish families with breast and/or ovarian cancer but not in 12 sporadic patients with early-onset disease. Mutations in brief no. 224. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Claes K, etal., Hum Mutat. 1999;13(3):256.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:17:22.000-05:00",
    "volume" : "13",
    "pages" : "256",
    "abstract" : "Since the identification of the BRCA1 and BRCA2 genes (MIM#s 113705 and 600185),  more than hundred different mutations throughout both genes have been reported. Recurrent mutations are rare and mainly due to founder effects. We analyzed 12 sporadic female patients with breast cancer before age 35, as well as 16 unrelated families, presenting with either (i) at least 3 first degree relatives  with breast and/or ovarian cancer diagnosed at any age, or (ii) at least 2 first  and/or second degree relatives with breast and/or ovarian cancer before age 45 years. We performed a protein truncation test for BRCA1 exon 11 and BRCA2 exons 10 and 11 and heteroduplex analysis for all the remaining exons of BRCA1 and 2. Presence of genomic deletions encompassing exons 13 or 22 of BRCA1, known to be Dutch founder mutations, was investigated by PCR. In 6/16 (37.5%) unrelated families the causal mutation in either the BRCA1 or BRCA2 gene was identified. Four different mutations were found in the BRCA1 gene: IVS5+3A>G (intron 5), 1191delC (exon 11), R1443X (exon 13), IVS22+5G>A (intron 22) and two in the BRCA2 gene: 6503delTT (exon 11), 6831delTG (exon 11). 1191delC (BRCA1) and 6831delTG (BRCA2) are novel mutations. IVS5+3A>G in exon 5 of BRCA1 published by Peelen et  al. (1997) as a novel Belgian mutation, was identified in one additional family,  not fulfilling our inclusion criteria. In the group of 12 sporadic female patients no mutations were found.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Claes",
      "authorRank" : 1,
      "name" : "Claes",
      "referenceId" : "RGD:A189126"
    }, {
      "firstName" : "E",
      "lastName" : "Machackova",
      "authorRank" : 2,
      "name" : "Machackova",
      "referenceId" : "RGD:A255031"
    }, {
      "firstName" : "M",
      "lastName" : "De Vos",
      "authorRank" : 3,
      "name" : "De Vos M",
      "referenceId" : "RGD:A50125"
    }, {
      "firstName" : "G",
      "lastName" : "Mortier",
      "authorRank" : 4,
      "name" : "Mortier G",
      "referenceId" : "RGD:A44807"
    }, {
      "firstName" : "A",
      "lastName" : "De Paepe",
      "authorRank" : 5,
      "name" : "De Paepe A",
      "referenceId" : "RGD:A37387"
    }, {
      "firstName" : "L",
      "lastName" : "Messiaen",
      "authorRank" : 6,
      "name" : "Messiaen",
      "referenceId" : "RGD:A263505"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067139"
    } ]
  }, {
    "primaryId" : "PMID:10090484",
    "title" : "Mutation analysis in 46 German families with familial hypercholesterolemia: identification of 8 new mutations. Mutations in brief no. 226. Online.",
    "datePublished" : "1000-08-01T00:00:00.000-06:00",
    "citation" : "Ebhardt M, etal., Hum Mutat. 1999;13(3):257.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:14:19.000-05:00",
    "volume" : "13",
    "pages" : "257",
    "abstract" : "In order to obtain a survey of the mutations being prevalent in Northern Germany  and to enable molecular genetic testing for families with clinically diagnosed familial hypercholesterolemia (FH), we screened 46 unrelated German individuals with elevated LDL levels for mutations in the 18 exons and their flanking intron  sequences including the promotor region of the LDL receptor (LDLR) gene. In addition, we tested all patients for the presence of mutations in the gene coding for apolipoprotein B-100 (apoB-100). We detected 15 mutations affecting the LDLR  gene, 8 of which, designated A29S, 195insAT, 313+1insG, 553insG, 680insGGACAAATCTG, D200N, E267K and L411V have not yet been reported. One patient is heterozygous for the double mutant N543H and 2393del9Bp. Two patients carried  the mutation R3500Q (Arg-->Glu) within the apoB-100 gene.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Ebhardt",
      "authorRank" : 1,
      "name" : "Ebhardt",
      "referenceId" : "RGD:A292382"
    }, {
      "firstName" : "H",
      "lastName" : "Schmidt",
      "authorRank" : 2,
      "name" : "Schmidt H",
      "referenceId" : "RGD:A21340"
    }, {
      "firstName" : "T",
      "lastName" : "Doerk",
      "authorRank" : 3,
      "name" : "Doerk",
      "referenceId" : "RGD:A360592"
    }, {
      "firstName" : "U",
      "lastName" : "Tietge",
      "authorRank" : 4,
      "name" : "Tietge",
      "referenceId" : "RGD:A360593"
    }, {
      "firstName" : "R",
      "lastName" : "Haas",
      "authorRank" : 5,
      "name" : "Haas R",
      "referenceId" : "RGD:A35987"
    }, {
      "firstName" : "MP",
      "lastName" : "Manns",
      "authorRank" : 6,
      "name" : "Manns MP",
      "referenceId" : "RGD:A35335"
    }, {
      "firstName" : "J",
      "lastName" : "Schmidtke",
      "authorRank" : 7,
      "name" : "Schmidtke J",
      "referenceId" : "RGD:A23782"
    }, {
      "firstName" : "M",
      "lastName" : "Stuhrmann",
      "authorRank" : 8,
      "name" : "Stuhrmann M",
      "referenceId" : "RGD:A126447"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11526387"
    } ]
  }, {
    "primaryId" : "PMID:10090487",
    "title" : "Mutation screening of neurofibromatosis type 1 (NF1) exons 28 and 29 with single  strand conformation polymorphism (SSCP): five novel mutations, one recurrent transition and two polymorphisms in a panel of 118 unrelated NF1 patients. Mutations in brief no. 229. Online.",
    "datePublished" : "1000-06-01T00:00:00.000-06:00",
    "citation" : "Peters H, etal., Hum Mutat. 1999;13(3):258.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T20:27:22.000-05:00",
    "volume" : "13",
    "pages" : "258",
    "abstract" : "Neurofibromatosis type 1 is a clinically variable disorder caused mostly by small mutations within the NF1 gene on chromosome 17q11.2. We used Single Strand Conformation Polymorphism (SSCP) and radioactive sequencing to screen NF1 exons 28 and 29 from 118 unrelated patients, diagnosed with NF1 according to the NIH criteria, identifying five novel and one recurrent germline mutations, two novel  polymorphisms and a variant base exchange. All but one cause protein truncation and represent typical NF1 mutations. There are reports that NF1 patients with mutations in exons 28 and 29 could be at greater risk of developing myeloid leukemia. This question was given consideration in this investigation, but none of the children involved have yet shown any symptoms of myeloid leukemia. 4 out of the 6 mutations were de novo.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Peters",
      "authorRank" : 1,
      "name" : "Peters H",
      "referenceId" : "RGD:A46918"
    }, {
      "firstName" : "A",
      "lastName" : "Luder",
      "authorRank" : 2,
      "name" : "Luder",
      "referenceId" : "RGD:A279560"
    }, {
      "firstName" : "A",
      "lastName" : "Harder",
      "authorRank" : 3,
      "name" : "Harder",
      "referenceId" : "RGD:A322782"
    }, {
      "firstName" : "M",
      "lastName" : "Schuelke",
      "authorRank" : 4,
      "name" : "Schuelke M",
      "referenceId" : "RGD:A39230"
    }, {
      "firstName" : "S",
      "lastName" : "Tinschert",
      "authorRank" : 5,
      "name" : "Tinschert S",
      "referenceId" : "RGD:A35920"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11098971"
    } ]
  }, {
    "primaryId" : "PMID:10090526",
    "title" : "The multiple cases of Fabry disease in a Russian family caused by an E341K amino  acid substitution in the alpha-galactosidase A.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Beyer EM, etal., Clin Chim Acta. 1999 Feb;280(1-2):81-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:59:47.000-05:00",
    "volume" : "280",
    "pages" : "81-9",
    "abstract" : "A large Russian family with multiple cases of Fabry disease in several generations is presented. Fourteen family members were clinico-biochemically examined. Among 12 adult children (19-32 years old) of one couple, five sons manifested angiokeratotic skin lesions and other Fabry symptoms. Biochemical studies including an enzyme assay, the analysis of glycosphingolipid excretion and isoelectric focusing of a patient leukocyte extract allowed us to identify Fabry disease in four affected brothers and to establish the heterozygous status  of their mother. The analysis of genomic DNA of four patients and their mother revealed a novel E341K missense mutation caused by a G to A transition (codon 341 GAA-AAA) in the alpha-galactosidase A gene.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EM",
      "lastName" : "Beyer",
      "authorRank" : 1,
      "name" : "Beyer",
      "referenceId" : "RGD:A270480"
    }, {
      "firstName" : "EA",
      "lastName" : "Karpova",
      "authorRank" : 2,
      "name" : "Karpova",
      "referenceId" : "RGD:A270481"
    }, {
      "firstName" : "OV",
      "lastName" : "Udalova",
      "authorRank" : 3,
      "name" : "Udalova",
      "referenceId" : "RGD:A270482"
    }, {
      "firstName" : "JK",
      "lastName" : "Ploos van Amstel",
      "authorRank" : 4,
      "name" : "Ploos van Amstel JK",
      "referenceId" : "RGD:A80624"
    }, {
      "firstName" : "OP",
      "lastName" : "Van Diggelen",
      "authorRank" : 5,
      "name" : "Van Diggelen",
      "referenceId" : "RGD:A250170"
    }, {
      "firstName" : "IV",
      "lastName" : "Tsvetkova",
      "authorRank" : 6,
      "name" : "Tsvetkova IV",
      "referenceId" : "RGD:A124637"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068254"
    } ]
  }, {
    "primaryId" : "PMID:10090529",
    "title" : "A single strand conformation polymorphism/heteroduplex (SSCP/HD) method for detection of mutations in 15 exons of the KVLQT1 gene, associated with long QT syndrome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Larsen LA, etal., Clin Chim Acta. 1999 Feb;280(1-2):113-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:50:18.000-05:00",
    "volume" : "280",
    "pages" : "113-25",
    "abstract" : "Congenital long QT syndrome (LQTS) is characterised by prolongation of the QT interval on ECG and cardiac arrhythmias, syncopes and sudden death. A rapid and reliable genetic diagnosis of the disease may be of great importance for diagnosis and treatment of LQTS. Mutations in the KVLQT1 gene, encoding a potassium-channel subunit of importance for the depolarisation of cardiac myocytes, is believed to be associated with 50% of all LQTS cases. Our data confirms that KvLQT1 isoform 1 is encoded by 16 exons, and not 15, as reported previously. We have used genomic DNA sequences to design intronic PCR primers for amplification of 15 exons of KVLQT1 and optimised a non-radioactive single stranded conformation polymorphism/heteroduplex (SSCP/HD) method for detection of mutations in KVLQT1. The sensitivity of the method was 100% when it was tested on 15 in vitro constructed mutants. By multiplexing the PCR amplification of KVLQT1, it is possible to cover all 15 exons in four PCR reactions.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LA",
      "lastName" : "Larsen",
      "authorRank" : 1,
      "name" : "Larsen LA",
      "referenceId" : "RGD:A61734"
    }, {
      "firstName" : "PS",
      "lastName" : "Andersen",
      "authorRank" : 2,
      "name" : "Andersen PS",
      "referenceId" : "RGD:A61730"
    }, {
      "firstName" : "JK",
      "lastName" : "Kanters",
      "authorRank" : 3,
      "name" : "Kanters",
      "referenceId" : "RGD:A253786"
    }, {
      "firstName" : "JR",
      "lastName" : "Jacobsen",
      "authorRank" : 4,
      "name" : "Jacobsen",
      "referenceId" : "RGD:A252634"
    }, {
      "firstName" : "J",
      "lastName" : "Vuust",
      "authorRank" : 5,
      "name" : "Vuust J",
      "referenceId" : "RGD:A61738"
    }, {
      "firstName" : "M",
      "lastName" : "Christiansen",
      "authorRank" : 6,
      "name" : "Christiansen M",
      "referenceId" : "RGD:A61739"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071613"
    } ]
  }, {
    "primaryId" : "PMID:10090880",
    "title" : "Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Aksentijevich I, etal., Am J Hum Genet. 1999 Apr;64(4):949-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:25:40.000-05:00",
    "volume" : "64",
    "pages" : "949-62",
    "abstract" : "Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis. The FMF gene (MEFV) was cloned recently, and four missense mutations were identified. Here we present data from  non-Ashkenazi Jewish and Arab patients in whom we had not originally found mutations and from a new, more ethnically diverse panel. Among 90 symptomatic mutation-positive individuals, 11 mutations accounted for 79% of carrier chromosomes. Of the two mutations that are novel, one alters the same residue (680) as a previously known mutation, and the other (P369S) is located in exon 3. Consistent with another recent report, the E148Q mutation was observed in patients of several ethnicities and on multiple microsatellite haplotypes, but haplotype data indicate an ancestral relationships between non-Jewish Italian and Ashkenazi Jewish patients with FMF and other affected populations. Among approximately 200 anonymous Ashkenazi Jewish DNA samples, the MEFV carrier frequency was 21%, with E148Q the most common mutation. Several lines of evidence indicate reduced penetrance among Ashkenazi Jews, especially for E148Q, P369S, and K695R. Nevertheless, E148Q helps account for recessive inheritance in an Ashkenazi family previously reported as an unusual case of dominantly inherited FMF. The presence of three frequent MEFV mutations in multiple Mediterranean populations strongly suggests a heterozygote advantage in this geographic region.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Aksentijevich",
      "authorRank" : 1,
      "name" : "Aksentijevich",
      "referenceId" : "RGD:A413769"
    }, {
      "firstName" : "Y",
      "lastName" : "Torosyan",
      "authorRank" : 2,
      "name" : "Torosyan Y",
      "referenceId" : "RGD:A95571"
    }, {
      "firstName" : "J",
      "lastName" : "Samuels",
      "authorRank" : 3,
      "name" : "Samuels",
      "referenceId" : "RGD:A267876"
    }, {
      "firstName" : "M",
      "lastName" : "Centola",
      "authorRank" : 4,
      "name" : "Centola",
      "referenceId" : "RGD:A353307"
    }, {
      "firstName" : "E",
      "lastName" : "Pras",
      "authorRank" : 5,
      "name" : "Pras",
      "referenceId" : "RGD:A414147"
    }, {
      "firstName" : "JJ",
      "lastName" : "Chae",
      "authorRank" : 6,
      "name" : "Chae",
      "referenceId" : "RGD:A386748"
    }, {
      "firstName" : "C",
      "lastName" : "Oddoux",
      "authorRank" : 7,
      "name" : "Oddoux C",
      "referenceId" : "RGD:A30455"
    }, {
      "firstName" : "G",
      "lastName" : "Wood",
      "authorRank" : 8,
      "name" : "Wood",
      "referenceId" : "RGD:A357055"
    }, {
      "firstName" : "MP",
      "lastName" : "Azzaro",
      "authorRank" : 9,
      "name" : "Azzaro",
      "referenceId" : "RGD:A267881"
    }, {
      "firstName" : "G",
      "lastName" : "Palumbo",
      "authorRank" : 10,
      "name" : "Palumbo G",
      "referenceId" : "RGD:A152086"
    }, {
      "firstName" : "R",
      "lastName" : "Giustolisi",
      "authorRank" : 11,
      "name" : "Giustolisi",
      "referenceId" : "RGD:A267882"
    }, {
      "firstName" : "M",
      "lastName" : "Pras",
      "authorRank" : 12,
      "name" : "Pras",
      "referenceId" : "RGD:A279433"
    }, {
      "firstName" : "H",
      "lastName" : "Ostrer",
      "authorRank" : 13,
      "name" : "Ostrer H",
      "referenceId" : "RGD:A73851"
    }, {
      "firstName" : "DL",
      "lastName" : "Kastner",
      "authorRank" : 14,
      "name" : "Kastner",
      "referenceId" : "RGD:A386751"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067360"
    } ]
  }, {
    "primaryId" : "PMID:10090883",
    "title" : "Germ-line mosaicism in tuberous sclerosis: how common?",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Rose VM, etal., Am J Hum Genet. 1999 Apr;64(4):986-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:11:48.000-05:00",
    "volume" : "64",
    "pages" : "986-92",
    "abstract" : "Two-thirds of cases of tuberous sclerosis complex (TSC) are sporadic and usually  are attributed to new mutations, but unaffected parents sometimes have more than  one affected child. We sought to determine how many of these cases represent germ-line mosaicism, as has been reported for other genetic diseases. In our sample of 120 families with TSC, 7 families had two affected children and clinically unaffected parents. These families were tested for mutations in the TSC1 and TSC2 genes, by Southern blotting and by single-strand conformational analysis. Unique variants were detected in six families. Each variant was present and identical in both affected children of a family but was absent in both parents and the unaffected siblings. Sequencing of the variants yielded two frameshift mutations, one missense mutation, and two nonsense mutations in TSC2 and one nonsense mutation in TSC1. To determine which parent contributed the affected gametes, the families were analyzed for linkage to TSC1 and TSC2, by construction of haplotypes with markers flanking the two genes. Linkage analysis  and loss-of-heterozygosity studies indicated maternal origin in three families, paternal origin in one family, and either being possible in two families. To evaluate the possibility of low-level somatic mosaicism for TSC, DNA from lymphocytes of members of the six families were tested by allele-specific PCR. In all the families, the mutant allele was detected only in the known affected individuals. We conclude that germ-line mosaicism was present in five families with mutations in the TSC2 gene and in one family with the causative mutation in  the TSC1 gene. The results have implications for genetic counseling of families with seemingly sporadic TSC.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "VM",
      "lastName" : "Rose",
      "authorRank" : 1,
      "name" : "Rose",
      "referenceId" : "RGD:A266716"
    }, {
      "firstName" : "KS",
      "lastName" : "Au",
      "authorRank" : 2,
      "name" : "Au",
      "referenceId" : "RGD:A242090"
    }, {
      "firstName" : "G",
      "lastName" : "Pollom",
      "authorRank" : 3,
      "name" : "Pollom",
      "referenceId" : "RGD:A266717"
    }, {
      "firstName" : "ES",
      "lastName" : "Roach",
      "authorRank" : 4,
      "name" : "Roach",
      "referenceId" : "RGD:A250370"
    }, {
      "firstName" : "HR",
      "lastName" : "Prashner",
      "authorRank" : 5,
      "name" : "Prashner",
      "referenceId" : "RGD:A266718"
    }, {
      "firstName" : "H",
      "lastName" : "Northrup",
      "authorRank" : 6,
      "name" : "Northrup H",
      "referenceId" : "RGD:A75524"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066989"
    } ]
  }, {
    "primaryId" : "PMID:10090886",
    "title" : "Mutations in a dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Mohammad-Panah R, etal., Am J Hum Genet. 1999 Apr;64(4):1015-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:09:34.000-05:00",
    "volume" : "64",
    "pages" : "1015-23",
    "abstract" : "The long QT syndrome is characterized by prolonged cardiac repolarization and a high risk of sudden death. Mutations in the KCNQ1 gene, which encodes the cardiac KvLQT1 potassium ion (K+) channel, cause both the autosomal dominant Romano-Ward  (RW) syndrome and the recessive Jervell and Lange-Nielsen (JLN) syndrome. JLN presents with cardiac arrhythmias and congenital deafness, and heterozygous carriers of JLN mutations exhibit a very mild cardiac phenotype. Despite the phenotypic differences between heterozygotes with RW and those with JLN mutations, both classes of variant protein fail to produce K+ currents in cultured cells. We have shown that an N-terminus-truncated KvLQT1 isoform endogenously expressed in the human heart exerts strong dominant-negative effects on the full-length KvLQT1 protein. Because RW and JLN mutations concern both truncated and full-length KvLQT1 isoforms, we investigated whether RW or JLN mutations would have different impacts on the dominant-negative properties of the truncated KvLQT1 splice variant. In a mammalian expression system, we found that  JLN, but not RW, mutations suppress the dominant-negative effects of the truncated KvLQT1. Thus, in JLN heterozygous carriers, the full-length KvLQT1 protein encoded by the unaffected allele should not be subject to the negative influence of the mutated truncated isoform, leaving some cardiac K+ current available for repolarization. This is the first report of a genetic disease in which the impact of a mutation on a dominant-negative isoform correlates with the phenotype.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Mohammad-Panah",
      "authorRank" : 1,
      "name" : "Mohammad-Panah",
      "referenceId" : "RGD:A262414"
    }, {
      "firstName" : "S",
      "lastName" : "Demolombe",
      "authorRank" : 2,
      "name" : "Demolombe S",
      "referenceId" : "RGD:A140325"
    }, {
      "firstName" : "N",
      "lastName" : "Neyroud",
      "authorRank" : 3,
      "name" : "Neyroud N",
      "referenceId" : "RGD:A62822"
    }, {
      "firstName" : "P",
      "lastName" : "Guicheney",
      "authorRank" : 4,
      "name" : "Guicheney P",
      "referenceId" : "RGD:A37505"
    }, {
      "firstName" : "F",
      "lastName" : "Kyndt",
      "authorRank" : 5,
      "name" : "Kyndt F",
      "referenceId" : "RGD:A35928"
    }, {
      "firstName" : "M",
      "lastName" : "Van den Hoff",
      "authorRank" : 6,
      "name" : "Van den Hoff",
      "referenceId" : "RGD:A262415"
    }, {
      "firstName" : "I",
      "lastName" : "Baro",
      "authorRank" : 7,
      "name" : "Baro",
      "referenceId" : "RGD:A257468"
    }, {
      "firstName" : "D",
      "lastName" : "Escande",
      "authorRank" : 8,
      "name" : "Escande D",
      "referenceId" : "RGD:A35931"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065600"
    } ]
  }, {
    "primaryId" : "PMID:10090888",
    "title" : "COL9A3: A third locus for multiple epiphyseal dysplasia.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Paassilta P, etal., Am J Hum Genet. 1999 Apr;64(4):1036-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-23T08:34:17.000-05:00",
    "volume" : "64",
    "pages" : "1036-44",
    "abstract" : "Multiple epiphyseal dysplasia (MED), an autosomal dominant osteochondrodysplasia, is a clinically and genetically heterogeneous disorder characterized by mild short stature and early-onset osteoarthritis. The phenotypic spectrum includes the mild Ribbing type, the more severe Fairbank type, and some unclassified forms. Linkage studies have identified two loci for MED. One of these, EDM1, is on chromosome 19, in a region that contains the cartilage oligomeric matrix protein (COMP) gene. Mutations have been identified in this gene in patients with the Ribbing type, the Fairbank type, and unclassified forms of MED. The second locus, EDM2, maps to chromosome 1, in a region spanning COL9A2. Recently, a splice-site mutation was found in COL9A2, causing skipping of exon 3 in one family with MED. Because of the exclusion of the EDM1 and EDM2 loci in some families, the existence of a third locus has been postulated. We report here one family with MED, evaluated clinically and radiologically and tested for linkage with candidate genes, including COMP, COL9A1, COL9A2, and COL9A3. No linkage was found with COMP, COL9A1, or COL9A2, but an inheritance pattern consistent with linkage was observed with COL9A3. Mutation analysis of COL9A3 identified an A-->T transversion in the acceptor splice site of intron 2 in affected family members. The mutation led to skipping of exon 3 and an in-frame deletion of 12 amino acid residues in the COL3 domain of the alpha3(IX) chain and thus appeared to be similar to that reported for COL9A2. This is the first disease-causing mutation identified in COL9A3. Our results also show that COL9A3, located on chromosome 20, is a third locus for MED.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Paassilta",
      "authorRank" : 1,
      "name" : "Paassilta P",
      "referenceId" : "RGD:A78153"
    }, {
      "firstName" : "J",
      "lastName" : "Lohiniva",
      "authorRank" : 2,
      "name" : "Lohiniva J",
      "referenceId" : "RGD:A78154"
    }, {
      "firstName" : "S",
      "lastName" : "Annunen",
      "authorRank" : 3,
      "name" : "Annunen S",
      "referenceId" : "RGD:A78155"
    }, {
      "firstName" : "J",
      "lastName" : "Bonaventure",
      "authorRank" : 4,
      "name" : "Bonaventure J",
      "referenceId" : "RGD:A37385"
    }, {
      "firstName" : "M",
      "lastName" : "Le Merrer",
      "authorRank" : 5,
      "name" : "Le Merrer M",
      "referenceId" : "RGD:A57952"
    }, {
      "firstName" : "L",
      "lastName" : "Pai",
      "authorRank" : 6,
      "name" : "Pai L",
      "referenceId" : "RGD:A78156"
    }, {
      "firstName" : "L",
      "lastName" : "Ala-Kokko",
      "authorRank" : 7,
      "name" : "Ala-Kokko L",
      "referenceId" : "RGD:A78157"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600695"
    } ]
  }, {
    "primaryId" : "PMID:10090915",
    "title" : "Prevalence of Bloom syndrome heterozygotes among Ashkenazi Jews.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Oddoux C, etal., Am J Hum Genet. 1999 Apr;64(4):1241-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-07-20T19:45:53.000-05:00",
    "volume" : "64",
    "pages" : "1241-3",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Oddoux",
      "authorRank" : 1,
      "name" : "Oddoux C",
      "referenceId" : "RGD:A30455"
    }, {
      "firstName" : "CM",
      "lastName" : "Clayton",
      "authorRank" : 2,
      "name" : "Clayton",
      "referenceId" : "RGD:A347614"
    }, {
      "firstName" : "HR",
      "lastName" : "Nelson",
      "authorRank" : 3,
      "name" : "Nelson",
      "referenceId" : "RGD:A347615"
    }, {
      "firstName" : "H",
      "lastName" : "Ostrer",
      "authorRank" : 4,
      "name" : "Ostrer H",
      "referenceId" : "RGD:A73851"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11353086"
    } ]
  }, {
    "primaryId" : "PMID:10090925",
    "title" : "Synergistic effects of prothrombotic polymorphisms and atherogenic factors on the risk of myocardial infarction in young males.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Inbal A, etal., Blood. 1999 Apr 1;93(7):2186-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-12-29T13:15:33.000-06:00",
    "volume" : "93",
    "pages" : "2186-90",
    "abstract" : "Several recent studies evaluated a possible effect of the prothrombotic polymorphisms such as 5,10 methylenetetrahydrofolate reductase (MTHFR) nt 677C --> T, factor V (F V) nt 1691G --> A (F V Leiden), and factor II (F II) nt 20210  G --> A on the risk of myocardial infarction. In the present study, we analyzed the effect of these prothrombotic polymorphisms, as well as apolipoprotein (Apo)  E4, smoking, hypertension, diabetes mellitus, and hypercholesterolemia, on the risk of myocardial infarction in young males. We conducted a case-control study of 112 young males with first acute myocardial infarction (AMI) before the age of 52 and 187 healthy controls of similar age. The prevalences of heterozygotes for  F V G1691A and F II G20210A were not significantly different between cases and controls (6.3% v 6.4% and 5.9% v 3.4% among cases and controls, respectively). In contrast, the prevalence of MTHFR 677T homozygosity and the allele frequency of Apo E4 were significantly higher among patients (24.1% v 10.7% and 9.4% v 5.3% among cases and controls, respectively). Concomitant presence of hypertension, hypercholesterolemia, or diabetes and one or more of the four examined polymorphisms increased the risk by almost ninefold (odds ratio [OR] = 8.66; 95%  confidence interval [CI], 3.49 to 21.5) and concomitant smoking by almost 18-fold (OR = 17.6; 95% CI, 6.30 to 48.9). When all atherogenic risk factors were analyzed simultaneously by a logistic model, the combination of prothrombotic and Apo E4 polymorphisms with current smoking increased the risk 25-fold (OR = 24.7;  95% CI, 7.17 to 84.9). The presented data suggest a synergistic effect between atherogenic and thrombogenic risk factors in the pathogenesis of AMI, as was recently found in a similar cohort of women.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Inbal",
      "authorRank" : 1,
      "name" : "Inbal",
      "referenceId" : "RGD:A167546"
    }, {
      "firstName" : "D",
      "lastName" : "Freimark",
      "authorRank" : 2,
      "name" : "Freimark",
      "referenceId" : "RGD:A209664"
    }, {
      "firstName" : "B",
      "lastName" : "Modan",
      "authorRank" : 3,
      "name" : "Modan",
      "referenceId" : "RGD:A209665"
    }, {
      "firstName" : "A",
      "lastName" : "Chetrit",
      "authorRank" : 4,
      "name" : "Chetrit A",
      "referenceId" : "RGD:A90355"
    }, {
      "firstName" : "S",
      "lastName" : "Matetzky",
      "authorRank" : 5,
      "name" : "Matetzky",
      "referenceId" : "RGD:A209666"
    }, {
      "firstName" : "N",
      "lastName" : "Rosenberg",
      "authorRank" : 6,
      "name" : "Rosenberg N",
      "referenceId" : "RGD:A50282"
    }, {
      "firstName" : "R",
      "lastName" : "Dardik",
      "authorRank" : 7,
      "name" : "Dardik R",
      "referenceId" : "RGD:A96728"
    }, {
      "firstName" : "Z",
      "lastName" : "Baron",
      "authorRank" : 8,
      "name" : "Baron",
      "referenceId" : "RGD:A209667"
    }, {
      "firstName" : "U",
      "lastName" : "Seligsohn",
      "authorRank" : 9,
      "name" : "Seligsohn U",
      "referenceId" : "RGD:A55048"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10449412"
    } ]
  }, {
    "primaryId" : "PMID:10090935",
    "title" : "ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Nichols WC, etal., Blood 1999 Apr 1;93(7):2261-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-29T15:38:00.000-05:00",
    "volume" : "93",
    "pages" : "2261-6",
    "abstract" : "Combined factors V and VIII deficiency is an autosomal recessive bleeding disorder associated with plasma levels of coagulation factors V and VIII approximately 5% to 30% of normal. The disease gene was recently identified as the endoplasmic reticulum-Golgi intermediate compartment protein ERGIC-53 by positional cloning, with the detection of two founder mutations in 10 Jewish families. To identify mutations in additional families, the structure of the ERGIC-53 gene was determined by genomic polymerase chain reaction (PCR) and sequence analysis of bacterial artificial chromosome clones containing the ERGIC-53 gene. Nineteen additional families were analyzed by direct sequence analysis of the entire coding region and the intron/exon junctions. Seven novel mutations were identified in 10 families, with one additional family found to harbor one of the two previously described mutations. All of the identified mutations would be predicted to result in complete absence of functional ERGIC-53 protein. In 8 of 19 families, no mutation was identified. Genotyping data indicate that at least two of these families are not linked to the ERGIC-53 locus. Taken together, these results suggest that a significant subset of combined factors V and VIII deficiency is due to mutation in one or more additional genes.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WC",
      "lastName" : "Nichols",
      "authorRank" : 1,
      "name" : "Nichols WC",
      "referenceId" : "RGD:A36433"
    }, {
      "firstName" : "VH",
      "lastName" : "Terry",
      "authorRank" : 2,
      "name" : "Terry VH",
      "referenceId" : "RGD:A55029"
    }, {
      "firstName" : "MA",
      "lastName" : "Wheatley",
      "authorRank" : 3,
      "name" : "Wheatley MA",
      "referenceId" : "RGD:A55030"
    }, {
      "firstName" : "A",
      "lastName" : "Yang",
      "authorRank" : 4,
      "name" : "Yang A",
      "referenceId" : "RGD:A55031"
    }, {
      "firstName" : "A",
      "lastName" : "Zivelin",
      "authorRank" : 5,
      "name" : "Zivelin A",
      "referenceId" : "RGD:A55032"
    }, {
      "firstName" : "N",
      "lastName" : "Ciavarella",
      "authorRank" : 6,
      "name" : "Ciavarella N",
      "referenceId" : "RGD:A55033"
    }, {
      "firstName" : "C",
      "lastName" : "Stefanile",
      "authorRank" : 7,
      "name" : "Stefanile C",
      "referenceId" : "RGD:A55034"
    }, {
      "firstName" : "T",
      "lastName" : "Matsushita",
      "authorRank" : 8,
      "name" : "Matsushita T",
      "referenceId" : "RGD:A55035"
    }, {
      "firstName" : "H",
      "lastName" : "Saito",
      "authorRank" : 9,
      "name" : "Saito H",
      "referenceId" : "RGD:A158375"
    }, {
      "firstName" : "NB",
      "lastName" : "De Bosch",
      "authorRank" : 10,
      "name" : "De Bosch NB",
      "referenceId" : "RGD:A55037"
    }, {
      "firstName" : "A",
      "lastName" : "Ruiz-Saez",
      "authorRank" : 11,
      "name" : "Ruiz-Saez A",
      "referenceId" : "RGD:A55038"
    }, {
      "firstName" : "A",
      "lastName" : "Torres",
      "authorRank" : 12,
      "name" : "Torres A",
      "referenceId" : "RGD:A55039"
    }, {
      "firstName" : "AR",
      "lastName" : "Thompson",
      "authorRank" : 13,
      "name" : "Thompson AR",
      "referenceId" : "RGD:A55040"
    }, {
      "firstName" : "DI",
      "lastName" : "Feinstein",
      "authorRank" : 14,
      "name" : "Feinstein DI",
      "referenceId" : "RGD:A55041"
    }, {
      "firstName" : "GC",
      "lastName" : "White",
      "authorRank" : 15,
      "name" : "White GC",
      "referenceId" : "RGD:A55042"
    }, {
      "firstName" : "C",
      "lastName" : "Negrier",
      "authorRank" : 16,
      "name" : "Negrier C",
      "referenceId" : "RGD:A55043"
    }, {
      "firstName" : "C",
      "lastName" : "Vinciguerra",
      "authorRank" : 17,
      "name" : "Vinciguerra C",
      "referenceId" : "RGD:A55044"
    }, {
      "firstName" : "M",
      "lastName" : "Aktan",
      "authorRank" : 18,
      "name" : "Aktan M",
      "referenceId" : "RGD:A55045"
    }, {
      "firstName" : "RJ",
      "lastName" : "Kaufman",
      "authorRank" : 19,
      "name" : "Kaufman RJ",
      "referenceId" : "RGD:A55046"
    }, {
      "firstName" : "D",
      "lastName" : "Ginsburg",
      "authorRank" : 20,
      "name" : "Ginsburg D",
      "referenceId" : "RGD:A55047"
    }, {
      "firstName" : "U",
      "lastName" : "Seligsohn",
      "authorRank" : 21,
      "name" : "Seligsohn U",
      "referenceId" : "RGD:A55048"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549455"
    } ]
  }, {
    "primaryId" : "PMID:10090943",
    "title" : "An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in B-chronic lymphocytic leukemia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Alfarano A, etal., Blood. 1999 Apr 1;93(7):2327-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-03-15T13:41:58.000-05:00",
    "volume" : "93",
    "pages" : "2327-35",
    "abstract" : "Several functional anomalies of B-chronic lymphocytic leukemia (B-CLL) cells may be explained by abnormalities of the B-cell receptor (BCR), a multimeric complex formed by the sIg homodimer and the noncovalently bound heterodimer Igalpha/Igbeta (CD79a/CD79b). Because the expression of the extracellular Ig-like domain of CD79b has been reported to be absent in the cells of most CLL cases, we have investigated the molecular mechanisms that may account for this defect. Peripheral blood lymphocytes (PBL) from 50 patients and two cell lines (MEC1, MEC2) obtained from the PBL of one of them were studied. MEC1, MEC2, and 75% of CLL cases did not express detectable levels of the extracellular Ig-like domain of CD79b, which was nevertheless present in greater than 80% CD19(+) cells from normal donors. In healthy subjects the expression of CD79b was equally distributed in CD5(+) and CD5(-) B-cell subsets. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of CD79b RNA from all patients and from MEC1 and MEC2 cell lines consistently yielded two fragments of different size (709 bp and 397 bp). The 709-bp band corresponds to CD79b entire transcript; the 397-bp band corresponds to an alternatively spliced form lacking exon 3 that encodes the extracellular Ig-like domain. Both fragments were also visible in normal PBL. The expression of the 397-bp fragment was increased in normal activated B cells, while no difference was seen between CD5(+) and CD5(-) B cells. To obtain a more accurate estimate of the relative proportions of the two spliced forms, a radioactive PCR was performed in 13 normal and 22 B-CLL samples and the results analyzed using a digital imager. The mean value of the CD79b to the CD79b internally deleted ratio was 0.64 +/- 0.20 SD in normal donors and 0.44 +/- 0.27 SD in B-CLL (P =.01). Direct sequencing of 397-bp RT-PCR products and of genomic DNA corresponding to exon 3 from MEC1, MEC2, their parental cells, and five fresh B-CLL samples did not show any causal mutation. Single-strand conformation polymorphism analysis of exon 3 performed in 18 additional B-CLL cases showed a single abnormal shift corresponding to a TGT --> TGC polymorphic change at amino acid 122. We propose a role for the alternative splicing of CD79b gene in causing the reduced expression of BCR on the surface of B-CLL cells. As normal B cells also present this variant, the mechanism of CD79b posttranscriptional regulation might reflect the activation stage of the normal B cell from which B-CLL derives.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Alfarano",
      "authorRank" : 1,
      "name" : "Alfarano A",
      "referenceId" : "RGD:A513264"
    }, {
      "firstName" : "S",
      "lastName" : "Indraccolo",
      "authorRank" : 2,
      "name" : "Indraccolo S",
      "referenceId" : "RGD:A513265"
    }, {
      "firstName" : "P",
      "lastName" : "Circosta",
      "authorRank" : 3,
      "name" : "Circosta P",
      "referenceId" : "RGD:A513266"
    }, {
      "firstName" : "S",
      "lastName" : "Minuzzo",
      "authorRank" : 4,
      "name" : "Minuzzo S",
      "referenceId" : "RGD:A513267"
    }, {
      "firstName" : "A",
      "lastName" : "Vallario",
      "authorRank" : 5,
      "name" : "Vallario A",
      "referenceId" : "RGD:A513268"
    }, {
      "firstName" : "R",
      "lastName" : "Zamarchi",
      "authorRank" : 6,
      "name" : "Zamarchi R",
      "referenceId" : "RGD:A513269"
    }, {
      "firstName" : "A",
      "lastName" : "Fregonese",
      "authorRank" : 7,
      "name" : "Fregonese A",
      "referenceId" : "RGD:A513270"
    }, {
      "firstName" : "F",
      "lastName" : "Calderazzo",
      "authorRank" : 8,
      "name" : "Calderazzo F",
      "referenceId" : "RGD:A513271"
    }, {
      "firstName" : "A",
      "lastName" : "Faldella",
      "authorRank" : 9,
      "name" : "Faldella A",
      "referenceId" : "RGD:A513272"
    }, {
      "firstName" : "M",
      "lastName" : "Aragno",
      "authorRank" : 10,
      "name" : "Aragno M",
      "referenceId" : "RGD:A12697"
    }, {
      "firstName" : "C",
      "lastName" : "Camaschella",
      "authorRank" : 11,
      "name" : "Camaschella C",
      "referenceId" : "RGD:A73519"
    }, {
      "firstName" : "A",
      "lastName" : "Amadori",
      "authorRank" : 12,
      "name" : "Amadori A",
      "referenceId" : "RGD:A513273"
    }, {
      "firstName" : "F",
      "lastName" : "Caligaris-Cappio",
      "authorRank" : 13,
      "name" : "Caligaris-Cappio F",
      "referenceId" : "RGD:A513274"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:151665190"
    } ]
  }, {
    "primaryId" : "PMID:10090949",
    "title" : "Acquisition of p16(INK4A) and p15(INK4B) gene abnormalities between initial diagnosis and relapse in children with acute lymphoblastic leukemia.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Maloney KW, etal., Blood. 1999 Apr 1;93(7):2380-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-22T09:46:53.000-05:00",
    "volume" : "93",
    "pages" : "2380-5",
    "abstract" : "Although numerous somatic mutations that contribute to the pathogenesis of childhood acute lymphoblastic leukemia (ALL) have been identified, no specific cytogenetic or molecular abnormalities are known to be consistently associated with relapse. The p16(INK4A) (p16), which encodes for both p16(INK4A) and p19(ARF) proteins, and p15(INK4B) (p15) genes are inactivated by homozygous deletion and/or p15 promoter hypermethylation in a significant proportion of cases of childhood ALL at the time of initial diagnosis. To determine whether alterations in these genes play a role in disease progression, we analyzed a panel of 18 matched specimen pairs collected from children with ALL at the time of initial diagnosis and first bone marrow relapse for homozygous p16 and/or p15  deletions or p15 promoter hypermethylation. Four sample pairs contained homozygous p16 and p15 deletions at both diagnosis and relapse. Among the 14 pairs that were p16/p15 germline at diagnosis, three ALLs developed homozygous deletions of both p16 and p15, and two developed homozygous p16 deletions and retained p15 germline status at relapse. In two patients, p15 promoter hypermethylation developed in the interval between initial diagnosis and relapse. In total, homozygous p16 deletions were present in nine of 18 cases, homozygous p15 deletions in seven of 18 cases, and p15 promoter hypermethylation in two of eight cases at relapse. These findings indicate that loss of function of proteins encoded by p16 and/or p15 plays an important role in the biology of relapsed childhood ALL, and is associated with disease progression in a subset of cases.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KW",
      "lastName" : "Maloney",
      "authorRank" : 1,
      "name" : "Maloney",
      "referenceId" : "RGD:A328675"
    }, {
      "firstName" : "L",
      "lastName" : "McGavran",
      "authorRank" : 2,
      "name" : "McGavran",
      "referenceId" : "RGD:A328676"
    }, {
      "firstName" : "LF",
      "lastName" : "Odom",
      "authorRank" : 3,
      "name" : "Odom",
      "referenceId" : "RGD:A328677"
    }, {
      "firstName" : "SP",
      "lastName" : "Hunger",
      "authorRank" : 4,
      "name" : "Hunger",
      "referenceId" : "RGD:A239885"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11251764"
    } ]
  }, {
    "primaryId" : "PMID:10091053",
    "title" : "The modulation of sperm function by fertilization promoting peptide.",
    "datePublished" : "1998-09-01T00:00:00.000-05:00",
    "citation" : "Fraser LR Hum Reprod 1998 Dec;13 Suppl 4:1-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-06T11:15:45.000-05:00",
    "volume" : "13 Suppl 4",
    "pages" : "1-10",
    "abstract" : "Fertilization promoting peptide (FPP; pGlu-Glu-ProNH2) is a peptide produced by the prostate gland and then secreted into seminal plasma. Recent studies have shown that the addition of FPP to uncapacitated mouse and human sperm suspensions stimulates capacitation as demonstrated by cytological assessment and increased fertilizing/penetrating ability in vitro, hence its name. Interestingly, the addition of FPP also has an effect on capacitated cells, namely inhibition of spontaneous acrosome loss; these spermatozoa retain high fertilizing ability, however, when tested with unfertilized oocytes. Adenosine, which is known to modulate adenylate cyclase activity, has been shown to elicit responses similar to those obtained with FPP in both uncapacitated and capacitated spermatozoa. Because the use of FPP and adenosine simultaneously is more effective than either used individually, it has been proposed that these two molecules interact with different receptors to modulate the adenylate cyclase/cAMP signal transduction pathway. FPP-related peptides have been found to vary in their biological activity in vitro, the most interesting one being Gln-FPP (pGlu-Gln-ProNH2). This peptide, identified in human seminal plasma and possibly produced by men with prostatic dysfunction, had no intrinsic activity itself but was able to competitively inhibit responses to FPP. Finally, very recent evidence suggests that the protein TCP-11, coded for by a mouse t-complex gene, may be the receptor for FPP. The existence of a human homologue for Tcp-11 suggests that TCP-11 and FPP could well play an important role in human fertility/subfertility. In vitro, FPP's ability to stimulate capacitation might reduce the incidence of delayed fertilization which results in impaired embryonic development and implantation.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LR",
      "lastName" : "Fraser",
      "authorRank" : 1,
      "name" : "Fraser LR",
      "referenceId" : "RGD:A55493"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549629"
    } ]
  }, {
    "primaryId" : "PMID:10091405",
    "title" : "Co-inherited Gilbert's syndrome: a factor determining hyperbilirubinemia in homozygous beta-thalassemia.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Galanello R, etal., Haematologica. 1999 Feb;84(2):103-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-02-10T11:47:33.000-06:00",
    "volume" : "84",
    "pages" : "103-5",
    "abstract" : "BACKGROUND AND OBJECTIVE: Patients with thalassemia major and intermedia show a marked variability of serum indirect bilirubin levels. In this paper we tested the hypothesis related to the variability of the glucuronidation bilirubin rate which depends on the configuration of the A(TA)nTAA motif of the UGT1*1 glucuronosyltransferase gene promoter. DESIGN AND METHODS: We studied the configuration of the A(TA)nTAA motif in 26 patients with thalassemia major and 34 with thalassemia intermedia. RESULTS: In patients with thalassemia major and in those with thalassemia intermedia significantly higher bilirubin levels were found in patients with the (TA)7/(TA)7 genotype, than in those with the (TA)7/(TA)6 or (TA)6/(TA)6 genotype. INTERPRETATION AND CONCLUSIONS: These results indicate that the (TA)7/(TA)7 genotype, the configuration found in patients with Gilbert's syndrome, is capable of modifying the clinical phenotype  of homozygous beta-thalassemia. This is an example of the role played by co-inherited modifying gene(s) on the extent of clinical heterogeneity of monogenic disorders.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Galanello",
      "authorRank" : 1,
      "name" : "Galanello R",
      "referenceId" : "RGD:A77679"
    }, {
      "firstName" : "MD",
      "lastName" : "Cipollina",
      "authorRank" : 2,
      "name" : "Cipollina",
      "referenceId" : "RGD:A211920"
    }, {
      "firstName" : "C",
      "lastName" : "Dessi",
      "authorRank" : 3,
      "name" : "Dessi",
      "referenceId" : "RGD:A211921"
    }, {
      "firstName" : "N",
      "lastName" : "Giagu",
      "authorRank" : 4,
      "name" : "Giagu",
      "referenceId" : "RGD:A211922"
    }, {
      "firstName" : "E",
      "lastName" : "Lai",
      "authorRank" : 5,
      "name" : "Lai E",
      "referenceId" : "RGD:A18162"
    }, {
      "firstName" : "A",
      "lastName" : "Cao",
      "authorRank" : 6,
      "name" : "Cao A",
      "referenceId" : "RGD:A53827"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10769337"
    } ]
  }, {
    "primaryId" : "PMID:10091612",
    "title" : "Variations in the monoamine oxidase B (MAOB) gene are associated with Parkinson's disease.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mellick GD, etal., Mov Disord 1999 Mar;14(2):219-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-14T12:20:16.000-05:00",
    "volume" : "14",
    "pages" : "219-24",
    "abstract" : "The monoamine oxidase B gene (MAOB; Xp15.21-4) is a candidate gene for Parkinson's disease (PD) given its role in dopamine metabolism and its possible role in the activation of neurotoxins. The association of MAOB polymorphisms (a [GT] repeat allelic variation in intron 2 and an A-G transition in intron 13) with Parkinson's disease (PD) was studied in an Australian cohort of 204 (male:female ratio 1.60) people with PD and 285 (male:female ratio 1.64) age- and gender-matched control subjects. Genomic DNA was extracted from venous blood and polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis and a DNA fragment analyzer, while the G-A genotype was determined using 2% agarose gel electrophoresis. The G-A polymorphism showed no association with PD (odds ratio [OR] = 0.80; p = 0.51; 95% confidence interval [CI] = 0.42-1.53). There was a significant difference in allele frequencies of the (GT) repeat allelic variation between patients and control subjects (chi2 = 20.09; p<0.01). After statistical adjustment for potential confounders using a logistic regression analysis, the (GT) repeat alleles > or =188 base pairs in the intron 2 marker of the MAOB gene were significantly associated with PD (OR = 4.60; p<0.00005; 95% CI = 1.97-10.77). The 186 base pair allele was also significantly associated with PD (OR = 1.85; p = 0.048; 95% CI = 1.01-3.42). The GT repeat in intron 2 of the MAOB gene is a powerful marker for PD in this large Australian cohort.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GD",
      "lastName" : "Mellick",
      "authorRank" : 1,
      "name" : "Mellick GD",
      "referenceId" : "RGD:A52681"
    }, {
      "firstName" : "DD",
      "lastName" : "Buchanan",
      "authorRank" : 2,
      "name" : "Buchanan DD",
      "referenceId" : "RGD:A52682"
    }, {
      "firstName" : "SJ",
      "lastName" : "McCann",
      "authorRank" : 3,
      "name" : "McCann SJ",
      "referenceId" : "RGD:A52683"
    }, {
      "firstName" : "KM",
      "lastName" : "James",
      "authorRank" : 4,
      "name" : "James KM",
      "referenceId" : "RGD:A52684"
    }, {
      "firstName" : "AG",
      "lastName" : "Johnson",
      "authorRank" : 5,
      "name" : "Johnson AG",
      "referenceId" : "RGD:A52685"
    }, {
      "firstName" : "DR",
      "lastName" : "Davis",
      "authorRank" : 6,
      "name" : "Davis DR",
      "referenceId" : "RGD:A16278"
    }, {
      "firstName" : "N",
      "lastName" : "Liyou",
      "authorRank" : 7,
      "name" : "Liyou N",
      "referenceId" : "RGD:A52686"
    }, {
      "firstName" : "D",
      "lastName" : "Chan",
      "authorRank" : 8,
      "name" : "Chan D",
      "referenceId" : "RGD:A52687"
    }, {
      "firstName" : "DG",
      "lastName" : "Le Couteur",
      "authorRank" : 9,
      "name" : "Le Couteur DG",
      "referenceId" : "RGD:A52688"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358483"
    } ]
  }, {
    "primaryId" : "PMID:10092062",
    "title" : "Expression of CD40/CD40 ligand and Bcl-2 family proteins in labial salivary glands of patients with Sjogren's syndrome.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Nakamura H, etal., Lab Invest. 1999 Mar;79(3):261-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-07-12T10:34:05.000-05:00",
    "volume" : "79",
    "pages" : "261-9",
    "abstract" : "Lymphocytes infiltrating the salivary glands of patients with Sjogren's syndrome  (SS) are activated and resist apoptosis. We determined the role of interactions between CD40 and CD40 ligand (CD40L) in these infiltrating lymphocytes on B-cell  differentiation and expression of Bcl-2 family proteins. Ten human T-cell leukemia/lymphoma virus-I (HTLV-I)-seronegative and eight HTLV-I-seropositive SS  patients were examined in the present study. Immunohistochemistry was performed to examine the expression of CD3, CD20, PCA-1, CD40, CD40L, Bcl-2, Bax, and Bcl-x on T and B lymphocytes infiltrating labial salivary glands of SS patients. We also examined the expression of CD40 and CD40L on peripheral blood lymphocytes of the same patients by using flow cytometry. CD40L was not expressed on peripheral  blood lymphocytes of SS patients. Peripheral blood B cells but not T cells expressed CD40. In contrast, >50% of mononuclear cells, including T and B cells infiltrating the glands, expressed CD40. In addition, a clear expression of CD40L in both infiltrating T cells and B cells, and that of PCA-1, was also demonstrated. Surprisingly, the expression of Bcl-2 and Bcl-x was colocalized with that of CD40 determined by mirror section technique. Bcl-x was also abundantly expressed on infiltrating mononuclear cells, but, Bax expression was relatively less than that of Bcl-2 or Bcl-x. The expression of the above molecules was not different between HTLV-I-seronegative and HTLV-I-seropositive SS patients. Our results indicate that CD40/CD40L pathways could be augmented in  salivary glands of SS patients, inducing B-cell differentiation to PCA-1 + plasma cells. Immunohistochemical analysis also suggests that signaling through CD40 by  means of CD40L increases the expression of Bcl-2 as well as Bcl-x in infiltrating lymphocytes, providing the resistance against apoptosis. Our findings were commonly observed in SS patients irrespective of HTLV-I seropositivity.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Nakamura",
      "authorRank" : 1,
      "name" : "Nakamura",
      "referenceId" : "RGD:A401423"
    }, {
      "firstName" : "A",
      "lastName" : "Kawakami",
      "authorRank" : 2,
      "name" : "Kawakami A",
      "referenceId" : "RGD:A155647"
    }, {
      "firstName" : "M",
      "lastName" : "Tominaga",
      "authorRank" : 3,
      "name" : "Tominaga M",
      "referenceId" : "RGD:A8187"
    }, {
      "firstName" : "K",
      "lastName" : "Migita",
      "authorRank" : 4,
      "name" : "Migita K",
      "referenceId" : "RGD:A59858"
    }, {
      "firstName" : "Y",
      "lastName" : "Kawabe",
      "authorRank" : 5,
      "name" : "Kawabe Y",
      "referenceId" : "RGD:A69857"
    }, {
      "firstName" : "T",
      "lastName" : "Nakamura",
      "authorRank" : 6,
      "name" : "Nakamura",
      "referenceId" : "RGD:A416904"
    }, {
      "firstName" : "K",
      "lastName" : "Eguchi",
      "authorRank" : 7,
      "name" : "Eguchi K",
      "referenceId" : "RGD:A59865"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11352241"
    } ]
  }, {
    "primaryId" : "PMID:10092119",
    "title" : "Tlk, a novel evolutionarily conserved murine serine threonine kinase, encodes multiple testis transcripts.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Shalom S and Don J, Mol Reprod Dev 1999 Apr;52(4):392-405.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:49:32.000-05:00",
    "volume" : "52",
    "pages" : "392-405",
    "abstract" : "Hypothesizing that genes important in meiotic processes in mammals might have evolutionarily conserved counterparts in lower organisms, we used the yeast IME2 meiotic gene (serine threonine kinase) as a probe for screening a mouse testis cDNA library. This screening resulted in identification of a novel putative serine threonine kinase. Although it did not exhibit significant homology to IME2, it did show significant sequence homology to the Tousled kinase in Arabidopsis. Tousled is associated with various differentiative processes including differentiation of the reproductive organs. The new murine gene was designated accordingly Tlk (Tousled like kinase). Tousled like kinase sequences have been reported to occur in C. elegans and in the human. Positive hybridization signals obtained in zooblot analysis suggest evolutionary conservation of Tlk throughout the phylogenetic ladder. Four distinct Tlk transcripts were detected in mouse testis, at least one of which is testis-specific. Northern and in situ hybridization analyses revealed that in normal testis, Tlk is expressed predominantly in pachytene spermatocytes and in round spermatids. Transcripts differ from one another in their 3' untranslated region, resulting from use of different polyadenylation sites, and in the length of their 5' region. Within the coding region, three of the putative peptides share the kinase and C-terminal domains but differ in their N-terminal domain, suggesting that the latter may be involved in the regulation of Tlk's function. We conclude that although Tlk might have an essential role in all tissues, these kinases are likely to take part in the complex array of phosphorylations involved in regulating spermatogenesis.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Shalom",
      "authorRank" : 1,
      "name" : "Shalom S",
      "referenceId" : "RGD:A45232"
    }, {
      "firstName" : "J",
      "lastName" : "Don",
      "authorRank" : 2,
      "name" : "Don J",
      "referenceId" : "RGD:A45233"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300457"
    } ]
  }, {
    "primaryId" : "PMID:10092307",
    "title" : "Inhibition of cytoplasmic phospholipase A2 expression by glucocorticoids in rat intestinal epithelial cells.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Dolan-O'keefe M and Nick HS, Gastroenterology. 1999 Apr;116(4):855-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-09-18T15:07:56.000-05:00",
    "volume" : "116",
    "pages" : "855-64",
    "abstract" : "BACKGROUND & AIMS: Glucocorticoids are the most potent and widely accepted anti-inflammatory agents in the treatment of pathological conditions of the gastrointestinal tract in part by inhibiting the synthesis of proinflammatory prostanoids and leukotrienes. Multiple forms of phospholipase A2 may be associated with the production of these metabolites; this study focused on the molecular mechanism(s) by which glucocorticoids control expression of the arachidonyl-selective, cytosolic phospholipase A2 (cPLA2) in intestinal cells. METHODS: Northern analysis, a transcriptional assay, and enzymatic evaluation were used to access expression of the cPLA2 gene in rat small intestinal epithelial and mouse fibroblast cell lines treated with dexamethasone. RESULTS: Basal cPLA2 messenger RNA (mRNA) expression was repressed 75% in the presence of dexamethasone with a concomitant decrease in enzymatic activity. Nuclear runoff assays showed a marked decline in de novo cPLA2 RNA synthesis, implicating a transcriptional mechanism associated with the dexamethasone-mediated suppression of cPLA2. Induced expression of cPLA2 mRNA by several proinflammatory cytokines was blocked by cotreatment with dexamethasone. CONCLUSIONS: Glucocorticoids are capable of markedly altering basal and cytokine-stimulated cPLA2 gene expression in intestinal epithelial cells, leading to a reduction in arachidonate pools in these cells. Dexamethasone-dependent inhibition occurs through a direct reduction of de novo cPLA2 gene transcription.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Dolan-O'keefe",
      "authorRank" : 1,
      "name" : "Dolan-O'keefe M",
      "referenceId" : "RGD:A88162"
    }, {
      "firstName" : "HS",
      "lastName" : "Nick",
      "authorRank" : 2,
      "name" : "Nick HS",
      "referenceId" : "RGD:A48185"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642478"
    } ]
  }, {
    "primaryId" : "PMID:10092309",
    "title" : "VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Sans M, etal., Gastroenterology. 1999 Apr;116(4):874-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-04T10:32:33.000-05:00",
    "volume" : "116",
    "pages" : "874-83",
    "abstract" : "BACKGROUND & AIMS: The molecular mechanisms responsible for leukocyte recruitment in experimental colitis are poorly understood. The aims of this study were to measure expression of endothelial intercellular adhesion molecule 1 (ICAM-1) and  vascular cell adhesion molecule 1 (VCAM-1) and to determine their role in leukocyte recruitment in experimental colitis. METHODS: Rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis and control rats were studied 1, 7, or 21 days after treatment. ICAM-1 and VCAM-1 expressions were measured by the double radiolabeled antibody technique. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic  effects of treatment with anti-VCAM-1 antibodies were also assessed. RESULTS: Colonic endothelial ICAM-1 was constitutively expressed and did not increase in colitic animals. In contrast, constitutive expression of VCAM-1 was low but markedly increased (6-fold) 1 and 7 days after induction of colitis. Increased colonic expression of VCAM-1 paralleled macroscopic damage score, myeloperoxidase activity, and increased leukocyte adhesion in colonic venules. The latter was significantly decreased by immunoneutralization of ICAM-1 and completely abrogated by immunoneutralization of VCAM-1. Long-term administration of anti-VCAM-1 antibody resulted in significant attenuation of colitis. CONCLUSIONS: Induction of colitis in rats by TNBS is followed by up-regulation of endothelial  VCAM-1. VCAM-1 and constitutive ICAM-1 are major determinants of leukocyte recruitment to the inflamed intestine.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Sans",
      "authorRank" : 1,
      "name" : "Sans M",
      "referenceId" : "RGD:A148462"
    }, {
      "firstName" : "J",
      "lastName" : "Panes",
      "authorRank" : 2,
      "name" : "Panes J",
      "referenceId" : "RGD:A148468"
    }, {
      "firstName" : "E",
      "lastName" : "Ardite",
      "authorRank" : 3,
      "name" : "Ardite",
      "referenceId" : "RGD:A359529"
    }, {
      "firstName" : "JI",
      "lastName" : "Elizalde",
      "authorRank" : 4,
      "name" : "Elizalde",
      "referenceId" : "RGD:A359530"
    }, {
      "firstName" : "Y",
      "lastName" : "Arce",
      "authorRank" : 5,
      "name" : "Arce",
      "referenceId" : "RGD:A359531"
    }, {
      "firstName" : "M",
      "lastName" : "Elena",
      "authorRank" : 6,
      "name" : "Elena",
      "referenceId" : "RGD:A359532"
    }, {
      "firstName" : "A",
      "lastName" : "Palacin",
      "authorRank" : 7,
      "name" : "Palacin",
      "referenceId" : "RGD:A359533"
    }, {
      "firstName" : "JC",
      "lastName" : "Fernandez-Checa",
      "authorRank" : 8,
      "name" : "Fernandez-Checa JC",
      "referenceId" : "RGD:A43136"
    }, {
      "firstName" : "DC",
      "lastName" : "Anderson",
      "authorRank" : 9,
      "name" : "Anderson DC",
      "referenceId" : "RGD:A33437"
    }, {
      "firstName" : "R",
      "lastName" : "Lobb",
      "authorRank" : 10,
      "name" : "Lobb R",
      "referenceId" : "RGD:A34526"
    }, {
      "firstName" : "JM",
      "lastName" : "Pique",
      "authorRank" : 11,
      "name" : "Pique",
      "referenceId" : "RGD:A259020"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11522714"
    } ]
  }, {
    "primaryId" : "PMID:10092505",
    "title" : "Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Langmann T, etal., Biochem Biophys Res Commun 1999 Apr 2;257(1):29-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T15:55:14.000-05:00",
    "volume" : "257",
    "pages" : "29-33",
    "abstract" : "We have cloned the full-length cDNA for the human ATP binding cassette transporter 1 (hABC1). The 6603-bp open reading frame encodes a polypeptide of 2201 amino acids resulting in a deduced molecular weight of 220 kDa. The hABC1 cDNA is highly homologous (62%) to the human rim ABC transporter (ABCR). hABC1 is expressed in a variety of human tissues with highest expression levels found in placenta, liver, lung, adrenal glands, and fetal tissues. We demonstrate that the hABC1 expression is induced during differentiation of human monocytes into macrophages in vitro. In macrophages, both the hABC1 mRNA and protein expression are upregulated in the presence of acetylated low-density lipoprotein (AcLDL). The AcLDL-induced increase in hABC1 expression is reversed by cholesterol depletion mediated by the addition of high-density lipoprotein (HDL3). Our data, demonstrating sterol-dependent regulation of hABC1 in human monocytes/macrophages, suggest a novel role for this transporter molecule in membrane lipid transport.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Langmann",
      "authorRank" : 1,
      "name" : "Langmann T",
      "referenceId" : "RGD:A24438"
    }, {
      "firstName" : "J",
      "lastName" : "Klucken",
      "authorRank" : 2,
      "name" : "Klucken J",
      "referenceId" : "RGD:A40400"
    }, {
      "firstName" : "M",
      "lastName" : "Reil",
      "authorRank" : 3,
      "name" : "Reil M",
      "referenceId" : "RGD:A40625"
    }, {
      "firstName" : "G",
      "lastName" : "Liebisch",
      "authorRank" : 4,
      "name" : "Liebisch G",
      "referenceId" : "RGD:A40626"
    }, {
      "firstName" : "MF",
      "lastName" : "Luciani",
      "authorRank" : 5,
      "name" : "Luciani MF",
      "referenceId" : "RGD:A31320"
    }, {
      "firstName" : "G",
      "lastName" : "Chimini",
      "authorRank" : 6,
      "name" : "Chimini G",
      "referenceId" : "RGD:A40627"
    }, {
      "firstName" : "WE",
      "lastName" : "Kaminski",
      "authorRank" : 7,
      "name" : "Kaminski WE",
      "referenceId" : "RGD:A40407"
    }, {
      "firstName" : "G",
      "lastName" : "Schmitz",
      "authorRank" : 8,
      "name" : "Schmitz G",
      "referenceId" : "RGD:A24437"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298604"
    } ]
  }, {
    "primaryId" : "PMID:10092645",
    "title" : "Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide].",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Mahajan S, etal., J Biol Chem. 1999 Apr 2;274(14):9587-99.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:23:17.000-05:00",
    "volume" : "274",
    "pages" : "9587-99",
    "abstract" : "In a systematic effort to design potent inhibitors of the anti-apoptotic tyrosine kinase BTK (Bruton's tyrosine kinase) as anti-leukemic agents with apoptosis-promoting and chemosensitizing properties, we have constructed a three-dimensional homology model of the BTK kinase domain. Our modeling studies revealed a distinct rectangular binding pocket near the hinge region of the BTK kinase domain with Leu460, Tyr476, Arg525, and Asp539 residues occupying the corners of the rectangle. The dimensions of this rectangle are approximately 18 x 8 x 9 x 17 A, and the thickness of the pocket is approximately 7 A. Advanced docking procedures were employed for the rational design of leflunomide metabolite (LFM) analogs with a high likelihood to bind favorably to the catalytic site within the kinase domain of BTK. The lead compound LFM-A13, for which we calculated a Ki value of 1.4 microM, inhibited human BTK in vitro with an IC50 value of 17.2 +/- 0.8 microM. Similarly, LFM-A13 inhibited recombinant BTK expressed in a baculovirus expression vector system with an IC50 value of 2.5 microM. The energetically favorable position of LFM-A13 in the binding pocket is  such that its aromatic ring is close to Tyr476, and its substituent group is sandwiched between residues Arg525 and Asp539. In addition, LFM-A13 is capable of favorable hydrogen bonding interactions with BTK via Asp539 and Arg525 residues.  Besides its remarkable potency in BTK kinase assays, LFM-A13 was also discovered  to be a highly specific inhibitor of BTK. Even at concentrations as high as 100 micrograms/ml (approximately 278 microM), this novel inhibitor did not affect the enzymatic activity of other protein tyrosine kinases, including JAK1, JAK3, HCK,  epidermal growth factor receptor kinase, and insulin receptor kinase. In accordance with the anti-apoptotic function of BTK, treatment of BTK+ B-lineage leukemic cells with LFM-A13 enhanced their sensitivity to ceramide- or vincristine-induced apoptosis. To our knowledge, LFM-A13 is the first BTK-specific tyrosine kinase inhibitor and the first anti-leukemic agent targeting BTK.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Mahajan",
      "authorRank" : 1,
      "name" : "Mahajan",
      "referenceId" : "RGD:A267699"
    }, {
      "firstName" : "S",
      "lastName" : "Ghosh",
      "authorRank" : 2,
      "name" : "Ghosh S",
      "referenceId" : "RGD:A6884"
    }, {
      "firstName" : "EA",
      "lastName" : "Sudbeck",
      "authorRank" : 3,
      "name" : "Sudbeck",
      "referenceId" : "RGD:A267700"
    }, {
      "firstName" : "Y",
      "lastName" : "Zheng",
      "authorRank" : 4,
      "name" : "Zheng Y",
      "referenceId" : "RGD:A12561"
    }, {
      "firstName" : "S",
      "lastName" : "Downs",
      "authorRank" : 5,
      "name" : "Downs",
      "referenceId" : "RGD:A267701"
    }, {
      "firstName" : "M",
      "lastName" : "Hupke",
      "authorRank" : 6,
      "name" : "Hupke",
      "referenceId" : "RGD:A267702"
    }, {
      "firstName" : "FM",
      "lastName" : "Uckun",
      "authorRank" : 7,
      "name" : "Uckun",
      "referenceId" : "RGD:A213406"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067312"
    } ]
  }, {
    "primaryId" : "PMID:10092682",
    "title" : "RGS7 and RGS8 differentially accelerate G protein-mediated modulation of K+ currents.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Saitoh O, etal., J Biol Chem 1999 Apr 2;274(14):9899-904.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-11T15:05:30.000-06:00",
    "volume" : "274",
    "pages" : "9899-904",
    "abstract" : "The recently discovered family of RGS (regulators of G protein signaling) proteins acts as GTPase activating proteins which bind to alpha subunits of heterotrimeric G proteins. We previously showed that a brain-specific RGS, RGS8 speeds up the activation and deactivation kinetics of the G protein-coupled inward rectifier K+ channel (GIRK) upon receptor stimulation (Saitoh, O., Kubo, Y., Miyatani, Y., Asano, T., and Nakata, H. (1997) Nature 390, 525-529). Here we report the isolation of a full-length rat cDNA of another brain-specific RGS, RGS7. In situ hybridization study revealed that RGS7 mRNA is predominantly expressed in Golgi cells within granule cell layer of cerebellar cortex. We observed that RGS7 recombinant protein binds preferentially to Galphao, Galphai3, and Galphaz. When co-expressed with GIRK1/2 in Xenopus oocytes, RGS7 and RGS8 differentially accelerate G protein-mediated modulation of GIRK. RGS7 clearly accelerated activation of GIRK current similarly with RGS8 but the acceleration effect of deactivation was significantly weaker than that of RGS8. These acceleration properties of RGS proteins may play important roles in the rapid regulation of neuronal excitability and the cellular responses to short-lived stimulations.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Saitoh",
      "authorRank" : 1,
      "name" : "Saitoh O",
      "referenceId" : "RGD:A7835"
    }, {
      "firstName" : "Y",
      "lastName" : "Kubo",
      "authorRank" : 2,
      "name" : "Kubo Y",
      "referenceId" : "RGD:A7836"
    }, {
      "firstName" : "M",
      "lastName" : "Odagiri",
      "authorRank" : 3,
      "name" : "Odagiri M",
      "referenceId" : "RGD:A7837"
    }, {
      "firstName" : "M",
      "lastName" : "Ichikawa",
      "authorRank" : 4,
      "name" : "Ichikawa M",
      "referenceId" : "RGD:A7838"
    }, {
      "firstName" : "K",
      "lastName" : "Yamagata",
      "authorRank" : 5,
      "name" : "Yamagata K",
      "referenceId" : "RGD:A125327"
    }, {
      "firstName" : "T",
      "lastName" : "Sekine",
      "authorRank" : 6,
      "name" : "Sekine T",
      "referenceId" : "RGD:A4123"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69962"
    } ]
  }, {
    "primaryId" : "PMID:10092827",
    "title" : "Regulatory effects of endogenous protease inhibitors in acute lung inflammatory injury.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Gipson TS, etal., J Immunol. 1999 Mar 15;162(6):3653-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-04-17T16:59:53.000-05:00",
    "volume" : "162",
    "pages" : "3653-62",
    "abstract" : "Inflammatory lung injury is probably regulated by the balance between proteases and protease inhibitors together with oxidants and antioxidants, and proinflammatory and anti-inflammatory cytokines. Rat tissue inhibitor of metalloprotease-2 (TIMP-2) and secreted leukoprotease inhibitor (SLPI) were cloned, expressed, and shown to be up-regulated at the levels of mRNA and protein during lung inflammation in rats induced by deposition of IgG immune complexes. Using immunoaffinity techniques, endogenous TIMP-2 in the inflamed lung was shown to exist as a complex with 72- and 92-kDa metalloproteinases (MMP-2 and MMP-9). In inflamed lung both TIMP-2 and SLPI appeared to exist as enzyme inhibitor complexes. Lung expression of both TIMP-2 and SLPI appeared to involve endothelial and epithelial cells as well as macrophages. To assess how these endogenous inhibitors might affect the lung inflammatory response, animals were treated with polyclonal rabbit Abs to rat TIMP-2 or SLPI. This intervention resulted in significant intensification of lung injury (as revealed by extravascular leak of albumin) and substantially increased neutrophil accumulation, as determined by cell content in bronchoalveolar lavage (BAL) fluids. These events were correlated with increased levels of C5a-related chemotactic activity in BAL fluids, while BAL levels of TNF-alpha and chemokines  were not affected by treatment with anti-TIMP-2 or anti-SLPI. The data suggest that endogenous TIMP-2 and SLPI dynamically regulate the intensity of lung inflammatory injury, doing so at least in part by affecting the generation of the inflammatory mediator, C5a.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TS",
      "lastName" : "Gipson",
      "authorRank" : 1,
      "name" : "Gipson",
      "referenceId" : "RGD:A200951"
    }, {
      "firstName" : "NM",
      "lastName" : "Bless",
      "authorRank" : 2,
      "name" : "Bless NM",
      "referenceId" : "RGD:A6296"
    }, {
      "firstName" : "TP",
      "lastName" : "Shanley",
      "authorRank" : 3,
      "name" : "Shanley TP",
      "referenceId" : "RGD:A6302"
    }, {
      "firstName" : "LD",
      "lastName" : "Crouch",
      "authorRank" : 4,
      "name" : "Crouch LD",
      "referenceId" : "RGD:A6303"
    }, {
      "firstName" : "MR",
      "lastName" : "Bleavins",
      "authorRank" : 5,
      "name" : "Bleavins",
      "referenceId" : "RGD:A200952"
    }, {
      "firstName" : "EM",
      "lastName" : "Younkin",
      "authorRank" : 6,
      "name" : "Younkin EM",
      "referenceId" : "RGD:A138265"
    }, {
      "firstName" : "V",
      "lastName" : "Sarma",
      "authorRank" : 7,
      "name" : "Sarma V",
      "referenceId" : "RGD:A6305"
    }, {
      "firstName" : "DF",
      "lastName" : "Gibbs",
      "authorRank" : 8,
      "name" : "Gibbs",
      "referenceId" : "RGD:A200953"
    }, {
      "firstName" : "W",
      "lastName" : "Tefera",
      "authorRank" : 9,
      "name" : "Tefera",
      "referenceId" : "RGD:A200954"
    }, {
      "firstName" : "PC",
      "lastName" : "McConnell",
      "authorRank" : 10,
      "name" : "McConnell",
      "referenceId" : "RGD:A200955"
    }, {
      "firstName" : "WT",
      "lastName" : "Mueller",
      "authorRank" : 11,
      "name" : "Mueller",
      "referenceId" : "RGD:A200956"
    }, {
      "firstName" : "KJ",
      "lastName" : "Johnson",
      "authorRank" : 12,
      "name" : "Johnson KJ",
      "referenceId" : "RGD:A5733"
    }, {
      "firstName" : "PA",
      "lastName" : "Ward",
      "authorRank" : 13,
      "name" : "Ward PA",
      "referenceId" : "RGD:A6308"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9999422"
    } ]
  }, {
    "primaryId" : "PMID:10093067",
    "title" : "3rd workshop of the European CMT consortium: 54th ENMC International Workshop on  genotype/phenotype correlations in Charcot-Marie-Tooth type 1 and hereditary neuropathy with liability to pressure palsies 28-30 November 1997, Naarden, The Netherlands.",
    "datePublished" : "1998-04-01T00:00:00.000-06:00",
    "citation" : "NO_AUTHOR Neuromuscul Disord. 1998 Dec;8(8):591-603.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:41:19.000-05:00",
    "volume" : "8",
    "pages" : "591-603",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "1998",
      "authorRank" : 1,
      "name" : "",
      "referenceId" : "RGD:A291591"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067774"
    } ]
  }, {
    "primaryId" : "PMID:10094189",
    "title" : "Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Weber B, etal., Eur J Hum Genet. 1999 Jan;7(1):34-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-02-20T12:13:03.000-06:00",
    "volume" : "7",
    "pages" : "34-44",
    "abstract" : "Sanfilippo B syndrome (mucopolysaccharidosis IIIB, MPS IIIB) is caused by a deficiency of alpha-N-acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes leads to degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. Age of onset and rate of progression vary considerably, whilst diagnosis is often delayed due to the absence of the pronounced skeletal changes observed in other mucopolysaccharidoses. Cloning of the gene and cDNA encoding alpha-N-acetylglucosaminidase enabled a study of the molecular basis of this syndrome. We were able to identify 31 mutations, 25 of them novel, and two polymorphisms in the 40 patients mostly of Australasian and Dutch origin included in this study. The observed allellic heterogeneity reflects the wide spectrum of  clinical phenotypes reported for MPS IIIB patients. The majority of changes are missense mutations; also four nonsense and nine frameshift mutations caused by insertions or deletions were identified. Only five mutations were found in more than one patient and the observed frequencies are well below those observed for the common mutations in MPS IIIA. R643C and R297X each account for around 20% of  MPS IIIB alleles in the Dutch patient group, whilst R297X, P521L, R565W and R626X each have a frequency of about 6% in Australasian patients. R643C seems to be a Dutch MPS IIIB allele and clearly confers the attenuated phenotype. One region of the gene shows a higher concentration of mutations, probably reflecting the instability of this area which contains a direct repeat. Several arginine residues seem to be 'hot-spots' for mutations, being affected by two or three individual base pair exchanges.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Weber",
      "authorRank" : 1,
      "name" : "Weber B",
      "referenceId" : "RGD:A74482"
    }, {
      "firstName" : "XH",
      "lastName" : "Guo",
      "authorRank" : 2,
      "name" : "Guo XH",
      "referenceId" : "RGD:A129995"
    }, {
      "firstName" : "WJ",
      "lastName" : "Kleijer",
      "authorRank" : 3,
      "name" : "Kleijer WJ",
      "referenceId" : "RGD:A35227"
    }, {
      "firstName" : "JJ",
      "lastName" : "Van de Kamp",
      "authorRank" : 4,
      "name" : "Van de Kamp",
      "referenceId" : "RGD:A167672"
    }, {
      "firstName" : "BJ",
      "lastName" : "Poorthuis",
      "authorRank" : 5,
      "name" : "Poorthuis",
      "referenceId" : "RGD:A167673"
    }, {
      "firstName" : "JJ",
      "lastName" : "Hopwood",
      "authorRank" : 6,
      "name" : "Hopwood JJ",
      "referenceId" : "RGD:A62113"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7241007"
    } ]
  }, {
    "primaryId" : "PMID:10094443",
    "title" : "5-Oxoprolinuria in patients with and without defects in the gamma-glutamyl cycle.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Mayatepek E, Eur J Pediatr. 1999 Mar;158(3):221-5. doi: 10.1007/s004310051054.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:07:15.000-05:00",
    "volume" : "158",
    "pages" : "221-5",
    "abstract" : "<br><b>UNLABELLED: </b>In patients with defects in the synthesis, breakdown and metabolism of glutathione (GSH), like glutathione synthetase deficiency (GSD) and 5-oxoprolinase deficiency, urinary excretion of 5-oxoproline, an intermediate of the gamma-glutamyl cycle, is increased. We identified 20 patients with significantly elevated urinary excretion of 5-oxoproline (> or =150 mmol/mol creatinine) during 5 years of selective screening for organic acidurias. In 6 of them, 5-oxoprolinuria was a constant finding including three patients with GSD and one with 5-oxoprolinase deficiency. One patient with constant 5-oxoprolinuria had GM2 gangliosidosis and one was clinically unaffected. In 14 patients, 5-oxoprolinuria was a transient abnormality and most often associated with an inborn error of metabolism outside the gamma-glutamyl cycle. In 9 of them 5-oxoprolinuria was associated with a neonatal urea cycle defect, with tyrosinaemia type I or occurred during metabolic decompensation in propionic acidaemia or methylmalonic acidaemia. Additionally, transient 5-oxoprolinuria was associated with homocystinuria, Stevens-Johnson syndrome, paracetamol intoxication, vigabatrin medication or extreme prematurity.<br><b>CONCLUSION: </b>5-Oxoprolinuria is a more common condition than hitherto thought and is primarily associated with defects in the gamma-glutamyl cycle. However, several other inborn errors of metabolism and pathophysiological conditions must be taken into account when discovering 5-oxoprolinuria.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Mayatepek",
      "authorRank" : 1,
      "name" : "Mayatepek E",
      "referenceId" : "RGD:A564582"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119313"
    } ]
  }, {
    "primaryId" : "PMID:10094463",
    "title" : "Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Lee JH, etal., FEBS Lett 1999 Feb 26;445(2-3):231-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:14.000-05:00",
    "volume" : "445",
    "pages" : "231-6",
    "abstract" : "Cloning has led to the discovery of more ion channels than predicted by functional studies, yet there remain channels that have not been cloned. We report the cloning of a novel protein that contains the four domain structure found in voltage-gated Ca2+ and Na+ channels. Phylogenetic relationships suggested that the protein might have diverged from an ancestral four repeat channel before the divergence of Ca2+ and Na+ channels. Northern blot analysis showed that mRNA transcripts encoding the protein are expressed predominantly in the brain, moderately in the heart, and weakly in the pancreas. Despite extensive expression attempts, currents from the putative channel were not detected. Based on its sequence, we propose that the novel protein might be a voltage-activated cation channel with unique gating properties.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JH",
      "lastName" : "Lee",
      "authorRank" : 1,
      "name" : "Lee JH",
      "referenceId" : "RGD:A5688"
    }, {
      "firstName" : "LL",
      "lastName" : "Cribbs",
      "authorRank" : 2,
      "name" : "Cribbs LL",
      "referenceId" : "RGD:A5681"
    }, {
      "firstName" : "E",
      "lastName" : "Perez-Reyes",
      "authorRank" : 3,
      "name" : "Perez-Reyes E",
      "referenceId" : "RGD:A5680"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634530"
    } ]
  }, {
    "primaryId" : "PMID:10094480",
    "title" : "Pax6 and Pdx1 form a functional complex on the rat somatostatin gene upstream enhancer.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Andersen FG, etal., FEBS Lett. 1999 Feb 26;445(2-3):315-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-14T14:52:27.000-06:00",
    "volume" : "445",
    "pages" : "315-20",
    "abstract" : "The somatostatin upstream enhancer (SMS-UE) is a highly complex enhancer element. The distal A-element contains overlapping Pdx1 and Pbx binding sites. However, a point mutation in the A-element that abolishes both Pdxl and Pbx binding does not impair promoter activity. In contrast, a point mutation that selectively eliminates Pdx1 binding to a proximal B-element reduces the promoter activity. The B-element completely overlaps with a Pax6 binding site, the C-element. A point mutation in the C-element demonstrates that Pax6 binding is essential for promoter activity. Interestingly, a block mutation in the A-element reduces both Pax6 binding and promoter activity. In heterologous cells, Pdx1 potentiated Pax6 mediated activation of a somatostatin reporter. We conclude that the beta/delta-cell-specific activity of the SMS-UE is achieved through simultaneous binding of Pdx1 and Pax6 to the B- and C-elements, respectively. Furthermore, the A-element appears to stabilise Pax6 binding.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FG",
      "lastName" : "Andersen",
      "authorRank" : 1,
      "name" : "Andersen FG",
      "referenceId" : "RGD:A71228"
    }, {
      "firstName" : "J",
      "lastName" : "Jensen",
      "authorRank" : 2,
      "name" : "Jensen J",
      "referenceId" : "RGD:A71229"
    }, {
      "firstName" : "RS",
      "lastName" : "Heller",
      "authorRank" : 3,
      "name" : "Heller RS",
      "referenceId" : "RGD:A71230"
    }, {
      "firstName" : "HV",
      "lastName" : "Petersen",
      "authorRank" : 4,
      "name" : "Petersen HV",
      "referenceId" : "RGD:A31966"
    }, {
      "firstName" : "LI",
      "lastName" : "Larsson",
      "authorRank" : 5,
      "name" : "Larsson LI",
      "referenceId" : "RGD:A17813"
    }, {
      "firstName" : "OD",
      "lastName" : "Madsen",
      "authorRank" : 6,
      "name" : "Madsen OD",
      "referenceId" : "RGD:A5989"
    }, {
      "firstName" : "P",
      "lastName" : "Serup",
      "authorRank" : 7,
      "name" : "Serup P",
      "referenceId" : "RGD:A5990"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598709"
    } ]
  }, {
    "primaryId" : "PMID:10094548",
    "title" : "Detection of mutations in COL4A5 in patients with Alport syndrome.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Plant KE, etal., Hum Mutat. 1999;13(2):124-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:42:40.000-05:00",
    "volume" : "13",
    "pages" : "124-32",
    "abstract" : "Alport syndrome (AS) can be caused by mutations in COL4A5, one of the six type IV collagen genes. For the purposes of confirming diagnoses, carrier screening and correlating genotype to phenotype, we have screened all 51 exons of this gene by  SSCP analysis in 153 families with suspected AS. Mutations were identified in 77  families (of which 20 have previously been reported) and are reported with all available clinical information. All types of mutation were found (missense, nonsense, splicing, small and large deletions and insertions), with the commonest type being those affecting glycine residues in the collagen triple helix. Our 50% detection rate is similar to that of other groups and may imply the presence of mutations outside of the COL4A5 coding region or the existence of a second X-linked AS gene.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KE",
      "lastName" : "Plant",
      "authorRank" : 1,
      "name" : "Plant",
      "referenceId" : "RGD:A251345"
    }, {
      "firstName" : "PM",
      "lastName" : "Green",
      "authorRank" : 2,
      "name" : "Green",
      "referenceId" : "RGD:A198495"
    }, {
      "firstName" : "D",
      "lastName" : "Vetrie",
      "authorRank" : 3,
      "name" : "Vetrie",
      "referenceId" : "RGD:A251346"
    }, {
      "firstName" : "FA",
      "lastName" : "Flinter",
      "authorRank" : 4,
      "name" : "Flinter",
      "referenceId" : "RGD:A251347"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062488"
    } ]
  }, {
    "primaryId" : "PMID:10094549",
    "title" : "Twelve novel myosin VIIA mutations in 34 patients with Usher syndrome type I: confirmation of genetic heterogeneity.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Janecke AR, etal., Hum Mutat. 1999;13(2):133-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:30:05.000-05:00",
    "volume" : "13",
    "pages" : "133-40",
    "abstract" : "Usher syndrome is a heterogeneous autosomal recessive trait and the most common cause of hereditary deaf-blindness. Usher syndrome type I (USH1) is characterised by profound congenital sensorineural hearing loss, vestibular dysfunction, and prepubertal onset of retinitis pigmentosa. Of the at least six different loci for USH1, USH1B maps on chromosome 11q13, and the MYO7A gene has been shown to be defective in USH1B. MYO7A encodes myosin VIIA, an unconventional myosin, and it consists of 48 coding exons. In this study, MYO7A was analysed in 34 unrelated Usher type I patients by single-strand conformation polymorphism analysis and direct sequencing. We identified a total of 12 novel and unique mutations, all single base changes. In addition, we found a previously reported nonsense mutation (C31X) on nine alleles of a total of six patients from Denmark.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AR",
      "lastName" : "Janecke",
      "authorRank" : 1,
      "name" : "Janecke AR",
      "referenceId" : "RGD:A73737"
    }, {
      "firstName" : "M",
      "lastName" : "Meins",
      "authorRank" : 2,
      "name" : "Meins",
      "referenceId" : "RGD:A192363"
    }, {
      "firstName" : "M",
      "lastName" : "Sadeghi",
      "authorRank" : 3,
      "name" : "Sadeghi",
      "referenceId" : "RGD:A258041"
    }, {
      "firstName" : "K",
      "lastName" : "Grundmann",
      "authorRank" : 4,
      "name" : "Grundmann",
      "referenceId" : "RGD:A214200"
    }, {
      "firstName" : "E",
      "lastName" : "Apfelstedt-Sylla",
      "authorRank" : 5,
      "name" : "Apfelstedt-Sylla E",
      "referenceId" : "RGD:A4112"
    }, {
      "firstName" : "E",
      "lastName" : "Zrenner",
      "authorRank" : 6,
      "name" : "Zrenner E",
      "referenceId" : "RGD:A36604"
    }, {
      "firstName" : "T",
      "lastName" : "Rosenberg",
      "authorRank" : 7,
      "name" : "Rosenberg T",
      "referenceId" : "RGD:A37257"
    }, {
      "firstName" : "A",
      "lastName" : "Gal",
      "authorRank" : 8,
      "name" : "Gal A",
      "referenceId" : "RGD:A4106"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064287"
    } ]
  }, {
    "primaryId" : "PMID:10094550",
    "title" : "Identification of a 5' splice site mutation in the RPGR gene in a family with X-linked retinitis pigmentosa (RP3).",
    "datePublished" : "1000-05-01T00:00:00.000-06:00",
    "citation" : "Dry KL, etal., Hum Mutat. 1999;13(2):141-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-07T14:34:56.000-05:00",
    "volume" : "13",
    "pages" : "141-5",
    "abstract" : "We have identified a novel RPGR gene mutation in a large Dutch family with X-linked retinitis pigmentosa (RP3). In affected members, a G-->T transversion was found at position +1 of the 5' splice site of intron 5 of the RPGR (retinitis pigmentosa GTPase regulator) gene. Analysis of this mutation at the RNA level showed cryptic splicing upstream of the mutation in exon 5 leading to a frameshift and downstream termination codon. Identification of the causative mutation in this family has facilitated the detection of females at risk of having an affected son.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KL",
      "lastName" : "Dry",
      "authorRank" : 1,
      "name" : "Dry",
      "referenceId" : "RGD:A183391"
    }, {
      "firstName" : "FD",
      "lastName" : "Manson",
      "authorRank" : 2,
      "name" : "Manson",
      "referenceId" : "RGD:A183392"
    }, {
      "firstName" : "A",
      "lastName" : "Lennon",
      "authorRank" : 3,
      "name" : "Lennon",
      "referenceId" : "RGD:A183393"
    }, {
      "firstName" : "AA",
      "lastName" : "Bergen",
      "authorRank" : 4,
      "name" : "Bergen AA",
      "referenceId" : "RGD:A39421"
    }, {
      "firstName" : "DB",
      "lastName" : "Van Dorp",
      "authorRank" : 5,
      "name" : "Van Dorp",
      "referenceId" : "RGD:A183394"
    }, {
      "firstName" : "AF",
      "lastName" : "Wright",
      "authorRank" : 6,
      "name" : "Wright AF",
      "referenceId" : "RGD:A60477"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553206"
    } ]
  }, {
    "primaryId" : "PMID:10094560",
    "title" : "Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline  phosphatase (TNSALP) gene in patients with severe hypophosphatasia. Mutations in  brief no. 217. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Taillandier A, etal., Hum Mutat. 1999;13(2):171-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:21:03.000-05:00",
    "volume" : "13",
    "pages" : "171-2",
    "abstract" : "Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/ bone/kidney tissue alkaline phosphatase (L/B/K ALP) activity. We report the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 9  families affected by severe hypophosphatasia. Fourteen distinct mutations were found, 3 of which were previously reported in the North American or Japanese populations. Seven of the 11 new mutations were missense mutations (M45L, R119H,  G145V, C184Y and H154Y, D289V, E459K), the four others were 2 single nucleotide deletions (544delG and 1172delC), a mutation affecting donor splice site (862 + 5A) and a nonsense mutation (R411X).",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Taillandier",
      "authorRank" : 1,
      "name" : "Taillandier",
      "referenceId" : "RGD:A253315"
    }, {
      "firstName" : "L",
      "lastName" : "Zurutuza",
      "authorRank" : 2,
      "name" : "Zurutuza",
      "referenceId" : "RGD:A258653"
    }, {
      "firstName" : "F",
      "lastName" : "Muller",
      "authorRank" : 3,
      "name" : "Muller F",
      "referenceId" : "RGD:A9848"
    }, {
      "firstName" : "B",
      "lastName" : "Simon-Bouy",
      "authorRank" : 4,
      "name" : "Simon-Bouy",
      "referenceId" : "RGD:A375539"
    }, {
      "firstName" : "JL",
      "lastName" : "Serre",
      "authorRank" : 5,
      "name" : "Serre",
      "referenceId" : "RGD:A253316"
    }, {
      "firstName" : "L",
      "lastName" : "Bird",
      "authorRank" : 6,
      "name" : "Bird",
      "referenceId" : "RGD:A284108"
    }, {
      "firstName" : "R",
      "lastName" : "Brenner",
      "authorRank" : 7,
      "name" : "Brenner R",
      "referenceId" : "RGD:A137168"
    }, {
      "firstName" : "O",
      "lastName" : "Boute",
      "authorRank" : 8,
      "name" : "Boute",
      "referenceId" : "RGD:A374722"
    }, {
      "firstName" : "J",
      "lastName" : "Cousin",
      "authorRank" : 9,
      "name" : "Cousin",
      "referenceId" : "RGD:A267830"
    }, {
      "firstName" : "D",
      "lastName" : "Gaillard",
      "authorRank" : 10,
      "name" : "Gaillard",
      "referenceId" : "RGD:A397349"
    }, {
      "firstName" : "PH",
      "lastName" : "Heidemann",
      "authorRank" : 11,
      "name" : "Heidemann PH",
      "referenceId" : "RGD:A73815"
    }, {
      "firstName" : "B",
      "lastName" : "Steinmann",
      "authorRank" : 12,
      "name" : "Steinmann B",
      "referenceId" : "RGD:A37353"
    }, {
      "firstName" : "M",
      "lastName" : "Wallot",
      "authorRank" : 13,
      "name" : "Wallot",
      "referenceId" : "RGD:A284109"
    }, {
      "firstName" : "E",
      "lastName" : "Mornet",
      "authorRank" : 14,
      "name" : "Mornet E",
      "referenceId" : "RGD:A35870"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073288"
    } ]
  }, {
    "primaryId" : "PMID:10094563",
    "title" : "Glycogen storage disease type Ia: four novel mutations (175delGG, R170X, G266V and V338F) identified. Mutations in brief no. 220. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Rake JP, etal., Hum Mutat. 1999;13(2):173.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:34:58.000-05:00",
    "volume" : "13",
    "pages" : "173",
    "abstract" : "Deficient activity of glucose-6-phosphatase (G6Pase) causes glycogen storage disease type Ia (GSD Ia). We analysed the G6Pase gene of 16 GSD Ia patients using single strand conformation polymorphism (SSCP) analysis prior to automated sequencing of exon(s) revealing an aberrant SSCP pattern. In all GSD Ia patients  we were able to identify mutations on both alleles of the G6Pase gene, indicating that this method is a reliable procedure to identify mutations. Four novel mutations (175delGG, R170X, G266V and V338F) were identified.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JP",
      "lastName" : "Rake",
      "authorRank" : 1,
      "name" : "Rake",
      "referenceId" : "RGD:A265071"
    }, {
      "firstName" : "AM",
      "lastName" : "Ten Berge",
      "authorRank" : 2,
      "name" : "Ten Berge",
      "referenceId" : "RGD:A259440"
    }, {
      "firstName" : "E",
      "lastName" : "Verlind",
      "authorRank" : 3,
      "name" : "Verlind E",
      "referenceId" : "RGD:A77084"
    }, {
      "firstName" : "G",
      "lastName" : "Visser",
      "authorRank" : 4,
      "name" : "Visser G",
      "referenceId" : "RGD:A75956"
    }, {
      "firstName" : "KE",
      "lastName" : "Niezen-Koning",
      "authorRank" : 5,
      "name" : "Niezen-Koning",
      "referenceId" : "RGD:A198280"
    }, {
      "firstName" : "CH",
      "lastName" : "Buys",
      "authorRank" : 6,
      "name" : "Buys CH",
      "referenceId" : "RGD:A38036"
    }, {
      "firstName" : "GP",
      "lastName" : "Smit",
      "authorRank" : 7,
      "name" : "Smit",
      "referenceId" : "RGD:A250168"
    }, {
      "firstName" : "H",
      "lastName" : "Scheffer",
      "authorRank" : 8,
      "name" : "Scheffer H",
      "referenceId" : "RGD:A82811"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070359"
    } ]
  }, {
    "primaryId" : "PMID:10094565",
    "title" : "Identification of three novel mutations in the dystrophin gene detected by the heteroduplex/SSCA screening procedure. Mutations in brief no. 222. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Dubourg C, etal., Hum Mutat. 1999;13(2):173.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:25:21.000-05:00",
    "volume" : "13",
    "pages" : "173",
    "abstract" : "Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked neuromuscular disorders associated with alterations in the dystrophin gene. Analysis of 45 DMD/BMD patients has identified 18 patients with no deletion in the dystrophin gene. Heteroduplex analysis (HD), single strand conformation analysis (SSCA), and subsequent sequencing, identified five mutations and nine polymorphisms. Three out of the 5 mutations (780C>G, 2501-1g-->t, 9812 9813ins9800-9812) are first reported here. Furthermore we compare the relative efficiencies of the two alternatives methods (HD and SSCA) for screening sequence alterations.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Dubourg",
      "authorRank" : 1,
      "name" : "Dubourg C",
      "referenceId" : "RGD:A52612"
    }, {
      "firstName" : "S",
      "lastName" : "Odent",
      "authorRank" : 2,
      "name" : "Odent S",
      "referenceId" : "RGD:A44749"
    }, {
      "firstName" : "P",
      "lastName" : "Fergelot",
      "authorRank" : 3,
      "name" : "Fergelot P",
      "referenceId" : "RGD:A96139"
    }, {
      "firstName" : "JY",
      "lastName" : "Le Gall",
      "authorRank" : 4,
      "name" : "Le Gall",
      "referenceId" : "RGD:A260513"
    }, {
      "firstName" : "V",
      "lastName" : "David",
      "authorRank" : 5,
      "name" : "David V",
      "referenceId" : "RGD:A52619"
    }, {
      "firstName" : "M",
      "lastName" : "Blayau",
      "authorRank" : 6,
      "name" : "Blayau M",
      "referenceId" : "RGD:A52616"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066004"
    } ]
  }, {
    "primaryId" : "PMID:10094932",
    "title" : "Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Lombardi MS, etal., FASEB J. 1999 Apr;13(6):715-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-02-29T15:21:53.000-06:00",
    "volume" : "13",
    "pages" : "715-25",
    "abstract" : "Beta2-Adrenergic and chemokine receptor antagonists delay the onset and reduce the severity of joint injury in rheumatoid arthritis. beta2-Adrenergic and chemokine receptors belong to the G-protein-coupled receptor family whose responsiveness is turned off by the G-protein-coupled receptor kinase family (GRK-1 to 6). GRKs phosphorylate receptors in an agonist-dependent manner resulting in receptor/G-protein uncoupling via subsequent binding of arrestin proteins. We assessed the activity of GRKs in lymphocytes of rheumatoid arthritis (RA) patients by rhodopsin phosphorylation. We found a significant decrease in GRK activity in RA subjects that is mirrored by a decrease in GRK-2 protein expression. Moreover, GRK-6 protein expression is reduced in RA patients whereas  GRK-5 protein levels were unchanged. In search of an underlying mechanism, we demonstrated that proinflammatory cytokines induce a decrease in GRK-2 protein levels in leukocytes from healthy donors. Since proinflammatory cytokines are abundantly expressed in RA, it may provide an explanation for the decrease in GRK-2 expression and activity in patients. No changes in beta2-adrenergic receptor number and Kd were detected. However, RA patients showed a significantly increased cAMP production and inhibition of TNF-alpha production by beta2-adrenergic stimulation, suggesting that reduced GRK activity is associated  with increased sensitivity to beta2-adrenergic activation.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MS",
      "lastName" : "Lombardi",
      "authorRank" : 1,
      "name" : "Lombardi MS",
      "referenceId" : "RGD:A49283"
    }, {
      "firstName" : "A",
      "lastName" : "Kavelaars",
      "authorRank" : 2,
      "name" : "Kavelaars A",
      "referenceId" : "RGD:A49285"
    }, {
      "firstName" : "M",
      "lastName" : "Schedlowski",
      "authorRank" : 3,
      "name" : "Schedlowski M",
      "referenceId" : "RGD:A53444"
    }, {
      "firstName" : "JW",
      "lastName" : "Bijlsma",
      "authorRank" : 4,
      "name" : "Bijlsma JW",
      "referenceId" : "RGD:A151550"
    }, {
      "firstName" : "KL",
      "lastName" : "Okihara",
      "authorRank" : 5,
      "name" : "Okihara KL",
      "referenceId" : "RGD:A151551"
    }, {
      "firstName" : "M",
      "lastName" : "Van de Pol",
      "authorRank" : 6,
      "name" : "Van de Pol M",
      "referenceId" : "RGD:A151552"
    }, {
      "firstName" : "S",
      "lastName" : "Ochsmann",
      "authorRank" : 7,
      "name" : "Ochsmann S",
      "referenceId" : "RGD:A151553"
    }, {
      "firstName" : "C",
      "lastName" : "Pawlak",
      "authorRank" : 8,
      "name" : "Pawlak C",
      "referenceId" : "RGD:A151554"
    }, {
      "firstName" : "RE",
      "lastName" : "Schmidt",
      "authorRank" : 9,
      "name" : "Schmidt RE",
      "referenceId" : "RGD:A55207"
    }, {
      "firstName" : "CJ",
      "lastName" : "Heijnen",
      "authorRank" : 10,
      "name" : "Heijnen CJ",
      "referenceId" : "RGD:A49288"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5688380"
    } ]
  }, {
    "primaryId" : "PMID:10094959",
    "title" : "Gap junctional communication and regulation of the glycogenic response to insulin by cell density and glucocorticoids in cultured fetal rat hepatocytes.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Siddiqui MU, etal., Hepatology. 1999 Apr;29(4):1147-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-09T16:47:29.000-06:00",
    "volume" : "29",
    "pages" : "1147-55",
    "abstract" : "Cell culture studies have revealed that metabolic functions of the adult hepatocyte are related to cell density. Development of the glycogenic response to insulin under glucocorticoid control was investigated in 15- and 18-day-old fetal rat hepatocytes plated at different cell densities. After culturing for 48 hours  with glucocorticoids, the stimulatory effect of insulin on [14C]glucose incorporation into glycogen after 3 hours progressed from weak response (less than 1.4-fold) in sparse cultures to a maximal response in dense ones (3.0- to 4.5-fold), depending on the fetal stage. The response was always no more than 2.0-fold in the absence of glucocorticoids, even with dense cultures. Such a dual regulation pattern was not found for the glycogenolytic effect of glucagon similarly expressed regardless of culture conditions. When cells were clustered in limited circular regions of the dish, the insulin response was higher than for sparse cultures for a similar number of cells per culture. Using the scrape-loading technique with Lucifer Yellow CH, a positive dye transfer was obtained in clustered cultures providing that they were grown in the presence of  glucocorticoids; insulin as well as glucagon stimulated twofold intercellular communication. Connexin32 (Cx32) and connexin26 (Cx26) protein levels were assayed by Western immunoblotting and developed according to age and exposure to  glucocorticoids. Thus, glucocorticoids through development of gap junctions enabled establishment of intercellular communication that could be stimulated by  insulin and glucagon in cultured fetal hepatocytes. Gap junction functioning and  the biologic effect of insulin correlated closely.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MU",
      "lastName" : "Siddiqui",
      "authorRank" : 1,
      "name" : "Siddiqui",
      "referenceId" : "RGD:A416290"
    }, {
      "firstName" : "S",
      "lastName" : "Benatmane",
      "authorRank" : 2,
      "name" : "Benatmane",
      "referenceId" : "RGD:A416291"
    }, {
      "firstName" : "JL",
      "lastName" : "Zachayus",
      "authorRank" : 3,
      "name" : "Zachayus",
      "referenceId" : "RGD:A416292"
    }, {
      "firstName" : "C",
      "lastName" : "Plas",
      "authorRank" : 4,
      "name" : "Plas",
      "referenceId" : "RGD:A416293"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568673"
    } ]
  }, {
    "primaryId" : "PMID:10094960",
    "title" : "Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Konig J, etal., Hepatology 1999 Apr;29(4):1156-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T13:36:23.000-05:00",
    "volume" : "29",
    "pages" : "1156-63",
    "abstract" : "Several members of the multidrug resistance protein (MRP) family are expressed in the liver. Adenosine triphosphate (ATP)-dependent transport of glutathione and glucuronoside conjugates across the hepatocyte canalicular membrane is mediated by the apical MRP isoform, MRP2 (APMRP), also known as canalicular multispecific organic anion transporter (cMOAT). We have cloned an additional MRP isoform, MRP3, from human liver and localized it to the basolateral membrane domain of hepatocytes. Basolateral MRP (BLMRP) is composed of 1,527 amino acids and encoded by 4,581 base pairs of complementary DNA. Northern blotting of various human tissues indicated an expression of MRP3 in the liver, colon, pancreas, and, at a lower level, in the kidney. The amino acid identity of MRP3 with MRP1 and MRP2 is 58% and 48%, respectively. These three isoforms, encoded by genes on different chromosomes, have a similar predicted topology of transmembrane segments and ATP-binding domains. Antibodies raised against two peptide sequences of MRP3 that are not shared by other MRP family members detected recombinant MRP3 expressed in polarized MDCK cells. Both antibodies served to localize MRP3 to the basolateral membrane of hepatocytes. Double-label immunofluorescence microscopy confirmed that MRP3 was not detectable in the canalicular membrane domain. A particularly strong expression of the MRP3 protein was observed in the basolateral hepatocyte membrane of two patients with Dubin-Johnson syndrome who are deficient in MRP2. These results indicate that the basolateral MRP isoform, MRP3, may be upregulated when the canalicular secretion of anionic conjugates by MRP2 is impaired.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Konig",
      "authorRank" : 1,
      "name" : "Konig J",
      "referenceId" : "RGD:A12462"
    }, {
      "firstName" : "D",
      "lastName" : "Rost",
      "authorRank" : 2,
      "name" : "Rost D",
      "referenceId" : "RGD:A26834"
    }, {
      "firstName" : "Y",
      "lastName" : "Cui",
      "authorRank" : 3,
      "name" : "Cui Y",
      "referenceId" : "RGD:A44680"
    }, {
      "firstName" : "D",
      "lastName" : "Keppler",
      "authorRank" : 4,
      "name" : "Keppler D",
      "referenceId" : "RGD:A15689"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300327"
    } ]
  }, {
    "primaryId" : "PMID:10094961",
    "title" : "High-level expression of rat class I alcohol dehydrogenase is sufficient for ethanol-induced fat accumulation in transduced HeLa cells.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Galli A, etal., Hepatology. 1999 Apr;29(4):1164-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-11-13T16:28:57.000-06:00",
    "volume" : "29",
    "pages" : "1164-70",
    "abstract" : "The mechanisms by which ethanol causes fatty liver are complex. Reducing equivalents generated during ethanol oxidation inhibit tricarboxylic acid cycle activity and fatty acid oxidation. In addition, ethanol inhibits lipoprotein export and increases fatty acid uptake and lipid peroxidation. To test the role that alcohol metabolism by alcohol dehydrogenase (ADH) has on cellular lipid metabolism, a cell line expressing rat ADH was generated by transducing HeLa cells with an ADH-expressing retrovirus. The cells expressed high levels of ADH protein and had ADH activity similar to that of liver. Exposure of the cells to 20 mmol/L ethanol for 24 hours led to substantial accumulation of free fatty acids and triacylglycerol in the transduced, but not wild-type, HeLa cells. The rate of synthesis of saponifiable lipid was increased significantly by ethanol under these conditions. Ethanol exposure also promoted triacylglycerol accumulation when the cells were incubated with linoleic acid. This was associated with a decrease in the rate at which the cells oxidized 1-[14-C]-linoleic acid. Fat accumulation was not prevented by including alpha-tocopherol in the medium, arguing against a role for lipid peroxidation. However, the presence of methylene blue completely prevented the fat accumulation. This was associated with a return of the elevated lactate/pyruvate ratio toward normal. These data suggest that generation of reducing equivalents by ADH was sufficient to cause fat accumulation in this cell model.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Galli",
      "authorRank" : 1,
      "name" : "Galli A",
      "referenceId" : "RGD:A84659"
    }, {
      "firstName" : "D",
      "lastName" : "Price",
      "authorRank" : 2,
      "name" : "Price D",
      "referenceId" : "RGD:A89221"
    }, {
      "firstName" : "D",
      "lastName" : "Crabb",
      "authorRank" : 3,
      "name" : "Crabb D",
      "referenceId" : "RGD:A89222"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642948"
    } ]
  }, {
    "primaryId" : "PMID:10095017",
    "title" : "Discriminant power of combined cerebrospinal fluid tau protein and of the soluble interleukin-6 receptor complex in the diagnosis of Alzheimer's disease.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Hampel H, etal., Brain Res. 1999 Mar 27;823(1-2):104-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-11-02T16:16:55.000-06:00",
    "volume" : "823",
    "pages" : "104-12",
    "abstract" : "Alzheimer's disease (AD) still can only be definitively diagnosed with certainty  by examination of brain tissue. There is a great need for a noninvasive, sensitive and specific in vivo test for AD. We combined cerebrospinal fluid analyses of tau protein (levels were significantly increased in AD patients [p=0.0001]), a putative marker of neuronal degeneration, with components of the soluble interleukin-6 receptor complex (sIL-6RC: IL-6, soluble IL-6 receptor and  soluble gp130), putative markers of neuroregulatory and inflammatory processes in the brain. A stepwise multivariate discriminant analysis revealed that tau protein and soluble gp130 (levels were significantly reduced in AD subjects [p=0.007]), the affinity converting and signal-transducing receptor of neuropoietic cytokines, maximized separation between the investigated groups. The discriminant function predicted 23 of 25 clinically diagnosed AD patients (sensitivity 92%) with mild to moderate dementia correctly as having AD. Furthermore, 17 of 19 physically and cognitively healthy age-matched control subjects (specificity 90%) were accurately distinguished by this test. Later predicting with the jackknife procedure each case in turn through the remaining patient group, the discriminant function remained stable. Our data suggest that multivariate discriminant analysis of combined CSF tau protein and sIL-6RC components may add more certainty to the diagnosis of AD, however, the method will need to be extended to an independent group of patients, comparisons and control subjects to assess the true applicability.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Hampel",
      "authorRank" : 1,
      "name" : "Hampel H",
      "referenceId" : "RGD:A36405"
    }, {
      "firstName" : "SJ",
      "lastName" : "Teipel",
      "authorRank" : 2,
      "name" : "Teipel",
      "referenceId" : "RGD:A207961"
    }, {
      "firstName" : "F",
      "lastName" : "Padberg",
      "authorRank" : 3,
      "name" : "Padberg",
      "referenceId" : "RGD:A207962"
    }, {
      "firstName" : "A",
      "lastName" : "Haslinger",
      "authorRank" : 4,
      "name" : "Haslinger",
      "referenceId" : "RGD:A207963"
    }, {
      "firstName" : "M",
      "lastName" : "Riemenschneider",
      "authorRank" : 5,
      "name" : "Riemenschneider M",
      "referenceId" : "RGD:A151683"
    }, {
      "firstName" : "MJ",
      "lastName" : "Schwarz",
      "authorRank" : 6,
      "name" : "Schwarz",
      "referenceId" : "RGD:A207964"
    }, {
      "firstName" : "HU",
      "lastName" : "Kotter",
      "authorRank" : 7,
      "name" : "Kotter",
      "referenceId" : "RGD:A207965"
    }, {
      "firstName" : "M",
      "lastName" : "Scheloske",
      "authorRank" : 8,
      "name" : "Scheloske",
      "referenceId" : "RGD:A207966"
    }, {
      "firstName" : "K",
      "lastName" : "Buch",
      "authorRank" : 9,
      "name" : "Buch",
      "referenceId" : "RGD:A207967"
    }, {
      "firstName" : "S",
      "lastName" : "Stubner",
      "authorRank" : 10,
      "name" : "Stubner",
      "referenceId" : "RGD:A207968"
    }, {
      "firstName" : "R",
      "lastName" : "Dukoff",
      "authorRank" : 11,
      "name" : "Dukoff",
      "referenceId" : "RGD:A207969"
    }, {
      "firstName" : "R",
      "lastName" : "Lasser",
      "authorRank" : 12,
      "name" : "Lasser",
      "referenceId" : "RGD:A207970"
    }, {
      "firstName" : "N",
      "lastName" : "Muller",
      "authorRank" : 13,
      "name" : "Muller N",
      "referenceId" : "RGD:A103317"
    }, {
      "firstName" : "T",
      "lastName" : "Sunderland",
      "authorRank" : 14,
      "name" : "Sunderland T",
      "referenceId" : "RGD:A52403"
    }, {
      "firstName" : "SI",
      "lastName" : "Rapoport",
      "authorRank" : 15,
      "name" : "Rapoport SI",
      "referenceId" : "RGD:A77725"
    }, {
      "firstName" : "HJ",
      "lastName" : "Moller",
      "authorRank" : 16,
      "name" : "Moller HJ",
      "referenceId" : "RGD:A62652"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10402847"
    } ]
  }, {
    "primaryId" : "PMID:10095056",
    "title" : "Cloning and functional expression of the cytoplasmic form of rat aminopeptidase P.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Czirjak G, etal., Biochim Biophys Acta 1999 Mar 19;1444(3):326-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:03.000-05:00",
    "volume" : "1444",
    "pages" : "326-36",
    "abstract" : "A rat cytoplasmic aminopeptidase P was purified from liver cytosol with a procedure including an affinity elution step with 3 microM inositol 1,3,4-trisphosphate. Proteolytic fragments were generated, sequenced and the enzyme was cloned from a rat liver cDNA library. The structure shows high (87.8% and 95.5%, respectively) sequence identity at the nucleotide and amino acid levels with the previously described human putative cytoplasmic aminopeptidase P. The cloned rat enzyme was functionally expressed in Escherichia coli and also in COS-1 cells. Western blot analysis, using an antibody generated against the recombinant protein, and Northern blot hybridization showed ubiquitous expression of the protein in different tissues with the highest expression level in the testis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Czirjak",
      "authorRank" : 1,
      "name" : "Czirjak G",
      "referenceId" : "RGD:A24221"
    }, {
      "firstName" : "WA",
      "lastName" : "Burkhart",
      "authorRank" : 2,
      "name" : "Burkhart WA",
      "referenceId" : "RGD:A24222"
    }, {
      "firstName" : "MB",
      "lastName" : "Moyer",
      "authorRank" : 3,
      "name" : "Moyer MB",
      "referenceId" : "RGD:A24223"
    }, {
      "firstName" : "J",
      "lastName" : "Antal",
      "authorRank" : 4,
      "name" : "Antal J",
      "referenceId" : "RGD:A24224"
    }, {
      "firstName" : "SB",
      "lastName" : "Shears",
      "authorRank" : 5,
      "name" : "Shears SB",
      "referenceId" : "RGD:A7580"
    }, {
      "firstName" : "P",
      "lastName" : "Enyedi",
      "authorRank" : 6,
      "name" : "Enyedi P",
      "referenceId" : "RGD:A24225"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634520"
    } ]
  }, {
    "primaryId" : "PMID:10095058",
    "title" : "Cloning and characterization of the rat and human phosducin-like protein genes: structure, expression and chromosomal localization.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Thibault C, etal., Biochim Biophys Acta 1999 Mar 19;1444(3):346-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T16:23:40.000-05:00",
    "volume" : "1444",
    "pages" : "346-54",
    "abstract" : "We isolated and characterized the rat gene encoding phosducin-like protein (PhLP), a putative heterotrimeric G protein modulator. The transcription start site was mapped by primer extension. The putative promoter region lacked a TATA sequence but contained a potential initiator element. Two splice variants were identified by RT-PCR of rat brain RNA, potentially generating either the full length or an amino-truncated protein. Only the full-length protein was immunodetected in all mouse tissues surveyed. Comparison of the conceptual translation product of the rat PhLP gene with those from human and Drosophila clones shows a striking conservation in the amino-terminal region of PhLP from these species. This contrasts with the relatively low degree of homology between PhLP and phosducin in this region, suggesting a functional role for this portion of the PhLP protein. Finally, we mapped the human PhLP gene by PCR analysis of somatic cell hybrids and the Stanford G3 radiation hybrid panel. The human PhLP gene (PDCL) is located on chromosome 9, linked to the polymorphic markers D9S1876 and D9S1674 (66-71 cM).",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Thibault",
      "authorRank" : 1,
      "name" : "Thibault C",
      "referenceId" : "RGD:A21982"
    }, {
      "firstName" : "J",
      "lastName" : "Feng Wang",
      "authorRank" : 2,
      "name" : "Feng Wang J",
      "referenceId" : "RGD:A21983"
    }, {
      "firstName" : "R",
      "lastName" : "Charnas",
      "authorRank" : 3,
      "name" : "Charnas R",
      "referenceId" : "RGD:A21984"
    }, {
      "firstName" : "D",
      "lastName" : "Mirel",
      "authorRank" : 4,
      "name" : "Mirel D",
      "referenceId" : "RGD:A21985"
    }, {
      "firstName" : "S",
      "lastName" : "Barhite",
      "authorRank" : 5,
      "name" : "Barhite S",
      "referenceId" : "RGD:A21986"
    }, {
      "firstName" : "MF",
      "lastName" : "Miles",
      "authorRank" : 6,
      "name" : "Miles MF",
      "referenceId" : "RGD:A21987"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633731"
    } ]
  }, {
    "primaryId" : "PMID:10095082",
    "title" : "Phase-dependent induction by light of rat Clock gene expression in the suprachiasmatic nucleus.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Abe H, etal., Brain Res Mol Brain Res 1999 Mar 20;66(1-2):104-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:21.000-05:00",
    "volume" : "66",
    "pages" : "104-10",
    "abstract" : "To clarify the role of Clock in the photic signal transduction of rat circadian clock, we cloned and sequenced rat Clock and examined the effect of a single light pulse on the Clock mRNA expression in the suprachiasmatic nucleus (SCN) by in situ hybridization. Rats were exposed to a 30 min light pulse ( approximately 300 lx) at one of six circadian phases in constant darkness (DD), and sacrificed 60 min after the light on. In the rats without light exposure, the mRNA level in the SCN was high at ZT (Zeitgeber time) 6 and low at ZT 18 and 22. Light exposure increased Clock mRNA level in the SCN in phase dependent manner. The mRNA level was significantly increased during the subjective night (ZT10-22). The light had no effect on the mRNA level during the subjective day (ZT2 and 6). The Clock mRNA was also detected in the piriform cortex (PC), and increased by light at ZT14. These results suggest that Clock transcription in the SCN is involved in the photic signal transduction of circadian clock in rats.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Abe",
      "authorRank" : 1,
      "name" : "Abe H",
      "referenceId" : "RGD:A4379"
    }, {
      "firstName" : "S",
      "lastName" : "Honma",
      "authorRank" : 2,
      "name" : "Honma S",
      "referenceId" : "RGD:A4377"
    }, {
      "firstName" : "M",
      "lastName" : "Namihira",
      "authorRank" : 3,
      "name" : "Namihira M",
      "referenceId" : "RGD:A4381"
    }, {
      "firstName" : "Y",
      "lastName" : "Tanahashi",
      "authorRank" : 4,
      "name" : "Tanahashi Y",
      "referenceId" : "RGD:A4380"
    }, {
      "firstName" : "M",
      "lastName" : "Ikeda",
      "authorRank" : 5,
      "name" : "Ikeda M",
      "referenceId" : "RGD:A162010"
    }, {
      "firstName" : "W",
      "lastName" : "Yu",
      "authorRank" : 6,
      "name" : "Yu W",
      "referenceId" : "RGD:A17108"
    }, {
      "firstName" : "K",
      "lastName" : "Honma",
      "authorRank" : 7,
      "name" : "Honma K",
      "referenceId" : "RGD:A4382"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632379"
    } ]
  }, {
    "primaryId" : "PMID:10095107",
    "title" : "Cloning, expression and chromosomal localization of a human testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Manzano A, etal., Gene. 1999 Mar 18;229(1-2):83-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-20T17:50:39.000-05:00",
    "volume" : "229",
    "pages" : "83-9",
    "abstract" : "6-Phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2/FBPase-2) is a bifunctional enzyme responsible for the synthesis and breakdown of Fru-2,6-P2, a  key metabolite in the regulation of glycolysis. Several genes encode distinct PFK-2/FBPase-2 isozymes that differ in their tissue distribution and enzyme regulation. In this paper, we present the isolation of a cDNA from a human testis cDNA library that encodes a PFK-2/FBPase-2 isozyme. Sequencing data show an open  reading frame of 1407 nucleotides that codifies for a protein of 469 amino acids. This has a calculated molecular weight of 54kDa and 97% similarity with rat testis PFK-2/FBPase-2, with complete conservation of the amino acid residues involved in the catalytic mechanism. Fluorescence in-situ hybridization (FISH) localized testis PFK-2/FBPase-2 gene (PFKFB4) in human chromosome 3 at bands p21-p22. A Northern blot analysis of different rat tissues showed the presence of a 2.4-kb mRNA expressed specifically in testis. In mammalian COS-1 cells, the human testis cDNA drives expression of an isozyme with a molecular weight of 55kDa. This isozyme shows clear PFK-2 activity. Taken together, these results provide evidence for a new PFK-2/FBPase-2 gene coding for a human testis isozyme.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Manzano",
      "authorRank" : 1,
      "name" : "Manzano A",
      "referenceId" : "RGD:A102783"
    }, {
      "firstName" : "JX",
      "lastName" : "Perez",
      "authorRank" : 2,
      "name" : "Perez JX",
      "referenceId" : "RGD:A102782"
    }, {
      "firstName" : "M",
      "lastName" : "Nadal",
      "authorRank" : 3,
      "name" : "Nadal",
      "referenceId" : "RGD:A247862"
    }, {
      "firstName" : "X",
      "lastName" : "Estivill",
      "authorRank" : 4,
      "name" : "Estivill",
      "referenceId" : "RGD:A376692"
    }, {
      "firstName" : "A",
      "lastName" : "Lange",
      "authorRank" : 5,
      "name" : "Lange A",
      "referenceId" : "RGD:A129715"
    }, {
      "firstName" : "R",
      "lastName" : "Bartrons",
      "authorRank" : 6,
      "name" : "Bartrons R",
      "referenceId" : "RGD:A102777"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11061453"
    } ]
  }, {
    "primaryId" : "PMID:10095122",
    "title" : "Cloning and chromosomal localization of the gene encoding human cyclin D-binding Myb-like protein (hDMP1).",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Bodner SM, etal., Gene 1999 Mar 18;229(1-2):223-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-02T20:28:22.000-06:00",
    "volume" : "229",
    "pages" : "223-8",
    "abstract" : "The murine transcription factor murine cyclin D-binding Myb-like protein (mDmp1) arrests the cell cycle in G1 phase, through an activity that can be overridden by direct interaction with the D-type cyclins. Here, we describe the identification, sequence, chromosomal localization, and expression of the human cognate, hDMP1. The hDMP1 cDNA contains a 2280bp open reading frame that shares a high degree of identity with the mDmp1 coding region. The 4.4kb hDMP1 messenger RNA is ubiquitously expressed in normal human tissues, with highest levels in testis and substructures within the brain. By use of fluorescence in situ hybridization with a human genomic P1 probe, we assigned hDMP1 to chromosome 7, band q21. This chromosomal region is frequently deleted as part of the 7q-minus and monosomy 7 abnormalities of human acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We analyzed hDMP1 copy number by fluorescence in situ hybridization in leukemic blasts from nine patients with abnormalities of the long arm of chromosome 7, and in each case one allele of the hDMP1 gene was deleted. Functional analysis of the mDmp1 protein has shown that it negatively regulates cell proliferation, which suggests that this gene is a candidate suppressor of malignant transformation. Further study will be needed to determine whether gene-specific mutations implicate hDMP1 as a tumor suppressor in acute leukemias with deletions of the long arm of chromosome 7 or in other types of human malignancy.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SM",
      "lastName" : "Bodner",
      "authorRank" : 1,
      "name" : "Bodner SM",
      "referenceId" : "RGD:A28866"
    }, {
      "firstName" : "CW",
      "lastName" : "Naeve",
      "authorRank" : 2,
      "name" : "Naeve CW",
      "referenceId" : "RGD:A28867"
    }, {
      "firstName" : "KM",
      "lastName" : "Rakestraw",
      "authorRank" : 3,
      "name" : "Rakestraw KM",
      "referenceId" : "RGD:A28868"
    }, {
      "firstName" : "BG",
      "lastName" : "Jones",
      "authorRank" : 4,
      "name" : "Jones BG",
      "referenceId" : "RGD:A28869"
    }, {
      "firstName" : "VA",
      "lastName" : "Valentine",
      "authorRank" : 5,
      "name" : "Valentine VA",
      "referenceId" : "RGD:A28870"
    }, {
      "firstName" : "MB",
      "lastName" : "Valentine",
      "authorRank" : 6,
      "name" : "Valentine MB",
      "referenceId" : "RGD:A28871"
    }, {
      "firstName" : "FW",
      "lastName" : "Luthardt",
      "authorRank" : 7,
      "name" : "Luthardt FW",
      "referenceId" : "RGD:A28872"
    }, {
      "firstName" : "CL",
      "lastName" : "Willman",
      "authorRank" : 8,
      "name" : "Willman CL",
      "referenceId" : "RGD:A28873"
    }, {
      "firstName" : "SC",
      "lastName" : "Raimondi",
      "authorRank" : 9,
      "name" : "Raimondi SC",
      "referenceId" : "RGD:A28874"
    }, {
      "firstName" : "JR",
      "lastName" : "Downing",
      "authorRank" : 10,
      "name" : "Downing JR",
      "referenceId" : "RGD:A28875"
    }, {
      "firstName" : "MF",
      "lastName" : "Roussel",
      "authorRank" : 11,
      "name" : "Roussel MF",
      "referenceId" : "RGD:A28876"
    }, {
      "firstName" : "CJ",
      "lastName" : "Sherr",
      "authorRank" : 12,
      "name" : "Sherr CJ",
      "referenceId" : "RGD:A28877"
    }, {
      "firstName" : "AT",
      "lastName" : "Look",
      "authorRank" : 13,
      "name" : "Look AT",
      "referenceId" : "RGD:A28878"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727758"
    } ]
  }, {
    "primaryId" : "PMID:10095770",
    "title" : "Iron regulatory protein as an endogenous sensor of iron in rat intestinal mucosa. Possible implications for the regulation of iron absorption.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Schümann K, etal., Eur J Biochem. 1999 Mar;260(2):362-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-06-21T11:38:01.000-05:00",
    "volume" : "260",
    "pages" : "362-72",
    "abstract" : "Duodenal enterocytes adjust intestinal iron absorption to the body's state of iron repletion. Here we tested how iron supply from the blood modulates the RNA-binding activity of iron regulatory proteins (IRP-1 and IRP-2) in immature duodenal rat enterocytes, and whether the modulation is compatible with the hypothesis that IRPs, in turn, may regulate the expression of iron transport proteins in maturating enterocytes during migration to the villus tips. Tissue uptake of parenterally applied 59Fe along the duodenal crypt-villus axis was compared to local IRP-1 and IRP-2 activity and to duodenal 59Fe transport capacity 12 h, 48 h, and 72 h after intravenous iron administration to iron-deficient rats. IRP-1 and IRP-2 activity was significantly increased in iron-deficiency. 59Fe administrated from the blood side was almost exclusively taken up by crypt enterocytes. Accordingly, the activity of IRP-1 decreased at this site 12 h after parenteral iron administration, but remained high at the villus tips. After 48 h the bulk of 59Fe containing enterocytes had migrated to the villus tips. Correspondingly, IRP-1 activity was decreased at duodenal villus tips after 48 h. IRP-2 activity also tended to decrease, though the change was statistically not significant. IRP-2 activity remained significantly higher at duodenal villus tips than in crypts, even after 72 h. Intestinal iron absorption capacity decreased with the same delay as IRP-1 activity after intravenous iron administration. In the ileum 59Fe uptake from the blood and IRP activity showed no significant difference between crypt and villus region. Luminal administration of iron decreased duodenal IRP-1 and IRP-2 activity at tips and crypts within 2 h. Thus, recently absorbed iron becomes available to cytosolic IRP during its passage through the enterocyte. Our results are compatible with a role of IRPs in gearing the expression of intestinal iron transporters in the duodenal brushborder to the body's state of iron repletion.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Schümann",
      "authorRank" : 1,
      "name" : "Schümann K",
      "referenceId" : "RGD:A445535"
    }, {
      "firstName" : "R",
      "lastName" : "Moret",
      "authorRank" : 2,
      "name" : "Moret R",
      "referenceId" : "RGD:A445536"
    }, {
      "firstName" : "H",
      "lastName" : "Künzle",
      "authorRank" : 3,
      "name" : "Künzle H",
      "referenceId" : "RGD:A445537"
    }, {
      "firstName" : "L C",
      "lastName" : "Kühn",
      "authorRank" : 4,
      "name" : "Kühn LC",
      "referenceId" : "RGD:A445538"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12910699"
    } ]
  }, {
    "primaryId" : "PMID:10096021",
    "title" : "Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres.",
    "datePublished" : "1998-02-01T00:00:00.000-06:00",
    "citation" : "Tanaka T, etal., Genes Cells 1998 Dec;3(12):801-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-04T12:04:49.000-06:00",
    "volume" : "3",
    "pages" : "801-10",
    "abstract" : "BACKGROUND: Activating transcription factor-4 (ATF4)--also termed CREB2, C/ATF, and TAXREB67--is a basic-leucine zipper (bZip) transcription factor that belongs to the ATF/CREB family. In addition to its own family members, ATF4 can also form heterodimers with other related but distinct bZIP proteins such as the C/EBP, AP-1 and Maf families, which may give rise to a variety of combinatorial diversity in gene regulation. In order to assess the in vivo essential role of ATF4, we have generated mice lacking ATF4 by gene targeting. RESULTS: ATF4-deficient mice exhibited severe microphthalmia. Although ATF4-deficient eyes revealed a normal gross lens structure up to embryonic day 14.5, later on the ATF4-deficient lens, degenerated due to apoptosis without the formation of lens secondary fibre cells. Retinal development was normal in the mutant mice. The lens-specific expression of ATF4 in the mutant mice led not only to the recovery of lens secondary fibres but also to the induction of hyperplasia of these fibres. CONCLUSION: These results demonstrated that ATF4 is essential for the later stages of lens fibre cell differentiation.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Tanaka",
      "authorRank" : 1,
      "name" : "Tanaka T",
      "referenceId" : "RGD:A404001"
    }, {
      "firstName" : "T",
      "lastName" : "Tsujimura",
      "authorRank" : 2,
      "name" : "Tsujimura T",
      "referenceId" : "RGD:A17969"
    }, {
      "firstName" : "K",
      "lastName" : "Takeda",
      "authorRank" : 3,
      "name" : "Takeda K",
      "referenceId" : "RGD:A4193"
    }, {
      "firstName" : "A",
      "lastName" : "Sugihara",
      "authorRank" : 4,
      "name" : "Sugihara A",
      "referenceId" : "RGD:A38433"
    }, {
      "firstName" : "A",
      "lastName" : "Maekawa",
      "authorRank" : 5,
      "name" : "Maekawa A",
      "referenceId" : "RGD:A25133"
    }, {
      "firstName" : "N",
      "lastName" : "Terada",
      "authorRank" : 6,
      "name" : "Terada N",
      "referenceId" : "RGD:A38434"
    }, {
      "firstName" : "N",
      "lastName" : "Yoshida",
      "authorRank" : 7,
      "name" : "Yoshida N",
      "referenceId" : "RGD:A5310"
    }, {
      "firstName" : "S",
      "lastName" : "Akira",
      "authorRank" : 8,
      "name" : "Akira S",
      "referenceId" : "RGD:A24089"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734979"
    } ]
  }, {
    "primaryId" : "PMID:10096042",
    "title" : "The expression of key oxidative stress-handling genes in different brain regions  in Alzheimer's disease.",
    "datePublished" : "1998-10-01T00:00:00.000-05:00",
    "citation" : "Aksenov MY, etal., J Mol Neurosci. 1998 Oct;11(2):151-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-10-08T10:44:04.000-05:00",
    "volume" : "11",
    "pages" : "151-64",
    "abstract" : "Alzheimer's disease (AD) has been hypothesized to be associated with oxidative stress. In this study, the expression of key oxidative stress-handling genes was  studied in hippocampus, inferior parietal lobule, and cerebellum of 10 AD subjects and 10 control subjects using reverse transcriptase-polymerase chain reaction (RT-PCR). The content of Mn-, Cu,Zn-superoxide dismutases (Mn- and Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) mRNAs, and the \"marker genes\" (beta-actin and cyclophilin) mRNAs was determined. This study suggests that gene responses to oxidative stress can be significantly modulated by the general decrease of transcription in the AD brain. To determine if the particular oxidative stress handling gene transcription was induced or suppressed in AD, the \"oxidative stress-handling gene/beta-actin\" ratios were quantified and compared with control values in all brain regions studied. The Mn-SOD mRNA/beta-actin mRNA ratio was unchanged in all regions of the AD brain studied, but an increase of the Cu,Zn-SOD mRNA/beta-actin mRNA ratio was observed in the AD inferior parietal lobule. The levels of peroxidation handling (CAT, GSHPx, and GSSG-R) mRNAs normalized to beta-actin mRNA level were elevated in hippocampus and inferior parietal lobule, but not in  cerebellum of AD patients, which may reflect the protective gene response to the  increased peroxidation in the brain regions showing severe AD pathology. The results of this study suggest that region-specific differences of the magnitude of ROS-mediated injury rather than primary deficits of oxidative stress handling  gene transcription are likely to contribute to the variable intensity of neurodegeneration in different areas of AD brain.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MY",
      "lastName" : "Aksenov",
      "authorRank" : 1,
      "name" : "Aksenov MY",
      "referenceId" : "RGD:A42685"
    }, {
      "firstName" : "HM",
      "lastName" : "Tucker",
      "authorRank" : 2,
      "name" : "Tucker HM",
      "referenceId" : "RGD:A146122"
    }, {
      "firstName" : "P",
      "lastName" : "Nair",
      "authorRank" : 3,
      "name" : "Nair P",
      "referenceId" : "RGD:A76699"
    }, {
      "firstName" : "MV",
      "lastName" : "Aksenova",
      "authorRank" : 4,
      "name" : "Aksenova MV",
      "referenceId" : "RGD:A146123"
    }, {
      "firstName" : "DA",
      "lastName" : "Butterfield",
      "authorRank" : 5,
      "name" : "Butterfield DA",
      "referenceId" : "RGD:A82148"
    }, {
      "firstName" : "S",
      "lastName" : "Estus",
      "authorRank" : 6,
      "name" : "Estus S",
      "referenceId" : "RGD:A78008"
    }, {
      "firstName" : "WR",
      "lastName" : "Markesbery",
      "authorRank" : 7,
      "name" : "Markesbery WR",
      "referenceId" : "RGD:A63353"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10401847"
    } ]
  }, {
    "primaryId" : "PMID:10096549",
    "title" : "Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by  a germ-line Tsc2 mutation in mice.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Kobayashi T, etal., Cancer Res. 1999 Mar 15;59(6):1206-11.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-09T10:59:55.000-06:00",
    "volume" : "59",
    "pages" : "1206-11",
    "abstract" : "Germ-line mutations of the human TSC2 tumor suppressor gene cause tuberous sclerosis (TSC), a disease characterized by the development of hamartomas in various organs. In the Eker rat, however, a germ-line Tsc2 mutation gives rise to renal cell carcinomas with a complete penetrance. The molecular mechanism for this phenotypic difference between man and rat is currently unknown, and the physiological function of the TSC2/Tsc2 product (tuberin) is not fully understood. To investigate these unsolved problems, we have generated a Tsc2 mutant mouse. Tsc2 heterozygous mutant (Tsc2+/-) mice developed renal carcinomas  with a complete penetrance, as seen in the Eker rat, but not the angiomyolipomas  characteristic of human TSC, confirming the existence of a species-specific mechanism of tumorigenesis caused by tuberin deficiency. Unexpectedly, approximately 80% of Tsc2+/- mice also developed hepatic hemangiomas that are not observed in either TSC or the Eker rat. Tsc2 homozygous (Tsc2-/-) mutants died around embryonic day 10.5, indicating an essential function for tuberin in mouse  embryonic development. Some Tsc2-/- embryos exhibited an unclosed neural tube and/or thickened myocardium. The latter is associated with increased cell density that may be a reflection of loss of a growth-suppressive function of tuberin. The mouse strain described here should provide a valuable experimental model to analyze the function of tuberin and its association with tumorigenesis.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kobayashi",
      "authorRank" : 1,
      "name" : "Kobayashi T",
      "referenceId" : "RGD:A5222"
    }, {
      "firstName" : "O",
      "lastName" : "Minowa",
      "authorRank" : 2,
      "name" : "Minowa O",
      "referenceId" : "RGD:A52607"
    }, {
      "firstName" : "J",
      "lastName" : "Kuno",
      "authorRank" : 3,
      "name" : "Kuno J",
      "referenceId" : "RGD:A126824"
    }, {
      "firstName" : "H",
      "lastName" : "Mitani",
      "authorRank" : 4,
      "name" : "Mitani H",
      "referenceId" : "RGD:A9170"
    }, {
      "firstName" : "O",
      "lastName" : "Hino",
      "authorRank" : 5,
      "name" : "Hino O",
      "referenceId" : "RGD:A5225"
    }, {
      "firstName" : "T",
      "lastName" : "Noda",
      "authorRank" : 6,
      "name" : "Noda T",
      "referenceId" : "RGD:A22581"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568655"
    } ]
  }, {
    "primaryId" : "PMID:10096595",
    "title" : "Complex camptopolydactyly: an unusual hand malformation.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Phadke SR and Gautam P, Am J Med Genet. 1999 Mar 19;83(3):191-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-09-02T10:20:27.000-05:00",
    "volume" : "83",
    "pages" : "191-2",
    "abstract" : "Different types of polydactylies and other hand malformations are commonly seen.  Here, we describe a very unusual type of hand malformation characterised by campto-polydactyly with totally disorganised configuration of digits. The role of possible genes involved in development of hands and digits is discussed.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SR",
      "lastName" : "Phadke",
      "authorRank" : 1,
      "name" : "Phadke",
      "referenceId" : "RGD:A193778"
    }, {
      "firstName" : "P",
      "lastName" : "Gautam",
      "authorRank" : 2,
      "name" : "Gautam P",
      "referenceId" : "RGD:A128724"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11532483"
    } ]
  }, {
    "primaryId" : "PMID:10096607",
    "title" : "Differential cellular expression of isoforms of inositol 1,4,5-triphosphate receptors in neurons and glia in brain.",
    "datePublished" : "1999-04-05T00:00:00.000-05:00",
    "citation" : "Sharp AH, etal., J Comp Neurol. 1999 Apr 5;406(2):207-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T02:12:07.000-05:00",
    "volume" : "406",
    "pages" : "207-20",
    "abstract" : "Inositol 1,4,5-trisphosphate receptors (IP3R) are mediators of second messenger-induced intracellular calcium release. Three isoforms are known to be expressed in brain, but their regional distributions and cellular localizations are little known. In order to better understand the roles of IP3 receptor isoforms in brain function, a first step is to define their distributions. We have used affinity-purified antibodies directed against peptides unique to each isoform to determine their sites of expression in rat brain. Type 1 IP3R (IP3R1) is dramatically enriched in Purkinje neurons in cerebellum and neurons in other regions, consistent with previous studies. By contrast, IP3R2 is only detected in glia, whereas IP3R3 is predominantly neuronal, with little detected in glia. IP3R3 is enriched in neuropil, especially in neuronal terminals (which often contain large dense core vesicles) in limbic and basal forebrain regions including olfactory tubercle, central nucleus of the amygdala, and bed nucleus of the stria terminalis. In addition, IP3R1 and IP3R3 have clearly distinct time courses of expression in developing brains. These data suggest separate roles for inositol 1,4,5-trisphosphate receptor isoforms in development, and for glial and neuronal function. The IP3R3 may be involved in regulation of neurotransmitter or neuropeptide release in terminals within specific nuclei of the basal forebrain and limbic system.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A H",
      "lastName" : "Sharp",
      "authorRank" : 1,
      "name" : "Sharp AH",
      "referenceId" : "RGD:A461403"
    }, {
      "firstName" : "F C",
      "lastName" : "Nucifora",
      "authorRank" : 2,
      "name" : "Nucifora FC",
      "referenceId" : "RGD:A450840"
    }, {
      "firstName" : "O",
      "lastName" : "Blondel",
      "authorRank" : 3,
      "name" : "Blondel O",
      "referenceId" : "RGD:A31317"
    }, {
      "firstName" : "C A",
      "lastName" : "Sheppard",
      "authorRank" : 4,
      "name" : "Sheppard CA",
      "referenceId" : "RGD:A461404"
    }, {
      "firstName" : "C",
      "lastName" : "Zhang",
      "authorRank" : 5,
      "name" : "Zhang C",
      "referenceId" : "RGD:A5654"
    }, {
      "firstName" : "S H",
      "lastName" : "Snyder",
      "authorRank" : 6,
      "name" : "Snyder SH",
      "referenceId" : "RGD:A461405"
    }, {
      "firstName" : "J T",
      "lastName" : "Russell",
      "authorRank" : 7,
      "name" : "Russell JT",
      "referenceId" : "RGD:A461406"
    }, {
      "firstName" : "D K",
      "lastName" : "Ryugo",
      "authorRank" : 8,
      "name" : "Ryugo DK",
      "referenceId" : "RGD:A461407"
    }, {
      "firstName" : "C A",
      "lastName" : "Ross",
      "authorRank" : 9,
      "name" : "Ross CA",
      "referenceId" : "RGD:A450845"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702443"
    } ]
  }, {
    "primaryId" : "PMID:10097140",
    "title" : "The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Ishii H, etal., Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3928-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-28T10:18:23.000-06:00",
    "volume" : "96",
    "pages" : "3928-33",
    "abstract" : "Alterations of human chromosome 8p occur frequently in many tumors. We identified a 1.5-Mb common region of allelic loss on 8p22 by allelotype analysis. cDNA selection allowed isolation of several genes, including FEZ1. The predicted Fez1 protein contained a leucine-zipper region with similarity to the DNA-binding domain of the cAMP-responsive activating-transcription factor 5. RNA blot analysis revealed that FEZ1 gene expression was undetectable in more than 60% of epithelial tumors. Mutations were found in primary esophageal cancers and in a prostate cancer cell line. Transcript analysis from several FEZ1-expressing tumors revealed truncated mRNAs, including a frameshift. Alteration and inactivation of the FEZ1 gene may play a role in various human tumors.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Ishii",
      "authorRank" : 1,
      "name" : "Ishii H",
      "referenceId" : "RGD:A20547"
    }, {
      "firstName" : "R",
      "lastName" : "Baffa",
      "authorRank" : 2,
      "name" : "Baffa R",
      "referenceId" : "RGD:A76201"
    }, {
      "firstName" : "SI",
      "lastName" : "Numata",
      "authorRank" : 3,
      "name" : "Numata SI",
      "referenceId" : "RGD:A76202"
    }, {
      "firstName" : "Y",
      "lastName" : "Murakumo",
      "authorRank" : 4,
      "name" : "Murakumo Y",
      "referenceId" : "RGD:A7547"
    }, {
      "firstName" : "S",
      "lastName" : "Rattan",
      "authorRank" : 5,
      "name" : "Rattan S",
      "referenceId" : "RGD:A76203"
    }, {
      "firstName" : "H",
      "lastName" : "Inoue",
      "authorRank" : 6,
      "name" : "Inoue H",
      "referenceId" : "RGD:A4194"
    }, {
      "firstName" : "M",
      "lastName" : "Mori",
      "authorRank" : 7,
      "name" : "Mori M",
      "referenceId" : "RGD:A7028"
    }, {
      "firstName" : "V",
      "lastName" : "Fidanza",
      "authorRank" : 8,
      "name" : "Fidanza V",
      "referenceId" : "RGD:A76204"
    }, {
      "firstName" : "H",
      "lastName" : "Alder",
      "authorRank" : 9,
      "name" : "Alder H",
      "referenceId" : "RGD:A49866"
    }, {
      "firstName" : "CM",
      "lastName" : "Croce",
      "authorRank" : 10,
      "name" : "Croce CM",
      "referenceId" : "RGD:A35770"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600104"
    } ]
  }, {
    "primaryId" : "PMID:10097163",
    "title" : "Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Reyes-Harde M, etal., Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4061-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-05-26T12:27:30.000-05:00",
    "volume" : "96",
    "pages" : "4061-6",
    "abstract" : "Ca2+ released from presynaptic and postsynaptic intracellular stores plays important roles in activity-dependent synaptic plasticity, including long-term depression (LTD) of synaptic strength. At Schaffer collateral-CA1 synapses in the hippocampus, presynaptic ryanodine receptor-gated stores appear to mobilize some of the Ca2+ necessary to induce LTD. Cyclic ADP-ribose (cADPR) has recently been proposed as an endogenous activator of ryanodine receptors in sea urchin eggs and several mammalian cell types. Here, we provide evidence that cADPR-mediated signaling pathways play a key role in inducing LTD. We show that biochemical production of cGMP increases cADPR concentration in hippocampal slices in vitro, and that blockade of cGMP-dependent protein kinase, cADPR receptors, or ryanodine-sensitive Ca2+ stores each prevent the induction of LTD at Schaffer collateral-CA1 synapses. A lack of effect of postsynaptic infusion of either cADPR antagonist indicates a probable presynaptic site of action.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Reyes-Harde",
      "authorRank" : 1,
      "name" : "Reyes-Harde M",
      "referenceId" : "RGD:A107432"
    }, {
      "firstName" : "R",
      "lastName" : "Empson",
      "authorRank" : 2,
      "name" : "Empson R",
      "referenceId" : "RGD:A107433"
    }, {
      "firstName" : "BV",
      "lastName" : "Potter",
      "authorRank" : 3,
      "name" : "Potter BV",
      "referenceId" : "RGD:A5538"
    }, {
      "firstName" : "A",
      "lastName" : "Galione",
      "authorRank" : 4,
      "name" : "Galione A",
      "referenceId" : "RGD:A107434"
    }, {
      "firstName" : "PK",
      "lastName" : "Stanton",
      "authorRank" : 5,
      "name" : "Stanton PK",
      "referenceId" : "RGD:A107435"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2307271"
    } ]
  }, {
    "primaryId" : "PMID:10098486",
    "title" : "Role of thyroid hormone in regulation of renal phosphate transport in young and aged rats.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Alcalde AI, etal., Endocrinology. 1999 Apr;140(4):1544-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-07T10:46:12.000-05:00",
    "volume" : "140",
    "pages" : "1544-51",
    "abstract" : "In the present study, we have examined the cellular mechanisms mediating the regulation of renal proximal tubular sodium-coupled inorganic phosphate (Na/Pi) transport by thyroid hormone (T3) in young and aged rats. Young hypothyroid rats  showed a marked decrease in Na/Pi cotransport activity, which was associated with parallel decreases in type II Na/Pi cotransporter (NaPi-2) protein and messenger  RNA (mRNA) abundance. In contrast, administration of long-term physiological and  supraphysiological doses of T3 resulted in significant increases in Na/Pi cotransport activity, protein, and mRNA levels. Nuclear run-on experiments indicated that thyroid hormone regulates NaPi-2 mRNA levels by a transcriptional  mechanism. In aged rats, although there were no changes in T3 serum levels (when  compared with young animals), there were significant decreases in serum Pi concentration, renal Na/Pi cotransport activity, and NaPi-2 protein and mRNA abundance. These effects were mediated, at least in part, by a reduction in the transcriptional rate of the NaPi-2 gene, probably caused by, among other factors, a smaller response to the stimulatory action of T3. Compared with young rats, the old rats exhibited less sensitivity of the Na/Pi cotransporter to thyroid hormone, with-decreased effects in both hypothyroid (inhibitory) and hyperthyroid (stimulatory) animals.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AI",
      "lastName" : "Alcalde",
      "authorRank" : 1,
      "name" : "Alcalde",
      "referenceId" : "RGD:A169643"
    }, {
      "firstName" : "M",
      "lastName" : "Sarasa",
      "authorRank" : 2,
      "name" : "Sarasa",
      "referenceId" : "RGD:A169644"
    }, {
      "firstName" : "D",
      "lastName" : "Raldua",
      "authorRank" : 3,
      "name" : "Raldua",
      "referenceId" : "RGD:A169645"
    }, {
      "firstName" : "J",
      "lastName" : "Aramayona",
      "authorRank" : 4,
      "name" : "Aramayona",
      "referenceId" : "RGD:A169646"
    }, {
      "firstName" : "R",
      "lastName" : "Morales",
      "authorRank" : 5,
      "name" : "Morales",
      "referenceId" : "RGD:A169647"
    }, {
      "firstName" : "J",
      "lastName" : "Biber",
      "authorRank" : 6,
      "name" : "Biber",
      "referenceId" : "RGD:A403617"
    }, {
      "firstName" : "H",
      "lastName" : "Murer",
      "authorRank" : 7,
      "name" : "Murer",
      "referenceId" : "RGD:A341576"
    }, {
      "firstName" : "M",
      "lastName" : "Levi",
      "authorRank" : 8,
      "name" : "Levi M",
      "referenceId" : "RGD:A11989"
    }, {
      "firstName" : "V",
      "lastName" : "Sorribas",
      "authorRank" : 9,
      "name" : "Sorribas V",
      "referenceId" : "RGD:A34595"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7243131"
    } ]
  }, {
    "primaryId" : "PMID:10098502",
    "title" : "Developmental expression and regulation of adrenocortical cytochrome P4501B1 in the rat.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Brake PB, etal., Endocrinology. 1999 Apr;140(4):1672-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-23T09:38:11.000-06:00",
    "volume" : "140",
    "pages" : "1672-80",
    "abstract" : "A 57-kDa protein whose expression in rat adrenocortical microsomes is increased after weaning has been identified as cytochrome P4501B1 (CYP1B1). Levels of CYP1B1 protein were moderately expressed in late gestation fetuses and on postnatal day 1 (pdl), but were nearly undetectable on pd6 and pd1O. CYP1B1 expression initially increased in the late preweaning period (pd17-19) and again  immediately postweaning (pd21-24). The temporal coincidence of CYP1B1 expression  and weaning was not due to transition from suckling to solid food, as neonates that were prematurely weaned showed no increase in adrenal CYP1B1 compared with normally weaned littermates. The pattern of CYP1B1 expression paralleled changes  in microsomal metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), a marker of CYP1B1 activity. Twice daily injections of ACTH to rat pups (pd3-10) failed to significantly increase the expression of CYP1B1 in pd 10 adrenals, although the injections weakly stimulated steroidogenesis. Adrenocortical cells from pd17 neonates and adult cells, when cultured for 3 days, responded similarly to ACTH induction, although neonates showed more than 4-fold less basal activity. It is concluded that rat adrenal CYP1B1 may be developmentally suppressed, and its expression is independent of diet or the presence of a dam. This suppression is retained in cell culture, but is not due to deficient ACTH signaling. These results may explain the reported resistance of neonatal rat adrenals to the toxic effects of polycyclic aromatic hydrocarbons, which are metabolized by CYP1B1 into mutagenic by-products.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PB",
      "lastName" : "Brake",
      "authorRank" : 1,
      "name" : "Brake PB",
      "referenceId" : "RGD:A29299"
    }, {
      "firstName" : "M",
      "lastName" : "Arai",
      "authorRank" : 2,
      "name" : "Arai M",
      "referenceId" : "RGD:A5879"
    }, {
      "firstName" : "S",
      "lastName" : "As-Sanie",
      "authorRank" : 3,
      "name" : "As-Sanie",
      "referenceId" : "RGD:A178386"
    }, {
      "firstName" : "CR",
      "lastName" : "Jefcoate",
      "authorRank" : 4,
      "name" : "Jefcoate CR",
      "referenceId" : "RGD:A133261"
    }, {
      "firstName" : "EP",
      "lastName" : "Widmaier",
      "authorRank" : 5,
      "name" : "Widmaier EP",
      "referenceId" : "RGD:A27877"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7829725"
    } ]
  }, {
    "primaryId" : "PMID:10098503",
    "title" : "Growth hormone regulates steroidogenic acute regulatory protein expression and steroidogenesis in Leydig cell progenitors.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Kanzaki M and Morris PL, Endocrinology. 1999 Apr;140(4):1681-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-26T09:26:42.000-06:00",
    "volume" : "140",
    "pages" : "1681-6",
    "abstract" : "Gonadal development and differentiation is dependent in part on GH, as GH deficiency has been implicated as a cause of lowered fertility and spermatogenic cessation in humans and some biological models. In this study, we demonstrate that GH receptor messenger RNA (mRNA) is preferentially expressed in progenitor Leydig cells (PLCs) isolated and purified from 21-day-old rats. GH induces significant increases in the levels of steroidogenic acute regulatory protein (StAR), 3beta-hydroxysteroid dehydrogenase (3beta-HSD) expression, and androgen production in PLCs. Additionally, the cytokine interferon-gamma (IFNgamma) markedly inhibits GH-stimulated StAR mRNA and protein levels. When cells are cultured with both GH and IFNgamma, IFNgamma decreases the stimulating effect of GH on androgen production. Treatment of PLCs with cycloheximide does not prevent the GH-induced StAR mRNA, indicating that GH induction of StAR transcripts does not require de novo protein synthesis. In contrast, the induction of 3beta-HSD mRNA by GH is altered by cycloheximide treatment. H7, a serine/threonine kinase inhibitor, completely abrogates the increases in StAR mRNA by GH, whereas the tyrosine kinase inhibitor genistein does not. Moreover, GH further enhances StAR and 3beta-HSD mRNA expression in isolated adult rat Leydig cells despite their increased basal expression subsequent to maturational acquisition of these steroidogenic components. These data provide the first demonstration of the direct effects of GH on testicular steroidogenesis during progenitor Leydig cell differentiation.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kanzaki",
      "authorRank" : 1,
      "name" : "Kanzaki M",
      "referenceId" : "RGD:A7500"
    }, {
      "firstName" : "PL",
      "lastName" : "Morris",
      "authorRank" : 2,
      "name" : "Morris PL",
      "referenceId" : "RGD:A12763"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4891987"
    } ]
  }, {
    "primaryId" : "PMID:10098510",
    "title" : "Leptin modulates the glucocorticoid-induced ovarian steroidogenesis.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Barkan D, etal., Endocrinology. 1999 Apr;140(4):1731-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-11-12T15:38:19.000-06:00",
    "volume" : "140",
    "pages" : "1731-8",
    "abstract" : "Leptin regulates food intake and other activities through its hypothalamic receptor. Leptin receptors are also found in other organs, including the ovary. Direct effects of leptin in ovarian steroid production were studied in primary rat granulosa cells and in rat and human granulosa cell lines. Leptin (0.6-18 nM) suppressed ovarian steroid synthesis costimulated by FSH and dexamethasone. Production of pregnenolone, progesterone, and 20alpha-hydroxy-4-pregnen-3-one was inhibited by leptin. This inhibition was due at least in part to reduced expression of adrenodoxin, a component of the P450scc system enzyme. Costimulation of progesterone production by forskolin and dexamethasone was also inhibited by leptin, whereas the forskolin-induced cAMP production was not affected. We find that leptin induces c-Jun expression and attenuates the transcriptional activity of the glucocorticoid receptor (GR) in granulosa cells. Elevation of c-Jun expression by other means, e.g. 12-O tetradecanoyl-phorbol-13-acetate or transfecting with a c-Jun expression vector, abolished the transcriptional activity of the GR. A leptin-induced elevation of c-Jun modulates the transcriptional activity of the GR, possibly leading to the observed attenuation of steroidogenesis. It was recently shown that glucocorticoids stimulate leptin expression in vivo, which in turn, inhibits cortisol synthesis. A direct action of leptin on the ovary is an additional element of a regulatory network that maintains the homeostasis of steroid production.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Barkan",
      "authorRank" : 1,
      "name" : "Barkan D",
      "referenceId" : "RGD:A115858"
    }, {
      "firstName" : "H",
      "lastName" : "Jia",
      "authorRank" : 2,
      "name" : "Jia H",
      "referenceId" : "RGD:A40095"
    }, {
      "firstName" : "A",
      "lastName" : "Dantes",
      "authorRank" : 3,
      "name" : "Dantes A",
      "referenceId" : "RGD:A41947"
    }, {
      "firstName" : "L",
      "lastName" : "Vardimon",
      "authorRank" : 4,
      "name" : "Vardimon L",
      "referenceId" : "RGD:A130715"
    }, {
      "firstName" : "A",
      "lastName" : "Amsterdam",
      "authorRank" : 5,
      "name" : "Amsterdam A",
      "referenceId" : "RGD:A41950"
    }, {
      "firstName" : "M",
      "lastName" : "Rubinstein",
      "authorRank" : 6,
      "name" : "Rubinstein M",
      "referenceId" : "RGD:A130693"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4145764"
    } ]
  }, {
    "primaryId" : "PMID:10098834",
    "title" : "Molecular cloning of multiple splicing variants of JIP-1 preferentially expressed in brain.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kim IJ, etal., J Neurochem 1999 Apr;72(4):1335-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:07:25.000-05:00",
    "volume" : "72",
    "pages" : "1335-43",
    "abstract" : "Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) is activated by a variety of cellular or environmental stresses. Proper regulation of the SAPK/JNK pathway may be critical for cell survival or death under various conditions. In this study, we report the molecular cloning of novel isoforms of JIP-1, which harbor a putative phosphotyrosine interaction domain and a helix-loop-helix domain, as well as an SH3 homologous region in the C terminus. Northern analysis indicates that transcription variant jip-1 is expressed in brain and kidney and transcription variants jip-2 and jip-3 are specifically expressed in brain. In situ hybridization data showed that the hybridized jip messages were heavily concentrated in adult brain, and were particularly enriched in the cerebral cortex and hippocampus, the brain regions vulnerable to pathological states such as hypoxia-ischemia, epilepsy, and Alzheimer's disease. All the deduced protein products of the jip transcription variants appear to have a similar property in that they inhibit the SAPK/JNK stimulation when overexpressed. Inhibition of SAPK activation by overexpression of the novel isoform JIP-2a resulted in suppression of etoposide-induced cell death in a neuroglioma cell line, N18TG. These findings suggest that JIP may play an important role in regulation of the SAPK pathway that is involved in stress-induced cellular responses.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "IJ",
      "lastName" : "Kim",
      "authorRank" : 1,
      "name" : "Kim IJ",
      "referenceId" : "RGD:A10237"
    }, {
      "firstName" : "KW",
      "lastName" : "Lee",
      "authorRank" : 2,
      "name" : "Lee KW",
      "referenceId" : "RGD:A10238"
    }, {
      "firstName" : "BY",
      "lastName" : "Park",
      "authorRank" : 3,
      "name" : "Park BY",
      "referenceId" : "RGD:A10239"
    }, {
      "firstName" : "JK",
      "lastName" : "Lee",
      "authorRank" : 4,
      "name" : "Lee JK",
      "referenceId" : "RGD:A10240"
    }, {
      "firstName" : "J",
      "lastName" : "Park",
      "authorRank" : 5,
      "name" : "Park J",
      "referenceId" : "RGD:A10241"
    }, {
      "firstName" : "IY",
      "lastName" : "Choi",
      "authorRank" : 6,
      "name" : "Choi IY",
      "referenceId" : "RGD:A10242"
    }, {
      "firstName" : "SJ",
      "lastName" : "Eom",
      "authorRank" : 7,
      "name" : "Eom SJ",
      "referenceId" : "RGD:A10243"
    }, {
      "firstName" : "TS",
      "lastName" : "Chang",
      "authorRank" : 8,
      "name" : "Chang TS",
      "referenceId" : "RGD:A10244"
    }, {
      "firstName" : "MJ",
      "lastName" : "Kim",
      "authorRank" : 9,
      "name" : "Kim MJ",
      "referenceId" : "RGD:A10245"
    }, {
      "firstName" : "YI",
      "lastName" : "Yeom",
      "authorRank" : 10,
      "name" : "Yeom YI",
      "referenceId" : "RGD:A10246"
    }, {
      "firstName" : "SK",
      "lastName" : "Chang",
      "authorRank" : 11,
      "name" : "Chang SK",
      "referenceId" : "RGD:A10247"
    }, {
      "firstName" : "YD",
      "lastName" : "Lee",
      "authorRank" : 12,
      "name" : "Lee YD",
      "referenceId" : "RGD:A10248"
    }, {
      "firstName" : "EJ",
      "lastName" : "Choi",
      "authorRank" : 13,
      "name" : "Choi EJ",
      "referenceId" : "RGD:A10249"
    }, {
      "firstName" : "PL",
      "lastName" : "Han",
      "authorRank" : 14,
      "name" : "Han PL",
      "referenceId" : "RGD:A10250"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70789"
    } ]
  }, {
    "primaryId" : "PMID:10098860",
    "title" : "Molecular cloning of a novel member of the HSP110 family of genes, ischemia-responsive protein 94 kDa (irp94), expressed in rat brain after transient forebrain ischemia.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Yagita Y, etal., J Neurochem 1999 Apr;72(4):1544-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:28:12.000-05:00",
    "volume" : "72",
    "pages" : "1544-51",
    "abstract" : "To identify genes induced by transient forebrain ischemia, we used the mRNA differential display technique in the four-vessel occlusion model in rats. Some genes were identified as candidates that encode ischemia-responsive protein, and one of them was cloned as ischemia-responsive protein 94 kDa (irp94) from the rat hippocampal cDNA library. Sequence analysis suggested that rat irp94 was a transcriptional variant or a homologue of mouse apg-2 and human heat shock protein (hsp) 70RY and a member of the HSP110 family, because IRP94 was >90% identical to APG-2 and HSP70RY and approximately 60% identical to the other members of the HSP110 family. Although irp94 mRNA was constitutively expressed in the normal hippocampus, it was clearly enhanced 4-24 h after ischemia for 10 (1.9-fold increase) and 15 min (3.4-fold increase). These changes mainly occurred in neuronal cells, as judged by the localization of irp94 mRNA using in situ hybridization histochemistry. On the other hand, hyperthermic stress did not enhance irp94 mRNA expression, suggesting that irp94 expression was enhanced under ischemic stress and not related to the heat shock signaling mechanism. Our study suggested that irp94, a novel member of the HSP110 family, might play an important role in the environment altering neuronal functions, especially after transient forebrain ischemia.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Yagita",
      "authorRank" : 1,
      "name" : "Yagita Y",
      "referenceId" : "RGD:A19990"
    }, {
      "firstName" : "K",
      "lastName" : "Kitagawa",
      "authorRank" : 2,
      "name" : "Kitagawa K",
      "referenceId" : "RGD:A17015"
    }, {
      "firstName" : "A",
      "lastName" : "Taguchi",
      "authorRank" : 3,
      "name" : "Taguchi A",
      "referenceId" : "RGD:A19991"
    }, {
      "firstName" : "T",
      "lastName" : "Ohtsuki",
      "authorRank" : 4,
      "name" : "Ohtsuki T",
      "referenceId" : "RGD:A19992"
    }, {
      "firstName" : "K",
      "lastName" : "Kuwabara",
      "authorRank" : 5,
      "name" : "Kuwabara K",
      "referenceId" : "RGD:A19993"
    }, {
      "firstName" : "T",
      "lastName" : "Mabuchi",
      "authorRank" : 6,
      "name" : "Mabuchi T",
      "referenceId" : "RGD:A19994"
    }, {
      "firstName" : "M",
      "lastName" : "Matsumoto",
      "authorRank" : 7,
      "name" : "Matsumoto M",
      "referenceId" : "RGD:A9603"
    }, {
      "firstName" : "T",
      "lastName" : "Yanagihara",
      "authorRank" : 8,
      "name" : "Yanagihara T",
      "referenceId" : "RGD:A18900"
    }, {
      "firstName" : "M",
      "lastName" : "Hori",
      "authorRank" : 9,
      "name" : "Hori M",
      "referenceId" : "RGD:A18584"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633150"
    } ]
  }, {
    "primaryId" : "PMID:10100302",
    "title" : "The effect of hormones on the expression of five isoforms of UDP-glucuronosyltransferase in primary cultures of rat hepatocytes.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Li YQ, etal., Pharm Res. 1999 Feb;16(2):191-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-11T11:29:11.000-06:00",
    "volume" : "16",
    "pages" : "191-7",
    "abstract" : "PURPOSE: To investigate the direct effects of sex hormones, growth hormone, thyroid hormones and dexamethasone on the regulation of UDP-glucuronosyltransferase (UGT). METHODS: Rat hepatocytes were cultured on matrigel and treated with various hormones. Northern blot analysis was carried out using cDNA probes to family 1 and family 2 isoforms. RESULTS: Treatment with 10(-5) M testosterone increased the mRNA levels of UGT 2B1 by 29% and UGT2B3 by 32%. Incubation of growth hormone (10 mU) with hepatocytes suppressed the expression of UGT2B1 and UGT2B3 by 17% and 38%, respectively. T3 administration resulted in a time and dose-dependent effect on the expression of UGT 1 isoforms, with increased UGT1A6 by 70%, and decreased UGT1A1 by 38% and UGT1A5 by 35%. All UGT isoforms except UGT 1A6 studied in this assay were up-regulated by dexamethasone, but to different degrees. The regulation of UGT1A1 and UGT2B1 by dexamethasone was dose and time dependent, and the induction of dexamethasone in the expression of UGT1A1 and UGT2B1 was blocked by cycloheximide but not dichloro-1-D-ribofuranosylbenzimidazole. CONCLUSIONS: This study demonstrates that multiple hormones take part in the regulation of UGT mRNA expression in the rat and individual genes can be differentially modulated.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YQ",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li YQ",
      "referenceId" : "RGD:A120248"
    }, {
      "firstName" : "DA",
      "lastName" : "Prentice",
      "authorRank" : 2,
      "name" : "Prentice DA",
      "referenceId" : "RGD:A120249"
    }, {
      "firstName" : "ML",
      "lastName" : "Howard",
      "authorRank" : 3,
      "name" : "Howard ML",
      "referenceId" : "RGD:A120250"
    }, {
      "firstName" : "ML",
      "lastName" : "Mashford",
      "authorRank" : 4,
      "name" : "Mashford ML",
      "referenceId" : "RGD:A120251"
    }, {
      "firstName" : "PV",
      "lastName" : "Desmond",
      "authorRank" : 5,
      "name" : "Desmond PV",
      "referenceId" : "RGD:A116648"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317062"
    } ]
  }, {
    "primaryId" : "PMID:10100614",
    "title" : "Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytes.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Tinton SA and Buc-Calderon PM, FEBS Lett. 1999 Mar 5;446(1):55-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-09-29T14:51:33.000-05:00",
    "volume" : "446",
    "pages" : "55-9",
    "abstract" : "Incubation of hepatocytes under hypoxia increases binding of translation initiation factor eIF-4E to its inhibitory regulator 4E-BP1, and this correlates  with dephosphorylation of 4E-BP1. Rapamycin induced the same effect in aerobic cells but no additive effect was observed when hypoxic cells were treated with rapamycin. This enhanced association of 4E-BP1 with eIF-4E might be mediated by mTOR. Nevertheless, only hypoxia produces a rapid inhibition of protein synthesis. Although hypoxia might be signalling via the rapamycin-sensitive pathway by changing eIF-4E availability, such a pathway is unlikely to be responsible for the depression in overall protein synthesis under hypoxia.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SA",
      "lastName" : "Tinton",
      "authorRank" : 1,
      "name" : "Tinton",
      "referenceId" : "RGD:A206479"
    }, {
      "firstName" : "PM",
      "lastName" : "Buc-Calderon",
      "authorRank" : 2,
      "name" : "Buc-Calderon",
      "referenceId" : "RGD:A206480"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10401146"
    } ]
  }, {
    "primaryId" : "PMID:10100623",
    "title" : "Discovery of a receptor related to the galanin receptors.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Lee DK, etal., FEBS Lett 1999 Mar 5;446(1):103-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:27:21.000-05:00",
    "volume" : "446",
    "pages" : "103-7",
    "abstract" : "We report the isolation of a cDNA clone named GPR54, which encodes a novel G protein-coupled receptor (GPCR). A PCR search of rat brain cDNA retrieved a clone partially encoding a GPCR. In a library screening this clone was used to isolate a cDNA with an open reading frame (ORF) encoding a receptor of 396 amino acids long which shared significant identities in the transmembrane regions with rat galanin receptors GalR1 (45%), GalR3 (45%) and GalR2 (44%). Northern blot and in situ hybridization analyses revealed that GPR54 is expressed in brain regions (pons, midbrain, thalamus, hypothalamus, hippocampus, amygdala, cortex, frontal cortex, and striatum) as well as peripheral regions (liver and intestine). In COS cell expression of GPR54 no specific binding was observed for 125I-galanin. A recent BLAST search with the rat GPR54 ORF nucleotide sequence recovered the human orthologue of GPR54 in a 3.5 Mb contig localized to chromosome 19p13.3.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DK",
      "lastName" : "Lee",
      "authorRank" : 1,
      "name" : "Lee DK",
      "referenceId" : "RGD:A10049"
    }, {
      "firstName" : "T",
      "lastName" : "Nguyen",
      "authorRank" : 2,
      "name" : "Nguyen T",
      "referenceId" : "RGD:A7420"
    }, {
      "firstName" : "GP",
      "lastName" : "O'Neill",
      "authorRank" : 3,
      "name" : "O'Neill GP",
      "referenceId" : "RGD:A10050"
    }, {
      "firstName" : "R",
      "lastName" : "Cheng",
      "authorRank" : 4,
      "name" : "Cheng R",
      "referenceId" : "RGD:A9599"
    }, {
      "firstName" : "Y",
      "lastName" : "Liu",
      "authorRank" : 5,
      "name" : "Liu Y",
      "referenceId" : "RGD:A6576"
    }, {
      "firstName" : "AD",
      "lastName" : "Howard",
      "authorRank" : 6,
      "name" : "Howard AD",
      "referenceId" : "RGD:A10051"
    }, {
      "firstName" : "N",
      "lastName" : "Coulombe",
      "authorRank" : 7,
      "name" : "Coulombe N",
      "referenceId" : "RGD:A10052"
    }, {
      "firstName" : "CP",
      "lastName" : "Tan",
      "authorRank" : 8,
      "name" : "Tan CP",
      "referenceId" : "RGD:A10053"
    }, {
      "firstName" : "AT",
      "lastName" : "Tang-Nguyen",
      "authorRank" : 9,
      "name" : "Tang-Nguyen AT",
      "referenceId" : "RGD:A10054"
    }, {
      "firstName" : "SR",
      "lastName" : "George",
      "authorRank" : 10,
      "name" : "George SR",
      "referenceId" : "RGD:A5997"
    }, {
      "firstName" : "BF",
      "lastName" : "O'Dowd",
      "authorRank" : 11,
      "name" : "O'Dowd BF",
      "referenceId" : "RGD:A5995"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70752"
    } ]
  }, {
    "primaryId" : "PMID:10100853",
    "title" : "Central role of epidermal growth factor (EGF) receptor density in anchorage-independent growth of normal rat kidney cells.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Lahaye DH, etal., FEBS Lett. 1999 Mar 12;446(2-3):256-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-26T13:57:28.000-05:00",
    "volume" : "446",
    "pages" : "256-60",
    "abstract" : "Epidermal growth factor (EGF) receptor levels are known to play a central role in density dependent growth regulation of normal rat kidney (NRK) fibroblasts. Here  we show that EGF receptor expression is strongly decreased when NRK cells are cultured under anchorage independent conditions, and that expression is returned  to original levels upon cell readherence. Agents that stimulate anchorage independent growth (AIG) of NRK cells in the presence of EGF are shown to upregulate both EGF receptor promoter activity and (125)I-EGF binding capacity. These data show that two aspects of phenotypic transformation of NRK cells, namely density arrest and AIG, can both directly be correlated to EGF receptor levels.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DH",
      "lastName" : "Lahaye",
      "authorRank" : 1,
      "name" : "Lahaye",
      "referenceId" : "RGD:A205694"
    }, {
      "firstName" : "MG",
      "lastName" : "Camps",
      "authorRank" : 2,
      "name" : "Camps",
      "referenceId" : "RGD:A205695"
    }, {
      "firstName" : "EJ",
      "lastName" : "Van Zoelen",
      "authorRank" : 3,
      "name" : "Van Zoelen EJ",
      "referenceId" : "RGD:A94669"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10395246"
    } ]
  }, {
    "primaryId" : "PMID:10100923",
    "title" : "Chronic hypertension in ANP knockout mice: contribution of peripheral resistance.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Melo LG, etal., Regul Pept. 1999 Feb 5;79(2-3):109-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-06T16:07:16.000-06:00",
    "volume" : "79",
    "pages" : "109-15",
    "abstract" : "Atrial Natriuretic Peptide (ANP) exerts a chronic hypotensive effect which is mediated by a reduction in total peripheral resistance (TPR). Mice with a homozygous disruption of the pro-ANP gene (-/-) fail to synthesize ANP and develop chronic hypertension in comparison to their normotensive wild-type (+/+) siblings. In order to determine whether alterations in basal hemodynamics underlie the hypertension associated with lack of endogenous ANP activity, we used anesthetized mice to measure arterial blood pressure (ABP) and heart rate (HR), as well as cardiac output (CO) by thermodilution technique. -/- (n = 7) and +/+ (n = 10) mice of comparable weight and age were used. Stroke volume (SV) and TPR were derived from CO, HR, and ABP by a standard formula. ABP (mm Hg) was significantly higher in -/- (132+/-4) (P < 0.0001) than in +/+ mice (95+/-2). CO (ml min(-1)), HR(beats min(-1))and SV (microl beat(-1)) did not differ significantly between -/- and +/+ mice (CO -/- = 7.3+/-0.5, +/+ = 8.3+/-0.6; HR -/- = 407+/-22, +/+ = 462+/-21; SV -/- = 17.6+/-1.1, +/+ = 17.6+/-1.7). However, TPR (mm Hg ml(-1) min(-1)) was significantly elevated in -/- mice (18.4+/-0.7) compared to +/+ mice (12.3+/-1) (P = 0.0003). Autonomic ganglion blockade with a mixture of hexamethonium and pentolinium was followed by comparable percent reductions in CO (-/- = 28+/-4, +/+ = 29+/-3), HR (-/- = 9+/-4, +/+ = 16+/-4) and SV(-/- = 21+/-4, +/+ = 15+/-6) in both genotypes. However, the concomitant decrease in ABP (%) in -/- (41+/-2) was significantly greater than in +/+ (23+/-4) mice (P = 0.0009) and was accompanied by a significant reduction in TPR. We conclude that the hypertension associated with lack of endogenous ANP is due to elevated TPR, which is determined by an increase in cardiovascular autonomic tone.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LG",
      "lastName" : "Melo",
      "authorRank" : 1,
      "name" : "Melo LG",
      "referenceId" : "RGD:A58585"
    }, {
      "firstName" : "AT",
      "lastName" : "Veress",
      "authorRank" : 2,
      "name" : "Veress AT",
      "referenceId" : "RGD:A58586"
    }, {
      "firstName" : "U",
      "lastName" : "Ackermann",
      "authorRank" : 3,
      "name" : "Ackermann U",
      "referenceId" : "RGD:A58587"
    }, {
      "firstName" : "SC",
      "lastName" : "Pang",
      "authorRank" : 4,
      "name" : "Pang SC",
      "referenceId" : "RGD:A8444"
    }, {
      "firstName" : "TG",
      "lastName" : "Flynn",
      "authorRank" : 5,
      "name" : "Flynn TG",
      "referenceId" : "RGD:A7599"
    }, {
      "firstName" : "H",
      "lastName" : "Sonnenberg",
      "authorRank" : 6,
      "name" : "Sonnenberg H",
      "referenceId" : "RGD:A58588"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578332"
    } ]
  }, {
    "primaryId" : "PMID:10100999",
    "title" : "Cloning and characterization of KPL2, a novel gene induced during ciliogenesis of tracheal epithelial cells.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Ostrowski LE, etal., Am J Respir Cell Mol Biol 1999 Apr;20(4):675-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:26:52.000-05:00",
    "volume" : "20",
    "pages" : "675-83",
    "abstract" : "To identify genes upregulated during the process of ciliated cell differentiation of airway epithelial cells, differential display was used to compare RNA from rat tracheal epithelial (RTE) cells cultured under conditions that inhibit/promote ciliated cell differentiation. Several partial complementary DNAs (cDNAs) were identified whose expression was regulated coordinately with ciliated cell differentiation. One of these, KPL2, detected a messenger RNA transcript of approximately 6 kb when used as a probe on Northern blots of RNA from ciliated cultures but was undetectable in RNA from nonciliated cultures. Sequencing of overlapping clones obtained by a modified rapid amplification of cDNA ends procedure generated a complete cDNA sequence that exhibited no significant homology to sequences in GenBank, indicating that KPL2 is a novel gene. Southern analysis demonstrated that KPL2 exists as a single-copy gene. KPL2 contains a long open reading frame predicted to code for a protein of > 200 kD. Several putative functional motifs are present in the protein, including a calponin homology domain, three nuclear localization signals, a consensus P-loop, and a proline-rich region, suggesting that KPL2 has a unique function. KPL2 was undetectable in heart and liver samples, but was expressed in brain and testis, tissues that contain axonemal structures. In seminiferous tubules of the testis, KPL2 expression was stage-specific and appeared to be highest in spermatocytes and round spermatids. During differentiation of RTE cells, the expression of KPL2 closely paralleled that of an axonemal dynein heavy chain. These results suggest that KPL2 plays an important role in the differentiation or function of ciliated cells in the airway.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LE",
      "lastName" : "Ostrowski",
      "authorRank" : 1,
      "name" : "Ostrowski LE",
      "referenceId" : "RGD:A7398"
    }, {
      "firstName" : "K",
      "lastName" : "Andrews",
      "authorRank" : 2,
      "name" : "Andrews K",
      "referenceId" : "RGD:A19802"
    }, {
      "firstName" : "P",
      "lastName" : "Potdar",
      "authorRank" : 3,
      "name" : "Potdar P",
      "referenceId" : "RGD:A19803"
    }, {
      "firstName" : "H",
      "lastName" : "Matsuura",
      "authorRank" : 4,
      "name" : "Matsuura H",
      "referenceId" : "RGD:A19804"
    }, {
      "firstName" : "A",
      "lastName" : "Jetten",
      "authorRank" : 5,
      "name" : "Jetten A",
      "referenceId" : "RGD:A19805"
    }, {
      "firstName" : "P",
      "lastName" : "Nettesheim",
      "authorRank" : 6,
      "name" : "Nettesheim P",
      "referenceId" : "RGD:A7397"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633099"
    } ]
  }, {
    "primaryId" : "PMID:10101022",
    "title" : "The negative regulation of the rat aldehyde dehydrogenase 3 gene by glucocorticoids: involvement of a single imperfect palindromic glucocorticoid responsive element.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Falkner KC, etal., Mol Pharmacol. 1999 Apr;55(4):649-57.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-09-11T16:16:07.000-05:00",
    "volume" : "55",
    "pages" : "649-57",
    "abstract" : "Glucocorticoids repressed the polycyclic aromatic hydrocarbon-dependent induction of Class 3 aldehyde dehydrogenase (ALDH3) enzyme activity and mRNA levels in isolated rat hepatocytes by more than 50 to 80%, with a concentration-dependence consistent with the involvement of the glucocorticoid receptor (GR). No consistent effect on the low basal transcription rate was observed. This effect of glucocorticoids (GC) on polycyclic aromatic hydrocarbon induction was effectively antagonized at the mRNA and protein level by the GR antagonist RU38486. The response was cycloheximide-sensitive, because the protein synthesis inhibitor caused a GC-dependent superinduction of ALDH3 mRNA levels. This suggests that the effects of GC on this gene are complex and both positive and negative gene regulation is possible. The GC-response was recapitulated in HepG2 cells using transient transfection experiments with CAT reporter constructs containing 3.5 kb of 5'-flanking region from ALDH3. This ligand-dependent response was also observed when a chimeric GR (GR DNA-binding domain and peroxisome proliferator-activated receptor ligand-binding domain) was used in place of GR in the presence of the peroxisome proliferator, nafenopin. A putative palindromic glucocorticoid-responsive element exists between -930 and -910 base pairs relative to the transcription start site. If this element was either deleted or mutated, the negative GC-response was completely lost, which suggests that this sequence is responsible, in part, for the negative regulation of the gene. Electrophoretic mobility shift analysis demonstrated that this palindromic glucocorticoid-responsive element is capable of forming a specific DNA-protein complex with human glucocorticoid receptor. In conclusion, the negative regulation of ALDH3 in rat liver is probably mediated through direct GR binding to its canonical responsive element.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KC",
      "lastName" : "Falkner",
      "authorRank" : 1,
      "name" : "Falkner KC",
      "referenceId" : "RGD:A100004"
    }, {
      "firstName" : "GH",
      "lastName" : "Xiao",
      "authorRank" : 2,
      "name" : "Xiao GH",
      "referenceId" : "RGD:A34318"
    }, {
      "firstName" : "JA",
      "lastName" : "Pinaire",
      "authorRank" : 3,
      "name" : "Pinaire JA",
      "referenceId" : "RGD:A100005"
    }, {
      "firstName" : "ML",
      "lastName" : "Pendleton",
      "authorRank" : 4,
      "name" : "Pendleton ML",
      "referenceId" : "RGD:A100006"
    }, {
      "firstName" : "R",
      "lastName" : "Lindahl",
      "authorRank" : 5,
      "name" : "Lindahl R",
      "referenceId" : "RGD:A15509"
    }, {
      "firstName" : "RA",
      "lastName" : "Prough",
      "authorRank" : 6,
      "name" : "Prough RA",
      "referenceId" : "RGD:A100007"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2300316"
    } ]
  }, {
    "primaryId" : "PMID:10101033",
    "title" : "Cloning and functional characterization of a new multispecific organic anion transporter, OAT-K2, in rat kidney.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Masuda S, etal., Mol Pharmacol 1999 Apr;55(4):743-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:18.000-05:00",
    "volume" : "55",
    "pages" : "743-52",
    "abstract" : "We have isolated a cDNA coding a new organic anion transporter, OAT-K2, expressed specifically in rat kidney. The OAT-K2 cDNA had an open reading frame encoding a 498-amino acid protein (calculated molecular mass of 55 kDa) that shows 91% identity with the rat kidney-specific organic anion transporter, OAT-K1. Reverse transcription-coupled polymerase chain reaction analyses revealed that the OAT-K2 mRNA was expressed predominantly in the proximal convoluted tubules, proximal straight tubules, and cortical collecting ducts. When expressed in Xenopus oocytes, OAT-K2 stimulated the uptake of hydrophobic organic anions, such as taurocholate, methotrexate, folate, and prostaglandin E2, although its homolog OAT-K1 transported methotrexate and folate, but not taurocholate and prostaglandin E2. In MDCK cells stably transfected with the OAT-K1 and OAT-K2 cDNAs, each transporter was localized functionally to the apical membranes and showed transport activity similar to that in the oocyte. Moreover, the efflux of preloaded taurocholate was also enhanced across the apical membrane in OAT-K2 transfectant. The taurocholate transport by OAT-K2-expressing cells showed saturability (Km = 10.3 microM). Several organic anions, bile acids, cardiac glycosides, and steroids had potent inhibitory effects on the OAT-K2-mediated taurocholate transport in the transfectant. These findings suggest that the OAT-K2 participates in epithelial transport of hydrophobic anionic compounds in the kidney.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Masuda",
      "authorRank" : 1,
      "name" : "Masuda S",
      "referenceId" : "RGD:A20714"
    }, {
      "firstName" : "K",
      "lastName" : "Ibaramoto",
      "authorRank" : 2,
      "name" : "Ibaramoto K",
      "referenceId" : "RGD:A33571"
    }, {
      "firstName" : "A",
      "lastName" : "Takeuchi",
      "authorRank" : 3,
      "name" : "Takeuchi A",
      "referenceId" : "RGD:A20715"
    }, {
      "firstName" : "H",
      "lastName" : "Saito",
      "authorRank" : 4,
      "name" : "Saito H",
      "referenceId" : "RGD:A158375"
    }, {
      "firstName" : "Y",
      "lastName" : "Hashimoto",
      "authorRank" : 5,
      "name" : "Hashimoto Y",
      "referenceId" : "RGD:A1169"
    }, {
      "firstName" : "KI",
      "lastName" : "Inui",
      "authorRank" : 6,
      "name" : "Inui KI",
      "referenceId" : "RGD:A33573"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:729753"
    } ]
  }, {
    "primaryId" : "PMID:10101226",
    "title" : "Overexpression of striatal enriched phosphatase (STEP) promotes the neurite outgrowth induced by a cAMP analogue in PC12 cells.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Okamura A, etal., Brain Res Mol Brain Res. 1999 Apr 6;67(1):1-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-03-16T13:05:47.000-05:00",
    "volume" : "67",
    "pages" : "1-9",
    "abstract" : "A cytoplasmic protein tyrosine phosphatase (PTPase) designated as striatal enriched phosphatase with a molecular weight of 46 kDa (STEP46) is highly expressed in striatal neurons with dopamine D1-receptors. To examine the hypothesis that STEP46 is involved in the neuronal functions modulated by the cyclic adenosine 3', 5'-monophosphate (cAMP)-signaling system, we introduced the  complementary DNA of STEP46 into the pheochromocytoma cell line PC12, which exhibits neuronal differentiation characterized by neurite outgrowth in response  to cAMP and nerve growth factor stimulation, and we established subclonal cell lines that constitutively overexpress STEP46 protein with PTPase activity. The subclones expressing STEP46 showed increased neurite outgrowth during differentiation induced by a cAMP analogue (dibutyryl cAMP). The positive regulatory role of STEP46 in the cAMP-induced neuronal differentiation of PC12 cells indicates that STEP46 may play a role in neuronal processes modulated by the cAMP-signaling cascade as a PTPase.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Okamura",
      "authorRank" : 1,
      "name" : "Okamura A",
      "referenceId" : "RGD:A54133"
    }, {
      "firstName" : "S",
      "lastName" : "Goto",
      "authorRank" : 2,
      "name" : "Goto S",
      "referenceId" : "RGD:A22148"
    }, {
      "firstName" : "T",
      "lastName" : "Nishi",
      "authorRank" : 3,
      "name" : "Nishi T",
      "referenceId" : "RGD:A30009"
    }, {
      "firstName" : "T",
      "lastName" : "Hamasaki",
      "authorRank" : 4,
      "name" : "Hamasaki T",
      "referenceId" : "RGD:A52168"
    }, {
      "firstName" : "Y",
      "lastName" : "Ushio",
      "authorRank" : 5,
      "name" : "Ushio Y",
      "referenceId" : "RGD:A28125"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9835028"
    } ]
  }, {
    "primaryId" : "PMID:10101232",
    "title" : "Overexpression of NeuroD in PC12 cells alters morphology and enhances expression of the adenylate kinase isozyme 1 gene.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Noma T, etal., Brain Res Mol Brain Res 1999 Apr 6;67(1):53-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:54:33.000-06:00",
    "volume" : "67",
    "pages" : "53-63",
    "abstract" : "NeuroD, a basic helix-loop-helix transcription factor, plays an important role in neuronal differentiation. A rat NeuroD cDNA was obtained by the aid of reverse transcription-polymerase chain reaction (RT-PCR) and ligated to an expression vector having a CMV promoter. Transfection of the NeuroD-expression plasmid into PC12 cells, a rat pheochromocytoma cell line, induced morphological changes featured by neurite-like processes and synapse-like structures without a differentiation-inducing reagent such as NGF. In the transfected cells, the overproduced NeuroD was detected by Western blot analysis, and the expression of the gene encoding mid-sized neurofilaments, a neuron-specific marker, was demonstrated by RT-PCR. Adenylate kinase isozyme 1 (AK1) is an enzyme involved in the homeostasis of energy metabolism and appears specifically in neuronal cells during differentiation. The CAT reporter assay of the 5'-flanking region of the AK1 gene suggests that NeuroD activates the AK1 expression through E-boxes in the promoter region. RT-PCR analysis indicated the enhanced level of AK1 mRNA in NeuroD-producing PC12 cells. Electrophoretic mobility shift assays demonstrated that NeuroD was able to interact with a proximal E-box element of the AK1 promoter. The results indicated that NeuroD promoted the PC12 cells to differentiate into neuron-like cells with concomitant activation of the target genes including the AK1 and the neurofilament genes.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Noma",
      "authorRank" : 1,
      "name" : "Noma T",
      "referenceId" : "RGD:A15101"
    }, {
      "firstName" : "YS",
      "lastName" : "Yoon",
      "authorRank" : 2,
      "name" : "Yoon YS",
      "referenceId" : "RGD:A27180"
    }, {
      "firstName" : "A",
      "lastName" : "Nakazawa",
      "authorRank" : 3,
      "name" : "Nakazawa A",
      "referenceId" : "RGD:A15103"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727267"
    } ]
  }, {
    "primaryId" : "PMID:10101265",
    "title" : "Analysis of the fatty acid components in a perchloric acid-soluble protein.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Sasagawa T, etal., Biochim Biophys Acta. 1999 Mar 25;1437(3):317-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-19T11:08:45.000-06:00",
    "volume" : "1437",
    "pages" : "317-24",
    "abstract" : "We had previously found that a perchloric acid-soluble protein (PSP1) occurs in rat liver, and that this novel protein inhibits protein synthesis in a rabbit reticulocyte lysate system (T. Oka, H. Tsuji, C. Noda, K. Sakai, Y.-H. Hong, I. Suzuki, S. Munoz, Y. Natori, J. Biol. Chem. 270 (1995) 30060-30067). In the present study, we analyzed lipid components bound to PSP1. Native PSP1 was purified from rat liver using Sephadex G-75, DE-52 cellulose and IgGPSP-affinity  chromatography, and the lipid components were extracted. The components obtained  from the purified PSP1 were shown to be free fatty acids by thin-layer chromatography. By GC-MS, six major fatty acids were identified as 14:0, 16:0, 18:0, 18:1, 18:2 and 20:4. 1 mol of PSP1 contained 1.26 mol of total fatty acid components. The fatty acid-binding assay of PSP1 showed that the Bmax was 1.25 mol fatty acid/mol PSP1 and the Kd value for palmitic acid was 6.03 microM. The concentration of PSP1 mRNA in rat liver increased 2.3-fold by the administration  of peroxisome proliferator, bezafibrate. These findings show that PSP1 is a fatty acid-binding protein-like protein, which is involved in the intracellular metabolism of fatty acid and is quite different from the known fatty acid-binding proteins.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Sasagawa",
      "authorRank" : 1,
      "name" : "Sasagawa T",
      "referenceId" : "RGD:A92017"
    }, {
      "firstName" : "T",
      "lastName" : "Oka",
      "authorRank" : 2,
      "name" : "Oka T",
      "referenceId" : "RGD:A9885"
    }, {
      "firstName" : "A",
      "lastName" : "Tokumura",
      "authorRank" : 3,
      "name" : "Tokumura",
      "referenceId" : "RGD:A198198"
    }, {
      "firstName" : "Y",
      "lastName" : "Nishimoto",
      "authorRank" : 4,
      "name" : "Nishimoto Y",
      "referenceId" : "RGD:A11653"
    }, {
      "firstName" : "S",
      "lastName" : "Munoz",
      "authorRank" : 5,
      "name" : "Munoz S",
      "referenceId" : "RGD:A42630"
    }, {
      "firstName" : "M",
      "lastName" : "Kuwahata",
      "authorRank" : 6,
      "name" : "Kuwahata M",
      "referenceId" : "RGD:A43311"
    }, {
      "firstName" : "M",
      "lastName" : "Okita",
      "authorRank" : 7,
      "name" : "Okita",
      "referenceId" : "RGD:A198433"
    }, {
      "firstName" : "H",
      "lastName" : "Tsuji",
      "authorRank" : 8,
      "name" : "Tsuji H",
      "referenceId" : "RGD:A9883"
    }, {
      "firstName" : "Y",
      "lastName" : "Natori",
      "authorRank" : 9,
      "name" : "Natori Y",
      "referenceId" : "RGD:A24227"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685549"
    } ]
  }, {
    "primaryId" : "PMID:10102268",
    "title" : "Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Brose K, etal., Cell 1999 Mar 19;96(6):795-806.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:54.000-05:00",
    "volume" : "96",
    "pages" : "795-806",
    "abstract" : "Extending axons in the developing nervous system are guided in part by repulsive cues. Genetic analysis in Drosophila, reported in a companion to this paper, identifies the Slit protein as a candidate ligand for the repulsive guidance receptor Roundabout (Robo). Here we describe the characterization of three mammalian Slit homologs and show that the Drosophila Slit protein and at least one of the mammalian Slit proteins, Slit2, are proteolytically processed and show specific, high-affinity binding to Robo proteins. Furthermore, recombinant Slit2 can repel embryonic spinal motor axons in cell culture. These results support the hypothesis that Slit proteins have an evolutionarily conserved role in axon guidance as repulsive ligands for Robo receptors.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Brose",
      "authorRank" : 1,
      "name" : "Brose K",
      "referenceId" : "RGD:A52299"
    }, {
      "firstName" : "KS",
      "lastName" : "Bland",
      "authorRank" : 2,
      "name" : "Bland KS",
      "referenceId" : "RGD:A5751"
    }, {
      "firstName" : "KH",
      "lastName" : "Wang",
      "authorRank" : 3,
      "name" : "Wang KH",
      "referenceId" : "RGD:A5752"
    }, {
      "firstName" : "D",
      "lastName" : "Arnott",
      "authorRank" : 4,
      "name" : "Arnott D",
      "referenceId" : "RGD:A5753"
    }, {
      "firstName" : "W",
      "lastName" : "Henzel",
      "authorRank" : 5,
      "name" : "Henzel W",
      "referenceId" : "RGD:A5754"
    }, {
      "firstName" : "CS",
      "lastName" : "Goodman",
      "authorRank" : 6,
      "name" : "Goodman CS",
      "referenceId" : "RGD:A52302"
    }, {
      "firstName" : "M",
      "lastName" : "Tessier-Lavigne",
      "authorRank" : 7,
      "name" : "Tessier-Lavigne M",
      "referenceId" : "RGD:A115977"
    }, {
      "firstName" : "T",
      "lastName" : "Kidd",
      "authorRank" : 8,
      "name" : "Kidd T",
      "referenceId" : "RGD:A52301"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68763"
    } ]
  }, {
    "primaryId" : "PMID:10102422",
    "title" : "Calpain III mutation analysis of a heterogeneous limb-girdle muscular dystrophy population.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Chou FL, etal., Neurology. 1999 Mar 23;52(5):1015-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:32:16.000-05:00",
    "volume" : "52",
    "pages" : "1015-20",
    "abstract" : "OBJECTIVE: To determine the frequency of calpain III mutations in a heterogeneous limb-girdle muscular dystrophy (LGMD) population. BACKGROUND: Mutations of the calpain III gene have been shown to cause a subset of autosomal recessive LGMDs.  Patient populations studied to date have been primarily of French and Spanish origin, in which calpain III may cause 30% of autosomal recessive MDs. The incidence of calpain III mutations in non-French/Spanish MD patients has not been studied thoroughly. No sensitive and specific biopsy screening methods for detecting patients with abnormal calpain III protein are available. Thus, detection of patients relies on direct detection of gene mutations. METHODS: The  authors studied the calpain III gene in 107 MD patient muscle biopsies exhibiting normal dystrophin. Muscle biopsy RNA was produced for each patient, and the entire calpain III complementary DNA was screened for mutations by reverse-transcriptase PCR/single-strand conformation polymorphism using three different conditions. RESULTS: The authors identified nine patients (eight unrelated) with causative mutations. Six of the seven distinct mutations identified are novel mutations and have not been described previously. CONCLUSION: The results suggest that approximately 9.2% of patients in the heterogeneous population with an LGMD diagnosis will show mutations of the calpain III gene. Interestingly, two patients were heterozygous for a single mutation at the DNA level, whereas only the mutant allele was observed at the RNA level. This suggests that there are undetectable, nondeletion mutations that ablate expression of the calpain III gene.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FL",
      "lastName" : "Chou",
      "authorRank" : 1,
      "name" : "Chou FL",
      "referenceId" : "RGD:A75916"
    }, {
      "firstName" : "C",
      "lastName" : "Angelini",
      "authorRank" : 2,
      "name" : "Angelini C",
      "referenceId" : "RGD:A71527"
    }, {
      "firstName" : "D",
      "lastName" : "Daentl",
      "authorRank" : 3,
      "name" : "Daentl D",
      "referenceId" : "RGD:A38114"
    }, {
      "firstName" : "C",
      "lastName" : "Garcia",
      "authorRank" : 4,
      "name" : "Garcia C",
      "referenceId" : "RGD:A43357"
    }, {
      "firstName" : "C",
      "lastName" : "Greco",
      "authorRank" : 5,
      "name" : "Greco C",
      "referenceId" : "RGD:A45800"
    }, {
      "firstName" : "I",
      "lastName" : "Hausmanowa-Petrusewicz",
      "authorRank" : 6,
      "name" : "Hausmanowa-Petrusewicz",
      "referenceId" : "RGD:A255506"
    }, {
      "firstName" : "A",
      "lastName" : "Fidzianska",
      "authorRank" : 7,
      "name" : "Fidzianska",
      "referenceId" : "RGD:A254111"
    }, {
      "firstName" : "H",
      "lastName" : "Wessel",
      "authorRank" : 8,
      "name" : "Wessel",
      "referenceId" : "RGD:A276435"
    }, {
      "firstName" : "EP",
      "lastName" : "Hoffman",
      "authorRank" : 9,
      "name" : "Hoffman EP",
      "referenceId" : "RGD:A12494"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070304"
    } ]
  }, {
    "primaryId" : "PMID:10102715",
    "title" : "Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "t Hart LM, etal., Diabetes. 1999 Apr;48(4):924-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-05-15T14:55:02.000-05:00",
    "volume" : "48",
    "pages" : "924-6",
    "abstract" : "Friedreich's ataxia is associated with GAA trinucleotide repeat expansions in the frataxin gene. In the general population, these trinucleotide expansions are variable in length, and three types of expansions are seen: short, intermediate, and long repeats. Friedreich's ataxia patients are generally homozygous for the long repeats and exhibit diabetes as pronounced comorbidity. Ristow et al. recently reported an association between the intermediate-length normal allele in the frataxin gene and type 2 diabetes. We have investigated in 94 subjects with impaired glucose tolerance (IGT) as to whether the length of the GAA trinucleotide repeat polymorphism in the frataxin gene associates with parameters reflecting beta-cell function. A hyperglycemic clamp at 10 mmol/l glucose for 3 h was used to quantitate beta-cell characteristics. Carriers of one or two intermediate repeat alleles (n = 32) had a 50% higher median first- phase insulin response to glucose than the noncarriers. Furthermore, they needed less time to reach peak insulin. An analysis of the distribution of the various repeat lengths in elderly type 2 diabetic (n = 179) and control subjects (n = 183), with the same age and ethnic background, did not provide evidence for an association of the intermediate-length repeat allele with type 2 diabetes in Dutch Caucasians.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LM",
      "lastName" : "T Hart",
      "authorRank" : 1,
      "name" : "T Hart LM",
      "referenceId" : "RGD:A106897"
    }, {
      "firstName" : "JB",
      "lastName" : "Ruige",
      "authorRank" : 2,
      "name" : "Ruige JB",
      "referenceId" : "RGD:A106898"
    }, {
      "firstName" : "JM",
      "lastName" : "Dekker",
      "authorRank" : 3,
      "name" : "Dekker JM",
      "referenceId" : "RGD:A106899"
    }, {
      "firstName" : "CD",
      "lastName" : "Stehouwer",
      "authorRank" : 4,
      "name" : "Stehouwer CD",
      "referenceId" : "RGD:A94610"
    }, {
      "firstName" : "JA",
      "lastName" : "Maassen",
      "authorRank" : 5,
      "name" : "Maassen JA",
      "referenceId" : "RGD:A77820"
    }, {
      "firstName" : "RJ",
      "lastName" : "Heine",
      "authorRank" : 6,
      "name" : "Heine RJ",
      "referenceId" : "RGD:A106900"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2307051"
    } ]
  }, {
    "primaryId" : "PMID:10102820",
    "title" : "Dynamic control of CaMKII translocation and localization in hippocampal neurons by NMDA receptor stimulation.",
    "datePublished" : "1999-04-02T00:00:00.000-06:00",
    "citation" : "Shen K and Meyer T, Science. 1999 Apr 2;284(5411):162-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-01-21T06:18:05.000-06:00",
    "volume" : "284",
    "pages" : "162-6",
    "abstract" : "Calcium-calmodulin-dependent protein kinase II (CaMKII) is thought to increase synaptic strength by phosphorylating postsynaptic density (PSD) ion channels and signaling proteins. It is shown that N-methyl-D-aspartate (NMDA) receptor stimulation reversibly translocates green fluorescent protein-tagged CaMKII from an F-actin-bound to a PSD-bound state. The translocation time was controlled by the ratio of expressed beta-CaMKII to alpha-CaMKII isoforms. Although F-actin dissociation into the cytosol required autophosphorylation of or calcium-calmodulin binding to beta-CaMKII, PSD translocation required binding of calcium-calmodulin to either the alpha- or beta-CaMKII subunits. Autophosphorylation of CaMKII indirectly prolongs its PSD localization by increasing the calmodulin-binding affinity.",
    "issueName" : "5411",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Shen",
      "authorRank" : 1,
      "name" : "Shen K",
      "referenceId" : "RGD:A119741"
    }, {
      "firstName" : "T",
      "lastName" : "Meyer",
      "authorRank" : 2,
      "name" : "Meyer T",
      "referenceId" : "RGD:A57451"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12050143"
    } ]
  }, {
    "primaryId" : "PMID:10102904",
    "title" : "Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: NMR spectroscopy study.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Moolenaar SH, etal., Clin Chem. 1999 Apr;45(4):459-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:56:11.000-05:00",
    "volume" : "45",
    "pages" : "459-64",
    "abstract" : "<br><b>BACKGROUND: </b>A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition.<br><b>METHODS: </b>We used 1H NMR spectroscopy to study serum and urine from the patient.<br><b>RESULTS: </b>The concentration of N, N-dimethylglycine (DMG) was increased approximately 100-fold in the serum and approximately 20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR spectroscopy and gas chromatography-mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient.<br><b>CONCLUSIONS: </b>DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR spectroscopy of body fluids.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S H",
      "lastName" : "Moolenaar",
      "authorRank" : 1,
      "name" : "Moolenaar SH",
      "referenceId" : "RGD:A562686"
    }, {
      "firstName" : "J",
      "lastName" : "Poggi-Bach",
      "authorRank" : 2,
      "name" : "Poggi-Bach J",
      "referenceId" : "RGD:A597413"
    }, {
      "firstName" : "U F",
      "lastName" : "Engelke",
      "authorRank" : 3,
      "name" : "Engelke UF",
      "referenceId" : "RGD:A562688"
    }, {
      "firstName" : "J M",
      "lastName" : "Corstiaensen",
      "authorRank" : 4,
      "name" : "Corstiaensen JM",
      "referenceId" : "RGD:A597414"
    }, {
      "firstName" : "A",
      "lastName" : "Heerschap",
      "authorRank" : 5,
      "name" : "Heerschap A",
      "referenceId" : "RGD:A44417"
    }, {
      "firstName" : "J G",
      "lastName" : "de Jong",
      "authorRank" : 6,
      "name" : "de Jong JG",
      "referenceId" : "RGD:A589163"
    }, {
      "firstName" : "B A",
      "lastName" : "Binzak",
      "authorRank" : 7,
      "name" : "Binzak BA",
      "referenceId" : "RGD:A597415"
    }, {
      "firstName" : "J",
      "lastName" : "Vockley",
      "authorRank" : 8,
      "name" : "Vockley J",
      "referenceId" : "RGD:A15054"
    }, {
      "firstName" : "R A",
      "lastName" : "Wevers",
      "authorRank" : 9,
      "name" : "Wevers RA",
      "referenceId" : "RGD:A562695"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118980"
    } ]
  }, {
    "primaryId" : "PMID:10103018",
    "title" : "Molecular cloning of human chondromodulin-I, a cartilage-derived growth modulating factor, and its expression in Chinese hamster ovary cells.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hiraki Y, etal., Eur J Biochem 1999 Mar;260(3):869-78.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-08T18:19:50.000-06:00",
    "volume" : "260",
    "pages" : "869-78",
    "abstract" : "Bovine chondromodulin-I (ChM-I) purified from fetal cartilage stimulated the matrix synthesis of chondrocytes, and inhibited the growth of vascular endothelial cells in vitro. The human counterpart of this bovine growth regulating factor has not been identified. We report here the cloning of human ChM-I precursor cDNA and its functional expression in Chinese hamster ovary (CHO) cells. We first identified a genomic DNA fragment which encoded the N-terminus of the ChM-I precursor, and then isolated human ChM-I cDNA from chondrosarcoma tissue by PCR. The deduced amino acid sequence revealed that mature human ChM-I consists of 120 amino acids. In total, 16 amino acid residues were substituted in the human sequence, compared to the bovine counterpart. Almost of all the substitutions were found in the N-terminal hydrophilic domain. In the C-terminal hydrophobic domain (from Phe42 to Val120), the amino acid sequence was identical except for Tyr90, indicating a functional significance of the domain. Northern blotting and in situ hybridization indicated a specific expression of ChM-I mRNA in cartilage. We also successfully determined the cartilage-specific localization of ChM-I protein, using a specific antibody against recombinant human ChM-I. Multiple transfection of the precursor cDNA into CHO cells enabled us to isolate the mature form of human ChM-I from the culture supernatant. Purified recombinant human ChM-I stimulated proteoglycan synthesis in cultured chondrocytes. In contrast, it inhibited the tube morphogenesis of cultured vascular endothelial cells in vitro and angiogenesis in chick chorioallantoic membrane in vivo.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Hiraki",
      "authorRank" : 1,
      "name" : "Hiraki Y",
      "referenceId" : "RGD:A34402"
    }, {
      "firstName" : "K",
      "lastName" : "Mitsui",
      "authorRank" : 2,
      "name" : "Mitsui K",
      "referenceId" : "RGD:A11706"
    }, {
      "firstName" : "N",
      "lastName" : "Endo",
      "authorRank" : 3,
      "name" : "Endo N",
      "referenceId" : "RGD:A38662"
    }, {
      "firstName" : "K",
      "lastName" : "Takahashi",
      "authorRank" : 4,
      "name" : "Takahashi K",
      "referenceId" : "RGD:A161373"
    }, {
      "firstName" : "T",
      "lastName" : "Hayami",
      "authorRank" : 5,
      "name" : "Hayami T",
      "referenceId" : "RGD:A38663"
    }, {
      "firstName" : "H",
      "lastName" : "Inoue",
      "authorRank" : 6,
      "name" : "Inoue H",
      "referenceId" : "RGD:A4194"
    }, {
      "firstName" : "C",
      "lastName" : "Shukunami",
      "authorRank" : 7,
      "name" : "Shukunami C",
      "referenceId" : "RGD:A34399"
    }, {
      "firstName" : "K",
      "lastName" : "Tokunaga",
      "authorRank" : 8,
      "name" : "Tokunaga K",
      "referenceId" : "RGD:A38664"
    }, {
      "firstName" : "T",
      "lastName" : "Kono",
      "authorRank" : 9,
      "name" : "Kono T",
      "referenceId" : "RGD:A31372"
    }, {
      "firstName" : "M",
      "lastName" : "Yamada",
      "authorRank" : 10,
      "name" : "Yamada M",
      "referenceId" : "RGD:A161371"
    }, {
      "firstName" : "HE",
      "lastName" : "Takahashi",
      "authorRank" : 11,
      "name" : "Takahashi HE",
      "referenceId" : "RGD:A38665"
    }, {
      "firstName" : "J",
      "lastName" : "Kondo",
      "authorRank" : 12,
      "name" : "Kondo J",
      "referenceId" : "RGD:A8475"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:737626"
    } ]
  }, {
    "primaryId" : "PMID:10103050",
    "title" : "Heme and acute inflammation role in vivo of heme in the hepatic expression of positive acute-phase reactants in rats.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Lyoumi S, etal., Eur J Biochem. 1999 Apr;261(1):190-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-01T15:34:03.000-06:00",
    "volume" : "261",
    "pages" : "190-6",
    "abstract" : "Acute-phase protein synthesis in the liver during inflammation is regulated via cytokines and glucocorticoids. Using quantitative reverse transcription (RT)-PCR analysis and immunoassay, we explored, in the rat, the response of the acute-phase protein, alpha-2 macroglobulin (A2M), after systemic inflammation induced by lipopolysaccharide (LPS) or localized inflammation induced by turpentine oil (TO). The results indicate that synthesis of A2M is higher following TO-induced inflammation than LPS-induced inflammation and is not correlated with interleukin (IL)-6 or glucocorticoid levels. We studied the putative role of heme in this differential A2M expression following localized vs. systemic inflammation; addition of heme during LPS-induced inflammation can boost the expression of A2M, whereas blocking heme synthesis (by succinyl acetone) or enhancing its consumption in parallel biosynthetic pathways (cytochrome P450 induction by phenobarbital) decreases A2M expression. This decrease was abolished by exogenous heme supplementation. Finally, we demonstrate that heme supplementation is also able to increase the A2M response in female rats to a level similar to that in male rats providing a new insight into the puzzling sexual dimorphism observed previously during localized inflammation. We propose that heme should be considered a new regulatory element in controlling liver A2M expression during inflammation.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Lyoumi",
      "authorRank" : 1,
      "name" : "Lyoumi S",
      "referenceId" : "RGD:A70543"
    }, {
      "firstName" : "H",
      "lastName" : "Puy",
      "authorRank" : 2,
      "name" : "Puy H",
      "referenceId" : "RGD:A70544"
    }, {
      "firstName" : "F",
      "lastName" : "Tamion",
      "authorRank" : 3,
      "name" : "Tamion F",
      "referenceId" : "RGD:A12514"
    }, {
      "firstName" : "C",
      "lastName" : "Bogard",
      "authorRank" : 4,
      "name" : "Bogard C",
      "referenceId" : "RGD:A9468"
    }, {
      "firstName" : "A",
      "lastName" : "Leplingard",
      "authorRank" : 5,
      "name" : "Leplingard A",
      "referenceId" : "RGD:A70545"
    }, {
      "firstName" : "M",
      "lastName" : "Scotte",
      "authorRank" : 6,
      "name" : "Scotte M",
      "referenceId" : "RGD:A70546"
    }, {
      "firstName" : "R",
      "lastName" : "Vranckx",
      "authorRank" : 7,
      "name" : "Vranckx R",
      "referenceId" : "RGD:A29628"
    }, {
      "firstName" : "F",
      "lastName" : "Gauthier",
      "authorRank" : 8,
      "name" : "Gauthier F",
      "referenceId" : "RGD:A16114"
    }, {
      "firstName" : "M",
      "lastName" : "Hiron",
      "authorRank" : 9,
      "name" : "Hiron M",
      "referenceId" : "RGD:A19786"
    }, {
      "firstName" : "M",
      "lastName" : "Daveau",
      "authorRank" : 10,
      "name" : "Daveau M",
      "referenceId" : "RGD:A5816"
    }, {
      "firstName" : "Y",
      "lastName" : "Nordmann",
      "authorRank" : 11,
      "name" : "Nordmann Y",
      "referenceId" : "RGD:A70547"
    }, {
      "firstName" : "JC",
      "lastName" : "Deybach",
      "authorRank" : 12,
      "name" : "Deybach JC",
      "referenceId" : "RGD:A70548"
    }, {
      "firstName" : "JP",
      "lastName" : "Lebreton",
      "authorRank" : 13,
      "name" : "Lebreton JP",
      "referenceId" : "RGD:A70549"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598507"
    } ]
  }, {
    "primaryId" : "PMID:10103072",
    "title" : "ZFM1/SF1 mRNA in rat and gerbil brain after global ischaemia.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Covini N, etal., Eur J Neurosci 1999 Mar;11(3):781-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-04T12:42:37.000-06:00",
    "volume" : "11",
    "pages" : "781-7",
    "abstract" : "Cerebral ischaemia results in significant brain damage, but the molecular mechanisms associated with ischaemia-induced brain injury are not well defined. We have adopted an improved differential-display method to search for new ischaemia-related genes. Among the different cDNAs isolated following transient forebrain ischaemia in rat, PH3.3 was selected for further studies. The search for homologies revealed that it is the rat homologue to human zinc finger motif 1 (ZFM1), also called mammalian splicing factor 1 (SF1). With Northern blot, PH3.3 hybridized with three mRNA species of 2.3, 2.9 and 3.6 kb, significantly increased at 6 h and 5 days after the ischaemic insult. These findings were extended also to another animal model. In situ hybridization in ischaemic gerbils showed that PH3.3 mRNA was induced in the dentate gyrus as early as 4 h post-ischaemia. Expression peaked at 2 days in the whole hippocampus and cortex, and then progressively decreased towards sham levels. By day 4, expression had disappeared almost entirely from the cells in the CA1 region of the hippocampus, concomitant with the degeneration of pyramidal neurons. Interestingly, ZFM1/SF1 has been recently identified as activated following p53-induced apoptosis. Several lines of evidence suggest that p53 may play two roles in the post-ischaemic brain. The primary role of p53 is to activate DNA repair processes, but if repair fails, apoptosis will be initiated. Thus, ZFM1/SF1 may represent a relevant link between p53 and the neuroprotective/neurodegenerative processes which follow cerebral ischaemia.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Covini",
      "authorRank" : 1,
      "name" : "Covini N",
      "referenceId" : "RGD:A28941"
    }, {
      "firstName" : "M",
      "lastName" : "Tamburin",
      "authorRank" : 2,
      "name" : "Tamburin M",
      "referenceId" : "RGD:A28942"
    }, {
      "firstName" : "G",
      "lastName" : "Consalez",
      "authorRank" : 3,
      "name" : "Consalez G",
      "referenceId" : "RGD:A28943"
    }, {
      "firstName" : "P",
      "lastName" : "Salvati",
      "authorRank" : 4,
      "name" : "Salvati P",
      "referenceId" : "RGD:A28944"
    }, {
      "firstName" : "L",
      "lastName" : "Benatti",
      "authorRank" : 5,
      "name" : "Benatti L",
      "referenceId" : "RGD:A10231"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727772"
    } ]
  }, {
    "primaryId" : "PMID:10103075",
    "title" : "The close homologue of the neural adhesion molecule L1 (CHL1): patterns of expression and promotion of neurite outgrowth by heterophilic interactions.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Hillenbrand R, etal., Eur J Neurosci 1999 Mar;11(3):813-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-14T16:09:23.000-05:00",
    "volume" : "11",
    "pages" : "813-26",
    "abstract" : "The close homologue of L1 (CHL1), a member of the L1 family of neural adhesion molecules, is first expressed at times of neurite outgrowth during brain development, and is detectable in subpopulations of neurons, astrocytes, oligodendrocyte precursors and Schwann cells of the mouse and rat. Aggregation assays with CHL1-transfected cells show that CHL1 does not promote homophilic adhesion or does it mediate heterophilic adhesion with L1. CHL1 promotes neurite outgrowth by hippocampal and small cerebellar neurons in substrate-bound and soluble form. The observation that CHL1 and L1 show overlapping, but also distinct patterns of synthesis in neurons and glia, suggests differential effects of L1-like molecules on neurite outgrowth.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Hillenbrand",
      "authorRank" : 1,
      "name" : "Hillenbrand R",
      "referenceId" : "RGD:A39725"
    }, {
      "firstName" : "M",
      "lastName" : "Molthagen",
      "authorRank" : 2,
      "name" : "Molthagen M",
      "referenceId" : "RGD:A52759"
    }, {
      "firstName" : "D",
      "lastName" : "Montag",
      "authorRank" : 3,
      "name" : "Montag D",
      "referenceId" : "RGD:A25244"
    }, {
      "firstName" : "M",
      "lastName" : "Schachner",
      "authorRank" : 4,
      "name" : "Schachner M",
      "referenceId" : "RGD:A11624"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358502"
    } ]
  }, {
    "primaryId" : "PMID:10103130",
    "title" : "Unexpected localization of the Na+/Cl--dependent-like orphan transporter, Rxt1, on synaptic vesicles in the rat central nervous system.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Masson J, etal., Eur J Neurosci. 1999 Apr;11(4):1349-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T02:01:44.000-05:00",
    "volume" : "11",
    "pages" : "1349-61",
    "abstract" : "Numerous features of its primary structure demonstrate that the orphan transporter Rxt1 belongs to the Na+/Cl--dependent neurotransmitter plasma membrane transporter superfamily, which includes the dopamine, norepinephrine, serotonin and gamma-aminobutyric acid (GABA) transporters. Initial immunocytochemical investigations with affinity-purified antibodies have established that Rxt1 is localized, almost exclusively, in axon terminals of glutamatergic neurons and subsets of GABAergic neurons in the CNS. Further studies were carried out to determine its subcellular distribution. In a first series of experiments, PC-12 cells were transfected with plasmids encoding either the dopamine transporter or Rxt1. Immunofluorescence experiments showed that the dopamine transporter was expressed in these cells, and, as expected, addressed to their plasma membrane. Surprisingly, this was never the case with Rxt1, which was targeted to the same subcellular compartment as synaptophysin, a vesicular protein. In a second set of experiments, subcellular fractionation of rat striatum showed that Rxt1, but not the dopamine transporter, was relatively abundant in the purified synaptic vesicle fraction. Finally, electron microscopic immunocytochemistry with anti-Rxt1 antibodies showed peroxidase as well as pre- and post-embedding immunogold labelling confined to the intracellular compartment in various brain regions. Moreover, quantitative analysis of post-embedding experiments demonstrated that the immunogold particles corresponding to Rxt1 immunoreactivity were mostly localized to small synaptic vesicles. These data indicate that, in contrast with the other members of the Na+/Cl--dependent neurotransmitter transporter superfamily, which are targeted to the plasma membrane, Rxt1 is distributed as a vesicular protein in the CNS.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Masson",
      "authorRank" : 1,
      "name" : "Masson J",
      "referenceId" : "RGD:A460507"
    }, {
      "firstName" : "M",
      "lastName" : "Riad",
      "authorRank" : 2,
      "name" : "Riad M",
      "referenceId" : "RGD:A82694"
    }, {
      "firstName" : "F",
      "lastName" : "Chaudhry",
      "authorRank" : 3,
      "name" : "Chaudhry F",
      "referenceId" : "RGD:A460508"
    }, {
      "firstName" : "M",
      "lastName" : "Darmon",
      "authorRank" : 4,
      "name" : "Darmon M",
      "referenceId" : "RGD:A120158"
    }, {
      "firstName" : "Z",
      "lastName" : "Aïdouni",
      "authorRank" : 5,
      "name" : "Aïdouni Z",
      "referenceId" : "RGD:A460509"
    }, {
      "firstName" : "M",
      "lastName" : "Conrath",
      "authorRank" : 6,
      "name" : "Conrath M",
      "referenceId" : "RGD:A120164"
    }, {
      "firstName" : "B",
      "lastName" : "Giros",
      "authorRank" : 7,
      "name" : "Giros B",
      "referenceId" : "RGD:A7760"
    }, {
      "firstName" : "M",
      "lastName" : "Hamon",
      "authorRank" : 8,
      "name" : "Hamon M",
      "referenceId" : "RGD:A13582"
    }, {
      "firstName" : "J",
      "lastName" : "Storm-Mathisen",
      "authorRank" : 9,
      "name" : "Storm-Mathisen J",
      "referenceId" : "RGD:A8027"
    }, {
      "firstName" : "L",
      "lastName" : "Descarries",
      "authorRank" : 10,
      "name" : "Descarries L",
      "referenceId" : "RGD:A82696"
    }, {
      "firstName" : "S",
      "lastName" : "El Mestikawy",
      "authorRank" : 11,
      "name" : "El Mestikawy S",
      "referenceId" : "RGD:A1268"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702218"
    } ]
  }, {
    "primaryId" : "PMID:1010970",
    "title" : "Effects of adrenalectomy and hypophysectomy on water and electrolyte metabolism in male and female rats with inherited hypothalamic diabetes insipidus (Brattleboro strain).",
    "datePublished" : "1976-08-01T00:00:00.000-05:00",
    "citation" : "Balment RJ, etal., J Endocrinol 1976 Nov;71(2):193-217.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-22T15:23:23.000-05:00",
    "volume" : "71",
    "pages" : "193-217",
    "abstract" : "Observations on water and electrolyte metabolism after hypophysectomy or adrenalectomy, in male and female rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) are confirmed and extended. The diabetic (homozygous, DI) state relative to the non-diabetic (heterozygous, non-DI) state was characterized by (1) water intake of 55-120% body weight; (2) copious urine hypo-osmotic to plasma; (3) greater excretory rates of total solute, Na, Ca and Mg; (4) similar plasma composition except that in male DI rats, K concentration was less, and in female DI rats osmolarity was higher; (5) glomerular filtration rates (GFR) were similar with close correlations between: food and water intakes, water intake and output, urinary Na and K, Na and Cl, K and Cl, and Ca and Mg; (6) both female DI and non-DI rats had lower urinary Na:K ratios and lower plasma Na concentrations than males; (7) female DI rats excreted relatively larger amounts of K and Cl, and had higher plasma Ca concentrations than other groups. Hypophysectomized DI rats had decreased water intake and urine output, decreased solute excretion, decreased loss of osmotically free water, lower excretory rates of Na, K and Cl, and increased urinary osmolarity and K concentrations. Hypophysectomized non-DI rats had increased urinary excretory rates, decreased solute excretion (by 60-70%), decreased osmotically free water absorption, decreased urinary osmolarity, Na and K concentrations, and increased excretory rates of Ca and Mg. Hypophysectomized DI and non-DI rats had increased plasma osmolarity and Na concentration. Plasma renin activities (PRA) were higher in DI than in non-DI rats with female values lower than those of males; values for both sexes of DI and non-DI rats were reduced after hypophysectomy. Adrenalectomized DI rats had about a 50% reduction in water intake, urine output and free water clearance, increased urinary concentration of electrolytes and total solute by day 4 after operation; their Na balance (dietary:urine) did not change significantly in contrast to adrenalectomized non-DI rats in which a greater percentage of dietary Na appeared in the urine. GFR was similarly reduced in adrenalectomized DI and non-DI rats. Plasma osmolarity increased in adrenalectomized male DI, decreased in female DI and non-DI, and did not change in male non-DI rats. Plasma K concentrations increased after adrenalectomy in all groups, only non-DI rats had a significantly decreased plasma Na concentration. There was no sex difference in pituitary oxytocic activity but it was consistently reduced in DI rats; there was little change after adrenalectomy in male DI and non-DI rats; but there was an increase in DI and non-DI females. Pituitaries of DI rats had no measurable ADH activity (except the inherent activity of oxytocin). Pituitary ADH values for male and female non-DI rats were similar and were unaffected by adrenalectomy.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RJ",
      "lastName" : "Balment",
      "authorRank" : 1,
      "name" : "Balment RJ",
      "referenceId" : "RGD:A16234"
    }, {
      "firstName" : "IC",
      "lastName" : "Jones",
      "authorRank" : 2,
      "name" : "Jones IC",
      "referenceId" : "RGD:A16235"
    }, {
      "firstName" : "IW",
      "lastName" : "Henderson",
      "authorRank" : 3,
      "name" : "Henderson IW",
      "referenceId" : "RGD:A16236"
    }, {
      "firstName" : "JA",
      "lastName" : "Oliver",
      "authorRank" : 4,
      "name" : "Oliver JA",
      "referenceId" : "RGD:A16237"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632039"
    } ]
  }, {
    "primaryId" : "PMID:10132",
    "title" : "Clinical use of narcotics.",
    "datePublished" : "1976-11-01T00:00:00.000-06:00",
    "citation" : "Adriani J and Naraghi M, Conn Med. 1976 Nov;40(11):745-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-01-03T09:09:22.000-06:00",
    "volume" : "40",
    "pages" : "745-50",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Adriani",
      "authorRank" : 1,
      "name" : "Adriani J",
      "referenceId" : "RGD:A58415"
    }, {
      "firstName" : "M",
      "lastName" : "Naraghi",
      "authorRank" : 2,
      "name" : "Naraghi M",
      "referenceId" : "RGD:A58416"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1576365"
    } ]
  }, {
    "primaryId" : "PMID:1013503",
    "title" : "Steroid receptor proteins and regulation of growth in mammary tumors.",
    "datePublished" : "1976-02-01T00:00:00.000-06:00",
    "citation" : "Bruchovsky N and Van Doorn E, Recent Results Cancer Res 1976;(57):121-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-02-22T12:23:11.000-06:00",
    "pages" : "121-42",
    "abstract" : "The failure of the estrogen receptor test to predict unequivocally whether a breast cancer will respond to endocrine therapy has prompted us to re-examine the spectrum of responses that might be expected in a hormone-sensitive tissue. Three basic responses are recognized; initiation of DNA synthesis and cell proliferation; negative feedback; and autophagia. The expression of these responses may be partly or totally deficient in tumors. In some tumors, resistance to hormone may result from the lack of entry of hormone into the nucleus; in others the interaction of hormone with chromatin is probably abnormal Evidence is presented in support of the idea that the presence of steroid in the nucleus is strongly correlated to the presence of cytoplasmic receptor. The results also suggest that there is a strong link between the presence of steroid in the nucleus and the initiation of DNA synthesis. Finally the disappearance of nuclear receptor and the onset of autophagia seem to be related catabolic events.",
    "issueName" : "57",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Bruchovsky",
      "authorRank" : 1,
      "name" : "Bruchovsky N",
      "referenceId" : "RGD:A8367"
    }, {
      "firstName" : "E",
      "lastName" : "Van Doorn",
      "authorRank" : 2,
      "name" : "Van Doorn E",
      "referenceId" : "RGD:A8368"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70256"
    } ]
  }, {
    "primaryId" : "PMID:1013649",
    "title" : "Genetic control of antibody responses to PHA in inbred rats.",
    "datePublished" : "1979-08-01T00:00:00.000-05:00",
    "citation" : "Koch C Scand J Immunol 1976;5(10):1149-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-22T15:24:13.000-05:00",
    "volume" : "5",
    "pages" : "1149-53",
    "abstract" : "Phytohemagglutinin (PHA-P; Difco) contains four immunogenic components. The antibody response in rats to two of these components is shown to be genetically determined: AS rats are high responders and BN rats are low responders to both antigens. Responsiveness to the two components segregates independently as autosomal, dominant traits in a manner that is compatible with a one-gene hypothesis for both responses.The antibody response to the mitogenic fraction of PHA segregates together with the in vitro mitogenic response to PHA and to other mitogens. These responses are not linked to the major histocompatibility complex (MHC) of the rat. The antibody response to a nonmitogenic fraction from PHA is, however, linked to the MHC.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Koch",
      "authorRank" : 1,
      "name" : "Koch C",
      "referenceId" : "RGD:A16363"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632090"
    } ]
  }, {
    "primaryId" : "PMID:10187793",
    "title" : "Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Chen J, etal., J Biol Chem. 1999 Apr 9;274(15):10113-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:08:48.000-05:00",
    "volume" : "274",
    "pages" : "10113-8",
    "abstract" : "Mutations in the human ether-a-go-go-related gene (HERG) cause long QT syndrome,  an inherited disorder of cardiac repolarization that predisposes affected individuals to life-threatening arrhythmias. HERG encodes the cardiac rapid delayed rectifier potassium channel that mediates repolarization of ventricular action potentials. In this study, we used the oocyte expression system and voltage clamp techniques to determine the functional consequences of eight long QT syndrome-associated mutations located in the amino-terminal region of HERG (F29L, N33T, G53R, R56Q, C66G, H70R, A78P, and L86R). Mutant subunits formed functional channels with altered gating properties when expressed alone in oocytes. Deactivation was accelerated by all mutations. Some mutants shifted the  voltage dependence of channel availability to more positive potentials. Voltage ramps indicated that fast deactivation of mutant channels would reduce outward current during the repolarization phase of the cardiac action potential and cause prolongation of the corrected QT interval, QTc. The amino-terminal region of HERG was recently crystallized and shown to possess a Per-Arnt-Sim (PAS) domain. The location of these mutations suggests they may disrupt the PAS domain and interfere with its interaction with the S4-S5 linker of the HERG channel.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Chen",
      "authorRank" : 1,
      "name" : "Chen",
      "referenceId" : "RGD:A415147"
    }, {
      "firstName" : "A",
      "lastName" : "Zou",
      "authorRank" : 2,
      "name" : "Zou",
      "referenceId" : "RGD:A255466"
    }, {
      "firstName" : "I",
      "lastName" : "Splawski",
      "authorRank" : 3,
      "name" : "Splawski I",
      "referenceId" : "RGD:A19586"
    }, {
      "firstName" : "MT",
      "lastName" : "Keating",
      "authorRank" : 4,
      "name" : "Keating MT",
      "referenceId" : "RGD:A18685"
    }, {
      "firstName" : "MC",
      "lastName" : "Sanguinetti",
      "authorRank" : 5,
      "name" : "Sanguinetti MC",
      "referenceId" : "RGD:A61429"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063532"
    } ]
  }, {
    "primaryId" : "PMID:10187832",
    "title" : "Identification of a novel DNA binding site for nuclear orphan receptor OR1.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Feltkamp D, etal., J Biol Chem. 1999 Apr 9;274(15):10421-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-11T00:37:14.000-05:00",
    "volume" : "274",
    "pages" : "10421-9",
    "abstract" : "The nuclear orphan receptor OR1 has been shown to bind as a heterodimer with retinoid X receptor (RXR) to direct repeat 4 (DR4) response elements. It remained unclear, however, whether this represents the only or the optimal binding site for this receptor. Therefore, we performed a DNA binding site selection assay that allows the identification of novel DNA binding sites for OR1 in an unbiased  manner. While OR1 alone was not able to select a specific sequence from the pool  of oligonucleotides, the OR1/RXR heterodimer selected a highly conserved DR1 element, termed DR1s, with two AGGTCA motifs spaced by one adenosine. The functional activity of the consensus binding site was verified in transient transfection assays and corroborated by in vitro studies. Based on the sequence of the consensus DR1s, we located putative natural binding sites in the 5'-promoter flanking regions of the rat S14 gene and the rat cholecystokinin type A receptor gene. Furthermore, we could show that although the OR1/RXR heterodimer has a distinct binding orientation on a DR4 element, it is able to bind in both orientations to the DR1s element. The OR1 paralog LXRalpha does not bind as a heterodimer with RXR to the DR1s element, indicating that these receptors, despite their homology, are involved in the regulation of different sets of genes.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Feltkamp",
      "authorRank" : 1,
      "name" : "Feltkamp D",
      "referenceId" : "RGD:A27210"
    }, {
      "firstName" : "FF",
      "lastName" : "Wiebel",
      "authorRank" : 2,
      "name" : "Wiebel FF",
      "referenceId" : "RGD:A89463"
    }, {
      "firstName" : "S",
      "lastName" : "Alberti",
      "authorRank" : 3,
      "name" : "Alberti S",
      "referenceId" : "RGD:A7288"
    }, {
      "firstName" : "JA",
      "lastName" : "Gustafsson",
      "authorRank" : 4,
      "name" : "Gustafsson JA",
      "referenceId" : "RGD:A5567"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8661622"
    } ]
  }, {
    "primaryId" : "PMID:10188224",
    "title" : "[Transcription factors STAT1 and STAT3 are localized in different compartments of rat embryo fibroblasts transformed by E1A and Ha-Ras oncogenes]",
    "datePublished" : "1998-02-01T00:00:00.000-06:00",
    "citation" : "Poselova TV, etal., Tsitologiia. 1998;40(12):1074-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-28T10:43:24.000-06:00",
    "volume" : "40",
    "pages" : "1074-9",
    "abstract" : "Intracellular distribution of STAT1 and STAT3 transcription factors in normal fibroblasts (REF) and in E1A + Ha-Ras transformed cells has been studied by means of indirect immunofluorescence. The obtained data evidence that in REF cells, in response to the growth factor addition, STAT1 and STAT3 proteins are redistributed from the cytoplasm to the nucleus. In transformants E1A + Ha-Ras, however, significantly different pictures can be seen: while STAT1 is found to be constitutively localized in the cell nuclei, STAT3 is predominantly revealed in the cytoplasm. The data obtained from fractionation of subcellular structures confirm in general the immunofluorescence results on the cytoplasmic localization of STAT3 protein in E1A + Ha-Ras transformants. Thus, transformation of REF cells with E1A + Ha-Ras oncogenes causes a constitutive activation of STAT1 and STAT3 transcription factors, the proteins, however, being distributed in different cell compartments.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TV",
      "lastName" : "Poselova",
      "authorRank" : 1,
      "name" : "Poselova TV",
      "referenceId" : "RGD:A76216"
    }, {
      "firstName" : "AL",
      "lastName" : "Evdonin",
      "authorRank" : 2,
      "name" : "Evdonin AL",
      "referenceId" : "RGD:A60540"
    }, {
      "firstName" : "ND",
      "lastName" : "Medvedeva",
      "authorRank" : 3,
      "name" : "Medvedeva ND",
      "referenceId" : "RGD:A60542"
    }, {
      "firstName" : "VA",
      "lastName" : "Pospelov",
      "authorRank" : 4,
      "name" : "Pospelov VA",
      "referenceId" : "RGD:A76217"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600109"
    } ]
  }, {
    "primaryId" : "PMID:10188904",
    "title" : "Mutation in the PTEN/MMAC1 gene in archival low grade and high grade gliomas.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Davies MP, etal., Br J Cancer. 1999 Mar;79(9-10):1542-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-07-11T16:15:14.000-05:00",
    "volume" : "79",
    "pages" : "1542-8",
    "abstract" : "The PTEN gene, located on 10q23.3, has recently been described as a candidate tumour suppressor gene that may be important in the development of advanced cancers, including gliomas. We have investigated mutation in the PTEN gene by direct sequence analysis of PCR products amplified from samples microdissected from 19 low grade (WHO Grade I and II) and 27 high grade (WHO grade III and IV) archival, formalin-fixed, paraffin-embedded gliomas. Eleven genetic variants in ten tumours have been identified. Eight of these are DNA sequence changes that could affect the encoded protein and were present in 0/2 pilocytic astrocytomas, 0/2 oligoastrocytomas, 0/1 oligodendroglioma, 0/14 astrocytomas, 3/13 (23%) anaplastic astrocytomas and 5/14 (36%) glioblastomas. PTEN mutations were found exclusively in high grade gliomas; this finding was statistically significant. Only two of the PTEN genetic variants have been reported in other studies; two of the genetic changes are in codons in which mutations have not been found previously. The results of this study indicate that mutation in the PTEN gene is present only in histologically more aggressive gliomas, may be associated with the transition from low histological grade to anaplasia, but is absent from the majority of high grade gliomas.",
    "issueName" : "9-10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M P",
      "lastName" : "Davies",
      "authorRank" : 1,
      "name" : "Davies MP",
      "referenceId" : "RGD:A446921"
    }, {
      "firstName" : "F E",
      "lastName" : "Gibbs",
      "authorRank" : 2,
      "name" : "Gibbs FE",
      "referenceId" : "RGD:A446922"
    }, {
      "firstName" : "N",
      "lastName" : "Halliwell",
      "authorRank" : 3,
      "name" : "Halliwell N",
      "referenceId" : "RGD:A446923"
    }, {
      "firstName" : "K A",
      "lastName" : "Joyce",
      "authorRank" : 4,
      "name" : "Joyce KA",
      "referenceId" : "RGD:A446924"
    }, {
      "firstName" : "M M",
      "lastName" : "Roebuck",
      "authorRank" : 5,
      "name" : "Roebuck MM",
      "referenceId" : "RGD:A446925"
    }, {
      "firstName" : "M L",
      "lastName" : "Rossi",
      "authorRank" : 6,
      "name" : "Rossi ML",
      "referenceId" : "RGD:A446926"
    }, {
      "firstName" : "J",
      "lastName" : "Salisbury",
      "authorRank" : 7,
      "name" : "Salisbury J",
      "referenceId" : "RGD:A446927"
    }, {
      "firstName" : "D R",
      "lastName" : "Sibson",
      "authorRank" : 8,
      "name" : "Sibson DR",
      "referenceId" : "RGD:A446928"
    }, {
      "firstName" : "L",
      "lastName" : "Tacconi",
      "authorRank" : 9,
      "name" : "Tacconi L",
      "referenceId" : "RGD:A446929"
    }, {
      "firstName" : "C",
      "lastName" : "Walker",
      "authorRank" : 10,
      "name" : "Walker C",
      "referenceId" : "RGD:A21311"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12914154"
    } ]
  }, {
    "primaryId" : "PMID:10188938",
    "title" : "N-methyl-D-aspartate receptor 1 in the caudate-putamen nucleus: ultrastructural localization and co-expression with sorcin, a 22,000 mol. wt calcium binding protein.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Gracy KN, etal., Neuroscience. 1999 Apr;90(1):107-17.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-09-17T10:35:23.000-05:00",
    "volume" : "90",
    "pages" : "107-17",
    "abstract" : "Entry of calcium through N-methyl-D-aspartate-type glutamate receptors in the caudate-putamen nucleus is essential for normal motor activity, but can produce cytotoxicity with continued stimulation and subsequent release of intracellular calcium. To determine potential functional sites for N-methyl-D-aspartate receptor activation in this region, we examined the ultrastructural localization  of the R1 subunit of the N-methyl-D-aspartate receptor (NMDAR1) in rat brain. In  addition, we comparatively examined the localization of NMDAR1 and sorcin, a 22,000 mol. wt calcium binding protein present in certain striatal neurons and involved in calcium-induced calcium release. NMDAR1-like immunoreactivity was seen at synaptic and non-synaptic sites on neuronal plasma membranes. Of 1514 NMDAR1-labeled profiles, 62% were dendrites and dendritic spines and the remainder were mainly unmyelinated axons and axon terminals. Sorcin-like immunoreactivity was present in 39% of the profiles that contained NMDAR1 labeling, most (533/595) of which were dendrites and dendritic spines. Of 1807 sorcin-labeled profiles, 42% were identified, however, as small processes including spine necks and unmyelinated axons or axon terminals. These profiles also occasionally contained NMDAR1 or showed synaptic or appositional contacts with other NMDAR1-immunoreactive neurons. The results of this study suggest that  in the caudate-putamen nucleus, activation of NMDA receptors permits calcium influx at plasmalemmal sites mainly on dendrites where sorcin may play a role in  calcium-induced calcium release. The presence of sorcin in some, but not all NMDA-containing neurons in the caudate-putamen nucleus has potential implications for the known differential vulnerability of certain striatal neurons to excitotoxins.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KN",
      "lastName" : "Gracy",
      "authorRank" : 1,
      "name" : "Gracy",
      "referenceId" : "RGD:A172881"
    }, {
      "firstName" : "CL",
      "lastName" : "Clarke",
      "authorRank" : 2,
      "name" : "Clarke",
      "referenceId" : "RGD:A172882"
    }, {
      "firstName" : "MB",
      "lastName" : "Meyers",
      "authorRank" : 3,
      "name" : "Meyers",
      "referenceId" : "RGD:A172844"
    }, {
      "firstName" : "VM",
      "lastName" : "Pickel",
      "authorRank" : 4,
      "name" : "Pickel VM",
      "referenceId" : "RGD:A15256"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7327208"
    } ]
  }, {
    "primaryId" : "PMID:10188960",
    "title" : "Effects of a new C5a receptor antagonist on C5a- and endotoxin-induced neutropenia in the rat.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Short A, etal., Br J Pharmacol. 1999 Feb;126(3):551-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-22T13:42:47.000-05:00",
    "volume" : "126",
    "pages" : "551-4",
    "abstract" : "A new C5a receptor antagonist, the cyclic peptide Phe-[Orn-Pro-D-cyclohexylalanine-Trp-Arg], (F-[OPdChaWR]), was tested for its ability to antagonize the neutropenic effects of both C5a and endotoxin in rats. Human recombinant C5a (2 microg kg(-1) i.v.) caused rapid neutropenia, characterized by an 83% decrease in circulating polymorphonuclear leukocytes (PMNs) at 5 min. Administration of F-[OPdChaWR] (0.3-3 mg kg(-1) i.v.), did not affect the levels of circulating PMNs but, when given 10 min prior to C5a, it inhibited the C5a-induced neutropenia by up to 70%. Administration of E. Coli lipopolysaccharide (LPS, 1 mg kg(-1) i.v.) also caused neutropenia with an 88% decrease in circulating PMNs after 30 min. When rats were pretreated with F-[OPdChaWR] (0.3 - 10 mg kg(-1) i.v.) 10 min prior to LPS, there was a dose-dependent antagonism of the neutropenia caused by LPS, with up to 69% reversal of neutropenia observed 30 min after LPS administration. These findings suggest that C5a receptor antagonists may have therapeutic potential in the many diseases known to involve either endotoxin or C5a.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Short",
      "authorRank" : 1,
      "name" : "Short A",
      "referenceId" : "RGD:A78056"
    }, {
      "firstName" : "AK",
      "lastName" : "Wong",
      "authorRank" : 2,
      "name" : "Wong AK",
      "referenceId" : "RGD:A78057"
    }, {
      "firstName" : "AM",
      "lastName" : "Finch",
      "authorRank" : 3,
      "name" : "Finch AM",
      "referenceId" : "RGD:A78058"
    }, {
      "firstName" : "G",
      "lastName" : "Haaima",
      "authorRank" : 4,
      "name" : "Haaima G",
      "referenceId" : "RGD:A78030"
    }, {
      "firstName" : "IA",
      "lastName" : "Shiels",
      "authorRank" : 5,
      "name" : "Shiels IA",
      "referenceId" : "RGD:A77783"
    }, {
      "firstName" : "DP",
      "lastName" : "Fairlie",
      "authorRank" : 6,
      "name" : "Fairlie DP",
      "referenceId" : "RGD:A77785"
    }, {
      "firstName" : "SM",
      "lastName" : "Taylor",
      "authorRank" : 7,
      "name" : "Taylor SM",
      "referenceId" : "RGD:A77786"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600665"
    } ]
  }, {
    "primaryId" : "PMID:10188975",
    "title" : "Bradykinin B1 and B2 receptors, tumour necrosis factor alpha and inflammatory hyperalgesia.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Poole S, etal., Br J Pharmacol. 1999 Feb;126(3):649-56.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-04T11:23:15.000-06:00",
    "volume" : "126",
    "pages" : "649-56",
    "abstract" : "The effects of BK agonists and antagonists, and other hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of hyperalgesic drugs) in a model of mechanical hyperalgesia (the end-point of which was indicated by a brief apnoea, the retraction of the head and forepaws, and muscular tremor). DALBK inhibited responses to carrageenin, bradykinin, DABK, and kallidin. Responses to kallidin and DABK were inhibited by indomethacin or atenolol and abolished by the combination of indomethacin + atenolol. DALBK or HOE 140, given 30 min before, but not 2 h after, carrageenin, BK, DABK and kallidin reduced hyperalgesic responses to these agents. A small dose of DABK+ a small dose of BK evoked a response similar to the response to a much larger dose of DABK or BK, given alone. Responses to BK were antagonized by HOE 140 whereas DALBK antagonized only responses to larger doses of BK. The combination of a small dose of DALBK with a small dose of HOE 140 abolished the response to BK. The hyperalgesic response to LPS (1 microg) was inhibited by DALBK or HOE 140 and abolished by DALBK + HOE 140. The hyperalgesic response to LPS (5 microg) was not antagonized by DALBK + HOE 140. These data suggest: (a) a predominant role for B2 receptors in mediating hyperalgesic responses to BK and to drugs that stimulate BK release, and (b) activation of the hyperalgesic cytokine cascade independently of both B1 and B2 receptors if the hyperalgesic stimulus is of sufficient magnitude.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Poole",
      "authorRank" : 1,
      "name" : "Poole S",
      "referenceId" : "RGD:A19816"
    }, {
      "firstName" : "BB",
      "lastName" : "Lorenzetti",
      "authorRank" : 2,
      "name" : "Lorenzetti BB",
      "referenceId" : "RGD:A106601"
    }, {
      "firstName" : "JM",
      "lastName" : "Cunha",
      "authorRank" : 3,
      "name" : "Cunha JM",
      "referenceId" : "RGD:A133065"
    }, {
      "firstName" : "FQ",
      "lastName" : "Cunha",
      "authorRank" : 4,
      "name" : "Cunha FQ",
      "referenceId" : "RGD:A76037"
    }, {
      "firstName" : "SH",
      "lastName" : "Ferreira",
      "authorRank" : 5,
      "name" : "Ferreira SH",
      "referenceId" : "RGD:A76036"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4891040"
    } ]
  }, {
    "primaryId" : "PMID:10189070",
    "title" : "Involvement of cytosolic phospholipase A2 in the ovulatory process in gonadotropin-primed immature rats.",
    "datePublished" : "1998-09-01T00:00:00.000-05:00",
    "citation" : "Kurusu S, etal., Prostaglandins Leukot Essent Fatty Acids. 1998 Jun;58(6):405-11.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-09-18T15:04:01.000-05:00",
    "volume" : "58",
    "pages" : "405-11",
    "abstract" : "The preovulatory LH surge induces a remarkable increase in ovarian prostaglandins (PGs) which help to mediate the ovulatory process. We investigated whether cytosolic phospholipase A2 (cPLA2) has a role in this PG production in PMSG/hCG-primed immature rats. The immunoreactive signal for cPLA2 was localized in both thecal and granulosa layers of mature follicles and became evident in response to gonadotropins. The PLA2 activity in the whole ovarian cytosol rose slightly after PMSG stimulation, persisted relatively constant until 24 h after hCG injection and thereafter increased gradually. Intra-ovarian bursal injection of arachidonyl trifluoromethyl ketone, a specific inhibitor for cPLA2 ( 1.0-3.0 mg/ovary), significantly reduced ovarian PGE2 content and the ovulation rate. These results suggest that cPLA2 exists in periovulatory follicles and functions in PG production related to the ovulation process.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kurusu",
      "authorRank" : 1,
      "name" : "Kurusu S",
      "referenceId" : "RGD:A11566"
    }, {
      "firstName" : "M",
      "lastName" : "Iwao",
      "authorRank" : 2,
      "name" : "Iwao M",
      "referenceId" : "RGD:A88161"
    }, {
      "firstName" : "M",
      "lastName" : "Kawaminami",
      "authorRank" : 3,
      "name" : "Kawaminami M",
      "referenceId" : "RGD:A11563"
    }, {
      "firstName" : "I",
      "lastName" : "Hashimoto",
      "authorRank" : 4,
      "name" : "Hashimoto I",
      "referenceId" : "RGD:A11567"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642477"
    } ]
  }, {
    "primaryId" : "PMID:10189220",
    "title" : "Novel mutations in African American patients with glycogen storage disease Type II. Mutations in brief no. 209. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Raben N, etal., Hum Mutat. 1999;13(1):83-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:47:03.000-05:00",
    "volume" : "13",
    "pages" : "83-4",
    "abstract" : "The infantile form of GSD II (an inherited deficiency of the lysosomal enzyme, acid alpha-glucosidase, Pompe disease) is a severe and invariably fatal disease characterized by a rapidly progressive generalized hypotonia, hepatomegaly, and cardiomegaly. We have recently demonstrated that African American patients share  a common nonsense R854X mutation in exon 18 (Becker et al., 1998). Two other mutations, D645E and M519V, have been identified in individual African American patients (Hermans et al., 1993a; Huie et al., 1994a). We describe here three novel mutations in this population group: a missense W481R in exon 10, a deletion of a T1441 in exon 10, and a splicing defect at the 5' donor site of intron 8 (IVS g+la) . The splicing defect is shared by two unrelated patients and it is linked to intragenic polymorphic sites identical to those found in patients bearing the common R854X mutation.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Raben",
      "authorRank" : 1,
      "name" : "Raben N",
      "referenceId" : "RGD:A20375"
    }, {
      "firstName" : "E",
      "lastName" : "Lee",
      "authorRank" : 2,
      "name" : "Lee E",
      "referenceId" : "RGD:A31902"
    }, {
      "firstName" : "L",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee L",
      "referenceId" : "RGD:A64198"
    }, {
      "firstName" : "R",
      "lastName" : "Hirschhorn",
      "authorRank" : 4,
      "name" : "Hirschhorn R",
      "referenceId" : "RGD:A44036"
    }, {
      "firstName" : "PH",
      "lastName" : "Plotz",
      "authorRank" : 5,
      "name" : "Plotz PH",
      "referenceId" : "RGD:A40674"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067919"
    } ]
  }, {
    "primaryId" : "PMID:10189222",
    "title" : "Identification of 8 new mutations in Brazilian families with Marfan syndrome. Mutations in brief no. 211. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Perez AB, etal., Hum Mutat. 1999;13(1):84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:37:48.000-05:00",
    "volume" : "13",
    "pages" : "84",
    "abstract" : "Marfan Syndrome (MFS) is a connective tissue disease caused by mutations in the fibrillin-1 FBN1) gene. Screening for mutations in all the 65 exons of the FBN1 gene in 34 unrelated patients were performed to compare the efficiency of SSCP versus Heteroduplex analysis and to verify if the spectrum of mutations in Brazilian patients is similar to the one previously reported. Fourteen different  band shifts were detected by SSCP analysis; among these only 6 were also were also detected through Heteroduplex analysis, suggesting that SSCP analysis was a  more efficient method. Except for one, the molecular alteration was confirmed in  the remaining 13 cases by sequencing; five of them were neutral polymorphisms and the eight others are new pathogenic mutations, as follows: 5 missense, one nonsense and two deletions leading to a premature termination codon (PTC). All of them are located in EGF-like-calcium binding motifs (EGF-like-cb). Our findings reinforce that cysteine substitutions and PTC mutations in the region between exons 24-32 are more likely not to be associated with the neonatal phenotypes.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AB",
      "lastName" : "Perez",
      "authorRank" : 1,
      "name" : "Perez",
      "referenceId" : "RGD:A213867"
    }, {
      "firstName" : "LV",
      "lastName" : "Pereira",
      "authorRank" : 2,
      "name" : "Pereira",
      "referenceId" : "RGD:A250273"
    }, {
      "firstName" : "D",
      "lastName" : "Brunoni",
      "authorRank" : 3,
      "name" : "Brunoni",
      "referenceId" : "RGD:A250274"
    }, {
      "firstName" : "M",
      "lastName" : "Zatz",
      "authorRank" : 4,
      "name" : "Zatz M",
      "referenceId" : "RGD:A26645"
    }, {
      "firstName" : "MR",
      "lastName" : "Passos-Bueno",
      "authorRank" : 5,
      "name" : "Passos-Bueno MR",
      "referenceId" : "RGD:A73369"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062226"
    } ]
  }, {
    "primaryId" : "PMID:10189359",
    "title" : "Identification and expression of delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hoch B, etal., Circ Res 1999 Apr 2;84(6):713-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:45:28.000-06:00",
    "volume" : "84",
    "pages" : "713-21",
    "abstract" : "Despite its importance for the regulation of heart function, little is known about the isoform expression of the multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII) in human myocardium. In this study, we investigated the spectrum of CaMKII isoforms delta2, delta3, delta4, delta8, and delta9 in human striated muscle tissue. Isoform delta3 is characteristically expressed in cardiac muscle. In skeletal muscle, specific expression of a new isoform termed delta11 is demonstrated. Complete sequencing of human delta2 cDNA, representing all common features of the investigated CaMKII subclass, revealed its high homology to the corresponding rat cDNA. Comparative semiquantitative reverse transcription-polymerase chain reaction analyses from left ventricular tissues of normal hearts and from patients suffering from dilated cardiomyopathy showed a significant increase in transcript levels of isoform delta3 relative to the expression of glyceraldehyde-3-phosphate dehydrogenase in diseased hearts (101. 6+/-11.0% versus 64.9+/-9.9% in the nonfailing group; P<0.05, n=6). Transcript levels of the other investigated cardiac CaMKII isoforms remained unchanged. At the protein level, by using a subclass-specific antibody, we observed a similar increase of a delta-CaMKII-specific signal (7.2+/-1.0 versus 3.8+/-0.7 optical density units in the nonfailing group; P<0.05, n=4 through 6). The diseased state of the failing hearts was confirmed by a significant increase in transcript levels for atrial natriuretic peptide (292. 9+/-76.4% versus 40.1+/-3.2% in the nonfailing group; P<0.05, n=3 through 6). Our data characterize for the first time the delta-CaMKII isoform expression pattern in human hearts and demonstrate changes in this expression pattern in heart failure.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Hoch",
      "authorRank" : 1,
      "name" : "Hoch B",
      "referenceId" : "RGD:A26361"
    }, {
      "firstName" : "R",
      "lastName" : "Meyer",
      "authorRank" : 2,
      "name" : "Meyer R",
      "referenceId" : "RGD:A15141"
    }, {
      "firstName" : "R",
      "lastName" : "Hetzer",
      "authorRank" : 3,
      "name" : "Hetzer R",
      "referenceId" : "RGD:A36657"
    }, {
      "firstName" : "EG",
      "lastName" : "Krause",
      "authorRank" : 4,
      "name" : "Krause EG",
      "referenceId" : "RGD:A36658"
    }, {
      "firstName" : "P",
      "lastName" : "Karczewski",
      "authorRank" : 5,
      "name" : "Karczewski P",
      "referenceId" : "RGD:A26362"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734682"
    } ]
  }, {
    "primaryId" : "PMID:10189842",
    "title" : "CTLA-4 gene polymorphism is associated with predisposition to coeliac disease.",
    "datePublished" : "1998-07-01T00:00:00.000-05:00",
    "citation" : "Djilali-Saiah I, etal., Gut 1998 Aug;43(2):187-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T14:20:37.000-05:00",
    "volume" : "43",
    "pages" : "187-9",
    "abstract" : "BACKGROUND: Susceptibility to coeliac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation. AIMS: To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in patients with coeliac disease. PATIENTS: 101 patients with coeliac disease and 130 healthy controls. METHODS: Allele specific hybridisation and restriction enzyme digestion of polymerase chain reaction amplified genomic DNA. RESULTS: The A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes in patients with coeliac disease compared with 65.8% in controls (p < 0.0001), mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p = 0.002). Four patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07 to 0.64, p = 0.002). These differences were maintained when subjects were stratified according to the HLA class II phenotype, in particular when patients and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2) allele or HLA-DQA1*0501/DQB1*02 heterodimer. CONCLUSION: The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Djilali-Saiah",
      "authorRank" : 1,
      "name" : "Djilali-Saiah I",
      "referenceId" : "RGD:A44981"
    }, {
      "firstName" : "J",
      "lastName" : "Schmitz",
      "authorRank" : 2,
      "name" : "Schmitz J",
      "referenceId" : "RGD:A44982"
    }, {
      "firstName" : "E",
      "lastName" : "Harfouch-Hammoud",
      "authorRank" : 3,
      "name" : "Harfouch-Hammoud E",
      "referenceId" : "RGD:A44983"
    }, {
      "firstName" : "JF",
      "lastName" : "Mougenot",
      "authorRank" : 4,
      "name" : "Mougenot JF",
      "referenceId" : "RGD:A44984"
    }, {
      "firstName" : "JF",
      "lastName" : "Bach",
      "authorRank" : 5,
      "name" : "Bach JF",
      "referenceId" : "RGD:A44966"
    }, {
      "firstName" : "S",
      "lastName" : "Caillat-Zucman",
      "authorRank" : 6,
      "name" : "Caillat-Zucman S",
      "referenceId" : "RGD:A44985"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300387"
    } ]
  }, {
    "primaryId" : "PMID:10190324",
    "title" : "Supravalvular aortic stenosis: a splice site mutation within the elastin gene results in reduced expression of two aberrantly spliced transcripts.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Urban Z, etal., Hum Genet. 1999 Feb;104(2):135-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:21:15.000-05:00",
    "volume" : "104",
    "pages" : "135-42",
    "abstract" : "We have screened the elastin gene for mutations responsible for supravalvular aortic stenosis (SVAS) in two large, independently collected families with isolated (nonsyndromic) SVAS. By single-strand conformation polymorphism and heteroduplex analysis, we have identified a C to G transversion within the acceptor splice site of exon 16 in SVAS patients from both families. This mutation segregates in both families with high penetrance of SVAS, and all affected individuals carry the mutation. Haplotype analysis by using closely linked polymorphisms, including a previously unreported BfaI restriction fragment length polymorphism within the 3'-UTR of the elastin gene, indicates that the mutations found in the two apparently non-overlapping kindreds are identical by descent. To study the effect of the mutation on the expression of the mutant allele, we have established a primary skin fibroblast culture from one of the affected individuals. Reverse transcription/polymerase chain reaction analysis of elastin mRNA species indicates that the mutation results in two abnormal elastin  mRNA species. One mutant elastin mRNA is generated by the activation of a cryptic splice site that lies within intron 15 and that adds 44 bp of intronic sequence to the sequence encoded by exon 16. This insertion creates a frame shift that results in a 59-amino-acid-long abnormal protein sequence and leads to a termination codon in the mRNA sequence encoded by exon 17. The smaller abnormal mRNA species arises as a consequence of the skipping of exon 16. This study demonstrates, for the first time, the expression of mutant alleles of the elastin gene in patients with isolated SVAS.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Urban",
      "authorRank" : 1,
      "name" : "Urban Z",
      "referenceId" : "RGD:A35265"
    }, {
      "firstName" : "VV",
      "lastName" : "Michels",
      "authorRank" : 2,
      "name" : "Michels VV",
      "referenceId" : "RGD:A57801"
    }, {
      "firstName" : "SN",
      "lastName" : "Thibodeau",
      "authorRank" : 3,
      "name" : "Thibodeau SN",
      "referenceId" : "RGD:A37105"
    }, {
      "firstName" : "H",
      "lastName" : "Donis-Keller",
      "authorRank" : 4,
      "name" : "Donis-Keller H",
      "referenceId" : "RGD:A29824"
    }, {
      "firstName" : "K",
      "lastName" : "Csiszar",
      "authorRank" : 5,
      "name" : "Csiszar K",
      "referenceId" : "RGD:A35266"
    }, {
      "firstName" : "CD",
      "lastName" : "Boyd",
      "authorRank" : 6,
      "name" : "Boyd CD",
      "referenceId" : "RGD:A29481"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063983"
    } ]
  }, {
    "primaryId" : "PMID:10190750",
    "title" : "Ultrastructure and immunohistochemical identification of the extracellular matrix of the chinchilla cochlea.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Tsuprun V and Santi P, Hear Res. 1999 Mar;129(1-2):35-49.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-28T15:59:32.000-05:00",
    "volume" : "129",
    "pages" : "35-49",
    "abstract" : "The molecular composition and three-dimensional organization of the extracellular matrix (ECM) was studied by immunofluorescent microscopy, transmission and scanning electron microscopy in three connective tissue structures of the cochlea: the spiral limbus, basilar membrane and spiral ligament. Type II collagen, fibronectin, tenascin, chondroitin sulfate proteoglycans, alphav and beta1 integrins were immunolocalized in the ECM of these connective tissue structures. Electron micrographs showed a continuum of cross-striated collagen fibrils having a similar diameter and axial periodicity that spread from the spiral limbus via the basilar membrane and into the spiral ligament. Some of collagen fibrils were aggregated laterally into bundles. Bundle images, and their digital Fourier transformations, showed a major 67-nm axial D-repeat characteristic for collagen fibrils. Transmission electron microscopy showed numerous proteoglycans associated with the collagen fibrils. The spiral limbus, basilar membrane and spiral ligament demonstrated regional differences in molecular composition and structural organization of their ECM. The glycoproteins fibronectin, tenascin and alphav integrin were immunolocalized mainly in the basilar membrane. Collagen fibrils of the spiral limbus and spiral ligament did not appear to be strongly oriented. However, most of the collagen fibrils in the  basilar membrane were arranged into radially directed bundles. Collagen fibrils in the basilar membrane were also surrounded by a homogeneous matrix, which was immunoreactive to fibronectin and tenascin antibodies. A more complete understanding of the composition and structural organization of the ECM in these  connective tissue structures in the cochlea provides a foundation upon which micromechanical models of cochlear function can be constructed.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Tsuprun",
      "authorRank" : 1,
      "name" : "Tsuprun",
      "referenceId" : "RGD:A174863"
    }, {
      "firstName" : "P",
      "lastName" : "Santi",
      "authorRank" : 2,
      "name" : "Santi",
      "referenceId" : "RGD:A403859"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11556225"
    } ]
  }, {
    "primaryId" : "PMID:10190819",
    "title" : "Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Takano H, etal., Arch Neurol. 1999 Mar;56(3):295-300.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:08:35.000-05:00",
    "volume" : "56",
    "pages" : "295-300",
    "abstract" : "BACKGROUND: X-linked adrenoleukodystrophy (ALD) is an inherited disease characterized by progressive neurologic dysfunction, occasionally associated with adrenal insufficiency. The classic form of ALD usually has onset in childhood (childhood cerebral ALD), with rapid neurologic deterioration leading to a vegetative state. Adult-onset cerebral ALD also presents with rapidly progressive neurologic dysfunction. Milder phenotypes such as adrenomyeloneuropathy and Addison disease only also have been recognized. Despite discovery of the causative gene, a molecular basis for the diverse clinical presentations remains  to be elucidated. OBJECTIVES: To conduct mutational analyses in 29 Japanese patients with ALD from 29 unrelated families, to obtain knowledge of the spectrum of mutations in this gene, and to study genotype-phenotype correlations in Japanese patients. METHODS: The 29 patients comprised 13 patients with childhood  cerebral ALD, 11 patients with adult-onset cerebral ALD, and 5 patients with adrenomyeloneuropathy. We conducted detailed mutational analyses of 29 unrelated  Japanese patients with ALD by genomic Southern blot analysis and direct nucleotide sequence analysis of reverse transcriptase-polymerase chain reaction products derived from total RNA that was extracted from cultured skin fibroblasts, lymphoblastoid cells, or peripheral blood leukocytes. RESULTS: Three patients with adult-onset cerebral ALD were identified as having large genomic rearrangements. The remaining 26 patients were identified as having 21 independent mutations, including 12 novel mutations resulting in small nucleotide alterations in the ALD gene. Eighteen (69%) of 26 mutations were missense mutations. Most missense mutations involved amino acids conserved in homologous gene products, including PMP70, mALDRP, and Pxa1p. The AG dinucleotide deletion at position 1081-1082, which has been reported previously to be the most common mutation in white patients (12%-17%), was also identified as the most common mutation in Japanese patients (12%). All phenotypes were associated with mutations resulting in protein truncation or subtle amino acid changes. There were no differences in phenotypic expressions between missense mutations involving conserved amino acids and those involving nonconserved amino acids. CONCLUSIONS: There are no obvious correlations between the phenotypes of patients with ALD and their genotypes, suggesting that other genetic or environmental factors modify the phenotypic expressions of ALD.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Takano",
      "authorRank" : 1,
      "name" : "Takano H",
      "referenceId" : "RGD:A14273"
    }, {
      "firstName" : "R",
      "lastName" : "Koike",
      "authorRank" : 2,
      "name" : "Koike R",
      "referenceId" : "RGD:A20175"
    }, {
      "firstName" : "O",
      "lastName" : "Onodera",
      "authorRank" : 3,
      "name" : "Onodera",
      "referenceId" : "RGD:A415454"
    }, {
      "firstName" : "R",
      "lastName" : "Sasaki",
      "authorRank" : 4,
      "name" : "Sasaki R",
      "referenceId" : "RGD:A29822"
    }, {
      "firstName" : "S",
      "lastName" : "Tsuji",
      "authorRank" : 5,
      "name" : "Tsuji",
      "referenceId" : "RGD:A416864"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069767"
    } ]
  }, {
    "primaryId" : "PMID:10190887",
    "title" : "LDL increases inactive tissue factor on vascular smooth muscle cell surfaces: hydrogen peroxide activates latent cell surface tissue factor.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Penn MS, etal., Circulation. 1999 Apr 6;99(13):1753-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-10-14T14:41:06.000-05:00",
    "volume" : "99",
    "pages" : "1753-9",
    "abstract" : "BACKGROUND: Tissue factor, which is required for the initiation of the extrinsic coagulation cascade, is known to be upregulated in cells within atherosclerotic lesions, including smooth muscle cells. Tissue factor expression on the smooth muscle cell surface could be of pathological significance as a contributor to plaque growth, thrombus formation, and the acute coronary syndrome after plaque rupture. METHODS AND RESULTS: In this study, we show that LDL increased tissue factor mRNA and cell surface protein in smooth muscle cells without a marked increase in surface tissue factor activity. Hydrogen peroxide activated tissue factor on the cell surface but did not increase tissue factor mRNA or cell surface protein. Sequentially added LDL and hydrogen peroxide increased mRNA, cell surface protein, and activity; surface activity was greater than that observed with hydrogen peroxide alone. The action of hydrogen peroxide did not involve a regulatory mechanism associated with the cytoplasmic tail of tissue factor because a truncated tissue factor lacking the cytoplasmic tail was activated by hydrogen peroxide. CONCLUSIONS: These results suggest a novel 2-step pathway for increased tissue factor activity on smooth muscle cell surfaces in which lipoproteins regulate synthesis of a latent tissue factor and oxidants activate the protein complex.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MS",
      "lastName" : "Penn",
      "authorRank" : 1,
      "name" : "Penn MS",
      "referenceId" : "RGD:A33606"
    }, {
      "firstName" : "CV",
      "lastName" : "Patel",
      "authorRank" : 2,
      "name" : "Patel CV",
      "referenceId" : "RGD:A7572"
    }, {
      "firstName" : "MZ",
      "lastName" : "Cui",
      "authorRank" : 3,
      "name" : "Cui MZ",
      "referenceId" : "RGD:A32919"
    }, {
      "firstName" : "PE",
      "lastName" : "DiCorleto",
      "authorRank" : 4,
      "name" : "DiCorleto PE",
      "referenceId" : "RGD:A29688"
    }, {
      "firstName" : "GM",
      "lastName" : "Chisolm",
      "authorRank" : 5,
      "name" : "Chisolm GM",
      "referenceId" : "RGD:A5874"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313771"
    } ]
  }, {
    "primaryId" : "PMID:10191119",
    "title" : "A murine model for juvenile NCL: gene targeting of mouse Cln3.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Greene ND, etal., Mol Genet Metab 1999 Apr;66(4):309-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-31T15:19:17.000-05:00",
    "volume" : "66",
    "pages" : "309-13",
    "abstract" : "JNCL is a neurodegenerative disease of childhood caused by mutations in the CLN3 gene. A mouse model for JNCL was created by disrupting exons 1-6 of Cln3, resulting in a null allele. Cln3 null mice appear clinically normal at 5 months of age; however, like JNCL patients, they exhibit intracellular accumulation of autofluorescent material. A second approach will generate mice in which exons 7 and 8 of Cln3 are deleted, mimicking the common mutation in JNCL patients.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ND",
      "lastName" : "Greene",
      "authorRank" : 1,
      "name" : "Greene ND",
      "referenceId" : "RGD:A37182"
    }, {
      "firstName" : "DL",
      "lastName" : "Bernard",
      "authorRank" : 2,
      "name" : "Bernard DL",
      "referenceId" : "RGD:A55143"
    }, {
      "firstName" : "PE",
      "lastName" : "Taschner",
      "authorRank" : 3,
      "name" : "Taschner PE",
      "referenceId" : "RGD:A36195"
    }, {
      "firstName" : "BD",
      "lastName" : "Lake",
      "authorRank" : 4,
      "name" : "Lake BD",
      "referenceId" : "RGD:A55144"
    }, {
      "firstName" : "N",
      "lastName" : "De Vos",
      "authorRank" : 5,
      "name" : "De Vos N",
      "referenceId" : "RGD:A55133"
    }, {
      "firstName" : "MH",
      "lastName" : "Breuning",
      "authorRank" : 6,
      "name" : "Breuning MH",
      "referenceId" : "RGD:A36199"
    }, {
      "firstName" : "RM",
      "lastName" : "Gardiner",
      "authorRank" : 7,
      "name" : "Gardiner RM",
      "referenceId" : "RGD:A29436"
    }, {
      "firstName" : "SE",
      "lastName" : "Mole",
      "authorRank" : 8,
      "name" : "Mole SE",
      "referenceId" : "RGD:A55145"
    }, {
      "firstName" : "RL",
      "lastName" : "Nussbaum",
      "authorRank" : 9,
      "name" : "Nussbaum RL",
      "referenceId" : "RGD:A55146"
    }, {
      "firstName" : "HM",
      "lastName" : "Mitchison",
      "authorRank" : 10,
      "name" : "Mitchison HM",
      "referenceId" : "RGD:A37945"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549477"
    } ]
  }, {
    "primaryId" : "PMID:10191259",
    "title" : "Cloning and expression of a human choline/ethanolaminephosphotransferase: synthesis of phosphatidylcholine and phosphatidylethanolamine.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Henneberry AL and McMaster CR, Biochem J 1999 Apr 15;339 ( Pt 2):291-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-03T08:58:32.000-06:00",
    "volume" : "339 ( Pt 2)",
    "pages" : "291-8",
    "abstract" : "Cholinephosphotransferase catalyses the final step in the synthesis of phosphatidylcholine (PtdCho) via the Kennedy pathway by the transfer of phosphocholine from CDP-choline to diacylglycerol. Ethanolaminephosphotransferase catalyses an analogous reaction with CDP-ethanolamine as the phosphobase donor for the synthesis of phosphatidylethanolamine (PtdEtn). Together these two enzyme activities determine both the site of synthesis and the fatty acyl composition of PtdCho and PtdEtn synthesized de novo. A human choline/ethanolaminephosphotransferase cDNA (hCEPT1) was cloned, expressed and characterized. Northern blot analysis revealed one hCEPT1 2.3 kb transcript that was ubiquitous and not enriched, with respect to actin, in any particular cell type. The open reading frame predicts a protein (hCEPT1p) of 416 amino acid residues with a molecular mass of 46550 Da containing seven membrane-spanning domains. A predicted amphipathic helix resides within the active site of the enzyme with the final two aspartic residues of the CDP-alcohol phosphotransferase motif, DG(X)2AR(X)8G(X)3D(X)3D, positioned within this helix. hCEPT1p was successfully expressed in a full-length, active form in Saccharomyces cerevisiae cells devoid of endogenous cholinephosphotransferase or ethanolaminephosphotransferase activities (HJ091, cpt1::LEU2 ept1-). In vitro, hCEPT1p displayed broad substrate specificity, utilizing both CDP-choline and CDP-ethanolamine as phosphobase donors to a broad range of diacylglycerols, resulting in the synthesis of both PtdCho and PtdEtn. In vivo, S. cerevisiae cells (HJ091, cpt1::LEU2 ept1-) expressing hCEPT1 efficiently incorporated both radiolabelled choline and ethanolamine into phospholipids, demonstrating that hCEPT1p has the ability to synthesize both choline- and ethanolamine- containing phospholipids in vitro and in vivo.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AL",
      "lastName" : "Henneberry",
      "authorRank" : 1,
      "name" : "Henneberry AL",
      "referenceId" : "RGD:A56437"
    }, {
      "firstName" : "CR",
      "lastName" : "McMaster",
      "authorRank" : 2,
      "name" : "McMaster CR",
      "referenceId" : "RGD:A25962"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556563"
    } ]
  }, {
    "primaryId" : "PMID:10191291",
    "title" : "Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Olivier LM, etal., J Lipid Res. 1999 Apr;40(4):672-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:35:00.000-05:00",
    "volume" : "40",
    "pages" : "672-9",
    "abstract" : "Phosphomevalonate kinase catalyzes the conversion of mevalonate-5-phosphate to mevalonate-5-diphosphate and was originally believed to be a cytosolic enzyme. In this study we have localized the phosphomevalonate kinase gene to chromosome 1p13-1q22-23 and present a genomic map indicating that the gene spans more than 8.4 kb in the human genome. Furthermore, we show that message levels and enzyme activity of rat liver phosphomevalonate kinase are regulated in response to dietary sterol levels and that this regulation is coordinate with 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol biosynthesis. In addition, we demonstrate that phosphomevalonate kinase is a peroxisomal protein which requires the C-terminal peroxisomal targeting signal, Ser-Arg-Leu, for localization to the organelle.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LM",
      "lastName" : "Olivier",
      "authorRank" : 1,
      "name" : "Olivier",
      "referenceId" : "RGD:A184464"
    }, {
      "firstName" : "KL",
      "lastName" : "Chambliss",
      "authorRank" : 2,
      "name" : "Chambliss KL",
      "referenceId" : "RGD:A16896"
    }, {
      "firstName" : "KM",
      "lastName" : "Gibson",
      "authorRank" : 3,
      "name" : "Gibson KM",
      "referenceId" : "RGD:A16902"
    }, {
      "firstName" : "SK",
      "lastName" : "Krisans",
      "authorRank" : 4,
      "name" : "Krisans SK",
      "referenceId" : "RGD:A31417"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553625"
    } ]
  }, {
    "primaryId" : "PMID:10191834",
    "title" : "Altered IGF-I and IGFBPs in senescent male and female rats.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Severgnini S, etal., J Gerontol A Biol Sci Med Sci. 1999 Mar;54(3):B111-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-08-10T16:38:28.000-05:00",
    "volume" : "54",
    "pages" : "B111-5",
    "abstract" : "The effects of senescence on muscle characteristics and the insulin-like growth factor I (IGF-I) pathway were assessed in male and female BN/F344 rats. The mass and total ATPase activity of gastrocnemius and plantaris muscles were reduced with age and to a greater extent in males than in females. The mass and total ATPase activity of soleus muscle were not significantly altered with age. Circulating IGF-I was also significantly reduced with age, 60% in females and 21% in males. Circulating IGF-binding protein 3 (IGFBP-3) was reduced with age. In liver and gastrocnemius muscle, mRNAs for IGF-1, IGFBP-2, and IGFBP-3 were analyzed in young and aged males of two strains, BN/F344 and Sprague-Dawley. In BN/F344 rats, liver mRNAs were unchanged with age. Also in BN/F344 rats, muscle mRNAs for IGFBP-2, and IGFBP-3 displayed nonsignificant trends toward increase with age. In aged Sprague-Dawley males, liver mRNA for IGF-I was increased 15% and muscle mRNA for IGFBP-2 was increased 110%. Thus, different age-related changes in the growth hormone (GH)/IGF pathway occur in males and females between the sexes and strains. These changes may play a role in the muscle atrophy associated with senescence.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Severgnini",
      "authorRank" : 1,
      "name" : "Severgnini S",
      "referenceId" : "RGD:A86429"
    }, {
      "firstName" : "DT",
      "lastName" : "Lowenthal",
      "authorRank" : 2,
      "name" : "Lowenthal DT",
      "referenceId" : "RGD:A86430"
    }, {
      "firstName" : "WJ",
      "lastName" : "Millard",
      "authorRank" : 3,
      "name" : "Millard WJ",
      "referenceId" : "RGD:A86431"
    }, {
      "firstName" : "FA",
      "lastName" : "Simmen",
      "authorRank" : 4,
      "name" : "Simmen FA",
      "referenceId" : "RGD:A19615"
    }, {
      "firstName" : "BH",
      "lastName" : "Pollock",
      "authorRank" : 5,
      "name" : "Pollock BH",
      "referenceId" : "RGD:A59554"
    }, {
      "firstName" : "SE",
      "lastName" : "Borst",
      "authorRank" : 6,
      "name" : "Borst SE",
      "referenceId" : "RGD:A86432"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1626514"
    } ]
  }, {
    "primaryId" : "PMID:10192234",
    "title" : "Polymorphisms of the endothelin-A and -B receptor genes in relation to blood pressure and myocardial infarction: the Etude Cas-Temoins sur l'Infarctus du Myocarde (ECTIM) Study.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Nicaud V, etal., Am J Hypertens. 1999 Mar;12(3):304-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-09-06T13:19:01.000-05:00",
    "volume" : "12",
    "pages" : "304-10",
    "abstract" : "Endothelin-1 is a potent vasoconstrictor that has also mitogenic properties, stimulating the synthesis and secretion of several vasoactive molecules. There is much evidence to suggest that endothelin-1 might be involved in the pathogenesis of hypertension, atherosclerosis, and ischemic heart disease. Endothelin-1 exerts its effects through at least two receptors, ET(A) and ET(B), which are encoded by different genes and have separate tissue distributions and biologic properties. The objective of this study was to identify polymorphisms of the ET(A) and ET(B) receptor genes and to study their association with myocardial infarction (MI) and blood pressure. The coding regions and 1.3 kb upstream of the ET(A) and ET(B) receptor genes were explored by polymerase chain reaction/single strand conformation polymorphism. Six polymorphisms were found in the ET(A) receptor gene and three in the ET(B) receptor gene. Most of these polymorphisms were frequent. Associations between the detected polymorphisms, blood pressure, and MI were examined in the ECTIM study, a multicenter study comparing 652 patients having survived an MI and 773 controls from Belfast (Northern Ireland) and France. Alleles at the different polymorphic sites were similarly distributed in patients with MI and controls. Allele frequencies were similar in both countries, except for the ET(A)/-231 G allele, which appeared more frequently in France than in Belfast (P < .01). The mean systolic and diastolic blood pressure levels did not significantly differ between genotypes. However, a C/T substitution located in the nontranslated part of exon 8 of the ET(A) receptor gene (ET(A)/EX8nt1363) was associated with pulse pressure (P < .005). These results do not support an involvement of the endothelin receptor genes in a predisposition to MI or the determination of blood pressure levels, but suggest that a polymorphism of the ET(A) receptor gene might influence the pulse pressure. This result will have to be confirmed in other studies.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Nicaud",
      "authorRank" : 1,
      "name" : "Nicaud V",
      "referenceId" : "RGD:A38081"
    }, {
      "firstName" : "O",
      "lastName" : "Poirier",
      "authorRank" : 2,
      "name" : "Poirier O",
      "referenceId" : "RGD:A38080"
    }, {
      "firstName" : "I",
      "lastName" : "Behague",
      "authorRank" : 3,
      "name" : "Behague I",
      "referenceId" : "RGD:A62300"
    }, {
      "firstName" : "SM",
      "lastName" : "Herrmann",
      "authorRank" : 4,
      "name" : "Herrmann SM",
      "referenceId" : "RGD:A61901"
    }, {
      "firstName" : "C",
      "lastName" : "Mallet",
      "authorRank" : 5,
      "name" : "Mallet C",
      "referenceId" : "RGD:A61257"
    }, {
      "firstName" : "A",
      "lastName" : "Troesch",
      "authorRank" : 6,
      "name" : "Troesch A",
      "referenceId" : "RGD:A50682"
    }, {
      "firstName" : "J",
      "lastName" : "Bouyer",
      "authorRank" : 7,
      "name" : "Bouyer J",
      "referenceId" : "RGD:A64843"
    }, {
      "firstName" : "A",
      "lastName" : "Evans",
      "authorRank" : 8,
      "name" : "Evans A",
      "referenceId" : "RGD:A59004"
    }, {
      "firstName" : "G",
      "lastName" : "Luc",
      "authorRank" : 9,
      "name" : "Luc G",
      "referenceId" : "RGD:A61537"
    }, {
      "firstName" : "JB",
      "lastName" : "Ruidavets",
      "authorRank" : 10,
      "name" : "Ruidavets JB",
      "referenceId" : "RGD:A61902"
    }, {
      "firstName" : "D",
      "lastName" : "Arveiler",
      "authorRank" : 11,
      "name" : "Arveiler D",
      "referenceId" : "RGD:A59002"
    }, {
      "firstName" : "A",
      "lastName" : "Bingham",
      "authorRank" : 12,
      "name" : "Bingham A",
      "referenceId" : "RGD:A64844"
    }, {
      "firstName" : "L",
      "lastName" : "Tiret",
      "authorRank" : 13,
      "name" : "Tiret L",
      "referenceId" : "RGD:A60968"
    }, {
      "firstName" : "F",
      "lastName" : "Cambien",
      "authorRank" : 14,
      "name" : "Cambien F",
      "referenceId" : "RGD:A59005"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580952"
    } ]
  }, {
    "primaryId" : "PMID:10192335",
    "title" : "Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Kurts C, etal., Nature. 1999 Mar 25;398(6725):341-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-01T11:40:01.000-05:00",
    "volume" : "398",
    "pages" : "341-4",
    "abstract" : "Autoantigens found on pancreatic islets can move to draining lymph nodes, where they are able to cause the activation and consequent deletion of autoreactive T cells by a mechanism termed cross-tolerance. This deletion depends on signalling through CD95 (also known as Fas), a member of the superfamily of tumour-necrosis-factor receptors. Here we describe a new mechanism that protects against autoimmunity: this mechanism involves another member of this superfamily, CD30, whose function was largely unknown. CD30-deficient islet-specific CD8-positive T cells are roughly 6,000-fold more autoaggressive than wild-type cells, with the transfer of as few as 160 CD30-deficient T cells leading to the complete destruction of pancreatic islets and the rapid onset of diabetes. We show that, in the absence of CD30 signalling, cells activated but not yet deleted by the CD95-dependent cross-tolerance mechanism gain the ability to proliferate extensively upon secondary encounter with antigen on parenchymal tissues, such as the pancreatic islets. Thus, CD30 signalling limits the proliferative potential of autoreactive CD8 effector T cells and protects the body against autoimmunity.",
    "issueName" : "6725",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Kurts",
      "authorRank" : 1,
      "name" : "Kurts C",
      "referenceId" : "RGD:A111334"
    }, {
      "firstName" : "FR",
      "lastName" : "Carbone",
      "authorRank" : 2,
      "name" : "Carbone FR",
      "referenceId" : "RGD:A111335"
    }, {
      "firstName" : "MF",
      "lastName" : "Krummel",
      "authorRank" : 3,
      "name" : "Krummel MF",
      "referenceId" : "RGD:A111336"
    }, {
      "firstName" : "KM",
      "lastName" : "Koch",
      "authorRank" : 4,
      "name" : "Koch KM",
      "referenceId" : "RGD:A111337"
    }, {
      "firstName" : "JF",
      "lastName" : "Miller",
      "authorRank" : 5,
      "name" : "Miller JF",
      "referenceId" : "RGD:A111338"
    }, {
      "firstName" : "WR",
      "lastName" : "Heath",
      "authorRank" : 6,
      "name" : "Heath WR",
      "referenceId" : "RGD:A111339"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2312735"
    } ]
  }, {
    "primaryId" : "PMID:10192380",
    "title" : "A mutation in NRL is associated with autosomal dominant retinitis pigmentosa.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Bessant DA, etal., Nat Genet. 1999 Apr;21(4):355-6. doi: 10.1038/7678.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:44:02.000-05:00",
    "volume" : "21",
    "pages" : "355-6",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D A",
      "lastName" : "Bessant",
      "authorRank" : 1,
      "name" : "Bessant DA",
      "referenceId" : "RGD:A595364"
    }, {
      "firstName" : "A M",
      "lastName" : "Payne",
      "authorRank" : 2,
      "name" : "Payne AM",
      "referenceId" : "RGD:A595365"
    }, {
      "firstName" : "K P",
      "lastName" : "Mitton",
      "authorRank" : 3,
      "name" : "Mitton KP",
      "referenceId" : "RGD:A595366"
    }, {
      "firstName" : "Q L",
      "lastName" : "Wang",
      "authorRank" : 4,
      "name" : "Wang QL",
      "referenceId" : "RGD:A595367"
    }, {
      "firstName" : "P K",
      "lastName" : "Swain",
      "authorRank" : 5,
      "name" : "Swain PK",
      "referenceId" : "RGD:A595368"
    }, {
      "firstName" : "C",
      "lastName" : "Plant",
      "authorRank" : 6,
      "name" : "Plant C",
      "referenceId" : "RGD:A595369"
    }, {
      "firstName" : "A C",
      "lastName" : "Bird",
      "authorRank" : 7,
      "name" : "Bird AC",
      "referenceId" : "RGD:A595370"
    }, {
      "firstName" : "D J",
      "lastName" : "Zack",
      "authorRank" : 8,
      "name" : "Zack DJ",
      "referenceId" : "RGD:A595371"
    }, {
      "firstName" : "A",
      "lastName" : "Swaroop",
      "authorRank" : 9,
      "name" : "Swaroop A",
      "referenceId" : "RGD:A50814"
    }, {
      "firstName" : "S S",
      "lastName" : "Bhattacharya",
      "authorRank" : 10,
      "name" : "Bhattacharya SS",
      "referenceId" : "RGD:A567153"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118625"
    } ]
  }, {
    "primaryId" : "PMID:10192385",
    "title" : "A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Yasunaga S, etal., Nat Genet. 1999 Apr;21(4):363-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-08-27T10:00:52.000-05:00",
    "volume" : "21",
    "pages" : "363-9",
    "abstract" : "Using a candidate gene approach, we identified a novel human gene, OTOF, underlying an autosomal recessive, nonsyndromic prelingual deafness, DFNB9. The same nonsense mutation was detected in four unrelated affected families of Lebanese origin. OTOF is the second member of a mammalian gene family related to  Caenorhabditis elegans fer-1. It encodes a predicted cytosolic protein (of 1,230  aa) with three C2 domains and a single carboxy-terminal transmembrane domain. The sequence homologies and predicted structure of otoferlin, the protein encoded by  OTOF, suggest its involvement in vesicle membrane fusion. In the inner ear, the expression of the orthologous mouse gene, mainly in the sensory hair cells, indicates that such a role could apply to synaptic vesicles.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Yasunaga",
      "authorRank" : 1,
      "name" : "Yasunaga S",
      "referenceId" : "RGD:A38754"
    }, {
      "firstName" : "M",
      "lastName" : "Grati",
      "authorRank" : 2,
      "name" : "Grati M",
      "referenceId" : "RGD:A38755"
    }, {
      "firstName" : "M",
      "lastName" : "Cohen-Salmon",
      "authorRank" : 3,
      "name" : "Cohen-Salmon",
      "referenceId" : "RGD:A173861"
    }, {
      "firstName" : "A",
      "lastName" : "El-Amraoui",
      "authorRank" : 4,
      "name" : "El-Amraoui A",
      "referenceId" : "RGD:A39198"
    }, {
      "firstName" : "M",
      "lastName" : "Mustapha",
      "authorRank" : 5,
      "name" : "Mustapha M",
      "referenceId" : "RGD:A63244"
    }, {
      "firstName" : "N",
      "lastName" : "Salem",
      "authorRank" : 6,
      "name" : "Salem N",
      "referenceId" : "RGD:A77228"
    }, {
      "firstName" : "E",
      "lastName" : "El-Zir",
      "authorRank" : 7,
      "name" : "El-Zir E",
      "referenceId" : "RGD:A73602"
    }, {
      "firstName" : "J",
      "lastName" : "Loiselet",
      "authorRank" : 8,
      "name" : "Loiselet J",
      "referenceId" : "RGD:A73604"
    }, {
      "firstName" : "C",
      "lastName" : "Petit",
      "authorRank" : 9,
      "name" : "Petit C",
      "referenceId" : "RGD:A38761"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9479153"
    } ]
  }, {
    "primaryId" : "PMID:10192393",
    "title" : "A common human skin tumour is caused by activating mutations in beta-catenin.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Chan EF, etal., Nat Genet 1999 Apr;21(4):410-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T16:08:40.000-06:00",
    "volume" : "21",
    "pages" : "410-3",
    "abstract" : "WNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EF",
      "lastName" : "Chan",
      "authorRank" : 1,
      "name" : "Chan EF",
      "referenceId" : "RGD:A37662"
    }, {
      "firstName" : "U",
      "lastName" : "Gat",
      "authorRank" : 2,
      "name" : "Gat U",
      "referenceId" : "RGD:A20719"
    }, {
      "firstName" : "JM",
      "lastName" : "McNiff",
      "authorRank" : 3,
      "name" : "McNiff JM",
      "referenceId" : "RGD:A37663"
    }, {
      "firstName" : "E",
      "lastName" : "Fuchs",
      "authorRank" : 4,
      "name" : "Fuchs E",
      "referenceId" : "RGD:A37664"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734851"
    } ]
  }, {
    "primaryId" : "PMID:10192395",
    "title" : "Identification of the gene responsible for gelatinous drop-like corneal dystrophy.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Tsujikawa M, etal., Nat Genet. 1999 Apr;21(4):420-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-19T08:56:36.000-06:00",
    "volume" : "21",
    "pages" : "420-3",
    "abstract" : "Gelatinous drop-like corneal dystrophy (GDLD; OMIM 204870) is an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness, with an incidence of 1 in 300,000 in Japan. Our previous genetic linkage study localized the gene responsible to a 2.6-cM interval on chromosome 1p. Clinical manifestations, which appear in the first decade of life, include blurred vision, photophobia and foreign-body sensation. By the third decade, raised, yellowish-grey, gelatinous masses severely impair visual acuity, and lamellar keratoplasty is required for most patients. Here we report DNA sequencing, cDNA cloning and mutational analyses of four deleterious mutations (Q118X, 632delA, Q207X and S170X) in M1S1 (formerly TROP2 and GA733-1), encoding a gastrointestinal tumour-associated antigen. The Q118X mutation was the most common alteration in the GDLD patients examined, accounting for 33 of 40 (82.5%) disease alleles in our panel of families. Protein expression analysis revealed aggregation of the mutated, truncated protein in the perinuclear region, whereas the normal protein was distributed diffusely in the cytoplasm with a homogenous or fine granular pattern. Our successful identification of the gene that is defective in GDLD should facilitate genetic diagnosis and potentially treatment of the disease, and enhance general understanding of the mechanisms of amyloidosis.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Tsujikawa",
      "authorRank" : 1,
      "name" : "Tsujikawa M",
      "referenceId" : "RGD:A72843"
    }, {
      "firstName" : "H",
      "lastName" : "Kurahashi",
      "authorRank" : 2,
      "name" : "Kurahashi H",
      "referenceId" : "RGD:A72844"
    }, {
      "firstName" : "T",
      "lastName" : "Tanaka",
      "authorRank" : 3,
      "name" : "Tanaka T",
      "referenceId" : "RGD:A404001"
    }, {
      "firstName" : "K",
      "lastName" : "Nishida",
      "authorRank" : 4,
      "name" : "Nishida K",
      "referenceId" : "RGD:A18627"
    }, {
      "firstName" : "Y",
      "lastName" : "Shimomura",
      "authorRank" : 5,
      "name" : "Shimomura Y",
      "referenceId" : "RGD:A116010"
    }, {
      "firstName" : "Y",
      "lastName" : "Tano",
      "authorRank" : 6,
      "name" : "Tano Y",
      "referenceId" : "RGD:A21729"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakamura",
      "authorRank" : 7,
      "name" : "Nakamura Y",
      "referenceId" : "RGD:A161073"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599194"
    } ]
  }, {
    "primaryId" : "PMID:10192398",
    "title" : "The gene encoding proline dehydrogenase modulates sensorimotor gating in mice.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Gogos JA, etal., Nat Genet 1999 Apr;21(4):434-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-12T16:13:32.000-05:00",
    "volume" : "21",
    "pages" : "434-9",
    "abstract" : "Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been associated with a number of psychiatric and behavioural phenotypes, including schizophrenia. Here we report the isolation and characterization of PRODH, a human homologue of Drosophila melanogaster sluggish-A (slgA), which encodes proline dehydrogenase responsible for the behavioural phenotype of the slgA mutant. PRODH is localized at chromosome 22q11 in a region deleted in some psychiatric patients. We also isolated the mouse homologue of slgA (Prodh), identified a mutation in this gene in the Pro/Re hyperprolinaemic mouse strain and found that these mice have a deficit in sensorimotor gating accompanied by regional neurochemical alterations in the brain. Sensorimotor gating is a neural filtering process that allows attention to be focused on a given stimulus, and is affected in patients with neuropsychiatric disorders. Furthermore, several lines of evidence suggest that proline may serve as a modulator of synaptic transmission in the mammalian brain. Our observations, in conjunction with the chromosomal location of PRODH, suggest a potential involvement of this gene in the 22q11-associated psychiatric and behavioural phenotypes.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Gogos",
      "authorRank" : 1,
      "name" : "Gogos JA",
      "referenceId" : "RGD:A25271"
    }, {
      "firstName" : "M",
      "lastName" : "Santha",
      "authorRank" : 2,
      "name" : "Santha M",
      "referenceId" : "RGD:A25272"
    }, {
      "firstName" : "Z",
      "lastName" : "Takacs",
      "authorRank" : 3,
      "name" : "Takacs Z",
      "referenceId" : "RGD:A25273"
    }, {
      "firstName" : "KD",
      "lastName" : "Beck",
      "authorRank" : 4,
      "name" : "Beck KD",
      "referenceId" : "RGD:A25274"
    }, {
      "firstName" : "V",
      "lastName" : "Luine",
      "authorRank" : 5,
      "name" : "Luine V",
      "referenceId" : "RGD:A25275"
    }, {
      "firstName" : "LR",
      "lastName" : "Lucas",
      "authorRank" : 6,
      "name" : "Lucas LR",
      "referenceId" : "RGD:A25276"
    }, {
      "firstName" : "JV",
      "lastName" : "Nadler",
      "authorRank" : 7,
      "name" : "Nadler JV",
      "referenceId" : "RGD:A25277"
    }, {
      "firstName" : "M",
      "lastName" : "Karayiorgou",
      "authorRank" : 8,
      "name" : "Karayiorgou M",
      "referenceId" : "RGD:A25278"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:635270"
    } ]
  }, {
    "primaryId" : "PMID:10192400",
    "title" : "Embryonic retinoic acid synthesis is essential for early mouse post-implantation development.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Niederreither K, etal., Nat Genet. 1999 Apr;21(4):444-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-02-27T12:06:35.000-06:00",
    "volume" : "21",
    "pages" : "444-8",
    "abstract" : "A number of studies have suggested that the active derivative of vitamin A, retinoic acid (RA), may be important for early development of mammalian embryos. Severe vitamin A deprivation in rodents results in maternal infertility, precluding a thorough investigation of the role of RA during embryogenesis. Here we show that production of RA by the retinaldehyde dehydrogenase-2 (Raldh2) enzyme is required for mouse embryo survival and early morphogenesis. Raldh2 is an NAD-dependent aldehyde dehydrogenase with high substrate specificity for retinaldehyde. Its pattern of expression during mouse development has suggested that it may be responsible for embryonic RA synthesis. We generated a targeted disruption of the mouse Raldh2 gene and found that Raldh2-/- embryos, which die at midgestation without undergoing axial rotation (body turning), exhibit shortening along the anterioposterior axis and do not form limb buds. Their heart consists of a single, medial, dilated cavity. Their frontonasal region is truncated and their otocysts are severely reduced. These defects result from a block in embryonic RA synthesis, as shown by the lack of activity of RA-responsive transgenes, the altered expression of an RA-target homeobox gene and the near full rescue of the mutant phenotype by maternal RA administration. Our data establish that RA synthesized by the post-implantation mammalian embryo is an essential developmental hormone whose lack leads to early embryo death.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Niederreither",
      "authorRank" : 1,
      "name" : "Niederreither K",
      "referenceId" : "RGD:A35800"
    }, {
      "firstName" : "V",
      "lastName" : "Subbarayan",
      "authorRank" : 2,
      "name" : "Subbarayan V",
      "referenceId" : "RGD:A58430"
    }, {
      "firstName" : "P",
      "lastName" : "Dolle",
      "authorRank" : 3,
      "name" : "Dolle P",
      "referenceId" : "RGD:A35802"
    }, {
      "firstName" : "P",
      "lastName" : "Chambon",
      "authorRank" : 4,
      "name" : "Chambon P",
      "referenceId" : "RGD:A25357"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1576424"
    } ]
  }, {
    "primaryId" : "PMID:10192552",
    "title" : "Ultrastructural localization and biochemical characterization of vitronectin in developing rat bone.",
    "datePublished" : "1998-04-01T00:00:00.000-06:00",
    "citation" : "Kumagai T, etal., Histochem J. 1998 Feb;30(2):111-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-04-30T17:55:25.000-05:00",
    "volume" : "30",
    "pages" : "111-9",
    "abstract" : "This study has used light and electron microscope immunohistochemical and biochemical methods to localize and characterize vitronectin in early bone formation of developing rat mandible with rabbit antimurine vitronectin IgG. Developing jaws of foetuses were collected at embryonic day 15 (day 15) to day 18 from pregnant Wistar rats. After aldehyde fixation, specimens with and without osmium post-fixation were dehydrated and embedded in paraffin, Spurr's resin or LR gold resin for morphological and immunohistochemical examinations. At the light microscope level, in day 15 samples, positive vitronectin immunostaining was observed in small elongated areas of intercellular matrix and osteoblasts. Concomitant with initiation of matrix mineralization at day 16, vitronectin staining was similarly observed in small elongated areas containing intercellular matrix and osteoblasts but not clearly detected in fully mineralized bone matrix. The same staining profile was observed at days 17 and 18. At the ultrastructural  level, immunogold particles were clearly detected over unmineralized matrix and cisterns of the rough-surfaced endoplasmic reticulum and the Golgi apparatus of osteoblasts as well as over demineralized bone matrix at day 16-18. In order to assess the presence of vitronectin in the mineral phase, mineral-binding bone proteins were extracted from fresh day 18 specimens using a three-step technique: 4M guanidine HCl (G1 extract), aqueous EDTA without guanidine HCl (E extract), followed by guanidine HCl. Subsequent Western blot analysis of sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis revealed that the antibodies produced only a single band at an M(r) of approximately 73000 in both G1 and E extracts, indicating the presence of vitronectin in the mineralized bone matrix.  These results indicate that, at the onset of bone formation, osteoblasts synthesize and release vitronectin, which is subsequently incorporated into the bone matrix and becomes a specific component of bone tissues. The observation of  vitronectin in these critical stages of bone formation suggests that it may be involved in the regulation of bone formation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kumagai",
      "authorRank" : 1,
      "name" : "Kumagai T",
      "referenceId" : "RGD:A129918"
    }, {
      "firstName" : "I",
      "lastName" : "Lee",
      "authorRank" : 2,
      "name" : "Lee I",
      "referenceId" : "RGD:A103471"
    }, {
      "firstName" : "Y",
      "lastName" : "Ono",
      "authorRank" : 3,
      "name" : "Ono",
      "referenceId" : "RGD:A409341"
    }, {
      "firstName" : "M",
      "lastName" : "Maeno",
      "authorRank" : 4,
      "name" : "Maeno",
      "referenceId" : "RGD:A201274"
    }, {
      "firstName" : "M",
      "lastName" : "Takagi",
      "authorRank" : 5,
      "name" : "Takagi M",
      "referenceId" : "RGD:A27086"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10003091"
    } ]
  }, {
    "primaryId" : "PMID:10193250",
    "title" : "Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schonlein purpura nephritis.",
    "datePublished" : "1998-02-01T00:00:00.000-06:00",
    "citation" : "Yoshioka T, etal., Arch Dis Child. 1998 Nov;79(5):394-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-02-29T11:30:42.000-06:00",
    "volume" : "79",
    "pages" : "394-9",
    "abstract" : "OBJECTIVE: To study the influence of deletion/insertion polymorphism in the 16th  intron of the angiotensin converting enzyme (ACE) gene on clinical manifestations of Henoch-Schonlein purpura nephritis. STUDY DESIGN: Cross sectional study. ACE gene polymorphism was determined in patients (4-15 years old at onset) with Henoch-Schonlein purpura nephritis (n = 40) and compared with that in patients with IgA nephropathy (n = 79). MAIN OUTCOME MEASURES: ACE genotypes, systemic blood pressures, urine protein excretion rate, haematuria, creatinine clearance,  serum ACE activities. RESULTS: The initial clinical manifestations of both Henoch-Schonlein purpura nephritis and IgA nephropathy were no different among homozygotes for insertion (II) and deletion (DD), and heterozygotes (ID) for the  ACE gene. In patients with Henoch-Schonlein purpura nephritis, the incidence of moderate to heavy proteinuria at four and eight years after onset was more than five times higher in the DD genotype than in the II or ID genotypes. No such trend was seen in patients with IgA nephropathy. The number of patients with Henoch-Schonlein purpura nephritis in whom proteinuria resolved at four and eight years after onset was significantly lower in the DD genotype compared with the II genotype, whereas no differences were detected among the three different genotypes in patients with IgA nephropathy. Plasma ACE activities in patients with the DD genotype were significantly higher than in those with non-DD genotypes. CONCLUSIONS: The ACE DD genotype predicts persistent proteinuria in Henoch-Schonlein purpura nephritis. The proteinuria might be related to a defective angiotensin system which is genetically determined by the D/I polymorphism.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Yoshioka",
      "authorRank" : 1,
      "name" : "Yoshioka",
      "referenceId" : "RGD:A400056"
    }, {
      "firstName" : "YX",
      "lastName" : "Xu",
      "authorRank" : 2,
      "name" : "Xu YX",
      "referenceId" : "RGD:A113090"
    }, {
      "firstName" : "H",
      "lastName" : "Yoshida",
      "authorRank" : 3,
      "name" : "Yoshida H",
      "referenceId" : "RGD:A24062"
    }, {
      "firstName" : "H",
      "lastName" : "Shiraga",
      "authorRank" : 4,
      "name" : "Shiraga",
      "referenceId" : "RGD:A212932"
    }, {
      "firstName" : "T",
      "lastName" : "Muraki",
      "authorRank" : 5,
      "name" : "Muraki T",
      "referenceId" : "RGD:A72170"
    }, {
      "firstName" : "K",
      "lastName" : "Ito",
      "authorRank" : 6,
      "name" : "Ito K",
      "referenceId" : "RGD:A4474"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11038828"
    } ]
  }, {
    "primaryId" : "PMID:10193764",
    "title" : "Effects of the prostanoid EP3-receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Zacharowski K, etal., Br J Pharmacol. 1999 Feb;126(4):849-58.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-05-21T15:52:32.000-05:00",
    "volume" : "126",
    "pages" : "849-58",
    "abstract" : "1. This study investigates the effects of two agonists of the prostanoid EP3-receptor (M&B 28767 and GR 63799X) on the infarct size caused by regional myocardial ischaemia and reperfusion in the anaesthetized rat. 2. One hundred and sixty-seven, male Wistar rats were anaesthetized (thiopentone, 120 mg kg(-1) i.p.), ventilated (8-10 ml kg(-1), 70 strokes min(-1), inspiratory oxygen concentration: 30%; PEEP: 1-2 mmHg) and subjected to occlusion of the left anterior descending coronary artery (LAD, for 7.5, 15, 25, 35, 45 or 60 min) followed by reperfusion (2 h). Infarct size was determined by staining of viable  myocardium with a tetrazolium stain (NBT), histological evaluation by light and electron microscopy and determination of the plasma levels of cardiac troponin T. 3. M&B 28767 (0.5 microg kg(-1) min(-1), i.v., n=7) or GR 63799X (3 microg kg(-1) min(-1), i.v., n=7) caused significant reductions in infarct size from 60+/-3% (25 min ischaemia and 2 h reperfusion; saline-control, n=8) to 39+/-6 and 38+/-4% of the area at risk, without causing a significant fall in blood pressure. Pretreatment of rats with 5-hydroxydecanoate (5-HD), an inhibitor of ATP-sensitive potassium channels, attenuated the cardioprotective effects of both EP3-receptor agonists. The reduction in infarct size afforded by M&B 28767 was also abolished by glibenclamide and the protein kinase C (PKC) inhibitors staurosporine and chelerythrine. 4. Thus, M&B 28767 and GR 63799X reduce myocardial infarct size in the rat by a mechanism(s) which involves the activation of PKC and the opening of ATP-sensitive potassium channels.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Zacharowski",
      "authorRank" : 1,
      "name" : "Zacharowski K",
      "referenceId" : "RGD:A101455"
    }, {
      "firstName" : "A",
      "lastName" : "Olbrich",
      "authorRank" : 2,
      "name" : "Olbrich",
      "referenceId" : "RGD:A202263"
    }, {
      "firstName" : "M",
      "lastName" : "Otto",
      "authorRank" : 3,
      "name" : "Otto",
      "referenceId" : "RGD:A202264"
    }, {
      "firstName" : "G",
      "lastName" : "Hafner",
      "authorRank" : 4,
      "name" : "Hafner G",
      "referenceId" : "RGD:A60967"
    }, {
      "firstName" : "C",
      "lastName" : "Thiemermann",
      "authorRank" : 5,
      "name" : "Thiemermann C",
      "referenceId" : "RGD:A76167"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10043342"
    } ]
  }, {
    "primaryId" : "PMID:10193948",
    "title" : "The prognostic significance of proliferation-associated nucleolar protein p120 expression in prostate adenocarcinoma: a comparison with cyclins A and B1, Ki-67, proliferating cell nuclear antigen, and p34cdc2.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Kallakury BV, etal., Cancer. 1999 Apr 1;85(7):1569-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-01-15T18:48:37.000-06:00",
    "volume" : "85",
    "pages" : "1569-76",
    "abstract" : "BACKGROUND: In this study, the authors evaluated the prognostic significance of the expression of nucleolar antigen p120, along with other cell proliferation-associated proteins, in prostate adenocarcinomas (PACs) and compared the results with previously reported data on p34cdc2 cyclin-dependent kinase (p34 cdk). METHODS: Archival sections from 132 PACs were immunostained with monoclonal antibodies against p120, cyclin A, cyclin B1, Ki-67, and proliferating cell nuclear antigen (PCNA). The DNA content of each tumor was determined by the Feulgen method using image analysis. The immunohistochemistry (IHC) results were correlated with tumor grade, stage, margin positivity, metastasis, ploidy, and postsurgical disease recurrence. RESULTS: The overall positivity for the various proteins follows: p120, 36%; cyclin A, 35%; cyclin B1, 43%; Ki-67, 46%; and PCNA, 32%. p120 correlated with grade (P = 0.004), stage (P = 0.01), ploidy (P = 0.02), margin positivity (P = 0.03), and metastasis (P = 0.004). Cyclin B1 correlated with ploidy (P = 0.04) and grade (P = 0.05), Ki-67 with grade (P = 0.02) and margins (P = 0.03), and PCNA with grade (P = 0.01). Significant coexpression among these proteins was noted, as was a significant association between the expression of these markers and that previously reported for p34 cdk. In univariate analysis, p120 (P = 0.01), cyclin A (P = 0.01) and p34 cdk (P = 0.002) correlated with disease recurrence. In multivariate analysis of all these proteins, only p34 cdk independently predicted postsurgical recurrence (P = 0.05). CONCLUSIONS: Nucleolar antigen p120 expression appears to be an additional marker of aggressiveness in PACs. The significant coexpression of the various cell cycle regulatory proteins support their collective role in tumor cell proliferation, with p34 cdk positivity being an independent predictor of postsurgical recurrence.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BV",
      "lastName" : "Kallakury",
      "authorRank" : 1,
      "name" : "Kallakury BV",
      "referenceId" : "RGD:A92772"
    }, {
      "firstName" : "CE",
      "lastName" : "Sheehan",
      "authorRank" : 2,
      "name" : "Sheehan CE",
      "referenceId" : "RGD:A92775"
    }, {
      "firstName" : "SJ",
      "lastName" : "Rhee",
      "authorRank" : 3,
      "name" : "Rhee SJ",
      "referenceId" : "RGD:A117940"
    }, {
      "firstName" : "HA",
      "lastName" : "Fisher",
      "authorRank" : 4,
      "name" : "Fisher HA",
      "referenceId" : "RGD:A117941"
    }, {
      "firstName" : "JR",
      "lastName" : "Kaufman RP",
      "authorRank" : 5,
      "name" : "Kaufman RP JR",
      "referenceId" : "RGD:A117942"
    }, {
      "firstName" : "MD",
      "lastName" : "Rifkin",
      "authorRank" : 6,
      "name" : "Rifkin MD",
      "referenceId" : "RGD:A117943"
    }, {
      "firstName" : "JS",
      "lastName" : "Ross",
      "authorRank" : 7,
      "name" : "Ross JS",
      "referenceId" : "RGD:A92777"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2315940"
    } ]
  }, {
    "primaryId" : "PMID:10194154",
    "title" : "Surfactant protein levels in severe respiratory syncytial virus infection.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Kerr MH and Paton JY, Am J Respir Crit Care Med. 1999 Apr;159(4 Pt 1):1115-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-23T13:14:12.000-05:00",
    "volume" : "159",
    "pages" : "1115-8",
    "abstract" : "Infection with respiratory syncytial virus (RSV) is a common cause of respiratory disease in infancy. Surfactant phospholipids have been shown to be reduced in severe RSV infection. Reduction in surfactant proteins might also contribute to the pathogenesis of this disease. We investigated daily levels of surfactant proteins in bronchoalveolar lavage (BAL) fluid from 18 ventilated infants with RSV infection (median age 3.1 mo) and in a control group of 16 ventilated surgical patients (median age 0.4 mo). Surfactant proteins were measured by ELISA, total protein by the Lowry method. Surfactant protein A (SP-A) was reduced in BAL fluid from children with RSV infection (median 5.6 micrograms/ml; range 0.6 to 151.9 micrograms/ml) compared with control samples (median 9.0 micrograms/ml; range 0.5 to 139.6 micrograms/ml, p = 0.0368). Surfactant protein B (SP-B) was lower in the RSV group (median 12.0 ng/ml; range 0 to 60. 8 ng/ml) than in control patients (median 118.1 ng/ml; range 0 to 778.2 ng/ml, p < 0.0000). Surfactant protein D (SP-D) was also reduced in the RSV group (median 130.3 ng/ml; range 0 to 1,486.0 ng/ml) versus median 600.4 ng/ml; range 0 to 1,869.0 ng/ml, p < 0. 0000. Total protein levels were higher in the RSV group (median 0.49 mg/ml; range 0.13 to 2.46 mg/ml versus median 0.36 mg/ml; range 0.07 to 1.65 mg/ml, p = 0.0079). The median value of SP-A was significantly lower in the initial sample (2.3 micrograms/ml) than in the final one (6.0 micrograms/ml). However, no significant correlation was found between surfactant protein concentrations and disease severity measured by arterial alveolar oxygen ratio. We conclude that alterations in surfactant protein concentrations are present in severe RSV infection and speculate that these may contribute to the abnormalities of lung function seen in this condition.",
    "issueName" : "4 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MH",
      "lastName" : "Kerr",
      "authorRank" : 1,
      "name" : "Kerr MH",
      "referenceId" : "RGD:A128152"
    }, {
      "firstName" : "JY",
      "lastName" : "Paton",
      "authorRank" : 2,
      "name" : "Paton JY",
      "referenceId" : "RGD:A128153"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4143439"
    } ]
  }, {
    "primaryId" : "PMID:10194414",
    "title" : "HP33: hepatocellular carcinoma-enriched 33-kDa protein with similarity to mitochondrial N-acyltransferase but localized in a microtubule-dependent manner at the centrosome.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Nakadai T, etal., J Cell Sci. 1999 May;112 ( Pt 9):1353-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-15T14:34:22.000-05:00",
    "volume" : "112 ( Pt 9)",
    "pages" : "1353-64",
    "abstract" : "Using a new subtraction method and chemically induced rat hepatocellular carcinomas, we identified a hepatocellular carcinogenesis and hepatocyte proliferation-related gene designated hp33 that encoded a 33-kDa protein. The predicted protein was similar to the bovine aralkyl N-acyltransferase and arylacetyl N-acyltransferase. HP33 was restrictively expressed in the liver and kidney, and its gene expression was stimulated in the regenerating liver as well as in hepatocellular carcinoma. Interestingly, it was demonstrated in various hepatic cells that HP33 was localized in regions surrounding the centrosome, where mitochondria were not concentrated. Moreover, its centrosomal localization was evident in the interphase but not in the mitotic phase of the cell cycle. The centrosomal localization of HP33 was dependent on microtubules, and ectopically expressed HP33 was seen at centrosomes even in fibroblasts, which do not exhibit a typical staining pattern of HP33. The centrosomal localization of HP33 became invisible by nocodazole treatment, whereas the mitochondrial staining pattern was not affected by it. In vitro cosedimentation experiments using purified microtubules indicated that HP33 bound to MTs directly and that its MT-binding ability was dependent on the C-terminal basic domain of the protein. These results suggest that, different from early predictions based on its primary structure, HP33 has a growth- and carcinogenesis-related function that may be independent of mitochondrial function.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Nakadai",
      "authorRank" : 1,
      "name" : "Nakadai T",
      "referenceId" : "RGD:A23890"
    }, {
      "firstName" : "T",
      "lastName" : "Kishimoto",
      "authorRank" : 2,
      "name" : "Kishimoto T",
      "referenceId" : "RGD:A5105"
    }, {
      "firstName" : "Y",
      "lastName" : "Miyazawa",
      "authorRank" : 3,
      "name" : "Miyazawa Y",
      "referenceId" : "RGD:A127436"
    }, {
      "firstName" : "N",
      "lastName" : "Okada",
      "authorRank" : 4,
      "name" : "Okada N",
      "referenceId" : "RGD:A7541"
    }, {
      "firstName" : "Y",
      "lastName" : "Makino",
      "authorRank" : 5,
      "name" : "Makino Y",
      "referenceId" : "RGD:A5103"
    }, {
      "firstName" : "T",
      "lastName" : "Obinata",
      "authorRank" : 6,
      "name" : "Obinata T",
      "referenceId" : "RGD:A119874"
    }, {
      "firstName" : "T",
      "lastName" : "Tamura",
      "authorRank" : 7,
      "name" : "Tamura T",
      "referenceId" : "RGD:A156706"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4143173"
    } ]
  }, {
    "primaryId" : "PMID:10194421",
    "title" : "Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal myocardial infarction in younger patients.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Santoso S, etal., Blood. 1999 Apr 15;93(8):2449-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-09-08T15:28:00.000-05:00",
    "volume" : "93",
    "pages" : "2449-53",
    "abstract" : "Recently, we have shown that two alleles of the glycoprotein (GP) Ia gene, designated C807 and T807, are associated with low or high platelet GPIa-IIa density and consequently with slower or faster rate of platelet adhesion to type I collagen, respectively. This polymorphism could therefore present a genetic predisposition for the development of thrombotic disease and hemostasis. We investigated the relationship of the GPIa C807T dimorphism to the risk of coronary artery disease (CAD) and myocardial infarction (MI). An allele-specific polymerase chain reaction (PCR) was developed for genotyping of C807T polymorphism. DNA samples from 2237 male patients who underwent coronary angiography on account of coronary heart disease as verified illness or presumptive diagnosis were genotyped. The odds ratio was calculated as an estimate of the relative risk by multiple logistic regression. We found a strong association between the T allele and nonfatal MI among individuals younger than the mean age of 62 years (n = 1,057; odds ratio, 1.57; P =.004). The odds ratio of MI increased for T807 carriers with decreasing age. The highest odds ratio was detected within the youngest 10% of the study sample (<49 years; n = 223; odds ratio, 2. 61; P =.009). In contrast, no evidence of an association between C807T dimorphism with CAD was found. Our findings suggest that inherited platelet GP variations might have an important impact on acute thrombotic disease.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Santoso",
      "authorRank" : 1,
      "name" : "Santoso S",
      "referenceId" : "RGD:A25930"
    }, {
      "firstName" : "TJ",
      "lastName" : "Kunicki",
      "authorRank" : 2,
      "name" : "Kunicki TJ",
      "referenceId" : "RGD:A65188"
    }, {
      "firstName" : "H",
      "lastName" : "Kroll",
      "authorRank" : 3,
      "name" : "Kroll H",
      "referenceId" : "RGD:A65189"
    }, {
      "firstName" : "W",
      "lastName" : "Haberbosch",
      "authorRank" : 4,
      "name" : "Haberbosch W",
      "referenceId" : "RGD:A58220"
    }, {
      "firstName" : "A",
      "lastName" : "Gardemann",
      "authorRank" : 5,
      "name" : "Gardemann A",
      "referenceId" : "RGD:A58213"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581029"
    } ]
  }, {
    "primaryId" : "PMID:10194428",
    "title" : "HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Mura C, etal., Blood. 1999 Apr 15;93(8):2502-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-08-04T14:27:25.000-05:00",
    "volume" : "93",
    "pages" : "2502-5",
    "abstract" : "Hereditary hemochromatosis (HH) is a common autosomal recessive genetic disorder  of iron metabolism. The HFE candidate gene encoding an HLA class I-like protein involved in HH was identified in 1996. Two missense mutations have been described: C282Y, accounting for 80% to 90% of HH chromosomes, and H63D, which is associated with a milder form of the disease representing 40% to 70% of non-C282Y HH chromosomes. We report here on the analysis of C282Y, H63D, and the 193A-->T substitution leading to the S65C missense substitution in a large series of probands and controls. The results confirm that the C282Y substitution was the main mutation involved in hemochromatosis, accounting for 85% of carrier chromosomes, whereas the H63D substitution represented 39% of the HH chromosomes  that did not carry the C282Y mutation. In addition, our screening showed that the S65C substitution was significantly enriched in probands with at least one chromosome without an assigned mutation. This substitution accounted for 7.8% of  HH chromosomes that were neither C282Y nor H63D. This enrichment of S65C among HH chromosomes suggests that the S65C substitution is associated with the mild form  of hemochromatosis.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Mura",
      "authorRank" : 1,
      "name" : "Mura",
      "referenceId" : "RGD:A192200"
    }, {
      "firstName" : "O",
      "lastName" : "Raguenes",
      "authorRank" : 2,
      "name" : "Raguenes",
      "referenceId" : "RGD:A192201"
    }, {
      "firstName" : "C",
      "lastName" : "Ferec",
      "authorRank" : 3,
      "name" : "Ferec C",
      "referenceId" : "RGD:A126267"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8694372"
    } ]
  }, {
    "primaryId" : "PMID:10194467",
    "title" : "Angiotensin II attenuates renal cortical cyclooxygenase-2 expression.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Cheng HF, etal., J Clin Invest 1999 Apr;103(7):953-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-25T08:15:20.000-05:00",
    "volume" : "103",
    "pages" : "953-61",
    "abstract" : "We have previously shown that in rat renal cortex, cyclooxygenase-2 (COX-2) expression is localized to cTALH cells in the region of the macula densa, and that dietary salt restriction increases COX-2 expression. Administration of the angiotensin converting inhibitor, captopril, further increased COX-2 mRNA and renal cortical COX-2 immunoreactivity, with the most pronounced expression in the macula densa. Administration of an AT1 receptor antagonist, losartan, also significantly increased cortical COX-2 mRNA expression and COX-2 immunoreactivity. Mutant mice homozygous for both Agtr1a and Agtr1b null mutations (Agtr1a-/-,Agtr1b-/-) demonstrated large increases in immunoreactive COX-2 expression inthe cTALH/macula densa. To determine whether increased COX-2expression in response to ACE inhibition mediated increases in renin production, rats were treated with captopril for one week with or without the specific COX-2 inhibitor, SC58236. Plasma renin activity increased significantly in the captropril group, and this increase was significantly inhibited by simultaneous treatment with SC58236. Thus, these studies indicated that angiotensin II inhibitors augment upregulation of renal cortical COX-2 in states of volume depletion, suggesting that negative feedback by the renin-angiotensin system modulates renal cortical COX-2 expression and that COX-2 is a mediator of increased renin production in response to inhibition of angiotension II production.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HF",
      "lastName" : "Cheng",
      "authorRank" : 1,
      "name" : "Cheng HF",
      "referenceId" : "RGD:A16558"
    }, {
      "firstName" : "JL",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang JL",
      "referenceId" : "RGD:A16559"
    }, {
      "firstName" : "MZ",
      "lastName" : "Zhang",
      "authorRank" : 3,
      "name" : "Zhang MZ",
      "referenceId" : "RGD:A16560"
    }, {
      "firstName" : "Y",
      "lastName" : "Miyazaki",
      "authorRank" : 4,
      "name" : "Miyazaki Y",
      "referenceId" : "RGD:A7510"
    }, {
      "firstName" : "I",
      "lastName" : "Ichikawa",
      "authorRank" : 5,
      "name" : "Ichikawa I",
      "referenceId" : "RGD:A16561"
    }, {
      "firstName" : "JA",
      "lastName" : "McKanna",
      "authorRank" : 6,
      "name" : "McKanna JA",
      "referenceId" : "RGD:A16562"
    }, {
      "firstName" : "RC",
      "lastName" : "Harris",
      "authorRank" : 7,
      "name" : "Harris RC",
      "referenceId" : "RGD:A16563"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632167"
    } ]
  }, {
    "primaryId" : "PMID:10194471",
    "title" : "Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Stafforini DM, etal., J Clin Invest. 1999 Apr;103(7):989-97. doi: 10.1172/JCI5574.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:26:34.000-05:00",
    "volume" : "103",
    "pages" : "989-97",
    "abstract" : "Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D M",
      "lastName" : "Stafforini",
      "authorRank" : 1,
      "name" : "Stafforini DM",
      "referenceId" : "RGD:A579831"
    }, {
      "firstName" : "T",
      "lastName" : "Numao",
      "authorRank" : 2,
      "name" : "Numao T",
      "referenceId" : "RGD:A579832"
    }, {
      "firstName" : "A",
      "lastName" : "Tsodikov",
      "authorRank" : 3,
      "name" : "Tsodikov A",
      "referenceId" : "RGD:A125724"
    }, {
      "firstName" : "D",
      "lastName" : "Vaitkus",
      "authorRank" : 4,
      "name" : "Vaitkus D",
      "referenceId" : "RGD:A579833"
    }, {
      "firstName" : "T",
      "lastName" : "Fukuda",
      "authorRank" : 5,
      "name" : "Fukuda T",
      "referenceId" : "RGD:A9510"
    }, {
      "firstName" : "N",
      "lastName" : "Watanabe",
      "authorRank" : 6,
      "name" : "Watanabe N",
      "referenceId" : "RGD:A6006"
    }, {
      "firstName" : "N",
      "lastName" : "Fueki",
      "authorRank" : 7,
      "name" : "Fueki N",
      "referenceId" : "RGD:A529937"
    }, {
      "firstName" : "T M",
      "lastName" : "McIntyre",
      "authorRank" : 8,
      "name" : "McIntyre TM",
      "referenceId" : "RGD:A579834"
    }, {
      "firstName" : "G A",
      "lastName" : "Zimmerman",
      "authorRank" : 9,
      "name" : "Zimmerman GA",
      "referenceId" : "RGD:A579835"
    }, {
      "firstName" : "S",
      "lastName" : "Makino",
      "authorRank" : 10,
      "name" : "Makino S",
      "referenceId" : "RGD:A10789"
    }, {
      "firstName" : "S M",
      "lastName" : "Prescott",
      "authorRank" : 11,
      "name" : "Prescott SM",
      "referenceId" : "RGD:A579836"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598116334"
    } ]
  }, {
    "primaryId" : "PMID:10194472",
    "title" : "Heteropolymerization of S, I, and Z alpha1-antitrypsin and liver cirrhosis.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mahadeva R, etal., J Clin Invest. 1999 Apr;103(7):999-1006.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T20:28:16.000-05:00",
    "volume" : "103",
    "pages" : "999-1006",
    "abstract" : "The association between Z alpha1-antitrypsin deficiency and juvenile cirrhosis is well-recognized, and there is now convincing evidence that the hepatic inclusions are the result of entangled polymers of mutant Z alpha1-antitrypsin. Four percent of the northern European Caucasian population are heterozygotes for the Z variant, but even more common is S alpha1-antitrypsin, which is found in up to 28% of southern Europeans. The S variant is known to have an increased susceptibility to polymerization, although this is marginal compared with the more conformationally unstable Z variant. There has been speculation that the two may interact to produce cirrhosis, but this has never been demonstrated experimentally. This hypothesis was raised again by the observation reported here of a mixed heterozygote for Z alpha1-antitrypsin and another conformationally unstable variant (I alpha1-antitrypsin; 39Arg-->Cys) identified in a 34-year-old  man with cirrhosis related to alpha1-antitrypsin deficiency. The conformational stability of the I variant has been characterized, and we have used fluorescence  resonance energy transfer to demonstrate the formation of heteropolymers between  S and Z alpha1-antitrypsin. Taken together, these results indicate that not only  may mixed variants form heteropolymers, but that this can causally lead to the development of cirrhosis.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Mahadeva",
      "authorRank" : 1,
      "name" : "Mahadeva R",
      "referenceId" : "RGD:A142612"
    }, {
      "firstName" : "WS",
      "lastName" : "Chang",
      "authorRank" : 2,
      "name" : "Chang",
      "referenceId" : "RGD:A189829"
    }, {
      "firstName" : "TR",
      "lastName" : "Dafforn",
      "authorRank" : 3,
      "name" : "Dafforn",
      "referenceId" : "RGD:A322921"
    }, {
      "firstName" : "DJ",
      "lastName" : "Oakley",
      "authorRank" : 4,
      "name" : "Oakley",
      "referenceId" : "RGD:A306170"
    }, {
      "firstName" : "RC",
      "lastName" : "Foreman",
      "authorRank" : 5,
      "name" : "Foreman",
      "referenceId" : "RGD:A322922"
    }, {
      "firstName" : "J",
      "lastName" : "Calvin",
      "authorRank" : 6,
      "name" : "Calvin",
      "referenceId" : "RGD:A322923"
    }, {
      "firstName" : "DG",
      "lastName" : "Wight",
      "authorRank" : 7,
      "name" : "Wight",
      "referenceId" : "RGD:A322924"
    }, {
      "firstName" : "DA",
      "lastName" : "Lomas",
      "authorRank" : 8,
      "name" : "Lomas DA",
      "referenceId" : "RGD:A128267"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11099015"
    } ]
  }, {
    "primaryId" : "PMID:10194769",
    "title" : "Expression cloning and characterization of PREB (prolactin regulatory element binding), a novel WD motif DNA-binding protein with a capacity to regulate prolactin promoter activity.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Fliss MS, etal., Mol Endocrinol 1999 Apr;13(4):644-57.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-10T11:27:24.000-05:00",
    "volume" : "13",
    "pages" : "644-57",
    "abstract" : "Previous studies have implied that a transcription factor(s) other than Pit-1 is involved in homeostatic regulation of PRL promoter activity via Pit-1-binding elements. One such element, 1P, was employed to clone from a rat pituitary cDNA expression library a novel 417-amino acid WD protein, designated PREB (PRL regulatory element binding) protein. PREB contains two PQ-rich potential transactivation domains, but no apparent DNA-binding motif, and exhibits sequence-specific binding to site 1P, to a site nonidentical to that for Pit-1. The PREB gene (or a related gene) is conserved, as an apparently single copy, in rat, human, fly, and yeast. A single approximately 1.9-kb PREB transcript accumulates in GH3 rat pituitary cells, to levels similar to Pit-1 mRNA. PREB transcripts were detected in all human tissues examined, but the observation of tissue-specific multiple transcript patterns suggests the possibility of tissue-specific alternative splicing. RT-PCR analysis of human brain tumor RNA samples suggested region-specific expression of PREB transcripts in brain. Western and immunocytochemical analysis implied that PREB accumulates specifically in GH3 cell nuclei. Transient transfection employing PREB-negative C6 rat glial cells showed that PREB is as active as, and additive with, Pit-1 in transactivation of a PRL promoter construct, and that PREB, but not Pit-1, can mediate transcriptional activation by protein kinase A (PKA). Expression in GH3 cells of a GAL4-PREB fusion protein both strongly transactivated a 5XGAL indicator construct and yielded a further stimulation of expression of this construct by coexpressed PKA, implying that PREB can mediate both basal and PKA-stimulated transcriptional responses in pituitary cells. These observations imply that PREB will prove to play a significant transcriptional regulatory role, both in the pituitary and in other organs in which transcripts of its gene are expressed.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MS",
      "lastName" : "Fliss",
      "authorRank" : 1,
      "name" : "Fliss MS",
      "referenceId" : "RGD:A3616"
    }, {
      "firstName" : "PM",
      "lastName" : "Hinkle",
      "authorRank" : 2,
      "name" : "Hinkle PM",
      "referenceId" : "RGD:A143412"
    }, {
      "firstName" : "C",
      "lastName" : "Bancroft",
      "authorRank" : 3,
      "name" : "Bancroft C",
      "referenceId" : "RGD:A50087"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61705"
    } ]
  }, {
    "primaryId" : "PMID:10195071",
    "title" : "Contribution of genetic factors other than CFTR to disease severity in cystic fibrosis.",
    "datePublished" : "1998-12-01T00:00:00.000-06:00",
    "citation" : "Hull J and Thomson AH, Thorax. 1998 Dec;53(12):1018-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-03-22T12:25:53.000-05:00",
    "volume" : "53",
    "pages" : "1018-21",
    "abstract" : "<br><b>BACKGROUND: </b>Disease severity in patients with cystic fibrosis shows marked variability. Attempts to explain this phenotypic heterogeneity on the basis of CFTR genotype have had limited success. A study was undertaken to test the hypothesis that naturally occurring variants of the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) and the detoxifying enzyme glutathione S-transferase M1 (GSTM1) could influence disease severity in cystic fibrosis.<br><b>METHODS: </b>Fifty-three children with cystic fibrosis were studied. To allow for the effect of age, all clinical details were collected during the eighth year of age. The subjects were divided into groups, both according to the presence or absence of the TNF2 TNF-alpha -308 promoter polymorphism (n = 20), and by homozygosity for the null allele of GSTM1 (n = 26).<br><b>RESULTS: </b>Percentage predicted forced expiratory volume in one second (FEV1) and weight z scores were significantly lower in the TNF2 group (mean difference (95% confidence intervals) for FEV1 11.6% (1.7 to 21.5) and 0.59 (0.06 to 1.12) for weight z score). The Chrispin-Norman chest radiographic score was significantly higher and the Shwachman score was significantly lower in patients homozygous for the GSTM1 null allele.<br><b>CONCLUSIONS: </b>Two independent genetic factors have been identified which appear to influence disease severity in cystic fibrosis. These results support the contention that inflammation in cystic fibrosis contributes to tissue damage. Isolation of further such factors may lead to identification of patients at risk of more severe disease and allow targeted aggressive therapy in this group.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Hull",
      "authorRank" : 1,
      "name" : "Hull J",
      "referenceId" : "RGD:A128177"
    }, {
      "firstName" : "A H",
      "lastName" : "Thomson",
      "authorRank" : 2,
      "name" : "Thomson AH",
      "referenceId" : "RGD:A441207"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12798506"
    } ]
  }, {
    "primaryId" : "PMID:10195193",
    "title" : "Neurotrophin-3 is required for proper cerebellar development.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Bates B, etal., Nat Neurosci 1999 Feb;2(2):115-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-09T13:55:38.000-05:00",
    "volume" : "2",
    "pages" : "115-7",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Bates",
      "authorRank" : 1,
      "name" : "Bates B",
      "referenceId" : "RGD:A52111"
    }, {
      "firstName" : "M",
      "lastName" : "Rios",
      "authorRank" : 2,
      "name" : "Rios M",
      "referenceId" : "RGD:A52112"
    }, {
      "firstName" : "A",
      "lastName" : "Trumpp",
      "authorRank" : 3,
      "name" : "Trumpp A",
      "referenceId" : "RGD:A38233"
    }, {
      "firstName" : "C",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen C",
      "referenceId" : "RGD:A161909"
    }, {
      "firstName" : "G",
      "lastName" : "Fan",
      "authorRank" : 5,
      "name" : "Fan G",
      "referenceId" : "RGD:A52113"
    }, {
      "firstName" : "JM",
      "lastName" : "Bishop",
      "authorRank" : 6,
      "name" : "Bishop JM",
      "referenceId" : "RGD:A36777"
    }, {
      "firstName" : "R",
      "lastName" : "Jaenisch",
      "authorRank" : 7,
      "name" : "Jaenisch R",
      "referenceId" : "RGD:A38566"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358330"
    } ]
  }, {
    "primaryId" : "PMID:10195194",
    "title" : "Snapin: a SNARE-associated protein implicated in synaptic transmission.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Ilardi JM, etal., Nat Neurosci. 1999 Feb;2(2):119-24. doi: 10.1038/5673.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T01:58:59.000-05:00",
    "volume" : "2",
    "pages" : "119-24",
    "abstract" : "Synaptic vesicle docking and fusion are mediated by the assembly of a stable SNARE core complex of proteins, which include the synaptic vesicle membrane protein VAMP/synaptobrevin and the plasmalemmal proteins syntaxin and SNAP-25. We have now identified another SNAP-25-binding protein, called Snapin. Snapin was enriched in neurons and exclusively located on synaptic vesicle membranes. It associated with the SNARE complex through direct interaction with SNAP-25. Binding of recombinant Snapin-CT to SNAP-25 blocked the association of the SNARE complex with synaptotagmin. Introduction of Snapin-CT and peptides containing the SNAP-25 binding sequence into presynaptic superior cervical ganglion neurons in culture reversibly inhibited synaptic transmission. These results suggest that Snapin is an important component of the neurotransmitter release process through its modulation of the sequential interactions between the SNAREs and synaptotagmin.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J M",
      "lastName" : "Ilardi",
      "authorRank" : 1,
      "name" : "Ilardi JM",
      "referenceId" : "RGD:A460280"
    }, {
      "firstName" : "S",
      "lastName" : "Mochida",
      "authorRank" : 2,
      "name" : "Mochida S",
      "referenceId" : "RGD:A12716"
    }, {
      "firstName" : "Z H",
      "lastName" : "Sheng",
      "authorRank" : 3,
      "name" : "Sheng ZH",
      "referenceId" : "RGD:A460281"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702160"
    } ]
  }, {
    "primaryId" : "PMID:10195214",
    "title" : "Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Wang HL, etal., Nat Neurosci. 1999 Mar;2(3):226-33. doi: 10.1038/6326.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:35:59.000-05:00",
    "volume" : "2",
    "pages" : "226-33",
    "abstract" : "By defining the functional defect in a congenital myasthenic syndrome (CMS), we show that the third transmembrane domain (M3) of the muscle acetylcholine receptor governs the speed and efficiency of gating of its channel. The clinical phenotype of this CMS results from the mutation V285I in M3 of the alpha subunit, which attenuates endplate currents, accelerates their decay and causes abnormally brief acetylcholine-induced single-channel currents. Kinetic analysis of engineered alpha V285I receptors demonstrated a predominant effect on channel gating, with abnormally slow opening and rapid closing rates. Analysis of site-directed mutations revealed stereochemical and volume-dependent contributions of alpha V285 to channel gating. Thus, we demonstrate a functional role for the M3 domain as a key component of the nicotinic acetylcholine receptor channel-gating mechanism.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H L",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang HL",
      "referenceId" : "RGD:A542315"
    }, {
      "firstName" : "M",
      "lastName" : "Milone",
      "authorRank" : 2,
      "name" : "Milone M",
      "referenceId" : "RGD:A566518"
    }, {
      "firstName" : "K",
      "lastName" : "Ohno",
      "authorRank" : 3,
      "name" : "Ohno K",
      "referenceId" : "RGD:A18083"
    }, {
      "firstName" : "X M",
      "lastName" : "Shen",
      "authorRank" : 4,
      "name" : "Shen XM",
      "referenceId" : "RGD:A593924"
    }, {
      "firstName" : "A",
      "lastName" : "Tsujino",
      "authorRank" : 5,
      "name" : "Tsujino A",
      "referenceId" : "RGD:A53663"
    }, {
      "firstName" : "A P",
      "lastName" : "Batocchi",
      "authorRank" : 6,
      "name" : "Batocchi AP",
      "referenceId" : "RGD:A589357"
    }, {
      "firstName" : "P",
      "lastName" : "Tonali",
      "authorRank" : 7,
      "name" : "Tonali P",
      "referenceId" : "RGD:A573042"
    }, {
      "firstName" : "J",
      "lastName" : "Brengman",
      "authorRank" : 8,
      "name" : "Brengman J",
      "referenceId" : "RGD:A53662"
    }, {
      "firstName" : "A G",
      "lastName" : "Engel",
      "authorRank" : 9,
      "name" : "Engel AG",
      "referenceId" : "RGD:A566523"
    }, {
      "firstName" : "S M",
      "lastName" : "Sine",
      "authorRank" : 10,
      "name" : "Sine SM",
      "referenceId" : "RGD:A566522"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118388"
    } ]
  }, {
    "primaryId" : "PMID:10195920",
    "title" : "A new promoter polymorphism in the gene of lipopolysaccharide receptor CD14 is associated with expired myocardial infarction in patients with low atherosclerotic risk profile.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Unkelbach K, etal., Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):932-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-07-18T15:03:39.000-05:00",
    "volume" : "19",
    "pages" : "932-8",
    "abstract" : "Recent findings suggest that inflammation plays a role in atherosclerosis and its acute complications. Cellular response in infections with Gram-negative bacteria is mediated by bacterial lipopolysaccharide (LPS), which activates monocytes to expression of cytokines, growth factors, and procoagulatory factors via LPS receptor CD14. Endothelial cells and smooth muscle cells are stimulated by a complex of LPS and soluble CD14. In this study, LPS receptor CD14 was analyzed to find genetic variants and check them for an association with coronary artery disease or myocardial infarction (MI). When screening the CD14 gene by single-strand conformation polymorphism analysis, a promoter polymorphism was detected and confirmed as a T-to-C exchange at position -159. We determined the genotypes of 2228 men who had undergone coronary angiography for diagnostic purposes. Within the total study group there was no significant association of either genotype with MI or coronary artery disease. However, in a subgroup with low coronary risk (normotensive nonsmokers), a relative risk for MI in probands homozygous for the T allele could be evaluated (OR, 1.6; 95% CI, 1.0 to 2.4; P<0.05). The association was even stronger in low-risk patients older than 62 years (OR, 3.8; 95% CI, 1.6 to 9.0; P<0.01). In conclusion, we describe a new CD14 promoter polymorphism that is associated with MI, especially in older patients with a low atherosclerotic risk profile.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Unkelbach",
      "authorRank" : 1,
      "name" : "Unkelbach K",
      "referenceId" : "RGD:A61763"
    }, {
      "firstName" : "A",
      "lastName" : "Gardemann",
      "authorRank" : 2,
      "name" : "Gardemann A",
      "referenceId" : "RGD:A58213"
    }, {
      "firstName" : "M",
      "lastName" : "Kostrzewa",
      "authorRank" : 3,
      "name" : "Kostrzewa M",
      "referenceId" : "RGD:A61764"
    }, {
      "firstName" : "M",
      "lastName" : "Philipp",
      "authorRank" : 4,
      "name" : "Philipp M",
      "referenceId" : "RGD:A58033"
    }, {
      "firstName" : "H",
      "lastName" : "Tillmanns",
      "authorRank" : 5,
      "name" : "Tillmanns H",
      "referenceId" : "RGD:A58217"
    }, {
      "firstName" : "W",
      "lastName" : "Haberbosch",
      "authorRank" : 6,
      "name" : "Haberbosch W",
      "referenceId" : "RGD:A58220"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580252"
    } ]
  }, {
    "primaryId" : "PMID:10196144",
    "title" : "Dominant negative isoform of rat norepinephrine transporter produced by alternative RNA splicing.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kitayama S, etal., J Biol Chem 1999 Apr 16;274(16):10731-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:19.000-05:00",
    "volume" : "274",
    "pages" : "10731-6",
    "abstract" : "We have cloned from rat brain a family of alternatively spliced cDNAs from a single gene, which encodes a norepinephrine transporter (NET) having variations at the 3'-region including both coding and noncoding regions. This produces two transporter isoforms, rNETa and rNETb, which differ at their COOH termini. The rNETa isoform reveals a COOH terminus homologous to human NET and transports norepinephrine. In contrast, rNETb revealed no detectable transport function but reduced functional expression of rNETa when both isoforms were expressed in the same cell. Thus, rNETb potentially functions as a dominant negative inhibitor of rNETa activity. Co-expression of rNETb with a gamma-aminobutyric acid transporter (rGAT1), a serotonin transporter (rSERT), and a dopamine transporter (rDAT) reduced their transport activity. No reduction was found with the glutamate/aspartate transporter (rGLAST). Alternative RNA splicing of NET suggests a novel mechanism for the regulation of synaptic transmission.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kitayama",
      "authorRank" : 1,
      "name" : "Kitayama S",
      "referenceId" : "RGD:A23312"
    }, {
      "firstName" : "T",
      "lastName" : "Ikeda",
      "authorRank" : 2,
      "name" : "Ikeda T",
      "referenceId" : "RGD:A135146"
    }, {
      "firstName" : "C",
      "lastName" : "Mitsuhata",
      "authorRank" : 3,
      "name" : "Mitsuhata C",
      "referenceId" : "RGD:A23314"
    }, {
      "firstName" : "T",
      "lastName" : "Sato",
      "authorRank" : 4,
      "name" : "Sato T",
      "referenceId" : "RGD:A9831"
    }, {
      "firstName" : "K",
      "lastName" : "Morita",
      "authorRank" : 5,
      "name" : "Morita K",
      "referenceId" : "RGD:A21712"
    }, {
      "firstName" : "T",
      "lastName" : "Dohi",
      "authorRank" : 6,
      "name" : "Dohi T",
      "referenceId" : "RGD:A23315"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634151"
    } ]
  }, {
    "primaryId" : "PMID:10196145",
    "title" : "mRNAs encoding a von Ebner's-like protein and the Huntington disease protein are induced in rat male germ cells by Sertoli cells.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Syed V, etal., J Biol Chem 1999 Apr 16;274(16):10737-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:13.000-05:00",
    "volume" : "274",
    "pages" : "10737-42",
    "abstract" : "The success of spermatogenesis is dependent upon closely coordinated interactions between Sertoli cells and germ cells. To identify specific molecules that mediate interactions between somatic cells and germ cells in the rat testis, Sertoli cell-germ cell co-cultures and mRNA differential display were used. Two cDNAs, clone 1 (660 nucleotides) and clone 2 (390 nucleotides) were up-regulated when Sertoli cells were co-cultured with pachytene spermatocytes or round spermatids. Northern blot analyses confirmed the differential display expression patterns. Sequence analyses indicated that clone 1 was similar to a von Ebner's gland protein (87% at the nucleotide level and 80% at the amino acid level) and clone 2 was identical to a region of the Huntington disease protein. The von Ebner's-like protein mRNA was induced after 4 h of co-culture, while the Huntington disease protein required 18 h of co-culture for expression. The von Ebner's-like protein was induced in germ cells by a secreted Sertoli cell factor(s) smaller than 10 kDa that is sensitive to freezing and thawing or boiling. The Huntington disease protein was induced in germ cells by a Sertoli cell secreted factor(s) larger than 10 kDa which survives freezing and thawing, but is inactivated by boiling.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Syed",
      "authorRank" : 1,
      "name" : "Syed V",
      "referenceId" : "RGD:A21253"
    }, {
      "firstName" : "E",
      "lastName" : "Gomez",
      "authorRank" : 2,
      "name" : "Gomez E",
      "referenceId" : "RGD:A27181"
    }, {
      "firstName" : "NB",
      "lastName" : "Hecht",
      "authorRank" : 3,
      "name" : "Hecht NB",
      "referenceId" : "RGD:A21254"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727268"
    } ]
  }, {
    "primaryId" : "PMID:10196146",
    "title" : "Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Heimann K, etal., J Biol Chem. 1999 Apr 16;274(16):10743-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-10T15:37:35.000-05:00",
    "volume" : "274",
    "pages" : "10743-50",
    "abstract" : "Golgi membranes and Golgi-derived vesicles are associated with multiple cytoskeletal proteins and motors, the diversity and distribution of which have not yet been defined. Carrier vesicles were separated from Golgi membranes, using an in vitro budding assay, and different populations of vesicles were separated using sucrose density gradients. Three main populations of vesicles labeled with  beta-COP, gamma-adaptin, or p200/myosin II were separated and analyzed for the presence of actin/actin-binding proteins. beta-Actin was bound to Golgi cisternae and to all populations of newly budded vesicles. Centractin was selectively associated with vesicles co-distributing with beta-COP-vesicles, while p200/myosin II (non-muscle myosin IIA) and non-muscle myosin IIB were found on different vesicle populations. Isoforms of the Tm5 tropomyosins were found on selected Golgi-derived vesicles, while other Tm isoforms did not colocalize with  Tm5 indicating the association of specialized actin filaments with Golgi-derived  vesicles. Golgi-derived vesicles were shown to bind to F-actin polymerized from cytosol with Jasplakinolide. Thus, newly budded, coated vesicles derived from Golgi membranes can bind to actin and are customized for differential interactions with microfilaments by the presence of selective arrays of actin-binding proteins.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Heimann",
      "authorRank" : 1,
      "name" : "Heimann",
      "referenceId" : "RGD:A203400"
    }, {
      "firstName" : "JM",
      "lastName" : "Percival",
      "authorRank" : 2,
      "name" : "Percival",
      "referenceId" : "RGD:A394293"
    }, {
      "firstName" : "R",
      "lastName" : "Weinberger",
      "authorRank" : 3,
      "name" : "Weinberger R",
      "referenceId" : "RGD:A57811"
    }, {
      "firstName" : "P",
      "lastName" : "Gunning",
      "authorRank" : 4,
      "name" : "Gunning P",
      "referenceId" : "RGD:A23575"
    }, {
      "firstName" : "JL",
      "lastName" : "Stow",
      "authorRank" : 5,
      "name" : "Stow JL",
      "referenceId" : "RGD:A26699"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11541123"
    } ]
  }, {
    "primaryId" : "PMID:10196175",
    "title" : "Alternative splicing determines the intracellular localization of the novel nuclear protein Nop30 and its interaction with the splicing factor SRp30c.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Stoss O, etal., J Biol Chem 1999 Apr 16;274(16):10951-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:43:27.000-06:00",
    "volume" : "274",
    "pages" : "10951-62",
    "abstract" : "We report on the molecular cloning of a novel human cDNA by its interaction with the splicing factor SRp30c in a yeast two-hybrid screen. This cDNA is predominantly expressed in muscle and encodes a protein that is present in the nucleoplasm and concentrated in nucleoli. It was therefore termed Nop30 (nucleolar protein of 30 kDa). We have also identified a related cDNA with a different carboxyl terminus. Sequencing of the NOP gene demonstrated that both cDNAs are generated by alternative 5' splice site usage from a single gene that consists of four exons, spans at least 1800 nucleotides, and is located on chromosome 16q21-q23. The alternative 5' splice site usage introduces a frameshift creating two different carboxyl termini. The carboxyl terminus of Nop30 is rich in serines and arginines and has been found to target the protein into the nucleus, whereas its isoform is characterized by proline/glutamic acid dipeptides in its carboxyl terminus and is predominantly found in the cytosol. Interaction studies in yeast, in vitro protein interaction assays, and co-immunoprecipitations demonstrated that Nop30 multimerizes and binds to the RS domain of SRp30c but not to other splicing factors tested. Overexpression of Nop30 changes alternative exon usage in preprotachykinin and SRp20 reporter genes, suggesting that Nop30 influences alternative splice site selection in vivo.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Stoss",
      "authorRank" : 1,
      "name" : "Stoss O",
      "referenceId" : "RGD:A18315"
    }, {
      "firstName" : "FW",
      "lastName" : "Schwaiger",
      "authorRank" : 2,
      "name" : "Schwaiger FW",
      "referenceId" : "RGD:A24197"
    }, {
      "firstName" : "TA",
      "lastName" : "Cooper",
      "authorRank" : 3,
      "name" : "Cooper TA",
      "referenceId" : "RGD:A36096"
    }, {
      "firstName" : "S",
      "lastName" : "Stamm",
      "authorRank" : 4,
      "name" : "Stamm S",
      "referenceId" : "RGD:A15553"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734603"
    } ]
  }, {
    "primaryId" : "PMID:10196347",
    "title" : "Contribution of virus-receptor interaction to distinct viral proliferation of neuropathogenic and nonneuropathogenic murine leukemia viruses in rat glial cells.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Takase-Yoden S and Watanabe R, J Virol 1999 May;73(5):4461-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:45.000-05:00",
    "volume" : "73",
    "pages" : "4461-4",
    "abstract" : "The efficiency of receptor-mediated entry of pseudotyped virus carrying the surface protein (SU) of clone A8, a neuropathogenic variant of Friend murine leukemia virus (FrMLV), to rat glial cell line F10 was 1 order of magnitude greater than that of pseudotyped virus carrying SU of nonneuropathogenic FrMLV clone 57. Introduction of the gene coding for ecotropic MLV receptor on F10 cells (F10-ecoR) into SIRC cells, which are naturally resistant to FrMLV infection, also revealed the difference in receptor recognition between the A8 and the 57 viruses. Our results show that the difference in receptor utilization between A8-SU and 57-SU only partially explains the 3-order-of-magnitude difference in proliferation between A8 and 57 viruses in F10 cells.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Takase-Yoden",
      "authorRank" : 1,
      "name" : "Takase-Yoden S",
      "referenceId" : "RGD:A27182"
    }, {
      "firstName" : "R",
      "lastName" : "Watanabe",
      "authorRank" : 2,
      "name" : "Watanabe R",
      "referenceId" : "RGD:A7309"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727269"
    } ]
  }, {
    "primaryId" : "PMID:10196363",
    "title" : "Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A).",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Allikmets R, etal., Hum Mol Genet. 1999 May;8(5):743-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-06T16:33:36.000-06:00",
    "volume" : "8",
    "pages" : "743-9",
    "abstract" : "X-linked sideroblastic anemia and ataxia (XLSA/A) is a recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar ataxia and mild anemia with hypochromia and microcytosis. A gene encoding an ATP-binding cassette (ABC) transporter was mapped to Xq13, a region previously shown by linkage analysis to harbor the XLSA/A gene. This gene, ABC7, is an ortholog of the yeast ATM1 gene whose product localizes to the mitochondrial inner membrane and is involved in iron homeostasis. The full-length ABC7 cDNA was cloned and the entire coding region screened for mutations in a kindred in which five male members manifested XLSA/A. An I400M variant was identified in a predicted transmembrane segment of the ABC7 gene in patients with XLSA/A. The mutation was shown to segregate with the disease in the family and was not detected in at least 600 chromosomes of general population controls. Introduction of the corresponding mutation into the Saccharomyces cerevisiae ATM1 gene resulted in a partial loss of function of the yeast Atm1 protein. In addition, the human wild-type ABC7 protein was able to complement ATM1 deletion in yeast. These data indicate that ABC7 is the causal gene of XLSA/A and that XLSA/A is a mitochondrial disease caused by a mutation in the nuclear genome.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Allikmets",
      "authorRank" : 1,
      "name" : "Allikmets R",
      "referenceId" : "RGD:A26840"
    }, {
      "firstName" : "WH",
      "lastName" : "Raskind",
      "authorRank" : 2,
      "name" : "Raskind WH",
      "referenceId" : "RGD:A39520"
    }, {
      "firstName" : "A",
      "lastName" : "Hutchinson",
      "authorRank" : 3,
      "name" : "Hutchinson A",
      "referenceId" : "RGD:A70671"
    }, {
      "firstName" : "ND",
      "lastName" : "Schueck",
      "authorRank" : 4,
      "name" : "Schueck ND",
      "referenceId" : "RGD:A70870"
    }, {
      "firstName" : "M",
      "lastName" : "Dean",
      "authorRank" : 5,
      "name" : "Dean M",
      "referenceId" : "RGD:A15953"
    }, {
      "firstName" : "DM",
      "lastName" : "Koeller",
      "authorRank" : 6,
      "name" : "Koeller DM",
      "referenceId" : "RGD:A70871"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598600"
    } ]
  }, {
    "primaryId" : "PMID:10196379",
    "title" : "Germline BRCA1 alterations in a population-based series of ovarian cancer cases.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Janezic SA, etal., Hum Mol Genet. 1999 May;8(5):889-97.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:15:13.000-05:00",
    "volume" : "8",
    "pages" : "889-97",
    "abstract" : "The objective of this study was to provide more accurate frequency estimates of breast cancer susceptibility gene 1 ( BRCA1 ) germline alterations in the ovarian cancer population. To achieve this, we determined the prevalence of BRCA1 alterations in a population-based series of consecutive ovarian cancer cases. This is the first population-based ovarian cancer study reporting BRCA1 alterations derived from a comprehensive screen of the entire coding region. One  hundred and seven ovarian cancer cases were analyzed for BRCA1 alterations using  the RNase mismatch cleavage assay followed by direct sequencing. Two truncating mutations, 962del4 and 3600del11, were identified. Both patients had a family history of breast or ovarian cancer. Several novel as well as previously reported uncharacterized variants were also identified, some of which were associated with a family history of cancer. The frequency distribution of common polymorphisms was determined in the 91 Caucasian cancer cases in this series and 24 sister controls using allele-specific amplification. The rare form of the Q356R polymorphism was significantly ( P = 0.03) associated with a family history of ovarian cancer, suggesting that this polymorphism may influence ovarian cancer risk. In summary, our data suggest a role for some uncharacterized variants and rare forms of polymorphisms in determining ovarian cancer risk, and highlight the necessity to screen for missense alterations as well as truncating mutations in this population.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SA",
      "lastName" : "Janezic",
      "authorRank" : 1,
      "name" : "Janezic",
      "referenceId" : "RGD:A271660"
    }, {
      "firstName" : "A",
      "lastName" : "Ziogas",
      "authorRank" : 2,
      "name" : "Ziogas",
      "referenceId" : "RGD:A230824"
    }, {
      "firstName" : "LM",
      "lastName" : "Krumroy",
      "authorRank" : 3,
      "name" : "Krumroy LM",
      "referenceId" : "RGD:A74523"
    }, {
      "firstName" : "M",
      "lastName" : "Krasner",
      "authorRank" : 4,
      "name" : "Krasner",
      "referenceId" : "RGD:A271661"
    }, {
      "firstName" : "SJ",
      "lastName" : "Plummer",
      "authorRank" : 5,
      "name" : "Plummer SJ",
      "referenceId" : "RGD:A74522"
    }, {
      "firstName" : "P",
      "lastName" : "Cohen",
      "authorRank" : 6,
      "name" : "Cohen P",
      "referenceId" : "RGD:A20611"
    }, {
      "firstName" : "M",
      "lastName" : "Gildea",
      "authorRank" : 7,
      "name" : "Gildea",
      "referenceId" : "RGD:A271662"
    }, {
      "firstName" : "D",
      "lastName" : "Barker",
      "authorRank" : 8,
      "name" : "Barker",
      "referenceId" : "RGD:A250625"
    }, {
      "firstName" : "R",
      "lastName" : "Haile",
      "authorRank" : 9,
      "name" : "Haile",
      "referenceId" : "RGD:A261363"
    }, {
      "firstName" : "G",
      "lastName" : "Casey",
      "authorRank" : 10,
      "name" : "Casey G",
      "referenceId" : "RGD:A56720"
    }, {
      "firstName" : "H",
      "lastName" : "Anton-Culver",
      "authorRank" : 11,
      "name" : "Anton-Culver",
      "referenceId" : "RGD:A222276"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068620"
    } ]
  }, {
    "primaryId" : "PMID:10196380",
    "title" : "Analysis of myocilin mutations in 1703 glaucoma patients from five different populations.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Fingert JH, etal., Hum Mol Genet. 1999 May;8(5):899-905.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-28T10:47:39.000-05:00",
    "volume" : "8",
    "pages" : "899-905",
    "abstract" : "A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JH",
      "lastName" : "Fingert",
      "authorRank" : 1,
      "name" : "Fingert JH",
      "referenceId" : "RGD:A78625"
    }, {
      "firstName" : "E",
      "lastName" : "Heon",
      "authorRank" : 2,
      "name" : "Heon E",
      "referenceId" : "RGD:A9698"
    }, {
      "firstName" : "JM",
      "lastName" : "Liebmann",
      "authorRank" : 3,
      "name" : "Liebmann JM",
      "referenceId" : "RGD:A78626"
    }, {
      "firstName" : "T",
      "lastName" : "Yamamoto",
      "authorRank" : 4,
      "name" : "Yamamoto T",
      "referenceId" : "RGD:A161440"
    }, {
      "firstName" : "JE",
      "lastName" : "Craig",
      "authorRank" : 5,
      "name" : "Craig JE",
      "referenceId" : "RGD:A78628"
    }, {
      "firstName" : "J",
      "lastName" : "Rait",
      "authorRank" : 6,
      "name" : "Rait J",
      "referenceId" : "RGD:A78629"
    }, {
      "firstName" : "K",
      "lastName" : "Kawase",
      "authorRank" : 7,
      "name" : "Kawase K",
      "referenceId" : "RGD:A15357"
    }, {
      "firstName" : "ST",
      "lastName" : "Hoh",
      "authorRank" : 8,
      "name" : "Hoh ST",
      "referenceId" : "RGD:A78630"
    }, {
      "firstName" : "YM",
      "lastName" : "Buys",
      "authorRank" : 9,
      "name" : "Buys YM",
      "referenceId" : "RGD:A78631"
    }, {
      "firstName" : "J",
      "lastName" : "Dickinson",
      "authorRank" : 10,
      "name" : "Dickinson J",
      "referenceId" : "RGD:A78632"
    }, {
      "firstName" : "RR",
      "lastName" : "Hockey",
      "authorRank" : 11,
      "name" : "Hockey RR",
      "referenceId" : "RGD:A78633"
    }, {
      "firstName" : "D",
      "lastName" : "Williams-Lyn",
      "authorRank" : 12,
      "name" : "Williams-Lyn D",
      "referenceId" : "RGD:A78634"
    }, {
      "firstName" : "G",
      "lastName" : "Trope",
      "authorRank" : 13,
      "name" : "Trope G",
      "referenceId" : "RGD:A78635"
    }, {
      "firstName" : "Y",
      "lastName" : "Kitazawa",
      "authorRank" : 14,
      "name" : "Kitazawa Y",
      "referenceId" : "RGD:A78636"
    }, {
      "firstName" : "R",
      "lastName" : "Ritch",
      "authorRank" : 15,
      "name" : "Ritch R",
      "referenceId" : "RGD:A78637"
    }, {
      "firstName" : "DA",
      "lastName" : "Mackey",
      "authorRank" : 16,
      "name" : "Mackey DA",
      "referenceId" : "RGD:A71620"
    }, {
      "firstName" : "WL",
      "lastName" : "Alward",
      "authorRank" : 17,
      "name" : "Alward WL",
      "referenceId" : "RGD:A39361"
    }, {
      "firstName" : "VC",
      "lastName" : "Sheffield",
      "authorRank" : 18,
      "name" : "Sheffield VC",
      "referenceId" : "RGD:A4262"
    }, {
      "firstName" : "EM",
      "lastName" : "Stone",
      "authorRank" : 19,
      "name" : "Stone EM",
      "referenceId" : "RGD:A9702"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600838"
    } ]
  }, {
    "primaryId" : "PMID:10196478",
    "title" : "Molecular cloning and characterization of two sets of alpha-theta genes in the rat alpha-like globin gene cluster.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Satoh H, etal., Gene 1999 Apr 1;230(1):91-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:59.000-05:00",
    "volume" : "230",
    "pages" : "91-9",
    "abstract" : "The highly heterogeneous rat hemoglobin system was investigated at the gene level. Two regions of the alpha-like globin gene cluster from a Wistar rat were isolated. Four lambda Dash recombinant clones carrying rat alpha-like globin genes were localized on two distinct gene regions. A region of approximately 16kb was found to contain the 5'-IIalpha1-psi theta 1-3' loci, and another of approximately 24kb the 5'-IIalpha2-psi theta2-psiI alpha3-3' loci. Both IIalpha1 and IIalpha2 are considered to be active, coding the IIalpha-globin chain. The nt sequences of IIalpha1 and IIalpha2 are identical except for six nt in the non-coding region. The psiI alpha3 locus is a truncated pseudogene. The putative promoter region of an alpha-like globin gene is joined directly to the third exon, homologous to that of Ialpha-globin cDNA. psi theta1 and psi theta2 are also pseudogenes, as evidenced by several deletions located in the protein-coding regions of these loci. The psi theta1 and psi theta2 loci exhibit extensive homology, but the restriction maps of these genes and their flanking regions differ considerably. Genomic Southern blot analyses of the total liver DNA from six rats showed the existence of three theta-globin-related genes, including psi theta1 and psi theta2. These results indicate that the two gene regions investigated are not allelic variants, but may be generated by block duplication. This is the first report of the existence of rodent theta-globin genes.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Satoh",
      "authorRank" : 1,
      "name" : "Satoh H",
      "referenceId" : "RGD:A4128"
    }, {
      "firstName" : "N",
      "lastName" : "Inokuchi",
      "authorRank" : 2,
      "name" : "Inokuchi N",
      "referenceId" : "RGD:A19366"
    }, {
      "firstName" : "Y",
      "lastName" : "Nagae",
      "authorRank" : 3,
      "name" : "Nagae Y",
      "referenceId" : "RGD:A19367"
    }, {
      "firstName" : "T",
      "lastName" : "Okazaki",
      "authorRank" : 4,
      "name" : "Okazaki T",
      "referenceId" : "RGD:A4706"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632974"
    } ]
  }, {
    "primaryId" : "PMID:10196578",
    "title" : "Two sodium channels contribute to the TTX-R sodium current in primary sensory neurons.",
    "datePublished" : "1998-01-01T00:00:00.000-06:00",
    "citation" : "Tate S, etal., Nat Neurosci 1998 Dec;1(8):653-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-11T15:05:30.000-06:00",
    "volume" : "1",
    "pages" : "653-5",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Tate",
      "authorRank" : 1,
      "name" : "Tate S",
      "referenceId" : "RGD:A7900"
    }, {
      "firstName" : "S",
      "lastName" : "Benn",
      "authorRank" : 2,
      "name" : "Benn S",
      "referenceId" : "RGD:A7901"
    }, {
      "firstName" : "C",
      "lastName" : "Hick",
      "authorRank" : 3,
      "name" : "Hick C",
      "referenceId" : "RGD:A7902"
    }, {
      "firstName" : "D",
      "lastName" : "Trezise",
      "authorRank" : 4,
      "name" : "Trezise D",
      "referenceId" : "RGD:A7903"
    }, {
      "firstName" : "V",
      "lastName" : "John",
      "authorRank" : 5,
      "name" : "John V",
      "referenceId" : "RGD:A7904"
    }, {
      "firstName" : "RJ",
      "lastName" : "Mannion",
      "authorRank" : 6,
      "name" : "Mannion RJ",
      "referenceId" : "RGD:A7905"
    }, {
      "firstName" : "M",
      "lastName" : "Costigan",
      "authorRank" : 7,
      "name" : "Costigan M",
      "referenceId" : "RGD:A7906"
    }, {
      "firstName" : "C",
      "lastName" : "Plumpton",
      "authorRank" : 8,
      "name" : "Plumpton C",
      "referenceId" : "RGD:A7907"
    }, {
      "firstName" : "D",
      "lastName" : "Grose",
      "authorRank" : 9,
      "name" : "Grose D",
      "referenceId" : "RGD:A7908"
    }, {
      "firstName" : "Z",
      "lastName" : "Gladwell",
      "authorRank" : 10,
      "name" : "Gladwell Z",
      "referenceId" : "RGD:A7909"
    }, {
      "firstName" : "G",
      "lastName" : "Kendall",
      "authorRank" : 11,
      "name" : "Kendall G",
      "referenceId" : "RGD:A7910"
    }, {
      "firstName" : "K",
      "lastName" : "Dale",
      "authorRank" : 12,
      "name" : "Dale K",
      "referenceId" : "RGD:A7911"
    }, {
      "firstName" : "C",
      "lastName" : "Bountra",
      "authorRank" : 13,
      "name" : "Bountra C",
      "referenceId" : "RGD:A7912"
    }, {
      "firstName" : "CJ",
      "lastName" : "Woolf",
      "authorRank" : 14,
      "name" : "Woolf CJ",
      "referenceId" : "RGD:A7913"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69980"
    } ]
  }, {
    "primaryId" : "PMID:10196584",
    "title" : "Astrocyte-mediated potentiation of inhibitory synaptic transmission.",
    "datePublished" : "1998-12-01T00:00:00.000-06:00",
    "citation" : "Kang J, etal., Nat Neurosci. 1998 Dec;1(8):683-92. doi: 10.1038/3684.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-04-10T03:02:22.000-05:00",
    "volume" : "1",
    "pages" : "683-92",
    "abstract" : "We investigated the role of astrocytes in activity-dependent modulation of inhibitory synaptic transmission in hippocampal slices. Repetitive firing of an interneuron decreased the probability of synaptic failures in spike-evoked inhibitory postsynaptic currents (unitary IPSCs) in CA1 pyramidal neurons. The GABAB-receptor antagonist CGP55845A abolished this effect. Direct stimulation of astrocytes, or application of the GABAB-receptor agonist baclofen, potentiated miniature inhibitory postsynaptic currents (mIPSCs) in pyramidal neurons. These effects were blocked by inhibition of astrocytic calcium signaling with the calcium chelator BAPTA or by antagonists of the ionotropic glutamate receptors. These observations suggest that interneuronal firing elicits a GABAB-receptor-mediated elevation of calcium in surrounding astrocytes, which in turn potentiates inhibitory transmission. Astrocytes may therefore be a necessary intermediary in activity-dependent modulation of inhibitory synapses in the hippocampus.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Kang",
      "authorRank" : 1,
      "name" : "Kang J",
      "referenceId" : "RGD:A59697"
    }, {
      "firstName" : "L",
      "lastName" : "Jiang",
      "authorRank" : 2,
      "name" : "Jiang L",
      "referenceId" : "RGD:A14816"
    }, {
      "firstName" : "S A",
      "lastName" : "Goldman",
      "authorRank" : 3,
      "name" : "Goldman SA",
      "referenceId" : "RGD:A468881"
    }, {
      "firstName" : "M",
      "lastName" : "Nedergaard",
      "authorRank" : 4,
      "name" : "Nedergaard M",
      "referenceId" : "RGD:A144213"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14397583"
    } ]
  }, {
    "primaryId" : "PMID:10196701",
    "title" : "Screening for minor changes in the distal part of the human dystrophin gene in Greek DMD/BMD patients.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kekou K, etal., Eur J Hum Genet. 1999 Feb-Mar;7(2):179-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:27:24.000-05:00",
    "volume" : "7",
    "pages" : "179-87",
    "abstract" : "The distal part of the human dystrophin gene is characterised by particular features and seems to play an important functional role. Additionally in recent years several data have implicated minor mutations in this gene region in some patients with mental retardation (MR). In order to screen for pathogenic mutations at the distal part of the human dystrophin gene we have used single-strand conformation analysis of products amplified by polymerase chain reaction (PCR-SSCA) in 35 unrelated male Greek DMD/BMD patients with no detectable deletions. Seven patients also had severe mental retardation. Direct sequencing of samples demonstrating a shift of SSCA mobility revealed six different and pathogenic minor changes, five in DMD and one in a BMD patient. Four of the mutations were found in DMD patients with severe MR. Three of these mutations were localised in exon 66, which presents an interesting similarity with part of the 3' end of the genome of eastern equine encephalomyelitis virus (EEEV). The present data from Greek DMD/BMD patients give further information about the phenotypic effects consequent on mutations in exons at the distal part  of the human dystrophin gene.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Kekou",
      "authorRank" : 1,
      "name" : "Kekou",
      "referenceId" : "RGD:A255004"
    }, {
      "firstName" : "A",
      "lastName" : "Mavrou",
      "authorRank" : 2,
      "name" : "Mavrou",
      "referenceId" : "RGD:A211089"
    }, {
      "firstName" : "L",
      "lastName" : "Florentin",
      "authorRank" : 3,
      "name" : "Florentin L",
      "referenceId" : "RGD:A94187"
    }, {
      "firstName" : "S",
      "lastName" : "Youroukos",
      "authorRank" : 4,
      "name" : "Youroukos",
      "referenceId" : "RGD:A268035"
    }, {
      "firstName" : "DI",
      "lastName" : "Zafiriou",
      "authorRank" : 5,
      "name" : "Zafiriou",
      "referenceId" : "RGD:A268036"
    }, {
      "firstName" : "HN",
      "lastName" : "Skouteli",
      "authorRank" : 6,
      "name" : "Skouteli",
      "referenceId" : "RGD:A268037"
    }, {
      "firstName" : "C",
      "lastName" : "Metaxotou",
      "authorRank" : 7,
      "name" : "Metaxotou",
      "referenceId" : "RGD:A268038"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067415"
    } ]
  }, {
    "primaryId" : "PMID:10196714",
    "title" : "Haplotypes and mutations of the PAH locus in Egyptian families with PKU.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Effat L, etal., Eur J Hum Genet. 1999 Feb-Mar;7(2):259-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:42:41.000-05:00",
    "volume" : "7",
    "pages" : "259-62",
    "abstract" : "A high degree of molecular heterogeneneity at the phenylalanine hydroxylase (PAH) locus was established by examining RFLP haplotypes and PAH mutations in the families of 13 Egyptians with phenylketenouria (PKU). Thirteen different haplotypes were unequivocally determined in these kindreds. Haplotypes 1.8, 3.9,  4.3, 7.8, 22.11, 27.6, and 52.8 were found segregating with normal chromosomes, whilst haplotypes 1.8, 5.9, 23.8, 32.8, the newly assigned 73.9, and two as yet incomplete but novel haplotypes were found segregating with the mutant chromosomes. There was no particular preference for a single haplotype among normal or mutant chromosomes. Nine different mutations were also identified among the 26 alleles. IVS 10nt11g (8/26), IVS 2nt5g-c (4/26), R261Q (3/26), R176X (2/26), Y206D (2/26), S231P (2/26), Y198fs [593-614del22bp]; (2/26), G46fs [136/137delG]; (1/26), and E178G (1/26). Six of these mutations (IVS 2nt5g-c, R176X, Y198fs, R261Q, S231P, and IVS 10nt11g) are common to other Mediterranean populations. Two mutations not previously reported in the Mediterranean basin were also observed (Y206D and G46fs). These intriguing preliminary findings confirm IVS 10nt11g as a major mutation among Mediterranean mutations and demonstrate the need for a more comprehensive study of Arab populations to confirm the uniqueness of the two novel mutations to the Egyptian population.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Effat",
      "authorRank" : 1,
      "name" : "Effat",
      "referenceId" : "RGD:A251363"
    }, {
      "firstName" : "A",
      "lastName" : "Kuzmin",
      "authorRank" : 2,
      "name" : "Kuzmin",
      "referenceId" : "RGD:A251364"
    }, {
      "firstName" : "N",
      "lastName" : "Kasem",
      "authorRank" : 3,
      "name" : "Kasem",
      "referenceId" : "RGD:A251365"
    }, {
      "firstName" : "NA",
      "lastName" : "Meguid",
      "authorRank" : 4,
      "name" : "Meguid",
      "referenceId" : "RGD:A251366"
    }, {
      "firstName" : "S",
      "lastName" : "Kotb",
      "authorRank" : 5,
      "name" : "Kotb",
      "referenceId" : "RGD:A251367"
    }, {
      "firstName" : "RC",
      "lastName" : "Eisensmith",
      "authorRank" : 6,
      "name" : "Eisensmith RC",
      "referenceId" : "RGD:A81289"
    }, {
      "firstName" : "SA",
      "lastName" : "Temtamy",
      "authorRank" : 7,
      "name" : "Temtamy SA",
      "referenceId" : "RGD:A37688"
    }, {
      "firstName" : "S",
      "lastName" : "Rushdi",
      "authorRank" : 8,
      "name" : "Rushdi S",
      "referenceId" : "RGD:A90785"
    }, {
      "firstName" : "S",
      "lastName" : "Woo",
      "authorRank" : 9,
      "name" : "Woo",
      "referenceId" : "RGD:A251368"
    }, {
      "firstName" : "M",
      "lastName" : "El-Awady",
      "authorRank" : 10,
      "name" : "El-Awady",
      "referenceId" : "RGD:A251369"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062496"
    } ]
  }, {
    "primaryId" : "PMID:10197429",
    "title" : "Identification of true differentially expressed mRNAs in a pair of human bladder transitional cell carcinomas using an improved differential display procedure.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Gromova I, etal., Electrophoresis 1999 Feb;20(2):241-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-01T08:15:36.000-05:00",
    "volume" : "20",
    "pages" : "241-8",
    "abstract" : "Differential display in combination with arbitrarily primed polymerase chain reaction (PCR) fingerprinting has become one of the most powerful techniques to identify and isolate mRNAs that are differentially expressed in pairs of biological samples. However, in many cases the cDNA band corresponding to the differentially amplified product contains several cDNA species that comigrate with the cDNA of interest due to the poor resolution of the fingerprinting gels, thus hampering further analysis and identification of the desirable cDNA. To improve the electrophoretic resolution of differentially amplified cDNAs, we have utilized Resolver Gold agarose gel electrophoresis (Ingenius) as an additional step to overcome downstream problems encountered during RNA fingerprinting experiments. To illustrate the power of the modified differential display procedure we present a detailed analysis of the cDNA products differentially displayed in tumor biopsies obtained from a noninvasive (grade II, Ta) and an invasive (grade III, T2-T4) human bladder transitional cell carcinoma (TCC). Several genes that were differentially expressed in this tumor pair were identified. These included: tropomyosin 4, the protein disulfide isomerase precursor (PDI), MRP14, signal transducer CD24, keratins 8 and 13, cytochrome oxidase subunit IV (COXIV), putative transcription factor HOX-1.3, as well as two novel genes of yet unknown function. All of the identified cDNAs were shown to be truly differentially expressed by Northern blotting, reverse transcriptase-PCR (RT-PCR), and two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) analysis of the corresponding lesions.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Gromova",
      "authorRank" : 1,
      "name" : "Gromova I",
      "referenceId" : "RGD:A24304"
    }, {
      "firstName" : "P",
      "lastName" : "Gromov",
      "authorRank" : 2,
      "name" : "Gromov P",
      "referenceId" : "RGD:A24305"
    }, {
      "firstName" : "JE",
      "lastName" : "Celis",
      "authorRank" : 3,
      "name" : "Celis JE",
      "referenceId" : "RGD:A24306"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634549"
    } ]
  }, {
    "primaryId" : "PMID:10197527",
    "title" : "Slit2-Mediated chemorepulsion and collapse of developing forebrain axons.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Nguyen Ba-Charvet KT, etal., Neuron 1999 Mar;22(3):463-73.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-10T13:59:56.000-05:00",
    "volume" : "22",
    "pages" : "463-73",
    "abstract" : "Diffusible chemorepellents play a major role in guiding developing axons toward their correct targets by preventing them from entering or steering them away from certain regions. Genetic studies in Drosophila revealed a novel repulsive guidance system that prevents inappropriate axons from crossing the CNS midline; this repulsive system is mediated by the Roundabout (Robo) receptor and its secreted ligand Slit. In rodents, Robo and Slit are expressed in the spinal cord and Slit can repel spinal motor axons in vitro. Here, we extend these findings into higher brain centers by showing that Robo1 and Robo2, as well as Slit1 and Slit2, are often expressed in complementary patterns in the developing forebrain. Furthermore, we show that human Slit2 can repel olfactory and hippocampal axons and collapse their growth cones.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KT",
      "lastName" : "Nguyen Ba-Charvet",
      "authorRank" : 1,
      "name" : "Nguyen Ba-Charvet KT",
      "referenceId" : "RGD:A52298"
    }, {
      "firstName" : "K",
      "lastName" : "Brose",
      "authorRank" : 2,
      "name" : "Brose K",
      "referenceId" : "RGD:A52299"
    }, {
      "firstName" : "V",
      "lastName" : "Marillat",
      "authorRank" : 3,
      "name" : "Marillat V",
      "referenceId" : "RGD:A52300"
    }, {
      "firstName" : "T",
      "lastName" : "Kidd",
      "authorRank" : 4,
      "name" : "Kidd T",
      "referenceId" : "RGD:A52301"
    }, {
      "firstName" : "CS",
      "lastName" : "Goodman",
      "authorRank" : 5,
      "name" : "Goodman CS",
      "referenceId" : "RGD:A52302"
    }, {
      "firstName" : "M",
      "lastName" : "Tessier-Lavigne",
      "authorRank" : 6,
      "name" : "Tessier-Lavigne M",
      "referenceId" : "RGD:A115977"
    }, {
      "firstName" : "C",
      "lastName" : "Sotelo",
      "authorRank" : 7,
      "name" : "Sotelo C",
      "referenceId" : "RGD:A23012"
    }, {
      "firstName" : "A",
      "lastName" : "Chedotal",
      "authorRank" : 8,
      "name" : "Chedotal A",
      "referenceId" : "RGD:A7960"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358394"
    } ]
  }, {
    "primaryId" : "PMID:10197531",
    "title" : "EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Bruckner K, etal., Neuron 1999 Mar;22(3):511-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:08:03.000-05:00",
    "volume" : "22",
    "pages" : "511-24",
    "abstract" : "Transmembrane ephrinB proteins have important functions during embryonic patterning as ligands for Eph receptor tyrosine kinases and presumably as signal-transducing receptor-like molecules. Consistent with \"reverse\" signaling, ephrinB1 is localized in sphingo-lipid/cholesterol-enriched raft microdomains, platforms for the localized concentration and activation of signaling molecules. Glutamate receptor-interacting protein (GRIP) and a highly related protein, which we have termed GRIP2, are recruited into these rafts through association with the C-terminal PDZ target site of ephrinB1. Stimulation of ephrinB1 with soluble EphB2 receptor ectodomain causes the formation of large raft patches that also contain GRIP proteins. Moreover, a GRIP-associated serine/threonine kinase activity is recruited into ephrinB1-GRIP complexes. Our findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Bruckner",
      "authorRank" : 1,
      "name" : "Bruckner K",
      "referenceId" : "RGD:A19289"
    }, {
      "firstName" : "J",
      "lastName" : "Pablo Labrador",
      "authorRank" : 2,
      "name" : "Pablo Labrador J",
      "referenceId" : "RGD:A19290"
    }, {
      "firstName" : "P",
      "lastName" : "Scheiffele",
      "authorRank" : 3,
      "name" : "Scheiffele P",
      "referenceId" : "RGD:A19291"
    }, {
      "firstName" : "A",
      "lastName" : "Herb",
      "authorRank" : 4,
      "name" : "Herb A",
      "referenceId" : "RGD:A45224"
    }, {
      "firstName" : "PH",
      "lastName" : "Seeburg",
      "authorRank" : 5,
      "name" : "Seeburg PH",
      "referenceId" : "RGD:A103850"
    }, {
      "firstName" : "R",
      "lastName" : "Klein",
      "authorRank" : 6,
      "name" : "Klein R",
      "referenceId" : "RGD:A15463"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632959"
    } ]
  }, {
    "primaryId" : "PMID:10197541",
    "title" : "Caspase-8 is required for cell death induced by expanded polyglutamine repeats.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Sanchez I, etal., Neuron 1999 Mar;22(3):623-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T12:03:12.000-06:00",
    "volume" : "22",
    "pages" : "623-33",
    "abstract" : "We show here that caspase-8 is required for the death of primary rat neurons induced by an expanded polyglutamine repeat (Q79). Expression of Q79 recruited and activated caspase-8. Inhibition of caspase-8 blocked polyglutamine-induced cell death. Coexpression of Q79 with the caspase inhibitor CrmA, a dominant-negative mutant of FADD (FADD DN), Bcl-2, or Bcl-xL, but not an N-terminally tagged Bcl-xL, prevented the recruitment of caspase-8 and inhibited polyglutamine-induced cell death. Furthermore, Western blot analysis revealed the presence of activated caspase-8 in the insoluble fraction of affected brain regions from Huntington's disease (HD) patients but not in those from neurologically unremarkable controls, suggesting the relocation and activation of caspase-8 during the pathogenesis of HD. These results suggest an essential role of caspase-8 in HD-related neural degenerative diseases.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Sanchez",
      "authorRank" : 1,
      "name" : "Sanchez I",
      "referenceId" : "RGD:A36725"
    }, {
      "firstName" : "CJ",
      "lastName" : "Xu",
      "authorRank" : 2,
      "name" : "Xu CJ",
      "referenceId" : "RGD:A36726"
    }, {
      "firstName" : "P",
      "lastName" : "Juo",
      "authorRank" : 3,
      "name" : "Juo P",
      "referenceId" : "RGD:A36727"
    }, {
      "firstName" : "A",
      "lastName" : "Kakizaka",
      "authorRank" : 4,
      "name" : "Kakizaka A",
      "referenceId" : "RGD:A36728"
    }, {
      "firstName" : "J",
      "lastName" : "Blenis",
      "authorRank" : 5,
      "name" : "Blenis J",
      "referenceId" : "RGD:A29705"
    }, {
      "firstName" : "J",
      "lastName" : "Yuan",
      "authorRank" : 6,
      "name" : "Yuan J",
      "referenceId" : "RGD:A36700"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734695"
    } ]
  }, {
    "primaryId" : "PMID:10197766",
    "title" : "Connexin30 in rodent, cat and human brain: selective expression in gray matter astrocytes, co-localization with connexin43 at gap junctions and late developmental appearance.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Nagy JI, etal., Neuroscience. 1999 Jan;88(2):447-68.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-16T16:44:23.000-06:00",
    "volume" : "88",
    "pages" : "447-68",
    "abstract" : "We previously presented evidence [Nagy et al. (1997) Neuroscience 78, 533-548] that, in addition to their ubiquitous expression of connexin43, astrocytes produce a second connexin suggested to be connexin30, a recently discovered member of the family of gap junction proteins. A connexin30 specific antibody was subsequently developed and utilized here to confirm and extend our earlier observations. On western blots, this antibody detected a 30,000 mol. wt protein in rat, mouse, cat and human brain, and exhibited no cross-reaction with connexin43, connexin26 or any other known connexins expressed in brain. Immunohistochemically, connexin30 was localized in astrocytes, at gap junctions between these cells and on the astrocyte side of gap junctions between astrocytes and oligodendrocytes. Double labelling revealed co-localization of connexin30 and connexin43 at astrocytic gap junctions. Punctate immunolabelling patterns for both connexins were qualitatively similar, but differences were evident. In contrast to regional connexin43 expression, diencephalic and hindbrain areas exhibited considerably greater expression than forebrain areas, subcortical perivascular astrocytic endfeet were more heavily labelled for connexin30, white matter tracts such as corpus callosum, internal capsule and anterior commissure were devoid of connexin30, and appreciable levels of connexin30 during development were not seen until about postnatal day 15. These results indicate that connexin30 is expressed by gray, but not white matter astrocytes, its distribution is highly heterogeneous in gray matter, it is co-localized with connexin43 at astrocytic gap junctions where it forms homotypic or heterotypic junctions, and its emergence is delayed until relatively late during brain maturation. Taken together, these results suggest that astrocytic connexin30 expression at both regional and cellular levels is subject to regulation in adult brain as well as during brain development.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JI",
      "lastName" : "Nagy",
      "authorRank" : 1,
      "name" : "Nagy JI",
      "referenceId" : "RGD:A18460"
    }, {
      "firstName" : "D",
      "lastName" : "Patel",
      "authorRank" : 2,
      "name" : "Patel D",
      "referenceId" : "RGD:A75288"
    }, {
      "firstName" : "PA",
      "lastName" : "Ochalski",
      "authorRank" : 3,
      "name" : "Ochalski PA",
      "referenceId" : "RGD:A75289"
    }, {
      "firstName" : "GL",
      "lastName" : "Stelmack",
      "authorRank" : 4,
      "name" : "Stelmack GL",
      "referenceId" : "RGD:A75290"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599836"
    } ]
  }, {
    "primaryId" : "PMID:10198040",
    "title" : "Protein interactions with the glucose transporter binding protein GLUT1CBP that provide a link between GLUT1 and the cytoskeleton.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Bunn RC, etal., Mol Biol Cell 1999 Apr;10(4):819-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:12.000-05:00",
    "volume" : "10",
    "pages" : "819-32",
    "abstract" : "Subcellular targeting and the activity of facilitative glucose transporters are likely to be regulated by interactions with cellular proteins. This report describes the identification and characterization of a protein, GLUT1 C-terminal binding protein (GLUT1CBP), that binds via a PDZ domain to the C terminus of GLUT1. The interaction requires the C-terminal four amino acids of GLUT1 and is isoform specific because GLUT1CBP does not interact with the C terminus of GLUT3 or GLUT4. Most rat tissues examined contain both GLUT1CBP and GLUT1 mRNA, whereas only small intestine lacked detectable GLUT1CBP protein. GLUT1CBP is also expressed in primary cultures of neurons and astrocytes, as well as in Chinese hamster ovary, 3T3-L1, Madin-Darby canine kidney, Caco-2, and pheochromocytoma-12 cell lines. GLUT1CBP is able to bind to native GLUT1 extracted from cell membranes, self-associate, or interact with the cytoskeletal proteins myosin VI, alpha-actinin-1, and the kinesin superfamily protein KIF-1B. The presence of a PDZ domain places GLUT1CBP among a growing family of structural and regulatory proteins, many of which are localized to areas of membrane specialization. This and its ability to interact with GLUT1 and cytoskeletal proteins implicate GLUT1CBP in cellular mechanisms for targeting GLUT1 to specific subcellular sites either by tethering the transporter to cytoskeletal motor proteins or by anchoring the transporter to the actin cytoskeleton.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RC",
      "lastName" : "Bunn",
      "authorRank" : 1,
      "name" : "Bunn RC",
      "referenceId" : "RGD:A22109"
    }, {
      "firstName" : "MA",
      "lastName" : "Jensen",
      "authorRank" : 2,
      "name" : "Jensen MA",
      "referenceId" : "RGD:A22110"
    }, {
      "firstName" : "BC",
      "lastName" : "Reed",
      "authorRank" : 3,
      "name" : "Reed BC",
      "referenceId" : "RGD:A22111"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633774"
    } ]
  }, {
    "primaryId" : "PMID:10198159",
    "title" : "The Bax inhibitor-1 gene is differentially regulated in adult testis and developing lung by two alternative TATA-less promoters.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Jean JC, etal., Genomics. 1999 Apr 15;57(2):201-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-07T13:56:01.000-05:00",
    "volume" : "57",
    "pages" : "201-8",
    "abstract" : "We identified Bax inhibitor-1, BI-1, as a developmentally regulated gene product in perinatal lung using suppressive subtractive hybridization. BI-1 is a novel suppressor of apoptosis that was previously cloned as testis-enhanced gene transcript (TEGT). However, sequence analysis of lung BI-1 revealed unique nucleotides starting 29 bases upstream of the ATG initiation codon and extending to the 5' end of lung-derived BI-1 cDNA compared to the original transcript from the testis. Cloning and sequencing of the upstream region of the BI-1 gene revealed that these unique sequences originated from two alternative first exons, located in tandem and separated by approximately 600 bases. Neither was preceded by a TATA box in the usual position, and S1 nuclease mapping at each exon 1 revealed multiple transcription start points with a major site being overlapped by a consensus initiator element. Promoter activity from each region was documented by transient transfection analysis in vitro using DNA sequences ligated to a reporter gene. The proximal promoter, P1, may exhibit cell type-specific differences in fibroblasts versus epithelia, whereas the distal promoter, P2, may exhibit species-specific differences in rat versus human cells. RT-PCR analysis for expression in adult tissues using exon 1-specific 5' primers and common 3' primers revealed that P1 is tissue-specific; P2 is ubiquitously active. The developmental regulation of BI-1 in the late fetal and early postnatal lung is specific for P2, indicating that these two TATA-less promoters are differentially regulated in adult testis and developing lung. Since Bax inhibitor-1 functions as a suppressor of apoptosis, its expression could provide a survival advantage for select cell populations during the peak period of apoptosis that occurs at birth.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JC",
      "lastName" : "Jean",
      "authorRank" : 1,
      "name" : "Jean JC",
      "referenceId" : "RGD:A94009"
    }, {
      "firstName" : "SM",
      "lastName" : "Oakes",
      "authorRank" : 2,
      "name" : "Oakes SM",
      "referenceId" : "RGD:A94010"
    }, {
      "firstName" : "M",
      "lastName" : "Joyce-Brady",
      "authorRank" : 3,
      "name" : "Joyce-Brady M",
      "referenceId" : "RGD:A94011"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2291962"
    } ]
  }, {
    "primaryId" : "PMID:10198196",
    "title" : "Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in the chronic phase of myocardial infarct scar healing.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hao J, etal., J Mol Cell Cardiol. 1999 Mar;31(3):667-78.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-26T09:53:53.000-05:00",
    "volume" : "31",
    "pages" : "667-78",
    "abstract" : "We have previously shown that non-myocytes present in healed 8-week infarct scar overexpress transduction proteins required for initiating the elevated deposition of structural matrix proteins in this tissue. Other work suggests that TGF-beta 1 may be involved in cardiac fibrosis and myocyte hypertrophy. However, the significance of the altered TGF-beta signaling in heart failure in the chronic phase of post-myocardial infarction (MI), particularly in the ongoing remodeling of the infarct scar, remains unexplored. Patterns of cardiac TGF beta 1 and Smad 2, 3, and 4 protein expression were investigated 8 weeks after MI and were compared to relative collagen deposition in border tissues (containing remnent myocytes) and the infarct scar (non-myocytes). Both TGF-beta 1 mRNA abundance and protein levels were significantly increased in the infarct scar v control values, and this trend was positively correlated to increased collagen type I expression. Cardiac Smad 2, 3, and 4 proteins were significantly increased in border and scar tissues v control values. Immunofluorescent studies indicated that Smad proteins localized proximal to the cellular nuclei present in the infarct scar. Decorin mRNA abundance was elevated in border and infarct scar, and the pattern of decorin immunostaining was markedly altered in remote remnant heart and scar v staining patterns of control sections. Expression of T beta RI (53 kDa) protein was significantly reduced in the scar, while the 75 kDa and 110 kDa isoforms of T beta RII were unchanged and significantly increased in scar, respectively. These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Hao",
      "authorRank" : 1,
      "name" : "Hao J",
      "referenceId" : "RGD:A13108"
    }, {
      "firstName" : "H",
      "lastName" : "Ju",
      "authorRank" : 2,
      "name" : "Ju H",
      "referenceId" : "RGD:A20437"
    }, {
      "firstName" : "S",
      "lastName" : "Zhao",
      "authorRank" : 3,
      "name" : "Zhao S",
      "referenceId" : "RGD:A21777"
    }, {
      "firstName" : "A",
      "lastName" : "Junaid",
      "authorRank" : 4,
      "name" : "Junaid A",
      "referenceId" : "RGD:A81620"
    }, {
      "firstName" : "T",
      "lastName" : "Scammell-La Fleur",
      "authorRank" : 5,
      "name" : "Scammell-La Fleur T",
      "referenceId" : "RGD:A81621"
    }, {
      "firstName" : "IM",
      "lastName" : "Dixon",
      "authorRank" : 6,
      "name" : "Dixon IM",
      "referenceId" : "RGD:A13112"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601617"
    } ]
  }, {
    "primaryId" : "PMID:10198213",
    "title" : "73-kDa heat shock cognate protein interacts directly with P27Kip1, a cyclin-dependent kinase inhibitor, during G1/S transition.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Nakamura S, etal., Biochem Biophys Res Commun. 1999 Apr 13;257(2):340-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-23T17:00:01.000-05:00",
    "volume" : "257",
    "pages" : "340-3",
    "abstract" : "Although heat shock proteins (HSPs) were discovered as inducible proteins by the physical stress to protect cells, recent evidence has suggested that HSPs are likely involved in cell cycle control under normal conditions without stress. In the present study, we demonstrated that 73hsc (heat shock cognate protein), which belongs to the HSP70 family of molecular chaperones, interacts with P27Kip1, an inhibitor of cyclin-dependent kinase, during G1/S transition. 73hsc was detected in the immunoprecipitates with anti-P27Kip1 antibody and, vice versa, P27Kip1 was present in the immunoprecipitates with anti-73hsc antibody by Western blotting using growth-stimulated rat thyroid FRTL-5 cells. This complex formation of 73hsc and P27Kip1 was cell cycle dependent and its maximum formation was observed at G1/S transition where the level of P27Kip1 dramatically decreased. ATP dissociated this complex formation in a dose-dependent manner. These data indicated that 73hsc might be involved in the cell cycle progression through the regulation of cell cycle regulators such as P27Kip1.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Nakamura",
      "authorRank" : 1,
      "name" : "Nakamura S",
      "referenceId" : "RGD:A161688"
    }, {
      "firstName" : "I",
      "lastName" : "Tatuno",
      "authorRank" : 2,
      "name" : "Tatuno I",
      "referenceId" : "RGD:A125344"
    }, {
      "firstName" : "Y",
      "lastName" : "Noguchi",
      "authorRank" : 3,
      "name" : "Noguchi Y",
      "referenceId" : "RGD:A6936"
    }, {
      "firstName" : "M",
      "lastName" : "Kitagawa",
      "authorRank" : 4,
      "name" : "Kitagawa M",
      "referenceId" : "RGD:A8528"
    }, {
      "firstName" : "LD",
      "lastName" : "Kohn",
      "authorRank" : 5,
      "name" : "Kohn LD",
      "referenceId" : "RGD:A17541"
    }, {
      "firstName" : "Y",
      "lastName" : "Saito",
      "authorRank" : 6,
      "name" : "Saito Y",
      "referenceId" : "RGD:A7298"
    }, {
      "firstName" : "A",
      "lastName" : "Hirai",
      "authorRank" : 7,
      "name" : "Hirai A",
      "referenceId" : "RGD:A125345"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2326098"
    } ]
  }, {
    "primaryId" : "PMID:10198244",
    "title" : "Nonspecific inhibition of myogenic tone by PD98059, a MEK1 inhibitor, in rat middle cerebral arteries.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Lagaud GJ, etal., Biochem Biophys Res Commun. 1999 Apr 13;257(2):523-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-05-27T17:18:27.000-05:00",
    "volume" : "257",
    "pages" : "523-7",
    "abstract" : "Activation of MAP kinase kinase, also called ERK kinase (MEK), may lead to desinhibition of thin filament regulatory proteins and we therefore investigated the acute effects of the potent MEK inhibitor, PD98059 on the contractile properties of pressurized rat middle cerebral arteries. Cerebral arteries (diameter 100-150 microm) were mounted on a pressure myograph and PD98059 (10 microM, 40 microM) significantly inhibited (15% and 64%) myogenic tone (P < 0.001). At these concentrations, PD98059 also significantly reduced the vasopressin (0.1 microM)- and KCl (60 mM)-induced tone. Cumulative addition of exogenous Ca2+ (0.4-1.6 mM) increased myogenic tone to approximately 50% of constriction at 80 mmHg. This effect was inhibited by PD98059 (P < 0.001). These results demonstrate that pressure-induced myogenic tone is inhibited by PD98059 at the concentrations that have been reported to be selective for inhibition of MEK and the MAP kinase cascade. However, our results also demonstrate that PD98059 may have nonspecific effects on voltage-sensitive Ca2+ entry in vascular smooth muscle.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GJ",
      "lastName" : "Lagaud",
      "authorRank" : 1,
      "name" : "Lagaud GJ",
      "referenceId" : "RGD:A96314"
    }, {
      "firstName" : "E",
      "lastName" : "Lam",
      "authorRank" : 2,
      "name" : "Lam E",
      "referenceId" : "RGD:A67433"
    }, {
      "firstName" : "A",
      "lastName" : "Lui",
      "authorRank" : 3,
      "name" : "Lui A",
      "referenceId" : "RGD:A96315"
    }, {
      "firstName" : "C",
      "lastName" : "Van Breemen",
      "authorRank" : 4,
      "name" : "Van Breemen C",
      "referenceId" : "RGD:A53585"
    }, {
      "firstName" : "I",
      "lastName" : "Laher",
      "authorRank" : 5,
      "name" : "Laher I",
      "referenceId" : "RGD:A96316"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2293329"
    } ]
  }, {
    "primaryId" : "PMID:10198255",
    "title" : "A novel apolipoprotein A-1 variant, Arg173Pro, associated with cardiac and cutaneous amyloidosis.",
    "datePublished" : "1999-04-13T00:00:00.000-05:00",
    "citation" : "Hamidi Asl K, etal., Biochem Biophys Res Commun. 1999 Apr 13;257(2):584-8. doi: 10.1006/bbrc.1999.0518.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:24:18.000-05:00",
    "volume" : "257",
    "pages" : "584-8",
    "abstract" : "An American kindred was found to have hereditary amyloidosis with cutaneous and cardiac involvement. Characterization of fibrils isolated from skin identified the amyloid protein as the N-terminal 90 to 100 residues of apolipoprotein A-1. Sequence of the apolipoprotein A-1 gene was normal except for a G/C transversion at position 1638 which predicts an Arg to Pro substitution at residue 173. This mutation, unlike previously described amyloidogenic mutations is not in the N-terminal fragment which is incorporated into the fibril. The mutation is at the same residue as in apolipoprotein A-1 Milano (Arg173Cys) which does not result in amyloid formation. Decreased plasma HDL cholesterol levels in carriers of the Arg173Pro mutation suggest an increased rate of catabolism as has been shown for the amyloidogenic Gly26Arg mutation. This suggests that altered metabolism caused by the mutation may be a significant factor in apolipoprotein A-1 fibrillogenesis.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Hamidi Asl",
      "authorRank" : 1,
      "name" : "Hamidi Asl K",
      "referenceId" : "RGD:A579285"
    }, {
      "firstName" : "J J",
      "lastName" : "Liepnieks",
      "authorRank" : 2,
      "name" : "Liepnieks JJ",
      "referenceId" : "RGD:A571378"
    }, {
      "firstName" : "M",
      "lastName" : "Nakamura",
      "authorRank" : 3,
      "name" : "Nakamura M",
      "referenceId" : "RGD:A295475"
    }, {
      "firstName" : "F",
      "lastName" : "Parker",
      "authorRank" : 4,
      "name" : "Parker F",
      "referenceId" : "RGD:A94949"
    }, {
      "firstName" : "M D",
      "lastName" : "Benson",
      "authorRank" : 5,
      "name" : "Benson MD",
      "referenceId" : "RGD:A571379"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598116268"
    } ]
  }, {
    "primaryId" : "PMID:10198260",
    "title" : "Human very-long-chain acyl-CoA synthetase: cloning, topography, and relevance to  branched-chain fatty acid metabolism.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Steinberg SJ, etal., Biochem Biophys Res Commun. 1999 Apr 13;257(2):615-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:45:16.000-05:00",
    "volume" : "257",
    "pages" : "615-21",
    "abstract" : "Very-long-chain acyl-CoA synthetases (VLCS) activate very-long-chain fatty acids  (VLCFA) containing 22 or more carbons to their CoA derivatives. We cloned the human ortholog (hVLCS) of the gene encoding the rat liver enzyme (rVLCS). Both hVLCS and rVLCS contain 620 amino acids, are expressed primarily in liver and kidney, and have a potential peroxisome targeting signal 1 (-LKL) at their carboxy termini. When expressed in COS-1 cells, hVLCS activated the VLCFA lignoceric acid (C24:0), a long-chain fatty acid (C16:0), and two branched-chain  fatty acids, phytanic acid and pristanic acid. Immunofluorescence and immunoblot  studies localized hVLCS to both peroxisomes and endoplasmic reticulum. In peroxisomes of HepG2 cells, hVLCS was topographically oriented facing the matrix  and not the cytoplasm. This orientation, coupled with the observation that hVLCS  activates branched-chain fatty acids, suggests that hVLCS could play a role in the intraperoxisomal reactivation of pristanic acid produced via alpha-oxidation  of phytanic acid.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SJ",
      "lastName" : "Steinberg",
      "authorRank" : 1,
      "name" : "Steinberg",
      "referenceId" : "RGD:A187028"
    }, {
      "firstName" : "SJ",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang SJ",
      "referenceId" : "RGD:A52422"
    }, {
      "firstName" : "DG",
      "lastName" : "Kim",
      "authorRank" : 3,
      "name" : "Kim DG",
      "referenceId" : "RGD:A58657"
    }, {
      "firstName" : "SJ",
      "lastName" : "Mihalik",
      "authorRank" : 4,
      "name" : "Mihalik",
      "referenceId" : "RGD:A187029"
    }, {
      "firstName" : "PA",
      "lastName" : "Watkins",
      "authorRank" : 5,
      "name" : "Watkins PA",
      "referenceId" : "RGD:A121851"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554608"
    } ]
  }, {
    "primaryId" : "PMID:10198426",
    "title" : "Stoichiometry and Na+ binding cooperativity of rat and flounder renal type II Na+-Pi cotransporters.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Forster IC, etal., Am J Physiol. 1999 Apr;276(4):F644-9. doi: 10.1152/ajprenal.1999.276.4.F644.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-05-04T01:55:58.000-05:00",
    "volume" : "276",
    "pages" : "F644-9",
    "abstract" : "The stoichiometry of the rat and flounder isoforms of the renal type II sodium-phosphate (Na+-Pi) cotransporter was determined directly by simultaneous measurements of phosphate (Pi)-induced inward current and uptake of radiolabeled Pi and Na+ in Xenopus laevis oocytes expressing the cotransporters. There was a direct correlation between the Pi-induced inward charge and Pi uptake into the oocytes; the slope indicated that one net inward charge was transported per Pi. There was also a direct correlation between the Pi-induced inward charge and Na+ influx; the slope indicated that the influx of three Na+ ions resulted in one net inward charge. This behavior was similar for both isoforms. We conclude that for both Na+-Pi cotransporter isoforms the Na+:Pi stoichiometry is 3:1 and that divalent Pi is the transported substrate. Steady-state activation of the currents showed that the Hill coefficients for Pi were unity for both isoforms, whereas for Na+, they were 1.8 (flounder) and 2.5 (rat). Therefore, despite significant differences in the apparent Na+ binding cooperativity, the estimated Na+:Pi stoichiometry was the same for both isoforms.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I C",
      "lastName" : "Forster",
      "authorRank" : 1,
      "name" : "Forster IC",
      "referenceId" : "RGD:A515692"
    }, {
      "firstName" : "D D",
      "lastName" : "Loo",
      "authorRank" : 2,
      "name" : "Loo DD",
      "referenceId" : "RGD:A515693"
    }, {
      "firstName" : "S",
      "lastName" : "Eskandari",
      "authorRank" : 3,
      "name" : "Eskandari S",
      "referenceId" : "RGD:A515694"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:152025515"
    } ]
  }, {
    "primaryId" : "PMID:10198638",
    "title" : "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Ito M, etal., Mol Cell. 1999 Mar;3(3):361-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-09-07T19:59:03.000-05:00",
    "volume" : "3",
    "pages" : "361-70",
    "abstract" : "The human thyroid hormone receptor-associated protein (TRAP) complex, an earlier  described coactivator for nuclear receptors, and an SRB- and MED-containing cofactor complex (SMCC) that mediates activation by Gal4-p53 are shown to be virtually the same with respect to specific polypeptide subunits, coactivator functions, and mechanisms of action (activator interactions). In parallel with ligand-dependent interactions of nuclear receptors with the TRAP220 subunit, p53  and VP16 activation domains interact directly with a newly cloned TRAP80 subunit. These results indicate novel pathways for the function of nuclear receptors and other activators (p53 and VP16) through a common coactivator complex that is likely to target RNA polymerase II. Identification of the TRAP230 subunit as a previously predicted gene product also suggests a coactivator-related transcription defect in certain disease states.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Ito",
      "authorRank" : 1,
      "name" : "Ito M",
      "referenceId" : "RGD:A5288"
    }, {
      "firstName" : "CX",
      "lastName" : "Yuan",
      "authorRank" : 2,
      "name" : "Yuan",
      "referenceId" : "RGD:A185954"
    }, {
      "firstName" : "S",
      "lastName" : "Malik",
      "authorRank" : 3,
      "name" : "Malik S",
      "referenceId" : "RGD:A61792"
    }, {
      "firstName" : "W",
      "lastName" : "Gu",
      "authorRank" : 4,
      "name" : "Gu W",
      "referenceId" : "RGD:A19964"
    }, {
      "firstName" : "JD",
      "lastName" : "Fondell",
      "authorRank" : 5,
      "name" : "Fondell JD",
      "referenceId" : "RGD:A141213"
    }, {
      "firstName" : "S",
      "lastName" : "Yamamura",
      "authorRank" : 6,
      "name" : "Yamamura S",
      "referenceId" : "RGD:A145336"
    }, {
      "firstName" : "ZY",
      "lastName" : "Fu",
      "authorRank" : 7,
      "name" : "Fu",
      "referenceId" : "RGD:A216167"
    }, {
      "firstName" : "X",
      "lastName" : "Zhang",
      "authorRank" : 8,
      "name" : "Zhang X",
      "referenceId" : "RGD:A6544"
    }, {
      "firstName" : "J",
      "lastName" : "Qin",
      "authorRank" : 9,
      "name" : "Qin J",
      "referenceId" : "RGD:A62721"
    }, {
      "firstName" : "RG",
      "lastName" : "Roeder",
      "authorRank" : 10,
      "name" : "Roeder RG",
      "referenceId" : "RGD:A19409"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11532895"
    } ]
  }, {
    "primaryId" : "PMID:10199409",
    "title" : "Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "McDermott MF, etal., Cell. 1999 Apr 2;97(1):133-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:39:31.000-05:00",
    "volume" : "97",
    "pages" : "133-44",
    "abstract" : "Autosomal dominant periodic fever syndromes are characterized by unexplained episodes of fever and severe localized inflammation. In seven affected families,  we found six different missense mutations of the 55 kDa tumor necrosis factor receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds.  Soluble plasma TNFR1 levels in patients were approximately half normal. Leukocytes bearing a C52F mutation showed increased membrane TNFR1 and reduced receptor cleavage following stimulation. We propose that the autoinflammatory phenotype results from impaired downregulation of membrane TNFR1 and diminished shedding of potentially antagonistic soluble receptor. TNFR1-associated periodic  syndromes (TRAPS) establish an important class of mutations in TNF receptors. Detailed analysis of one such mutation suggests impaired cytokine receptor clearance as a novel mechanism of disease.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MF",
      "lastName" : "McDermott",
      "authorRank" : 1,
      "name" : "McDermott MF",
      "referenceId" : "RGD:A79268"
    }, {
      "firstName" : "I",
      "lastName" : "Aksentijevich",
      "authorRank" : 2,
      "name" : "Aksentijevich",
      "referenceId" : "RGD:A413769"
    }, {
      "firstName" : "J",
      "lastName" : "Galon",
      "authorRank" : 3,
      "name" : "Galon",
      "referenceId" : "RGD:A258756"
    }, {
      "firstName" : "EM",
      "lastName" : "McDermott",
      "authorRank" : 4,
      "name" : "McDermott",
      "referenceId" : "RGD:A254358"
    }, {
      "firstName" : "BW",
      "lastName" : "Ogunkolade",
      "authorRank" : 5,
      "name" : "Ogunkolade",
      "referenceId" : "RGD:A259226"
    }, {
      "firstName" : "M",
      "lastName" : "Centola",
      "authorRank" : 6,
      "name" : "Centola",
      "referenceId" : "RGD:A353307"
    }, {
      "firstName" : "E",
      "lastName" : "Mansfield",
      "authorRank" : 7,
      "name" : "Mansfield",
      "referenceId" : "RGD:A258758"
    }, {
      "firstName" : "M",
      "lastName" : "Gadina",
      "authorRank" : 8,
      "name" : "Gadina",
      "referenceId" : "RGD:A259228"
    }, {
      "firstName" : "L",
      "lastName" : "Karenko",
      "authorRank" : 9,
      "name" : "Karenko",
      "referenceId" : "RGD:A255738"
    }, {
      "firstName" : "T",
      "lastName" : "Pettersson",
      "authorRank" : 10,
      "name" : "Pettersson",
      "referenceId" : "RGD:A255744"
    }, {
      "firstName" : "J",
      "lastName" : "McCarthy",
      "authorRank" : 11,
      "name" : "McCarthy",
      "referenceId" : "RGD:A259229"
    }, {
      "firstName" : "DM",
      "lastName" : "Frucht",
      "authorRank" : 12,
      "name" : "Frucht",
      "referenceId" : "RGD:A215750"
    }, {
      "firstName" : "M",
      "lastName" : "Aringer",
      "authorRank" : 13,
      "name" : "Aringer",
      "referenceId" : "RGD:A259230"
    }, {
      "firstName" : "Y",
      "lastName" : "Torosyan",
      "authorRank" : 14,
      "name" : "Torosyan Y",
      "referenceId" : "RGD:A95571"
    }, {
      "firstName" : "AM",
      "lastName" : "Teppo",
      "authorRank" : 15,
      "name" : "Teppo",
      "referenceId" : "RGD:A175444"
    }, {
      "firstName" : "M",
      "lastName" : "Wilson",
      "authorRank" : 16,
      "name" : "Wilson M",
      "referenceId" : "RGD:A72550"
    }, {
      "firstName" : "HM",
      "lastName" : "Karaarslan",
      "authorRank" : 17,
      "name" : "Karaarslan",
      "referenceId" : "RGD:A259231"
    }, {
      "firstName" : "Y",
      "lastName" : "Wan",
      "authorRank" : 18,
      "name" : "Wan Y",
      "referenceId" : "RGD:A67774"
    }, {
      "firstName" : "I",
      "lastName" : "Todd",
      "authorRank" : 19,
      "name" : "Todd I",
      "referenceId" : "RGD:A141942"
    }, {
      "firstName" : "G",
      "lastName" : "Wood",
      "authorRank" : 20,
      "name" : "Wood",
      "referenceId" : "RGD:A357055"
    }, {
      "firstName" : "R",
      "lastName" : "Schlimgen",
      "authorRank" : 21,
      "name" : "Schlimgen",
      "referenceId" : "RGD:A259233"
    }, {
      "firstName" : "TR",
      "lastName" : "Kumarajeewa",
      "authorRank" : 22,
      "name" : "Kumarajeewa",
      "referenceId" : "RGD:A259234"
    }, {
      "firstName" : "SM",
      "lastName" : "Cooper",
      "authorRank" : 23,
      "name" : "Cooper",
      "referenceId" : "RGD:A259235"
    }, {
      "firstName" : "JP",
      "lastName" : "Vella",
      "authorRank" : 24,
      "name" : "Vella",
      "referenceId" : "RGD:A259236"
    }, {
      "firstName" : "CI",
      "lastName" : "Amos",
      "authorRank" : 25,
      "name" : "Amos CI",
      "referenceId" : "RGD:A39955"
    }, {
      "firstName" : "J",
      "lastName" : "Mulley",
      "authorRank" : 26,
      "name" : "Mulley J",
      "referenceId" : "RGD:A45022"
    }, {
      "firstName" : "KA",
      "lastName" : "Quane",
      "authorRank" : 27,
      "name" : "Quane",
      "referenceId" : "RGD:A259237"
    }, {
      "firstName" : "MG",
      "lastName" : "Molloy",
      "authorRank" : 28,
      "name" : "Molloy MG",
      "referenceId" : "RGD:A119315"
    }, {
      "firstName" : "A",
      "lastName" : "Ranki",
      "authorRank" : 29,
      "name" : "Ranki",
      "referenceId" : "RGD:A181067"
    }, {
      "firstName" : "RJ",
      "lastName" : "Powell",
      "authorRank" : 30,
      "name" : "Powell RJ",
      "referenceId" : "RGD:A146244"
    }, {
      "firstName" : "GA",
      "lastName" : "Hitman",
      "authorRank" : 31,
      "name" : "Hitman GA",
      "referenceId" : "RGD:A39902"
    }, {
      "firstName" : "JJ",
      "lastName" : "O'Shea",
      "authorRank" : 32,
      "name" : "O'Shea JJ",
      "referenceId" : "RGD:A76740"
    }, {
      "firstName" : "DL",
      "lastName" : "Kastner",
      "authorRank" : 33,
      "name" : "Kastner",
      "referenceId" : "RGD:A386751"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064617"
    } ]
  }, {
    "primaryId" : "PMID:10199628",
    "title" : "Strain differences in Fos expression following airpuff startle in Spontaneously Hypertensive and Wistar Kyoto rats.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Palmer AA and Printz MP, Neuroscience 1999 Mar;89(3):965-78.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-07-18T20:47:51.000-05:00",
    "volume" : "89",
    "pages" : "965-78",
    "abstract" : "The airpuff startle stimulus elicits both a behavioral and a concurrent sympathetic and parasympathetic activation, which have been shown to differ between inbred normotensive Wistar Kyoto and Spontaneously Hypertensive rat strains. Neither the brain sites responsible for the cardiovascular and motor responses, nor the origins of the strain differential responses, have yet been elucidated. The goals of the present study were (i) to define the neuronal pattern of immunoreactive Fos expression to the airpuff stimulus, and (ii) to determine whether this pattern of expression differed between the two contrasting inbred rat strains, thereby relating to observed differences in response. The airpuff stimulus induced Fos protein expression in discrete nuclei within the hypothalamus, thalamus, midbrain, pons and medulla of both strains, with strain-dependent differences evident in the hypothalamus (lateral, ventromedial and dorsomedial), pons (locus coeruleus) and medulla (rostroventrolateral medulla and solitary tract nuclei). To remove Fos expression arising from test chamber novelty, which was observed in both strains, a subset of animals was habituated to the test chamber for four days prior to testing. Habituation reduced Fos expression in several brain regions in the Wistar Kyoto, but failed to do so in the Spontaneously Hypertensive rat. The present results are the first to identify a set of brain regions likely to be responsible for the mediation of the cardiovascular and motor responses associated with the airpuff startle stimulus. Several of the identified areas contain neurotransmitters implicated by prior pharmacological studies. Further, these data identify differences in the degree of activation of specific neuronal structures that probably underlie strain differences in the cardiovascular response to the airpuff. Additionally, the results provide a cellular correlate to reported deficits in behavioral habituation by the Spontaneously Hypertensive rat and suggest a potentially profound difference between the ability of these two strains to adapt to repeated mild stress stimuli.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AA",
      "lastName" : "Palmer",
      "authorRank" : 1,
      "name" : "Palmer AA",
      "referenceId" : "RGD:A14575"
    }, {
      "firstName" : "MP",
      "lastName" : "Printz",
      "authorRank" : 2,
      "name" : "Printz MP",
      "referenceId" : "RGD:A6485"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358971"
    } ]
  }, {
    "primaryId" : "PMID:10199795",
    "title" : "A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Khoo DH, etal., J Clin Endocrinol Metab. 1999 Apr;84(4):1459-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-24T17:21:33.000-05:00",
    "volume" : "84",
    "pages" : "1459-62",
    "abstract" : "Activating mutations of the TSH receptor (TSH-R) have been reported to result in toxic adenomas, multinodular goiters, sporadic neonatal hyperthyroidism, and familial autosomal dominant nonautoimmune hyperthyroidism. To date, all descriptions of such mutations, whether somatic or genomic, have been confined to the Caucasian population. We describe a Chinese family in whom a germline proline to serine substitution in position 639 resulted in familial thyrotoxicosis. This constitutively activating mutation has been previously described in a hyperfunctioning thyroid nodule. The three children in this family developed thyrotoxicosis during childhood; their father was diagnosed as thyrotoxic at the age of 38 yr. Two of the children and the father had mitral valve prolapse (MVP) associated with mitral regurgitation. There was a close temporal relationship between the onset of thyrotoxicosis and the diagnosis of mitral valvular disease in these patients. An increased prevalence of MVP has been reported in Graves' disease and chronic lymphocytic thyroiditis, but the pathophysiological mechanisms linking MVP and autoimmune thyroid disease are still not understood. This is the first report of an association between activating TSH-R mutations and MVP. We postulate that TSH-R activation may increase the clinical expression of MVP in genetically predisposed individuals.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DH",
      "lastName" : "Khoo",
      "authorRank" : 1,
      "name" : "Khoo DH",
      "referenceId" : "RGD:A63991"
    }, {
      "firstName" : "J",
      "lastName" : "Parma",
      "authorRank" : 2,
      "name" : "Parma J",
      "referenceId" : "RGD:A40930"
    }, {
      "firstName" : "C",
      "lastName" : "Rajasoorya",
      "authorRank" : 3,
      "name" : "Rajasoorya C",
      "referenceId" : "RGD:A63992"
    }, {
      "firstName" : "SC",
      "lastName" : "Ho",
      "authorRank" : 4,
      "name" : "Ho SC",
      "referenceId" : "RGD:A63993"
    }, {
      "firstName" : "G",
      "lastName" : "Vassart",
      "authorRank" : 5,
      "name" : "Vassart G",
      "referenceId" : "RGD:A20638"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580775"
    } ]
  }, {
    "primaryId" : "PMID:10199843",
    "title" : "Expression of endothelin-1, ETA and ETB receptors, and ECE and distribution of endothelin-1 in failing rat heart.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kobayashi T, etal., Am J Physiol. 1999 Apr;276(4 Pt 2):H1197-206.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-23T13:46:58.000-05:00",
    "volume" : "276",
    "pages" : "H1197-206",
    "abstract" : "Endothelin (ET)-1 has a positive inotropic effect and induces hypertrophy in cardiomyocytes. We previously reported that the peptide level of ET-1 is increased in the failing heart of rats with chronic heart failure (CHF) and that  treatment with an ETA-receptor antagonist greatly improves survival in rats with  CHF. However, precise analysis for alteration of the myocardial ET system in the  failing heart is not known. In this study, we used rats with CHF due to chronic myocardial infarction. Sham-operated rats served as a control. The results showed that the level of preproendothelin (preproET)-1 mRNA and the peptide level of ET-1 were markedly increased in the heart of rats with CHF, whereas the expression of endothelin-converting enzyme (ECE)-1 mRNA in the heart did not differ between CHF and control rats. The intensity of ET-1 staining (ET-1-like immunoreactivity) in cardiomyocytes was markedly stronger in rats with CHF than in control rats, and the fibrotic tissues of the infarcted area were not stained. The mRNA and protein levels of both ETA and ETB receptors in the heart were significantly higher in rats with CHF than in control rats. The present study suggests that the increase in ET-1 peptide level in the heart of the rats with CHF originated from upregulation of preproET-1 mRNA, which was not attendant with the alteration of ECE-1 mRNA expression, and that both the ETA- and ETB-receptor  systems are greatly accelerated in the failing heart.",
    "issueName" : "4 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kobayashi",
      "authorRank" : 1,
      "name" : "Kobayashi T",
      "referenceId" : "RGD:A5222"
    }, {
      "firstName" : "T",
      "lastName" : "Miyauchi",
      "authorRank" : 2,
      "name" : "Miyauchi T",
      "referenceId" : "RGD:A36548"
    }, {
      "firstName" : "S",
      "lastName" : "Sakai",
      "authorRank" : 3,
      "name" : "Sakai S",
      "referenceId" : "RGD:A38869"
    }, {
      "firstName" : "M",
      "lastName" : "Kobayashi",
      "authorRank" : 4,
      "name" : "Kobayashi M",
      "referenceId" : "RGD:A4939"
    }, {
      "firstName" : "I",
      "lastName" : "Yamaguchi",
      "authorRank" : 5,
      "name" : "Yamaguchi I",
      "referenceId" : "RGD:A14209"
    }, {
      "firstName" : "K",
      "lastName" : "Goto",
      "authorRank" : 6,
      "name" : "Goto K",
      "referenceId" : "RGD:A9892"
    }, {
      "firstName" : "Y",
      "lastName" : "Sugishita",
      "authorRank" : 7,
      "name" : "Sugishita",
      "referenceId" : "RGD:A170080"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7244167"
    } ]
  }, {
    "primaryId" : "PMID:10199853",
    "title" : "Estradiol modulates vascular response to melatonin in rat caudal artery.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Doolen S, etal., Am J Physiol. 1999 Apr;276(4 Pt 2):H1281-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-11-04T14:42:02.000-06:00",
    "volume" : "276",
    "pages" : "H1281-8",
    "abstract" : "The purpose of this study was to determine whether estrogen modulates the function of vascular melatonin receptors. We used the rat caudal artery and found that the contractile effects of melatonin were influenced by the estrous cycle, ovariectomy, and estrogen replacement. In arterial ring segments isolated from female rats, melatonin potentiated, in a concentration-dependent manner, contractions produced either by adrenergic nerve stimulation or by phenylephrine. Constrictor responses to melatonin were smaller in arteries from female rats in proestrus compared with other stages of the estrous cycle and after ovariectomy.  Administration of 17beta-estradiol to ovariectomized female rats also resulted in decreased constriction of isolated arteries to melatonin; however, in vitro addition of 17beta-estradiol (10(-7) M) had no effect. In the caudal artery, melatonin appears to act on two receptor subtypes that mediate contraction and relaxation, respectively. The selective melatonin MT2-receptor antagonist 4-phenyl-2-propionamidotetraline (4P-PDOT) enhanced constrictor responses to melatonin in arterial segments from intact female rats, consistent with the inhibition of MT2 receptor-mediated relaxation. In contrast, 4P-PDOT had no significant effect in arteries from ovariectomized female rats. However, when estradiol was replaced in vivo, the effect of 4P-PDOT on melatonin responses was  restored. Thus circulating estradiol appears to enhance MT2 melatonin-receptor function in the thermoregulatory caudal artery of the female rat resulting in increased vasodilatation in response to melatonin.",
    "issueName" : "4 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Doolen",
      "authorRank" : 1,
      "name" : "Doolen",
      "referenceId" : "RGD:A196108"
    }, {
      "firstName" : "DN",
      "lastName" : "Krause",
      "authorRank" : 2,
      "name" : "Krause DN",
      "referenceId" : "RGD:A14195"
    }, {
      "firstName" : "SP",
      "lastName" : "Duckles",
      "authorRank" : 3,
      "name" : "Duckles SP",
      "referenceId" : "RGD:A14194"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9588661"
    } ]
  }, {
    "primaryId" : "PMID:10199887",
    "title" : "Generation of humanized mice susceptible to peptide-induced inflammatory heart disease.",
    "datePublished" : "1999-04-13T00:00:00.000-05:00",
    "citation" : "Bachmaier K, etal., Circulation. 1999 Apr 13;99(14):1885-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-03-16T13:51:23.000-05:00",
    "volume" : "99",
    "pages" : "1885-91",
    "abstract" : "<br><b>BACKGROUND: </b>Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death. In certain mouse major histocompatibility complex (MHC) backgrounds, myocarditis and inflammatory cardiomyopathy can be triggered by immunization with heart muscle-specific proteins. Similarly, chronic heart disease in humans has been linked to certain HLA alleles, such as HLA-DQ6. However, there is no experimental evidence showing that human MHC class II molecules and peptides derived from human proteins are involved in the pathogenesis of myocarditis and DCM.<br><b>METHODS AND RESULTS: </b>We generated double CD4- and CD8-deficient mice transgenic for human CD4 (hCD4) and human HLA-DQ6 to specifically reconstitute the human CD4/DQ6 arm of the immune system in mice. Transgenic hCD4 and HLA-DQ6 expression rendered genetically resistant C57BL/6 mice susceptible to the induction of autoimmune myocarditis induced by immunization with cardiac myosin. Moreover, we identified heart-specific peptides derived from both mouse and human alpha-myosin heavy chains capable of inducing inflammatory heart disease in hCD4 and HLA-DQ6 double transgenic mice but not in hCD4 single transgenic littermates. The autoimmune inflammatory heart disease induced by the human heart muscle-specific peptide in hCD4 and HLA-DQ6 double transgenic mice shared functional and phenotypic features with the disease occurring in disease-susceptible nontransgenic mice.<br><b>CONCLUSIONS: </b>Our data provide the first genetic and functional evidence that human MHC class II molecules and a human alpha-myosin heavy chain-derived peptide can cause inflammatory heart disease and suggest that human inflammatory cardiomyopathy can be caused by organ-specific autoimmunity. The humanized mice generated in this study will be an ideal animal model to further elucidate the pathogenesis of inflammatory heart disease and facilitate the development of rational treatment strategies.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Bachmaier",
      "authorRank" : 1,
      "name" : "Bachmaier K",
      "referenceId" : "RGD:A440661"
    }, {
      "firstName" : "N",
      "lastName" : "Neu",
      "authorRank" : 2,
      "name" : "Neu N",
      "referenceId" : "RGD:A440662"
    }, {
      "firstName" : "R S",
      "lastName" : "Yeung",
      "authorRank" : 3,
      "name" : "Yeung RS",
      "referenceId" : "RGD:A440663"
    }, {
      "firstName" : "T W",
      "lastName" : "Mak",
      "authorRank" : 4,
      "name" : "Mak TW",
      "referenceId" : "RGD:A440664"
    }, {
      "firstName" : "P",
      "lastName" : "Liu",
      "authorRank" : 5,
      "name" : "Liu P",
      "referenceId" : "RGD:A40675"
    }, {
      "firstName" : "J M",
      "lastName" : "Penninger",
      "authorRank" : 6,
      "name" : "Penninger JM",
      "referenceId" : "RGD:A440665"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12792956"
    } ]
  }, {
    "primaryId" : "PMID:10200023",
    "title" : "Association of 3 gene polymorphisms with atopic diseases.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Holla L, etal., J Allergy Clin Immunol. 1999 Apr;103(4):702-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-30T10:21:25.000-06:00",
    "volume" : "103",
    "pages" : "702-8",
    "abstract" : "BACKGROUND: Various peptidases, including angiotensin-converting enzyme (ACE), inactivate some inflammatory peptides that are considered to influence the pathogenesis of atopic diseases. This enzyme is also involved in the conversion or activation of 2 bronchoconstriction mediators: angiotensin II from angiotensinogen and endothelin (ET), respectively. OBJECTIVE: We tested a hypothesis that asthma or other atopic diseases are associated with insertion/deletion ACE, M235T angiotensinogen, and TaqI ET-1 gene polymorphisms.  METHODS: A case-control approach was used in the study. Healthy subjects (141 persons) were used as control subjects, and 231 patients with histories of atopic asthma, allergic rhinitis, atopic dermatitis, or a combination thereof were studied. ACE genotype was determined by PCR, angiotensinogen M235T and ET-1 by PCR, and restriction analysis by AspI and TaqI, respectively. RESULTS: We found the significant association of the insertion/deletion polymorphism of the ACE, as well as that of M235T polymorphism of the angiotensinogen genes, with the group of patients with atopic diseases ( P =.0025 and P =.0204, respectively). No difference was proved for the intron 4 (position 8000) polymorphism in the ET-1 gene when comparing the atopic patients with the control group (P =.1774). A significant difference was found between groups of patients with both asthma and  rhinitis and patients without both respiratory atopic diseases (P =.0033). CONCLUSION: It follows that the examined polymorphisms in the genes for ACE, angiotensinogen, and ET-1 could participate in the etiopathogenesis of atopic diseases.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Holla",
      "authorRank" : 1,
      "name" : "Holla",
      "referenceId" : "RGD:A178765"
    }, {
      "firstName" : "A",
      "lastName" : "Vasku",
      "authorRank" : 2,
      "name" : "Vasku A",
      "referenceId" : "RGD:A61523"
    }, {
      "firstName" : "V",
      "lastName" : "Znojil",
      "authorRank" : 3,
      "name" : "Znojil V",
      "referenceId" : "RGD:A61525"
    }, {
      "firstName" : "L",
      "lastName" : "Siskova",
      "authorRank" : 4,
      "name" : "Siskova L",
      "referenceId" : "RGD:A61524"
    }, {
      "firstName" : "J",
      "lastName" : "Vacha",
      "authorRank" : 5,
      "name" : "Vacha J",
      "referenceId" : "RGD:A61526"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8142344"
    } ]
  }, {
    "primaryId" : "PMID:10200050",
    "title" : "Genetic findings in congenital bilateral aplasia of vas deferens patients and identification of six novel mutatations. Mutations in brief no. 138. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "de Meeus A, etal., Hum Mutat. 1998;11(6):480.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:15:32.000-05:00",
    "volume" : "11",
    "pages" : "480",
    "abstract" : "Congential bilateral aplasia of vas deferens (CBAVD), a form of male sterility, has been suggested to represent a \"genital\" form of cystic fibrosis (CF), as mutations in the CFTR gene have been identified in most patients with this condition. Interestingly, the 5T allele in intron 8 appeared to be the most frequent mutation associated with CBAVD. However, the molecular basis of CBAVD is not completely understood. We have analysed the complete coding and flanking CFTR sequences by PCR-DGGE in 64 men with CBAVD from southern France with the aim to list any sequence alteration. Fourty-two of the 64 patients (65.6%) had mutations on both copies of the CFTR gene, including one patient with two mutations in the  same copy (DF508 + A1067T). The 5T allele was present in 21/64 cases (33%). Six of the 28 different mutations identified in this study had never been described previously, and appeared to be specific to CBAVD (P111L, M244K, A1364V, G544V, 2896insAG,-33G->A).",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "De Meeus",
      "authorRank" : 1,
      "name" : "De Meeus",
      "referenceId" : "RGD:A262975"
    }, {
      "firstName" : "C",
      "lastName" : "Guittard",
      "authorRank" : 2,
      "name" : "Guittard",
      "referenceId" : "RGD:A258421"
    }, {
      "firstName" : "M",
      "lastName" : "Desgeorges",
      "authorRank" : 3,
      "name" : "Desgeorges",
      "referenceId" : "RGD:A252561"
    }, {
      "firstName" : "S",
      "lastName" : "Carles",
      "authorRank" : 4,
      "name" : "Carles",
      "referenceId" : "RGD:A262976"
    }, {
      "firstName" : "J",
      "lastName" : "Demaille",
      "authorRank" : 5,
      "name" : "Demaille J",
      "referenceId" : "RGD:A37275"
    }, {
      "firstName" : "M",
      "lastName" : "Claustres",
      "authorRank" : 6,
      "name" : "Claustres",
      "referenceId" : "RGD:A400975"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065781"
    } ]
  }, {
    "primaryId" : "PMID:10200052",
    "title" : "A novel point mutation in a splice acceptor site of intron 1 of the human low density lipoprotein receptor gene which causes severe hypercholesterolemia: an unexpected absence of exon skipping. Mutations in brief no. 139. Online.",
    "datePublished" : "1000-08-01T00:00:00.000-06:00",
    "citation" : "Maruyama T, etal., Hum Mutat. 1998;11(6):480-1.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T21:01:27.000-05:00",
    "volume" : "11",
    "pages" : "480-1",
    "abstract" : "Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in the low density lipoprotein (LDL)-receptor gene. We found a new mutation in the splice acceptor site of intron 1 of the LDL receptor gene, which is designated as 68-1 G->C according to the nomenclature suggested by Beaudet and Tsui (1993), in  a Japanese FH homozygote. She was born from consanguineous marriage and has this  mutation as a true homozygous form. Her cultured fibroblasts showed no LDL receptor protein synthesis. This mutation caused activation of a cryptic splice acceptor side in the downstream exon 2, leading to frameshift and appearance of premature in-frame stop codon. The mutation was detected by Dde I restriction enzyme. The identical mutation was not found among 24 patients with homozygous and 120 patients with heterozygous FH. The mutation was very rare among the Japanese population.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Maruyama",
      "authorRank" : 1,
      "name" : "Maruyama T",
      "referenceId" : "RGD:A24069"
    }, {
      "firstName" : "Y",
      "lastName" : "Miyake",
      "authorRank" : 2,
      "name" : "Miyake",
      "referenceId" : "RGD:A409328"
    }, {
      "firstName" : "T",
      "lastName" : "Yamamura",
      "authorRank" : 3,
      "name" : "Yamamura T",
      "referenceId" : "RGD:A57359"
    }, {
      "firstName" : "S",
      "lastName" : "Tajima",
      "authorRank" : 4,
      "name" : "Tajima S",
      "referenceId" : "RGD:A54597"
    }, {
      "firstName" : "T",
      "lastName" : "Funahashi",
      "authorRank" : 5,
      "name" : "Funahashi T",
      "referenceId" : "RGD:A84919"
    }, {
      "firstName" : "Y",
      "lastName" : "Matsuzawa",
      "authorRank" : 6,
      "name" : "Matsuzawa",
      "referenceId" : "RGD:A366205"
    }, {
      "firstName" : "A",
      "lastName" : "Yamamoto",
      "authorRank" : 7,
      "name" : "Yamamoto",
      "referenceId" : "RGD:A413967"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11528398"
    } ]
  }, {
    "primaryId" : "PMID:10200053",
    "title" : "A de novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic long QT sydrome. Mutations in brief no. 140. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Yamagishi H, etal., Hum Mutat. 1998;11(6):481.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:46:03.000-05:00",
    "volume" : "11",
    "pages" : "481",
    "abstract" : "Two missense mutations and a nine-nucleotide deletion of the cardiac sodium channel (SCN5A) gene have been shown to cause long QT syndrome (LQTS) in several  familial cases. We identified a novel missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic LQTS. We used polymerase chain reaction, single-strand conformation polymorphism analysis and DNA sequence analysis to identify a mutation of the SCN5A gene in the patient. A single nucleotide substitution of guanine to adenine, in codon 1612, changed the coding sense of the SCN5A from arginine to glutamine (R1623Q) in the S4 segment of domain IV which is a highly conserved region of the SCN5A. This mutation was not identified in the unaffected biological parents and brother of the patient, and 100 normal,  unrelated individuals. This finding is the first evidence of a de nova mutation in SCN5A associated with LQTS.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Yamagishi",
      "authorRank" : 1,
      "name" : "Yamagishi H",
      "referenceId" : "RGD:A58730"
    }, {
      "firstName" : "M",
      "lastName" : "Furutani",
      "authorRank" : 2,
      "name" : "Furutani M",
      "referenceId" : "RGD:A7051"
    }, {
      "firstName" : "M",
      "lastName" : "Kamisago",
      "authorRank" : 3,
      "name" : "Kamisago M",
      "referenceId" : "RGD:A56223"
    }, {
      "firstName" : "Y",
      "lastName" : "Morikawa",
      "authorRank" : 4,
      "name" : "Morikawa Y",
      "referenceId" : "RGD:A82598"
    }, {
      "firstName" : "Y",
      "lastName" : "Kojima",
      "authorRank" : 5,
      "name" : "Kojima Y",
      "referenceId" : "RGD:A60979"
    }, {
      "firstName" : "Y",
      "lastName" : "Hino",
      "authorRank" : 6,
      "name" : "Hino Y",
      "referenceId" : "RGD:A87191"
    }, {
      "firstName" : "Y",
      "lastName" : "Furutani",
      "authorRank" : 7,
      "name" : "Furutani Y",
      "referenceId" : "RGD:A65042"
    }, {
      "firstName" : "M",
      "lastName" : "Kimura",
      "authorRank" : 8,
      "name" : "Kimura M",
      "referenceId" : "RGD:A14901"
    }, {
      "firstName" : "S",
      "lastName" : "Imamura",
      "authorRank" : 9,
      "name" : "Imamura S",
      "referenceId" : "RGD:A33356"
    }, {
      "firstName" : "A",
      "lastName" : "Takao",
      "authorRank" : 10,
      "name" : "Takao",
      "referenceId" : "RGD:A256529"
    }, {
      "firstName" : "K",
      "lastName" : "Momma",
      "authorRank" : 11,
      "name" : "Momma",
      "referenceId" : "RGD:A201222"
    }, {
      "firstName" : "R",
      "lastName" : "Matsuoka",
      "authorRank" : 12,
      "name" : "Matsuoka R",
      "referenceId" : "RGD:A62346"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072664"
    } ]
  }, {
    "primaryId" : "PMID:10200056",
    "title" : "Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del. Mutations in brief no. 142. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Arrendondo-Vega FX, etal., Hum Mutat. 1998;11(6):482.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:38:01.000-05:00",
    "volume" : "11",
    "pages" : "482",
    "abstract" : "The degree of immunodeficiency associated with deficiency of adenosine deaminase  (ADA) is variable. Most patients are infants with severe combined immunodeficiency (SCID), but in about 20 percent immune dysfunction becomes manifest later in childhood (\"delayed-onset\"); several patients with \"late\" or \"adult\" onset of immune dysfunction have been diagnosed at 15-39 years. Over 40 ADA gene mutations have thus far been identified. To better define the genotype-phenotype relationship, we report 7 novel ADA mutations, including 5 missense mutations (G74C, V129M, G140E, R149W, Q199P) and two short deletions (462delG, E337del). These were identified among 7 patients (3 with SCID and 4 with delayed-onset). A homozygote for 462delG had SCID, whereas patients homozygous or heterozyous for V129M had delayed-onset. Two other delayed-onset patients, one heterozygous for G74C and the other for Q199P, each had a second allele carrying the previously reported \"severe\" mutation G216R. These findings are consistent with previous observations suggesting that, in general, SCID occurs when both alleles eliminate ADA function, and a milder phenotype when at least one allele can supply a low level of function.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FX",
      "lastName" : "Arrendondo-Vega",
      "authorRank" : 1,
      "name" : "Arrendondo-Vega",
      "referenceId" : "RGD:A259053"
    }, {
      "firstName" : "I",
      "lastName" : "Santisteban",
      "authorRank" : 2,
      "name" : "Santisteban I",
      "referenceId" : "RGD:A44759"
    }, {
      "firstName" : "LD",
      "lastName" : "Notarangelo",
      "authorRank" : 3,
      "name" : "Notarangelo LD",
      "referenceId" : "RGD:A71687"
    }, {
      "firstName" : "J",
      "lastName" : "El Dahr",
      "authorRank" : 4,
      "name" : "El Dahr",
      "referenceId" : "RGD:A259054"
    }, {
      "firstName" : "R",
      "lastName" : "Buckley",
      "authorRank" : 5,
      "name" : "Buckley",
      "referenceId" : "RGD:A259055"
    }, {
      "firstName" : "C",
      "lastName" : "Roifman",
      "authorRank" : 6,
      "name" : "Roifman",
      "referenceId" : "RGD:A254154"
    }, {
      "firstName" : "ME",
      "lastName" : "Conley",
      "authorRank" : 7,
      "name" : "Conley ME",
      "referenceId" : "RGD:A77483"
    }, {
      "firstName" : "MS",
      "lastName" : "Hershfield",
      "authorRank" : 8,
      "name" : "Hershfield MS",
      "referenceId" : "RGD:A30567"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064566"
    } ]
  }, {
    "primaryId" : "PMID:10200059",
    "title" : "Novel acceptor splice site mutation in the invariant AG of intron 6 of alpha-galactosidase A gene, causing Fabry disease. Mutations in brief no. 146. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Matsumura T, etal., Hum Mutat. 1998;11(6):483.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:34:39.000-05:00",
    "volume" : "11",
    "pages" : "483",
    "abstract" : "We found a novel acceptor splice site mutation in the invariant AG of intron 6 of alpha-galactosidase A (alpha-Gal A) gene (IVS6-1G->A) in a patient with Fabry disease by sequencing of genomic DNA. Sequencing of RT-PCR revealed the deletion  of first base pair (c909del) of exon 7 in mRNA and a frameshift resulting in premature termination. This mutation gives rise to a rare aberrant splicing (Simultaneous 3' destruction and 3' creation).",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Matsumura",
      "authorRank" : 1,
      "name" : "Matsumura T",
      "referenceId" : "RGD:A14852"
    }, {
      "firstName" : "H",
      "lastName" : "Osaka",
      "authorRank" : 2,
      "name" : "Osaka H",
      "referenceId" : "RGD:A26996"
    }, {
      "firstName" : "N",
      "lastName" : "Sugiyama",
      "authorRank" : 3,
      "name" : "Sugiyama N",
      "referenceId" : "RGD:A81739"
    }, {
      "firstName" : "C",
      "lastName" : "Kawanishi",
      "authorRank" : 4,
      "name" : "Kawanishi",
      "referenceId" : "RGD:A224212"
    }, {
      "firstName" : "Y",
      "lastName" : "Maruyama",
      "authorRank" : 5,
      "name" : "Maruyama Y",
      "referenceId" : "RGD:A27133"
    }, {
      "firstName" : "K",
      "lastName" : "Suzuki",
      "authorRank" : 6,
      "name" : "Suzuki",
      "referenceId" : "RGD:A399969"
    }, {
      "firstName" : "H",
      "lastName" : "Onishi",
      "authorRank" : 7,
      "name" : "Onishi H",
      "referenceId" : "RGD:A16749"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamada",
      "authorRank" : 8,
      "name" : "Yamada Y",
      "referenceId" : "RGD:A4593"
    }, {
      "firstName" : "M",
      "lastName" : "Morita",
      "authorRank" : 9,
      "name" : "Morita M",
      "referenceId" : "RGD:A30710"
    }, {
      "firstName" : "M",
      "lastName" : "Aoki",
      "authorRank" : 10,
      "name" : "Aoki M",
      "referenceId" : "RGD:A24367"
    }, {
      "firstName" : "K",
      "lastName" : "Kosaka",
      "authorRank" : 11,
      "name" : "Kosaka K",
      "referenceId" : "RGD:A17224"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070353"
    } ]
  }, {
    "primaryId" : "PMID:10200300",
    "title" : "Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia.",
    "datePublished" : "1999-04-13T00:00:00.000-05:00",
    "citation" : "Martin DA, etal., Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4552-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-05-15T09:38:34.000-05:00",
    "volume" : "96",
    "pages" : "4552-7",
    "abstract" : "Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism. We show that local or global alterations in the structure of the cytoplasmic death domain from nine independent ALPS CD95 death-domain mutations result in a failure to bind the FADD/MORT1 signaling protein. Despite heterozygosity for the abnormal allele, lymphocytes from ALPS patients showed markedly decreased FADD association and a loss of caspase recruitment and activation after CD95 crosslinking. These data suggest that intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting death-domain interactions with the signaling protein FADD/MORT1.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D A",
      "lastName" : "Martin",
      "authorRank" : 1,
      "name" : "Martin DA",
      "referenceId" : "RGD:A443763"
    }, {
      "firstName" : "L",
      "lastName" : "Zheng",
      "authorRank" : 2,
      "name" : "Zheng L",
      "referenceId" : "RGD:A18139"
    }, {
      "firstName" : "R M",
      "lastName" : "Siegel",
      "authorRank" : 3,
      "name" : "Siegel RM",
      "referenceId" : "RGD:A443764"
    }, {
      "firstName" : "B",
      "lastName" : "Huang",
      "authorRank" : 4,
      "name" : "Huang B",
      "referenceId" : "RGD:A32866"
    }, {
      "firstName" : "G H",
      "lastName" : "Fisher",
      "authorRank" : 5,
      "name" : "Fisher GH",
      "referenceId" : "RGD:A443765"
    }, {
      "firstName" : "J",
      "lastName" : "Wang",
      "authorRank" : 6,
      "name" : "Wang J",
      "referenceId" : "RGD:A404003"
    }, {
      "firstName" : "C E",
      "lastName" : "Jackson",
      "authorRank" : 7,
      "name" : "Jackson CE",
      "referenceId" : "RGD:A441586"
    }, {
      "firstName" : "J M",
      "lastName" : "Puck",
      "authorRank" : 8,
      "name" : "Puck JM",
      "referenceId" : "RGD:A443599"
    }, {
      "firstName" : "J",
      "lastName" : "Dale",
      "authorRank" : 9,
      "name" : "Dale J",
      "referenceId" : "RGD:A443766"
    }, {
      "firstName" : "S E",
      "lastName" : "Straus",
      "authorRank" : 10,
      "name" : "Straus SE",
      "referenceId" : "RGD:A443767"
    }, {
      "firstName" : "M E",
      "lastName" : "Peter",
      "authorRank" : 11,
      "name" : "Peter ME",
      "referenceId" : "RGD:A443768"
    }, {
      "firstName" : "P H",
      "lastName" : "Krammer",
      "authorRank" : 12,
      "name" : "Krammer PH",
      "referenceId" : "RGD:A427148"
    }, {
      "firstName" : "S",
      "lastName" : "Fesik",
      "authorRank" : 13,
      "name" : "Fesik S",
      "referenceId" : "RGD:A443769"
    }, {
      "firstName" : "M J",
      "lastName" : "Lenardo",
      "authorRank" : 14,
      "name" : "Lenardo MJ",
      "referenceId" : "RGD:A443770"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12904015"
    } ]
  }, {
    "primaryId" : "PMID:10200313",
    "title" : "An intronic enhancer containing an N-box motif is required for synapse- and tissue-specific expression of the acetylcholinesterase gene in skeletal muscle fibers.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Chan RY, etal., Proc Natl Acad Sci U S A 1999 Apr 13;96(8):4627-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:54.000-05:00",
    "volume" : "96",
    "pages" : "4627-32",
    "abstract" : "mRNAs encoding acetylcholinesterase (AChE; EC 3.1.1.7) are highly concentrated within the postsynaptic sarcoplasm of adult skeletal muscle fibers, where their expression is markedly influenced by nerve-evoked electrical activity and trophic factors. To determine whether transcriptional regulatory mechanisms account for the synaptic accumulation of AChE transcripts at the mammalian neuromuscular synapse, we cloned a 5.3-kb DNA fragment that contained the 5' regulatory region of the rat AChE gene and generated several constructs in which AChE promoter fragments were placed upstream of the reporter gene lacZ and a nuclear localization signal (nls). Using a recently described transient expression assay system in intact skeletal muscle, we show that this AChE promoter fragment directs the synapse-specific expression of the reporter gene. Deletion analysis revealed that a 499-bp fragment located in the first intron of the AChE gene is essential for expression in muscle fibers. Further analysis showed that sequences contained within this intronic fragment were (i) functionally independent of position and orientation and (ii) inactive in hematopoietic cells. Disruption of an N-box motif located within this DNA fragment reduced by more than 80% the expression of the reporter gene in muscle fibers. In contrast, mutation of an adjacent CArG element had no effect on nlsLacZ expression. Taken together, these results indicate that a muscle-specific enhancer is present within the first intron of the AChE gene and that an intronic N-box is essential for the regulation of AChE along skeletal muscle fibers.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RY",
      "lastName" : "Chan",
      "authorRank" : 1,
      "name" : "Chan RY",
      "referenceId" : "RGD:A5618"
    }, {
      "firstName" : "C",
      "lastName" : "Boudreau-Lariviere",
      "authorRank" : 2,
      "name" : "Boudreau-Lariviere C",
      "referenceId" : "RGD:A5619"
    }, {
      "firstName" : "LM",
      "lastName" : "Angus",
      "authorRank" : 3,
      "name" : "Angus LM",
      "referenceId" : "RGD:A5620"
    }, {
      "firstName" : "FA",
      "lastName" : "Mankal",
      "authorRank" : 4,
      "name" : "Mankal FA",
      "referenceId" : "RGD:A5621"
    }, {
      "firstName" : "BJ",
      "lastName" : "Jasmin",
      "authorRank" : 5,
      "name" : "Jasmin BJ",
      "referenceId" : "RGD:A5622"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68738"
    } ]
  }, {
    "primaryId" : "PMID:10200314",
    "title" : "Evectins: vesicular proteins that carry a pleckstrin homology domain and localize to post-Golgi membranes.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Krappa R, etal., Proc Natl Acad Sci U S A 1999 Apr 13;96(8):4633-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:51.000-05:00",
    "volume" : "96",
    "pages" : "4633-8",
    "abstract" : "We have identified two vesicular proteins, designated evectin (evt)-1 and -2. These proteins are approximately 25 kDa in molecular mass, lack a cleaved N-terminal signal sequence, and appear to be inserted into membranes through a C-terminal hydrophobic anchor. They also carry a pleckstrin homology domain at their N termini, which potentially couples them to signal transduction pathways that result in the production of lipid second messengers. evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia, polarized cell types in which plasma membrane biosynthesis is prodigious and regulated; in contrast, evt-2 is widely expressed in both neural and nonneural tissues. In photoreceptors, evt-1 localizes to rhodopsin-bearing membranes of the post-Golgi, an important transport compartment for which specific molecular markers have heretofore been lacking. The structure and subcellular distribution of evt-1 strongly implicate this protein as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. Its restricted cellular distribution and genetic locus make it a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and suggest that it also may be a susceptibility gene for multiple sclerosis.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Krappa",
      "authorRank" : 1,
      "name" : "Krappa R",
      "referenceId" : "RGD:A18691"
    }, {
      "firstName" : "A",
      "lastName" : "Nguyen",
      "authorRank" : 2,
      "name" : "Nguyen A",
      "referenceId" : "RGD:A18692"
    }, {
      "firstName" : "P",
      "lastName" : "Burrola",
      "authorRank" : 3,
      "name" : "Burrola P",
      "referenceId" : "RGD:A18693"
    }, {
      "firstName" : "D",
      "lastName" : "Deretic",
      "authorRank" : 4,
      "name" : "Deretic D",
      "referenceId" : "RGD:A18694"
    }, {
      "firstName" : "G",
      "lastName" : "Lemke",
      "authorRank" : 5,
      "name" : "Lemke G",
      "referenceId" : "RGD:A7624"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632809"
    } ]
  }, {
    "primaryId" : "PMID:10200468",
    "title" : "Anti-CD95 (APO-1/Fas) autoantibodies and T cell depletion in human immunodeficiency virus type 1 (HIV-1)-infected children.",
    "datePublished" : "1998-04-01T00:00:00.000-06:00",
    "citation" : "Stricker K, etal., Cell Death Differ. 1998 Mar;5(3):222-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-06T10:29:11.000-05:00",
    "volume" : "5",
    "pages" : "222-30",
    "abstract" : "Advanced stages of HIV-1-infection are characterized by progressive CD4+ T cell depletion. Peripheral T cells from HIV-1+ donors show accelerated apoptosis in vitro. The CD95 (APO-1/Fas) receptor/ligand system is involved in this process. To further study deregulation of the CD95 system in peripheral T cells during HIV-1-infection, we measured CD95-expression on CD4+ and CD8+ T cells together with serum levels of soluble CD95 (sCD95) and anti-CD95 autoantibodies in HIV-1+  children and healthy controls. Anti-CD95 levels in HIV-1+ children were significantly elevated when compared to uninfected controls, whereas serum levels of sCD95 were not different. In HIV-1+ children, CD95-expression on CD4+ and CD8+ T cells increased with age. A strong correlation between depletion of CD4+ cells  in vivo and increase in CD95-expression on CD4+ T cells was observed. In contrast, such a correlation was not found for CD8+ T cells. A negative correlation between anti-CD95 autoantibody levels and CD4+ T cell counts, that was predicted by multiple linear regression analysis of pooled data, was found in individual patients observed longitudinally by repeated measurements. Since anti-CD95 autoantibodies isolated from HIV-infected adults have previously been shown to induce apoptosis of sensitive target cells in vitro, we speculate that the interaction of these antibodies with CD95-positive and CD95-sensitive T cells in vivo might be involved in progressive T cell loss during HIV-1-infection.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Stricker",
      "authorRank" : 1,
      "name" : "Stricker",
      "referenceId" : "RGD:A215511"
    }, {
      "firstName" : "E",
      "lastName" : "Knipping",
      "authorRank" : 2,
      "name" : "Knipping",
      "referenceId" : "RGD:A215512"
    }, {
      "firstName" : "T",
      "lastName" : "Bohler",
      "authorRank" : 3,
      "name" : "Bohler T",
      "referenceId" : "RGD:A101915"
    }, {
      "firstName" : "A",
      "lastName" : "Benner",
      "authorRank" : 4,
      "name" : "Benner",
      "referenceId" : "RGD:A215513"
    }, {
      "firstName" : "PH",
      "lastName" : "Krammer",
      "authorRank" : 5,
      "name" : "Krammer PH",
      "referenceId" : "RGD:A38551"
    }, {
      "firstName" : "KM",
      "lastName" : "Debatin",
      "authorRank" : 6,
      "name" : "Debatin KM",
      "referenceId" : "RGD:A76911"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11049451"
    } ]
  }, {
    "primaryId" : "PMID:10201001",
    "title" : "A laboratory model of toxin-induced hemolytic uremic syndrome.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Taylor CM, etal., Kidney Int. 1999 Apr;55(4):1367-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-11T10:45:43.000-05:00",
    "volume" : "55",
    "pages" : "1367-74",
    "abstract" : "BACKGROUND: Verocytotoxin-producing (Shiga-like toxin-producing) Escherichia coli infection is the principal cause of hemolytic uremic syndrome (HUS). The pathogenesis is unclear, and there is a need for animal models. These are impeded by the different distribution of verocytotoxin receptors between species. We have circumvented this restriction using ricin, which gains entry into cells via various galactose receptors. Like verocytotoxin, ricin specifically cleaves a single adenine from ribosomal RNA. METHODS: Rats were given ricin at a dose of 6.7 micrograms/100 g body wt, with or without lipopolysaccharide at 10 micrograms/100 g body wt. Lipopolysaccharide alone or saline were used as controls. Changes in glomerular filtration rate, hematological parameters, histology, and plasma cytokine concentrations were measured. RESULTS: Extensive glomerular thrombosis, pyknotic nuclei, and an infiltration of ED1-positive cells into glomeruli were observed eight hours after an injection of ricin. Other vascular beds were unaffected. Histologic changes were preceded by oliguric renal failure, hemolysis, and thrombocytopenia. Ricin produced a rise in plasma concentrations of monocyte chemotactic protein-1, > tumor necrosis factor-alpha,  > interleukin-1 beta, > interleukin-6. Interferon-gamma showed a small increase at the end of the experiment. CONCLUSIONS: Ricin induces glomerular thrombotic microangiopathy, closely resembling that which occurs in verocytotoxin-producing  E. coli-induced HUS. As in HUS, high concentrations of proinflammatory cytokines  are present, which are probably a result of cytokine superinduction by the toxin.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CM",
      "lastName" : "Taylor",
      "authorRank" : 1,
      "name" : "Taylor CM",
      "referenceId" : "RGD:A53648"
    }, {
      "firstName" : "JM",
      "lastName" : "Williams",
      "authorRank" : 2,
      "name" : "Williams JM",
      "referenceId" : "RGD:A4816"
    }, {
      "firstName" : "CJ",
      "lastName" : "Lote",
      "authorRank" : 3,
      "name" : "Lote",
      "referenceId" : "RGD:A366560"
    }, {
      "firstName" : "AJ",
      "lastName" : "Howie",
      "authorRank" : 4,
      "name" : "Howie AJ",
      "referenceId" : "RGD:A130606"
    }, {
      "firstName" : "A",
      "lastName" : "Thewles",
      "authorRank" : 5,
      "name" : "Thewles",
      "referenceId" : "RGD:A366561"
    }, {
      "firstName" : "JA",
      "lastName" : "Wood",
      "authorRank" : 6,
      "name" : "Wood",
      "referenceId" : "RGD:A366562"
    }, {
      "firstName" : "DV",
      "lastName" : "Milford",
      "authorRank" : 7,
      "name" : "Milford DV",
      "referenceId" : "RGD:A64244"
    }, {
      "firstName" : "F",
      "lastName" : "Raafat",
      "authorRank" : 8,
      "name" : "Raafat",
      "referenceId" : "RGD:A366563"
    }, {
      "firstName" : "I",
      "lastName" : "Chant",
      "authorRank" : 9,
      "name" : "Chant",
      "referenceId" : "RGD:A366564"
    }, {
      "firstName" : "PE",
      "lastName" : "Rose",
      "authorRank" : 10,
      "name" : "Rose",
      "referenceId" : "RGD:A366565"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11528527"
    } ]
  }, {
    "primaryId" : "PMID:10201375",
    "title" : "A capsaicin-receptor homologue with a high threshold for noxious heat.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Caterina MJ, etal., Nature 1999 Apr 1;398(6726):436-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-11T15:05:32.000-06:00",
    "volume" : "398",
    "pages" : "436-41",
    "abstract" : "Pain-producing heat is detected by several classes of nociceptive sensory neuron that differ in their thermal response thresholds. The cloned capsaicin receptor, also known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel that has been proposed to mediate responses of small-diameter sensory neurons to moderate (43 degrees C) thermal stimuli. VR1 is also activated by protons, indicating that it may participate in the detection of noxious thermal and chemical stimuli in vivo. Here we identify a structurally related receptor, VRL-1, that does not respond to capsaicin, acid or moderate heat. Instead, VRL-1 is activated by high temperatures, with a threshold of approximately 52 degrees C. Within sensory ganglia, VRL-1 is most prominently expressed by a subset of medium- to large-diameter neurons, making it a candidate receptor for transducing high-threshold heat responses in this class of cells. VRL-1 transcripts are not restricted to the sensory nervous system, indicating that this channel may be activated by stimuli other than heat. We propose that responses to noxious heat involve these related, but distinct, ion-channel subtypes that together detect a range of stimulus intensities.",
    "issueName" : "6726",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MJ",
      "lastName" : "Caterina",
      "authorRank" : 1,
      "name" : "Caterina MJ",
      "referenceId" : "RGD:A8185"
    }, {
      "firstName" : "TA",
      "lastName" : "Rosen",
      "authorRank" : 2,
      "name" : "Rosen TA",
      "referenceId" : "RGD:A8186"
    }, {
      "firstName" : "M",
      "lastName" : "Tominaga",
      "authorRank" : 3,
      "name" : "Tominaga M",
      "referenceId" : "RGD:A8187"
    }, {
      "firstName" : "AJ",
      "lastName" : "Brake",
      "authorRank" : 4,
      "name" : "Brake AJ",
      "referenceId" : "RGD:A8188"
    }, {
      "firstName" : "D",
      "lastName" : "Julius",
      "authorRank" : 5,
      "name" : "Julius D",
      "referenceId" : "RGD:A8189"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70055"
    } ]
  }, {
    "primaryId" : "PMID:10201790",
    "title" : "Inhibition of platelet-activating factor, intercellular adhesion molecule 1 and platelet endothelial cell adhesion molecule 1 reduces experimental pancreatitis-associated gut endothelial barrier dysfunction.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wang X, etal., Br J Surg. 1999 Mar;86(3):411-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-03T11:09:47.000-05:00",
    "volume" : "86",
    "pages" : "411-6",
    "abstract" : "BACKGROUND: Endothelial barrier dysfunction is a critical link in the development of tissue injury and organ dysfunction, via upregulation and exposure of adhesion molecules, intercellular signals and leucocyte-endothelial cell interactions. Inhibitors of inflammatory mediators and receptors have been suggested as a means of downregulating the cascade of both local and systemic inflammation. METHODS: The potential therapeutic inhibition of platelet-activating factor (PAF), intercellular adhesion molecule (ICAM) 1 and platelet endothelial cell adhesion molecule (PECAM) 1 was investigated in pancreatitis-associated gut endothelial dysfunction in rats, by treatment with a PAF antagonist (lexipafant, BB-882) and  monoclonal antibodies against rat ICAM-1 (anti-ICAM1-Mb) and PECAM (anti-PECAMA1-Mb). Alterations in gut endothelial barrier dysfunction and leucocyte recruitment, and systemic levels of interleukins were evaluated. RESULTS: Plasma exudation measured by the albumin leakage index and tissue leucocyte recruitment in the distal small intestine and colon increased significantly 12 h after induction of pancreatitis and treatment with saline. These alterations were to varying degrees counteracted by treatment with lexipafant, anti-ICAM1-Mb or anti-PECAM1-Mb. Alterations in levels of interleukin (IL) 1 paralleled the changes in gut endothelial barrier dysfunction and leucocyte trapping. CONCLUSION: Treatment with lexipafant and monoclonal antibodies against ICAM-1 or PECAM-1 reduced the severity of pancreatitis-associated gut endothelial dysfunction, and decreased systemic concentrations of IL-1 and local leucocyte recruitment.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang",
      "referenceId" : "RGD:A416757"
    }, {
      "firstName" : "Z",
      "lastName" : "Sun",
      "authorRank" : 2,
      "name" : "Sun Z",
      "referenceId" : "RGD:A24717"
    }, {
      "firstName" : "A",
      "lastName" : "Borjesson",
      "authorRank" : 3,
      "name" : "Borjesson A",
      "referenceId" : "RGD:A108250"
    }, {
      "firstName" : "R",
      "lastName" : "Andersson",
      "authorRank" : 4,
      "name" : "Andersson R",
      "referenceId" : "RGD:A110050"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11520782"
    } ]
  }, {
    "primaryId" : "PMID:10201810",
    "title" : "Immunological localization and ontogenetic development of inhibin alpha subunit in rat brain.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Fujimura H, etal., J Neuroendocrinol. 1999 Mar;11(3):157-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-03-11T17:26:05.000-05:00",
    "volume" : "11",
    "pages" : "157-63",
    "abstract" : "This study examined the immunolocalization and ontogeny of the inhibin-specific alpha subunit in the brain of male rats. Immunohistochemistry using antiserum directed against the mature region of porcine inhibin alpha (1-19, Tyr20) revealed positive reactions in process-bearing cells resembling astroglia in several regions, especially in the dorsal region of the third ventricle, medial and ventral arcuate nucleus, hippocampal dentate gyrus, and layers 1-3 of the cerebral cortex. Generally, inhibin alpha-positive cells in the limbic cortex had larger cell bodies and longer processes than those in the hypothalamus. These inhibin alpha-positive cells were verified to be positive for glial fibrillary acidic protein (GFAP), a differentiated astroglial marker, by double immunolabelling. The expression of inhibin alpha mRNA was higher in the brains of neonatal rats than in those of adult rats, as revealed by reverse transcription-competitive polymerase chain reaction, although the similar changes of immunoreactive inhibin alpha subunit in the brain was not observed. Orchiectomy did not affect expression of inhibin alpha mRNA in the hypothalamic area. This study suggests that inhibin-related peptide is produced by differentiated astrocytes, especially in the hypothalamic arcuate nucleus, the hippocampal dentate gyrus, and the cerebral cortex, and that the expression of inhibin alpha is regulated during brain development.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Fujimura",
      "authorRank" : 1,
      "name" : "Fujimura H",
      "referenceId" : "RGD:A18899"
    }, {
      "firstName" : "K",
      "lastName" : "Ohsawa",
      "authorRank" : 2,
      "name" : "Ohsawa K",
      "referenceId" : "RGD:A15838"
    }, {
      "firstName" : "M",
      "lastName" : "Funaba",
      "authorRank" : 3,
      "name" : "Funaba M",
      "referenceId" : "RGD:A92920"
    }, {
      "firstName" : "T",
      "lastName" : "Murata",
      "authorRank" : 4,
      "name" : "Murata T",
      "referenceId" : "RGD:A27335"
    }, {
      "firstName" : "E",
      "lastName" : "Murata",
      "authorRank" : 5,
      "name" : "Murata E",
      "referenceId" : "RGD:A92921"
    }, {
      "firstName" : "M",
      "lastName" : "Takahashi",
      "authorRank" : 6,
      "name" : "Takahashi M",
      "referenceId" : "RGD:A4629"
    }, {
      "firstName" : "M",
      "lastName" : "Abe",
      "authorRank" : 7,
      "name" : "Abe M",
      "referenceId" : "RGD:A157851"
    }, {
      "firstName" : "K",
      "lastName" : "Torii",
      "authorRank" : 8,
      "name" : "Torii K",
      "referenceId" : "RGD:A92923"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2290404"
    } ]
  }, {
    "primaryId" : "PMID:10201963",
    "title" : "The role of the human Fc receptor Fc gamma RIIA in the immune clearance of platelets: a transgenic mouse model.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "McKenzie SE, etal., J Immunol. 1999 Apr 1;162(7):4311-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-17T10:47:59.000-05:00",
    "volume" : "162",
    "pages" : "4311-8",
    "abstract" : "In humans, the Fc receptor for IgG, FcgammaRIIA, is expressed on macrophages and  platelets and may play an important role in the pathophysiology of immune-mediated thrombocytopenia. Mice lack the genetic equivalent of human FcgammaRIIA. To better understand the role of FcgammaRIIA in vivo, FcgammaRIIA transgenic mice were generated and characterized. One transgenic mouse line expressed FcgammaRIIA on platelets and macrophages at levels equivalent to human  cells, and cross-linking FcgammaRIIA on these platelets induced platelet aggregation. Immune-mediated thrombocytopenia in this transgenic line was studied using i.v. and i.p. administration of anti-mouse platelet Ab. In comparison with  matched wild-type littermates that are negative for the FcgammaRIIA transgene, Ab-mediated thrombocytopenia was significantly more severe in the FcgammaRIIA transgenic mice. In contrast, FcR gamma-chain knockout mice that lack functional  expression of the Fc receptors FcgammaRI and FcgammaRIII on splenic macrophages did not demonstrate Ab-mediated thrombocytopenia. We generated FcgammaRIIA transgenic x FcR gamma-chain knockout mice to examine the role of FcgammaRIIA in  immune clearance in the absence of functional FcgammaRI and FcgammaRIII. In FcgammaRIIA transgenic x FcR gamma-chain knockout mice, severe immune thrombocytopenia mediated by FcgammaRIIA was observed. These results demonstrate  that FcgammaRIIA does not require the FcR gamma-chain for expression or function  in vivo. Furthermore, taken together, the data suggest that the human Fc receptor FcgammaRIIA plays a significant role in the immune clearance of platelets in vivo.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SE",
      "lastName" : "McKenzie",
      "authorRank" : 1,
      "name" : "McKenzie SE",
      "referenceId" : "RGD:A144119"
    }, {
      "firstName" : "SM",
      "lastName" : "Taylor",
      "authorRank" : 2,
      "name" : "Taylor SM",
      "referenceId" : "RGD:A77786"
    }, {
      "firstName" : "P",
      "lastName" : "Malladi",
      "authorRank" : 3,
      "name" : "Malladi P",
      "referenceId" : "RGD:A66510"
    }, {
      "firstName" : "H",
      "lastName" : "Yuhan",
      "authorRank" : 4,
      "name" : "Yuhan",
      "referenceId" : "RGD:A213913"
    }, {
      "firstName" : "DL",
      "lastName" : "Cassel",
      "authorRank" : 5,
      "name" : "Cassel",
      "referenceId" : "RGD:A213914"
    }, {
      "firstName" : "P",
      "lastName" : "Chien",
      "authorRank" : 6,
      "name" : "Chien",
      "referenceId" : "RGD:A213915"
    }, {
      "firstName" : "E",
      "lastName" : "Schwartz",
      "authorRank" : 7,
      "name" : "Schwartz E",
      "referenceId" : "RGD:A74858"
    }, {
      "firstName" : "AD",
      "lastName" : "Schreiber",
      "authorRank" : 8,
      "name" : "Schreiber",
      "referenceId" : "RGD:A213916"
    }, {
      "firstName" : "S",
      "lastName" : "Surrey",
      "authorRank" : 9,
      "name" : "Surrey",
      "referenceId" : "RGD:A213846"
    }, {
      "firstName" : "MP",
      "lastName" : "Reilly",
      "authorRank" : 10,
      "name" : "Reilly MP",
      "referenceId" : "RGD:A64421"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11040944"
    } ]
  }, {
    "primaryId" : "PMID:10202016",
    "title" : "A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Neville MJ and Campbell RD, J Immunol 1999 Apr 15;162(8):4745-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:51:34.000-05:00",
    "volume" : "162",
    "pages" : "4745-54",
    "abstract" : "It is becoming increasingly apparent that many of the genes in the class III region of the human MHC encode proteins involved in the immune and inflammatory responses. Furthermore, genetic studies have indicated that genes within the class III region, particularly the telomeric segment containing the TNF gene, could contribute to susceptibility to diseases of immune-related etiology. We have sequenced an 82-kb segment of DNA around the TNF gene to identify candidate disease susceptibility genes in this region. The 10 known genes in this region have been precisely positioned with the order allograft inflammatory factor 1, G1, 1C7, leukocyte-specific transcript 1 (B144), lymphotoxin B, TNF, lymphotoxin A, NB6, IKBL, BAT1 (centromere to telomere), and their genomic structures have been defined. Comparison of the G1 genomic region with previously described cDNA and genomic sequences, together with the results of reverse transcriptase-PCR, indicates that three alternative transcripts, G1, allograft inflammatory factor 1, and IFN-gamma-responsive transcript, are all derived from this gene. The completion of the sequence of 1C7 (D6S2570) has revealed that this gene encodes a putative novel member of the Ig superfamily. A number of alternatively spliced transcripts of 1C7 were identified by reverse transcriptase-PCR, all of which are expressed in immune-related cell lines. Alternative splicing within the Ig domain-encoding region was seen to result in possible set switching between an IgV domain and an IgC2 domain. Lastly, a previously unidentified gene, homologous to a number of V-ATPase G subunits, has been located 1 kb telomeric of IKBL.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MJ",
      "lastName" : "Neville",
      "authorRank" : 1,
      "name" : "Neville MJ",
      "referenceId" : "RGD:A47853"
    }, {
      "firstName" : "RD",
      "lastName" : "Campbell",
      "authorRank" : 2,
      "name" : "Campbell RD",
      "referenceId" : "RGD:A40325"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302931"
    } ]
  }, {
    "primaryId" : "PMID:10202049",
    "title" : "4-1BBL cooperates with B7-1 and B7-2 in converting a B cell lymphoma cell line into a long-lasting antitumor vaccine.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Guinn BA, etal., J Immunol. 1999 Apr 15;162(8):5003-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-30T09:36:27.000-05:00",
    "volume" : "162",
    "pages" : "5003-10",
    "abstract" : "A20 is a B cell lymphoma that constitutively expresses the costimulatory molecule B7-2 yet grows readily as a tumor in syngeneic BALB/c mice. We have compared the tumorigenicity of A20 variants expressing either B7-1 (A20/B7-1) or B7-2 (A20/B7-2) with an A20 variant expressing B7-1 and B7-2 with 4-1BBL (A20/4-1BBL), a costimulatory member of the TNF family. Mice injected with tumors expressing the vector backbone (A20/CMV) or B7-1 developed tumors within 25 days of s.c. injection. In contrast, mice injected with A20/4-1BBL were tumor free for the 150-day follow-up period, while 25% of mice injected with A20/B7-2 developed tumors. Tumorigenicity experiments using nude mice indicated the requirement for T cells for variant rejection. Almost all mice that resisted the initial tumor challenge were resistant to further challenge with the parental tumor. Splenocytes from these mice showed high CTL lytic activity against the parental tumor, A20, as well as the syngeneic BALB/c lymphoma K46J, but showed background levels of lytic activity against the congenic SCID thymoma line ST-D2 or the allogeneic EL4 thymoma. In vitro blocking experiments with anti-B7-1 plus anti-B7-2 and/or soluble 4-1BB receptor showed B7-1, B7-2, and 4-1BBL all contributed to the CTL activity. Thus, the data show that neither B7-1 or B7-2 alone can confer full immunogenicity to the A20 lymphoma but that the addition of 4-1BBL results in a tumor that is highly immunogenic and can confer long-lasting protection against challenge with parental tumor in vivo.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BA",
      "lastName" : "Guinn",
      "authorRank" : 1,
      "name" : "Guinn BA",
      "referenceId" : "RGD:A121154"
    }, {
      "firstName" : "MA",
      "lastName" : "DeBenedette",
      "authorRank" : 2,
      "name" : "DeBenedette MA",
      "referenceId" : "RGD:A121155"
    }, {
      "firstName" : "TH",
      "lastName" : "Watts",
      "authorRank" : 3,
      "name" : "Watts TH",
      "referenceId" : "RGD:A43420"
    }, {
      "firstName" : "NL",
      "lastName" : "Berinstein",
      "authorRank" : 4,
      "name" : "Berinstein NL",
      "referenceId" : "RGD:A121156"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317349"
    } ]
  }, {
    "primaryId" : "PMID:10202168",
    "title" : "Clinical features of 52 neonates with hyperinsulinism.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "de Lonlay-Debeney P, etal., N Engl J Med. 1999 Apr 15;340(15):1169-75.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:26:35.000-05:00",
    "volume" : "340",
    "pages" : "1169-75",
    "abstract" : "BACKGROUND: Neonatal hyperinsulinemic hypoglycemia is often resistant to medical  therapy and is often treated with near-total pancreatectomy. However, the pancreatic lesions may be focal and treatable by partial pancreatic resection. METHODS: We studied 52 neonates with hyperinsulinism who were treated surgically. The type and location of the pancreatic lesions were determined by preoperative pancreatic catheterization and intraoperative histologic studies. Partial pancreatectomy was performed in infants with focal lesions, and near-total pancreatectomy was performed in those with diffuse lesions. The postoperative outcome was determined by measurements of plasma glucose and glycosylated hemoglobin and by oral glucose-tolerance tests. RESULTS: Thirty neonates had diffuse beta-cell hyperfunction, and 22 had focal adenomatous islet-cell hyperplasia. Among the latter, the lesions were in the head of the pancreas in nine, the isthmus in three, the body in eight, and the tail in two. The clinical  manifestations were similar in both groups. The infants with focal lesions had no symptoms of hypoglycemia and had normal preprandial and postprandial plasma glucose and glycosylated hemoglobin values and normal results on oral glucose-tolerance tests after partial pancreatectomy (performed in 19 of 22 neonates). By contrast, after near-total pancreatectomy, 13 of the patients with  diffuse lesions had persistent hypoglycemia, type 1 diabetes mellitus developed in 8, and hyperglycemia developed in another 7; overall, only 2 patients with diffuse lesions had normal plasma glucose concentrations in the first year after  surgery. CONCLUSIONS: Among neonates with hyperinsulinism, about half may have focal islet-cell hyperplasia that can be treated with partial pancreatectomy. These neonates can be identified through pancreatic catheterization and intraoperative histologic studies.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "De Lonlay-Debeney",
      "authorRank" : 1,
      "name" : "De Lonlay-Debeney P",
      "referenceId" : "RGD:A57108"
    }, {
      "firstName" : "F",
      "lastName" : "Poggi-Travert",
      "authorRank" : 2,
      "name" : "Poggi-Travert",
      "referenceId" : "RGD:A276096"
    }, {
      "firstName" : "JC",
      "lastName" : "Fournet",
      "authorRank" : 3,
      "name" : "Fournet JC",
      "referenceId" : "RGD:A71024"
    }, {
      "firstName" : "C",
      "lastName" : "Sempoux",
      "authorRank" : 4,
      "name" : "Sempoux C",
      "referenceId" : "RGD:A100838"
    }, {
      "firstName" : "C",
      "lastName" : "Dionisi Vici",
      "authorRank" : 5,
      "name" : "Dionisi Vici",
      "referenceId" : "RGD:A276097"
    }, {
      "firstName" : "F",
      "lastName" : "Brunelle",
      "authorRank" : 6,
      "name" : "Brunelle F",
      "referenceId" : "RGD:A123790"
    }, {
      "firstName" : "G",
      "lastName" : "Touati",
      "authorRank" : 7,
      "name" : "Touati G",
      "referenceId" : "RGD:A74875"
    }, {
      "firstName" : "J",
      "lastName" : "Rahier",
      "authorRank" : 8,
      "name" : "Rahier J",
      "referenceId" : "RGD:A123789"
    }, {
      "firstName" : "C",
      "lastName" : "Junien",
      "authorRank" : 9,
      "name" : "Junien C",
      "referenceId" : "RGD:A60289"
    }, {
      "firstName" : "C",
      "lastName" : "Nihoul-Fekete",
      "authorRank" : 10,
      "name" : "Nihoul-Fekete C",
      "referenceId" : "RGD:A79225"
    }, {
      "firstName" : "JJ",
      "lastName" : "Robert",
      "authorRank" : 11,
      "name" : "Robert JJ",
      "referenceId" : "RGD:A77815"
    }, {
      "firstName" : "JM",
      "lastName" : "Saudubray",
      "authorRank" : 12,
      "name" : "Saudubray JM",
      "referenceId" : "RGD:A74878"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070185"
    } ]
  }, {
    "primaryId" : "PMID:10202362",
    "title" : "Identification of a highly promiscuous and an HLA allele-specific T-cell epitope in the birch major allergen Bet v 1: HLA restriction, epitope mapping and TCR sequence comparisons.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Friedl-Hajek R, etal., Clin Exp Allergy. 1999 Apr;29(4):478-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-08-25T16:01:28.000-05:00",
    "volume" : "29",
    "pages" : "478-87",
    "abstract" : "BACKGROUND: Allergen-specific CD4+ T cells play an important regulatory role in atopic allergy. OBJECTIVE: To investigate the human leucocyte antigen (HLA) restriction and T-cell receptor (TCR) usage of allergen-specific T-cell clones (TCCs) that react with defined epitopes of Bet v 1, the major birch pollen allergen. METHODS: Five Bet v 1-specific TCCs derived from two birch pollen-allergic individuals and specific for Bet v 1, were epitope-mapped with overlapping synthetic peptides. In addition, HLA-restriction and TCR CDR3 sequences were determined. RESULTS: Three TCCs reacted with a Bet v 1 peptide containing amino acid residues 21-33 (BP21), the other two TCCs reacted with a minimal peptide comprising residues 37-45 (BP37). Studies using neutralizing anti-HLA-monoclonal antibodies and HLA-typed APCs showed that the BP37-specific TCCs were restricted by a HLA-DQA1*0301/DQB1*0603 heterodimer. In contrast, BP21 was recognized in a highly promiscuous manner. TCCs recognizing this sequence were restricted by HLA-DPB1*0201, a HLA-DQA1*0201/DQB1*0201 heterodimer, or HLA-DRB3*0101. Reverse transcription-polymerase chain reaction with primers for all known TCRAV and TCRBV gene segments, followed by CDR3 region sequencing, revealed the usage of five different TCRAV and four different TCRBV gene segments by the TCCs, as well as diversity in the joining region. All BP21-specific TCCs contained a negatively charged residue in their CDR3alpha regions, the CDR3beta regions showed a high concentration of polar and OH-group bearing residues. BP37-specific TCCs shared the amino acid combination LY in the middle of their CDR3alpha regions, the CDR3beta regions showed high concentration of OH-group bearing or charged residues. CONCLUSIONS: This study shows the existence of a highly promiscuous T-cell epitope in Bet v 1. The presence of additional T-cell epitopes in Bet v 1 may, however, hamper the clinical applicability of the epitope. Likewise, the diversity in TCR usage by T cells recognizing the epitope does not support the development of TCR-directed immunotherapy for birch pollen allergy.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Friedl-Hajek",
      "authorRank" : 1,
      "name" : "Friedl-Hajek R",
      "referenceId" : "RGD:A143850"
    }, {
      "firstName" : "MD",
      "lastName" : "Spangfort",
      "authorRank" : 2,
      "name" : "Spangfort MD",
      "referenceId" : "RGD:A143851"
    }, {
      "firstName" : "C",
      "lastName" : "Schou",
      "authorRank" : 3,
      "name" : "Schou C",
      "referenceId" : "RGD:A143852"
    }, {
      "firstName" : "H",
      "lastName" : "Breiteneder",
      "authorRank" : 4,
      "name" : "Breiteneder H",
      "referenceId" : "RGD:A143853"
    }, {
      "firstName" : "H",
      "lastName" : "Yssel",
      "authorRank" : 5,
      "name" : "Yssel H",
      "referenceId" : "RGD:A130960"
    }, {
      "firstName" : "RJ",
      "lastName" : "Joost van Neerven",
      "authorRank" : 6,
      "name" : "Joost van Neerven RJ",
      "referenceId" : "RGD:A143854"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5147866"
    } ]
  }, {
    "primaryId" : "PMID:10202854",
    "title" : "A decrease in the amount and function of inhibitory GTP-binding protein in the resistance small artery from spontaneously hypertensive rats.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Masutani M, etal., Jpn J Pharmacol 1999 Feb;79(2):185-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-10-05T08:14:20.000-05:00",
    "volume" : "79",
    "pages" : "185-93",
    "abstract" : "The inhibitory GTP-binding protein (Gi protein) plays an important role in regulation of vascular tone. Many studies have implicated the role of Gi protein in conduit vessels. However, the physiological role of Gi protein in the control of peripheral microvascular tone in hypertension has not been established yet. Therefore, we investigated the concentration of Gi protein in the peripheral resistance arteries and aorta in the spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY) and renovascular hypertensive rats (RHR), using immunohistochemical methods semiquantitatively. Changes in the function of Gi protein in relation to alpha2-adrenoceptor were also investigated by microcannulation techniques. We have shown that the amount of alpha2 subunits of Gi protein in the cremaster small artery was significantly lower in SHR aged 4 weeks and older than in age-matched WKY and that there were no significant differences between RHR and WKY. We also demonstrated that the function of Gi protein in relation to alpha2-adrenoceptor was already lower in SHR before the onset of hypertension. The quantitative and functional decline in Gi protein in the smooth muscle cells of peripheral small arteries were observed in SHR even before the onset of hypertension, whereas rats with secondary hypertension did not exhibit this finding.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Masutani",
      "authorRank" : 1,
      "name" : "Masutani M",
      "referenceId" : "RGD:A46191"
    }, {
      "firstName" : "M",
      "lastName" : "Ohyanagi",
      "authorRank" : 2,
      "name" : "Ohyanagi M",
      "referenceId" : "RGD:A46192"
    }, {
      "firstName" : "J",
      "lastName" : "Shibuya",
      "authorRank" : 3,
      "name" : "Shibuya J",
      "referenceId" : "RGD:A46193"
    }, {
      "firstName" : "Y",
      "lastName" : "Ishigami",
      "authorRank" : 4,
      "name" : "Ishigami Y",
      "referenceId" : "RGD:A46194"
    }, {
      "firstName" : "T",
      "lastName" : "Iwasaki",
      "authorRank" : 5,
      "name" : "Iwasaki T",
      "referenceId" : "RGD:A11690"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302378"
    } ]
  }, {
    "primaryId" : "PMID:10203020",
    "title" : "HLA-DR-DQ alleles and HLA-DP alleles are independently associated with susceptibility to different stages of post-schistosomal hepatic fibrosis in the Chinese population.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Hirayama K, etal., Tissue Antigens. 1999 Mar;53(3):269-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-06-19T14:54:18.000-05:00",
    "volume" : "53",
    "pages" : "269-74",
    "abstract" : "Abstract: Evaluation of human leukocyte antigen (HLA) class I and class II genes was performed on patients from China with Schistosomiasis japonica. Patients were categorized as grade 0 (n=44), grade I (n=81), grade II (n=99), or grade III (n=6) based on increasing severity of hepatic fibrosis due to repeated Schistosoma japonicum infections. These results show that the HLA-DRB1*1101-DQA1*0501-DQB1*0301 (Pc<0.02) and HLA-DRB1*1501-DRB5*0101 (Pc<0.02) haplotypes are associated with protection and susceptibility to grade I fibrosis, respectively, and that the HLA-DPA1*0103 -DPB1*0201 haplotype (Pc<0.02) is associated with protection from both grade II and III severe fibrosis. There was no association between HLA-B DNA haplotypes and the disease. These findings indicate that the HLA-class II molecules play a role in preventing or promoting fibrotic liver change after deposition with Schistosome eggs. Moreover, a tendency was observed within the HLA class II genes for the HLA-DR-DQ alleles to be associated with protection against early changes in liver fibrosis, whereas HLA-DP alleles were associated with protection from the late phase of fibrosis or severe hepatosplenic schistosomiasis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Hirayama",
      "authorRank" : 1,
      "name" : "Hirayama K",
      "referenceId" : "RGD:A48189"
    }, {
      "firstName" : "H",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen H",
      "referenceId" : "RGD:A6110"
    }, {
      "firstName" : "M",
      "lastName" : "Kikuchi",
      "authorRank" : 3,
      "name" : "Kikuchi M",
      "referenceId" : "RGD:A5166"
    }, {
      "firstName" : "T",
      "lastName" : "Yin",
      "authorRank" : 4,
      "name" : "Yin T",
      "referenceId" : "RGD:A470714"
    }, {
      "firstName" : "X",
      "lastName" : "Gu",
      "authorRank" : 5,
      "name" : "Gu X",
      "referenceId" : "RGD:A63274"
    }, {
      "firstName" : "J",
      "lastName" : "Liu",
      "authorRank" : 6,
      "name" : "Liu J",
      "referenceId" : "RGD:A394450"
    }, {
      "firstName" : "S",
      "lastName" : "Zhang",
      "authorRank" : 7,
      "name" : "Zhang S",
      "referenceId" : "RGD:A26006"
    }, {
      "firstName" : "H",
      "lastName" : "Yuan",
      "authorRank" : 8,
      "name" : "Yuan H",
      "referenceId" : "RGD:A21021"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14694972"
    } ]
  }, {
    "primaryId" : "PMID:10203252",
    "title" : "Effects of the acute and chronic restraint stresses on the central histaminergic neuron system of Fischer rat.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ito C, etal., Neurosci Lett. 1999 Mar 5;262(2):143-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-01T09:37:53.000-06:00",
    "volume" : "262",
    "pages" : "143-5",
    "abstract" : "The effects of acute and chronic restraint stresses on the brain histamine level and histamine N-methyltransferase activity in Fischer rat brain were studied. The acute restraint stress increased the histamine levels in the diencephalon and nucleus accumbens, and increased the histamine N-methyltransferase activities in the nucleus accumbens and striatum. The chronic restraint stress also increased histamine N-methyltransferase activities in the nucleus accumbens and striatum. These results indicate that the acute and chronic restraint stresses increase the brain histamine turnover, which may partly relate to the vulnerability for stress-induced anxiety and depression.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Ito",
      "authorRank" : 1,
      "name" : "Ito C",
      "referenceId" : "RGD:A55674"
    }, {
      "firstName" : "H",
      "lastName" : "Shen",
      "authorRank" : 2,
      "name" : "Shen H",
      "referenceId" : "RGD:A33600"
    }, {
      "firstName" : "H",
      "lastName" : "Toyota",
      "authorRank" : 3,
      "name" : "Toyota H",
      "referenceId" : "RGD:A119837"
    }, {
      "firstName" : "Y",
      "lastName" : "Kubota",
      "authorRank" : 4,
      "name" : "Kubota Y",
      "referenceId" : "RGD:A19696"
    }, {
      "firstName" : "E",
      "lastName" : "Sakurai",
      "authorRank" : 5,
      "name" : "Sakurai E",
      "referenceId" : "RGD:A119838"
    }, {
      "firstName" : "T",
      "lastName" : "Watanabe",
      "authorRank" : 6,
      "name" : "Watanabe T",
      "referenceId" : "RGD:A158984"
    }, {
      "firstName" : "M",
      "lastName" : "Sato",
      "authorRank" : 7,
      "name" : "Sato M",
      "referenceId" : "RGD:A154914"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316832"
    } ]
  }, {
    "primaryId" : "PMID:10204114",
    "title" : "Molecular biology of adenosine triphosphate-sensitive potassium channels.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Aguilar-Bryan L and Bryan J, Endocr Rev. 1999 Apr;20(2):101-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:17:47.000-05:00",
    "volume" : "20",
    "pages" : "101-35",
    "abstract" : "KATP channels are a newly defined class of potassium channels based on the physical association of an ABC protein, the sulfonylurea receptor, and a K+ inward rectifier subunit. The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2,  a weak inward rectifier, in a 1:1 stoichiometry. The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4. The two subunits form a tightly integrated whole. KIR6.2 can be expressed in the plasma membrane either by deletion of an ER retention signal at its C-terminal end or by high-level expression to overwhelm the retention mechanism. The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane. Coexpression with SUR restores the normal channel properties. The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity. KATP channels set the resting membrane potential of beta-cells, and their loss results in a constitutive depolarization that allows voltage-gated Ca2+ channels to open spontaneously, increasing the cytosolic Ca2+ levels enough to trigger continuous release of insulin. The loss of KATP channels, in effect, uncouples the electrical activity  of beta-cells from their metabolic activity. PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides. The results indicate that SUR1 is important in sensing nucleotide changes, as implied by its sequence similarity to other ABC proteins, in addition to being the drug sensor. An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1. A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP. The  result implies that ATP tonically inhibits KATP channels, but that the ADP level  in a fasting beta-cell antagonizes this inhibition. Decreases in the ADP level as glucose is metabolized result in KATP channel closure. Although KATP channels are the target for sulfonylureas used in the treatment of NIDDM, the available data suggest that the identified KATP channel mutations do not play a major role in diabetes. Understanding how KATP channels fit into the overall scheme of glucose  homeostasis, on the other hand, promises insight into diabetes and other disorders of glucose metabolism, while understanding the structure and regulation of these channels offers potential for development of novel compounds to regulate cellular electrical activity.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Aguilar-Bryan",
      "authorRank" : 1,
      "name" : "Aguilar-Bryan L",
      "referenceId" : "RGD:A25415"
    }, {
      "firstName" : "J",
      "lastName" : "Bryan",
      "authorRank" : 2,
      "name" : "Bryan J",
      "referenceId" : "RGD:A25417"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068676"
    } ]
  }, {
    "primaryId" : "PMID:10204803",
    "title" : "The regulation of ribonucleoside diphosphate reductase by the tumor promoter orotic acid in normal rat liver in vivo.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Manjeshwar S, etal., Mol Carcinog. 1999 Mar;24(3):188-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-06-24T08:33:57.000-05:00",
    "volume" : "24",
    "pages" : "188-96",
    "abstract" : "Our earlier studies have shown that in normal hepatocytes, orotic acid (OA) inhibits DNA synthesis induced by several growth factors in vitro and after two-thirds partial hepatectomy (PH) in vivo. As in the normal liver OA induces an imbalance in nucleotide pools (specifically, an increase in uridine nucleotides, including deoxyuridine nucleotides, and a decrease in adenosine nucleotides, including ATP) and creation of this imbalance is crucial for the mitoinhibitory effects of OA, we hypothesized that ribonucleoside diphosphate reductase (RNR), a key enzyme in DNA synthesis that is regulated by nucleotide/deoxynucleotide levels, might be one of the targets for the inhibition of DNA synthesis by OA. To test this hypothesis, we subjected male Fischer 344 rats (130-150 g) to two-thirds PH in the absence or in the presence of OA (a 300-mg tablet of OA methyl ester implanted intraperitoneally at the time of two-thirds PH). The rats were killed at different times later, and their livers were processed for analysis of levels of RNR enzyme activity, protein, and mRNA transcripts. The results obtained indicated that treatment with OA resulted in a near-100% inhibition of RNR induced by two-thirds PH in rat liver, as monitored by enzyme activity and protein level. Furthermore, this inhibition was paralleled by a decrease in the mRNA transcripts for both the M1 and M2 subunits of RNR. Nuclear run-off assays indicated that this decrease in the levels of mRNA transcripts could not be attributed to an effect on transcription. However, administration of OA 20 h after two-thirds PH, when RNR mRNA transcripts were maximally induced, resulted in increased degradation of the RNR M1 and M2 subunits. Taken together, these results indicate that OA treatment decreases RNR levels induced by two-thirds PH, at the levels of enzyme activity, protein, and mRNA transcripts, and the decreased levels of mRNA transcripts appeared to be due to increased degradation of the transcripts.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Manjeshwar",
      "authorRank" : 1,
      "name" : "Manjeshwar S",
      "referenceId" : "RGD:A140949"
    }, {
      "firstName" : "PM",
      "lastName" : "Rao",
      "authorRank" : 2,
      "name" : "Rao PM",
      "referenceId" : "RGD:A70720"
    }, {
      "firstName" : "S",
      "lastName" : "Rajalakshmi",
      "authorRank" : 3,
      "name" : "Rajalakshmi S",
      "referenceId" : "RGD:A70721"
    }, {
      "firstName" : "DS",
      "lastName" : "Sarma",
      "authorRank" : 4,
      "name" : "Sarma DS",
      "referenceId" : "RGD:A70722"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5133695"
    } ]
  }, {
    "primaryId" : "PMID:10204830",
    "title" : "The influence of dietary restriction on vitamin B-6 vitamer distribution and on vitamin B-6 metabolizing enzymes in rats.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Wei IL J Am Coll Nutr. 1999 Apr;18(2):144-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-01-27T14:42:28.000-06:00",
    "volume" : "18",
    "pages" : "144-51",
    "abstract" : "OBJECTIVE: The purpose of this study was to assess the effect of dietary restriction on tissue distribution of vitamin B-6 vitamers and activities of vitamin B-6 metabolizing enzymes in rats. METHODS: Male rats were subjected to a 40% dietary restriction for 10, 20 or 40 weeks. The tissue vitamin B-6 vitamer concentrations and activities of the vitamin B-6 metabolizing enzymes of the animals were determined. RESULTS: The plasma pyridoxal 5'-phosphate (PLP) concentrations of the diet-restricted (DR) rats were comparable to those of the control group at week ten but were significantly lower at weeks 20 and 40. These significantly lower levels of plasma PLP in DR rats might in part be related to lower hepatic pyridoxal kinase and pyridoxamine (pyridoxine) 5'-phosphate oxidase activities. The urinary 4-pyridoxic acid excretion of the DR groups responded to the reduced food intake and were lower at weeks 10 and 20. Tissue levels of PLP were not affected by dietary restriction. In contrast, greater levels of pyridoxamine 5'-phosphate were found in liver, kidney and heart of the DR animals. CONCLUSION: The duration of dietary restriction influenced the distribution of vitamin B-6 vitamers. When plasma PLP is used to evaluate vitamin B-6 status, the length of dietary restriction should be considered.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "IL",
      "lastName" : "Wei",
      "authorRank" : 1,
      "name" : "Wei IL",
      "referenceId" : "RGD:A103079"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303025"
    } ]
  }, {
    "primaryId" : "PMID:10204844",
    "title" : "A clinical study of type 1 neurofibromatosis in north west England.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "McGaughran JM, etal., J Med Genet. 1999 Mar;36(3):197-203.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:46:24.000-05:00",
    "volume" : "36",
    "pages" : "197-203",
    "abstract" : "A clinical study of patients on the North West Regional Genetic Register with neurofibromatosis type 1 (NF1) identified 523 affected cases from 304 families. In those for whom relevant information was available, 86.7% (383 of 442) had more than six café au lait patches, 83.8% (310 of 370) had axillary freckling, 42.3% (151 of 357) had inguinal freckling, and 63% (157 of 249) had Lisch nodules. Cutaneous neurofibromas were present in 59.4% (217 of 365) and 45.5% (150 of 330) were noted to have subcutaneous tumours. Plexiform neurofibromas were present in 15.3% (80 of 523). A positive family history of NF1 was found in 71.2% (327 of 459) and 28.8% (132 of 459) of affected patients were considered to be the result of a new mutation. Learning difficulties of varying severity occurred in 62% (186 of 300). CNS tumours associated with NF1 were reported in 9.4% (49) of patients, optic gliomas occurring in 25 of these, 4.8% of patients. Some degree of scoliosis was reported for 11.7% (61), 1.9% (10) had pseudoarthrosis, 4.3% (23) had epilepsy, and 2.1% (11) had spinal neurofibromas. Actuarial analyses were carried out for both optic glioma and malignant nerve sheath tumours and the data are presented.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J M",
      "lastName" : "McGaughran",
      "authorRank" : 1,
      "name" : "McGaughran JM",
      "referenceId" : "RGD:A584165"
    }, {
      "firstName" : "D I",
      "lastName" : "Harris",
      "authorRank" : 2,
      "name" : "Harris DI",
      "referenceId" : "RGD:A584166"
    }, {
      "firstName" : "D",
      "lastName" : "Donnai",
      "authorRank" : 3,
      "name" : "Donnai D",
      "referenceId" : "RGD:A54861"
    }, {
      "firstName" : "D",
      "lastName" : "Teare",
      "authorRank" : 4,
      "name" : "Teare D",
      "referenceId" : "RGD:A584167"
    }, {
      "firstName" : "R",
      "lastName" : "MacLeod",
      "authorRank" : 5,
      "name" : "MacLeod R",
      "referenceId" : "RGD:A584168"
    }, {
      "firstName" : "R",
      "lastName" : "Westerbeek",
      "authorRank" : 6,
      "name" : "Westerbeek R",
      "referenceId" : "RGD:A584169"
    }, {
      "firstName" : "H",
      "lastName" : "Kingston",
      "authorRank" : 7,
      "name" : "Kingston H",
      "referenceId" : "RGD:A584170"
    }, {
      "firstName" : "M",
      "lastName" : "Super",
      "authorRank" : 8,
      "name" : "Super M",
      "referenceId" : "RGD:A473952"
    }, {
      "firstName" : "R",
      "lastName" : "Harris",
      "authorRank" : 9,
      "name" : "Harris R",
      "referenceId" : "RGD:A99174"
    }, {
      "firstName" : "D G",
      "lastName" : "Evans",
      "authorRank" : 10,
      "name" : "Evans DG",
      "referenceId" : "RGD:A424772"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598116934"
    } ]
  }, {
    "primaryId" : "PMID:10205226",
    "title" : "Lack of evidence for association between the endothelial nitric oxide synthase gene and hypertension.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Kato N, etal., Hypertension. 1999 Apr;33(4):933-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-07-19T13:10:55.000-05:00",
    "volume" : "33",
    "pages" : "933-6",
    "abstract" : "Significant association between a Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene and essential hypertension was recently reported in Japanese populations, with the 298Asp variant showing a higher prevalence in hypertensive patients (10.3% to 12.0%) than in normotensive subjects (5.0% to 5.8%). In contrast, another study demonstrated that the 298Glu variant was significantly associated with hypertension in a Caucasian population. We therefore undertook an extensive association study in Japanese to resolve these contradictory claims. A total of 1165 individuals were selected from clinic outpatients and hospital staff in a single institution. The relevance of the Glu298Asp polymorphism to hypertension in this population was tested in 2 ways. First, a case-control study was conducted in 549 hypertensive and 513 normotensive subjects within the study population, with the chi2 statistic used to test the significance of an association between eNOS genotype and the presence of hypertension. Second, an ANOVA was used to test the significance of an association between eNOS genotype and the level of blood pressure within the entire population except for 167 hypertensive subjects who had been under treatment for hypertension. No significant association was observed in either of the statistics tested. Allele frequencies of 298Asp were concordant across the panels: 8.4% in hypertensive subjects, 8. 2% in normotensive subjects, and 7.9% and 9.5% in 2 additional sample populations used as reference panels. Taken together, our results do not support the previous observation that the molecular variant of the eNOS gene may confer principal susceptibility for essential hypertension but rather suggest the existence of sampling variation.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Kato",
      "authorRank" : 1,
      "name" : "Kato N",
      "referenceId" : "RGD:A159893"
    }, {
      "firstName" : "T",
      "lastName" : "Sugiyama",
      "authorRank" : 2,
      "name" : "Sugiyama T",
      "referenceId" : "RGD:A16566"
    }, {
      "firstName" : "H",
      "lastName" : "Morita",
      "authorRank" : 3,
      "name" : "Morita H",
      "referenceId" : "RGD:A10761"
    }, {
      "firstName" : "T",
      "lastName" : "Nabika",
      "authorRank" : 4,
      "name" : "Nabika T",
      "referenceId" : "RGD:A131371"
    }, {
      "firstName" : "H",
      "lastName" : "Kurihara",
      "authorRank" : 5,
      "name" : "Kurihara H",
      "referenceId" : "RGD:A15728"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamori",
      "authorRank" : 6,
      "name" : "Yamori Y",
      "referenceId" : "RGD:A7348"
    }, {
      "firstName" : "Y",
      "lastName" : "Yazaki",
      "authorRank" : 7,
      "name" : "Yazaki Y",
      "referenceId" : "RGD:A161904"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580279"
    } ]
  }, {
    "primaryId" : "PMID:10205229",
    "title" : "Genetic determination of cardiac mass in normotensive rats: results from an F344xWKY cross.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Sebkhi A, etal., Hypertension 1999 Apr;33(4):949-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-12-20T15:50:25.000-06:00",
    "volume" : "33",
    "pages" : "949-53",
    "abstract" : "Genetic determinants affect adult cardiac mass and the predisposition to develop cardiac hypertrophy. The aim of this study was to identify quantitative trait loci (QTL) that control heart and left ventricular (LV) weight by use of normotensive inbred rat strains that differ in their adult cardiac mass phenotype. We studied 126 male F2 rats derived from a cross of normotensive Wistar-Kyoto and Fischer 344 rats. At 12 weeks of age, total heart weight and LV weight were measured. Genomic DNA from these animals was screened by use of polymorphic microsatellite markers across the whole genome (excluding the sex chromosomes). In this cross, the genetic contribution to total heart weight variation was 56%, and the genetic contribution for LV weight was 55%. Using the Mapmaker/QTL computer package, we identified a significant QTL on chromosome 3 with a log10 likelihood (LOD) score of 4.8, which accounted for 16.5% of the total variance of LV weight. This QTL was centered close to the marker D3Rat29. The QTL was also found to be significantly linked with total heart weight (LOD=4.4). These data provide the first demonstration of a QTL on chromosome 3 that plays a role in determining the difference in LV mass between normotensive Fischer 344 and Wistar- Kyoto inbred rat strains. The prostaglandin synthase 1 gene is located within the QTL.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Sebkhi",
      "authorRank" : 1,
      "name" : "Sebkhi A",
      "referenceId" : "RGD:A6911"
    }, {
      "firstName" : "L",
      "lastName" : "Zhao",
      "authorRank" : 2,
      "name" : "Zhao L",
      "referenceId" : "RGD:A6192"
    }, {
      "firstName" : "L",
      "lastName" : "Lu",
      "authorRank" : 3,
      "name" : "Lu L",
      "referenceId" : "RGD:A6927"
    }, {
      "firstName" : "CS",
      "lastName" : "Haley",
      "authorRank" : 4,
      "name" : "Haley CS",
      "referenceId" : "RGD:A6914"
    }, {
      "firstName" : "DJ",
      "lastName" : "Nunez",
      "authorRank" : 5,
      "name" : "Nunez DJ",
      "referenceId" : "RGD:A6912"
    }, {
      "firstName" : "MR",
      "lastName" : "Wilkins",
      "authorRank" : 6,
      "name" : "Wilkins MR",
      "referenceId" : "RGD:A6916"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69706"
    } ]
  }, {
    "primaryId" : "PMID:10205261",
    "title" : "Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Jones AC, etal., Am J Hum Genet. 1999 May;64(5):1305-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:58:05.000-05:00",
    "volume" : "64",
    "pages" : "1305-15",
    "abstract" : "Tuberous sclerosis (TSC [MIM 191090 and MIM 191100]) is an autosomal dominant disorder characterized by hamartomas in many organs. Two thirds of cases are sporadic and are thought to represent new mutations. TSC is caused by mutations affecting either of the presumed tumor-suppressor genes, TSC1 and TSC2. Both appear to function as tumor suppressors, because somatic loss or intragenic mutation of the corresponding wild-type allele is seen in the associated hamartomas. Here we report the first comprehensive mutation analysis of TSC1 and  TSC2 in a cohort of 150 unrelated TSC patients and their families, using heteroduplex and SSCP analysis of all coding exons and using pulsed-field gel electrophoresis and conventional Southern blot analysis and long PCR to screen for large rearrangements. Mutations were characterized in 120 (80%) of the 150 cases, affecting TSC1 in 22 cases and TSC2 in 98 cases. TSC1 mutations were significantly underrepresented in sporadic cases (P=. 000185). Twenty-two patients had TSC2 missense mutations that were found predominantly in the GAP-related domain (eight cases) and in a small region encoded in exons 16 and 17, between nucleotides 1849 and 1859 (eight cases), consistent with the presence of residues performing key functions at these sites. In contrast, all TSC1 mutations were predicted to be truncating, consistent with a structural or adapter role for the encoded protein. Intellectual disability was significantly more frequent in TSC2 sporadic cases than in TSC1 sporadic cases (P=.0145). These data provide the first representative picture of the distribution and spectrum of mutations across the TSC1 and TSC2 loci in clinically ascertained TSC and support a difference in severity of TSC1- and TSC2-associated disease.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AC",
      "lastName" : "Jones",
      "authorRank" : 1,
      "name" : "Jones AC",
      "referenceId" : "RGD:A82006"
    }, {
      "firstName" : "MM",
      "lastName" : "Shyamsundar",
      "authorRank" : 2,
      "name" : "Shyamsundar",
      "referenceId" : "RGD:A253813"
    }, {
      "firstName" : "MW",
      "lastName" : "Thomas",
      "authorRank" : 3,
      "name" : "Thomas",
      "referenceId" : "RGD:A253814"
    }, {
      "firstName" : "J",
      "lastName" : "Maynard",
      "authorRank" : 4,
      "name" : "Maynard J",
      "referenceId" : "RGD:A76467"
    }, {
      "firstName" : "S",
      "lastName" : "Idziaszczyk",
      "authorRank" : 5,
      "name" : "Idziaszczyk",
      "referenceId" : "RGD:A253815"
    }, {
      "firstName" : "S",
      "lastName" : "Tomkins",
      "authorRank" : 6,
      "name" : "Tomkins",
      "referenceId" : "RGD:A252045"
    }, {
      "firstName" : "JR",
      "lastName" : "Sampson",
      "authorRank" : 7,
      "name" : "Sampson JR",
      "referenceId" : "RGD:A76472"
    }, {
      "firstName" : "JP",
      "lastName" : "Cheadle",
      "authorRank" : 8,
      "name" : "Cheadle JP",
      "referenceId" : "RGD:A76473"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063105"
    } ]
  }, {
    "primaryId" : "PMID:10205269",
    "title" : "A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Varret M, etal., Am J Hum Genet. 1999 May;64(5):1378-87. doi: 10.1086/302370.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:56:48.000-05:00",
    "volume" : "64",
    "pages" : "1378-87",
    "abstract" : "Autosomal dominant hypercholesterolemia (ADH), one of the most frequent hereditary disorders, is characterized by an isolated elevation of LDL particles that leads to premature mortality from cardiovascular complications. It is generally assumed that mutations in the LDLR and APOB genes account for ADH. We identified one large French pedigree (HC2) and 12 additional white families with ADH in which we excluded linkage to the LDLR and APOB, implicating a new locus we named \"FH3.\" A LOD score of 3.13 at a recombination fraction of 0 was obtained at markers D1S2892 and D1S2722. We localized the FH3 locus to a 9-cM interval at 1p34.1-p32. We tested four regional markers in another set of 12 ADH families. Positive LOD scores were obtained in three pedigrees, whereas linkage was excluded in the others. Heterogeneity tests indicated linkage to FH3 in approximately 27% of these non-LDLR/non-APOB ADH families and implied a fourth locus. Radiation hybrid mapping located four candidate genes at 1p34.1-p32, outside the critical region, showing no identity with FH3. Our results show that ADH is genetically more heterogeneous than conventionally accepted.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Varret",
      "authorRank" : 1,
      "name" : "Varret M",
      "referenceId" : "RGD:A60287"
    }, {
      "firstName" : "J P",
      "lastName" : "Rabès",
      "authorRank" : 2,
      "name" : "Rabès JP",
      "referenceId" : "RGD:A586314"
    }, {
      "firstName" : "B",
      "lastName" : "Saint-Jore",
      "authorRank" : 3,
      "name" : "Saint-Jore B",
      "referenceId" : "RGD:A586315"
    }, {
      "firstName" : "A",
      "lastName" : "Cenarro",
      "authorRank" : 4,
      "name" : "Cenarro A",
      "referenceId" : "RGD:A62829"
    }, {
      "firstName" : "J C",
      "lastName" : "Marinoni",
      "authorRank" : 5,
      "name" : "Marinoni JC",
      "referenceId" : "RGD:A586316"
    }, {
      "firstName" : "F",
      "lastName" : "Civeira",
      "authorRank" : 6,
      "name" : "Civeira F",
      "referenceId" : "RGD:A62837"
    }, {
      "firstName" : "M",
      "lastName" : "Devillers",
      "authorRank" : 7,
      "name" : "Devillers M",
      "referenceId" : "RGD:A65051"
    }, {
      "firstName" : "M",
      "lastName" : "Krempf",
      "authorRank" : 8,
      "name" : "Krempf M",
      "referenceId" : "RGD:A65061"
    }, {
      "firstName" : "M",
      "lastName" : "Coulon",
      "authorRank" : 9,
      "name" : "Coulon M",
      "referenceId" : "RGD:A586317"
    }, {
      "firstName" : "R",
      "lastName" : "Thiart",
      "authorRank" : 10,
      "name" : "Thiart R",
      "referenceId" : "RGD:A586318"
    }, {
      "firstName" : "M J",
      "lastName" : "Kotze",
      "authorRank" : 11,
      "name" : "Kotze MJ",
      "referenceId" : "RGD:A586319"
    }, {
      "firstName" : "H",
      "lastName" : "Schmidt",
      "authorRank" : 12,
      "name" : "Schmidt H",
      "referenceId" : "RGD:A21340"
    }, {
      "firstName" : "J C",
      "lastName" : "Buzzi",
      "authorRank" : 13,
      "name" : "Buzzi JC",
      "referenceId" : "RGD:A586320"
    }, {
      "firstName" : "G M",
      "lastName" : "Kostner",
      "authorRank" : 14,
      "name" : "Kostner GM",
      "referenceId" : "RGD:A586321"
    }, {
      "firstName" : "S",
      "lastName" : "Bertolini",
      "authorRank" : 15,
      "name" : "Bertolini S",
      "referenceId" : "RGD:A58872"
    }, {
      "firstName" : "M",
      "lastName" : "Pocovi",
      "authorRank" : 16,
      "name" : "Pocovi M",
      "referenceId" : "RGD:A62836"
    }, {
      "firstName" : "A",
      "lastName" : "Rosa",
      "authorRank" : 17,
      "name" : "Rosa A",
      "referenceId" : "RGD:A586322"
    }, {
      "firstName" : "M",
      "lastName" : "Farnier",
      "authorRank" : 18,
      "name" : "Farnier M",
      "referenceId" : "RGD:A65055"
    }, {
      "firstName" : "M",
      "lastName" : "Martinez",
      "authorRank" : 19,
      "name" : "Martinez M",
      "referenceId" : "RGD:A54189"
    }, {
      "firstName" : "C",
      "lastName" : "Junien",
      "authorRank" : 20,
      "name" : "Junien C",
      "referenceId" : "RGD:A60289"
    }, {
      "firstName" : "C",
      "lastName" : "Boileau",
      "authorRank" : 21,
      "name" : "Boileau C",
      "referenceId" : "RGD:A60292"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598117231"
    } ]
  }, {
    "primaryId" : "PMID:10205279",
    "title" : "Genomewide scan for familial combined hyperlipidemia genes in finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Pajukanta P, etal., Am J Hum Genet. 1999 May;64(5):1453-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-10-23T12:12:23.000-05:00",
    "volume" : "64",
    "pages" : "1453-63",
    "abstract" : "Familial combined hyperlipidemia (FCHL) is a common dyslipidemia predisposing to premature coronary heart disease (CHD). The disease is characterized by increased levels of serum total cholesterol (TC), triglycerides (TGs), or both. We recently localized the first locus for FCHL, on chromosome 1q21-q23. In the present study, a genomewide screen for additional FCHL loci was performed. In stage 1, we genotyped 368 polymorphic markers in 35 carefully characterized Finnish FCHL families. We identified six chromosomal regions with markers showing LOD score (Z) values >1.0, by using a dominant mode of inheritance for the FCHL trait. In addition, two more regions emerged showing Z>2.0 with a TG trait. In stage 2, we genotyped 26 more markers and seven additional FCHL families for these interesting regions. Two chromosomal regions revealed Z>2.0 in the linkage analysis: 10p11.2, Z=3.20 (theta=.00), with the TG trait; and 21q21, Z=2.24 (theta=.10), with the apoB trait. Furthermore, two more chromosomal regions produced Z>2.0 in the affected-sib-pair analysis: 10q11.2-10qter produced Z=2.59 with the TC trait and Z=2.29 with FCHL, and 2q31 produced Z=2.25 with the TG trait. Our results suggest additional putative loci influencing FCHL in Finnish families, some potentially affecting TG levels and some potentially affecting TC or apoB levels.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Pajukanta",
      "authorRank" : 1,
      "name" : "Pajukanta P",
      "referenceId" : "RGD:A40217"
    }, {
      "firstName" : "JD",
      "lastName" : "Terwilliger",
      "authorRank" : 2,
      "name" : "Terwilliger JD",
      "referenceId" : "RGD:A39899"
    }, {
      "firstName" : "M",
      "lastName" : "Perola",
      "authorRank" : 3,
      "name" : "Perola M",
      "referenceId" : "RGD:A166401"
    }, {
      "firstName" : "T",
      "lastName" : "Hiekkalinna",
      "authorRank" : 4,
      "name" : "Hiekkalinna T",
      "referenceId" : "RGD:A40218"
    }, {
      "firstName" : "I",
      "lastName" : "Nuotio",
      "authorRank" : 5,
      "name" : "Nuotio I",
      "referenceId" : "RGD:A89143"
    }, {
      "firstName" : "P",
      "lastName" : "Ellonen",
      "authorRank" : 6,
      "name" : "Ellonen P",
      "referenceId" : "RGD:A37897"
    }, {
      "firstName" : "M",
      "lastName" : "Parkkonen",
      "authorRank" : 7,
      "name" : "Parkkonen M",
      "referenceId" : "RGD:A89149"
    }, {
      "firstName" : "J",
      "lastName" : "Hartiala",
      "authorRank" : 8,
      "name" : "Hartiala J",
      "referenceId" : "RGD:A89150"
    }, {
      "firstName" : "K",
      "lastName" : "Ylitalo",
      "authorRank" : 9,
      "name" : "Ylitalo K",
      "referenceId" : "RGD:A64721"
    }, {
      "firstName" : "J",
      "lastName" : "Pihlajamaki",
      "authorRank" : 10,
      "name" : "Pihlajamaki J",
      "referenceId" : "RGD:A59169"
    }, {
      "firstName" : "K",
      "lastName" : "Porkka",
      "authorRank" : 11,
      "name" : "Porkka K",
      "referenceId" : "RGD:A89151"
    }, {
      "firstName" : "M",
      "lastName" : "Laakso",
      "authorRank" : 12,
      "name" : "Laakso M",
      "referenceId" : "RGD:A164269"
    }, {
      "firstName" : "J",
      "lastName" : "Viikari",
      "authorRank" : 13,
      "name" : "Viikari J",
      "referenceId" : "RGD:A89152"
    }, {
      "firstName" : "C",
      "lastName" : "Ehnholm",
      "authorRank" : 14,
      "name" : "Ehnholm C",
      "referenceId" : "RGD:A89147"
    }, {
      "firstName" : "MR",
      "lastName" : "Taskinen",
      "authorRank" : 15,
      "name" : "Taskinen MR",
      "referenceId" : "RGD:A65112"
    }, {
      "firstName" : "L",
      "lastName" : "Peltonen",
      "authorRank" : 16,
      "name" : "Peltonen L",
      "referenceId" : "RGD:A37206"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642889"
    } ]
  }, {
    "primaryId" : "PMID:10205677",
    "title" : "Cloning and functional expression of rAOP9L a new member of aquaporin family from rat liver.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Ko SB, etal., Biochem Mol Biol Int. 1999 Feb;47(2):309-18. doi: 10.1080/15216549900201333.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-10-26T06:05:39.000-05:00",
    "volume" : "47",
    "pages" : "309-18",
    "abstract" : "A new aquaporin was isolated from rat liver based on homology to known aquaporins. A 1408 bp cDNA was sequenced (designated rAQP9L) with a 885 bp open reading frame encoding a 295 amino acid hydrophobic protein. rAQP9L has the greatest amino-acid sequence identity with human AQP9 (75%) and a less homology with AQP3 (49%) and AQP7 (47%). Northern blot analysis indicated a 1.4-kb transcript expressed strongly in liver > testis > brain = lung. Expression of rAQP9L cRNA in Xenopus oocytes increased osmotic water permeability by 6-folds which was inhibited by 0.3 mM mercury chloride by 42%. rAQP9L also facilitated glycerol and urea transport by 2- and 5-folds, respectively. The large discrepancy of tissue distribution between hAQP9 and rAQP9L suggest that rAQP9L is a new aquaporin, which is involved in transport of urea as well as water in liver.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S B",
      "lastName" : "Ko",
      "authorRank" : 1,
      "name" : "Ko SB",
      "referenceId" : "RGD:A558625"
    }, {
      "firstName" : "S",
      "lastName" : "Uchida",
      "authorRank" : 2,
      "name" : "Uchida S",
      "referenceId" : "RGD:A154564"
    }, {
      "firstName" : "S",
      "lastName" : "Naruse",
      "authorRank" : 3,
      "name" : "Naruse S",
      "referenceId" : "RGD:A9352"
    }, {
      "firstName" : "M",
      "lastName" : "Kuwahara",
      "authorRank" : 4,
      "name" : "Kuwahara M",
      "referenceId" : "RGD:A5499"
    }, {
      "firstName" : "K",
      "lastName" : "Ishibashi",
      "authorRank" : 5,
      "name" : "Ishibashi K",
      "referenceId" : "RGD:A160807"
    }, {
      "firstName" : "F",
      "lastName" : "Marumo",
      "authorRank" : 6,
      "name" : "Marumo F",
      "referenceId" : "RGD:A4690"
    }, {
      "firstName" : "T",
      "lastName" : "Hayakawa",
      "authorRank" : 7,
      "name" : "Hayakawa T",
      "referenceId" : "RGD:A4681"
    }, {
      "firstName" : "S",
      "lastName" : "Sasaki",
      "authorRank" : 8,
      "name" : "Sasaki S",
      "referenceId" : "RGD:A158371"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:408345202"
    } ]
  }, {
    "primaryId" : "PMID:10206232",
    "title" : "Lipoprotein lipase mutations and Alzheimer's disease.",
    "datePublished" : "1999-04-16T00:00:00.000-05:00",
    "citation" : "Baum L, etal., Am J Med Genet. 1999 Apr 16;88(2):136-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-10-10T18:07:56.000-05:00",
    "volume" : "88",
    "pages" : "136-9",
    "abstract" : "Lipoprotein lipase (LPL) helps transfer lipids from lipoprotein particles to cells. In the brain, LPL is present in Alzheimer's disease (AD) amyloid plaques. LPL binds apolipoprotein E (ApoE) lipoprotein particles and low-density lipoprotein receptor-related protein (LRP), an ApoE receptor. Since polymorphisms in both ApoE and LRP influence AD risk, we sought to determine whether LPL mutations also affect AD risk. In a case-control study, the frequencies of two of the most common known LPL mutations were measured in European-Americans either clinically diagnosed or pathologically confirmed as AD or normal control (N) subjects. In clinically diagnosed subjects, the Ser447Ter mutation comprised 9.8% (62/630) of alleles in N and 3.8% (9/238) in AD, a significant difference (P = 0.0057), while the Asn291Ser mutation comprised 1.1% (5/460) of alleles in N and 5.1% (8/158) in AD, also a significant difference (P = 0.0073), though in pathologically confirmed subjects the allele frequencies for AD did not significantly differ from N for either mutation. In clinically diagnosed subjects, LPL mutations were associated with altered AD risk, suggesting a potential role for LPL in the causation of AD. Further studies in different populations should help clarify the questions raised by these results.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Baum",
      "authorRank" : 1,
      "name" : "Baum L",
      "referenceId" : "RGD:A106182"
    }, {
      "firstName" : "L",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen L",
      "referenceId" : "RGD:A9812"
    }, {
      "firstName" : "E",
      "lastName" : "Masliah",
      "authorRank" : 3,
      "name" : "Masliah E",
      "referenceId" : "RGD:A29712"
    }, {
      "firstName" : "Y S",
      "lastName" : "Chan",
      "authorRank" : 4,
      "name" : "Chan YS",
      "referenceId" : "RGD:A465314"
    }, {
      "firstName" : "H K",
      "lastName" : "Ng",
      "authorRank" : 5,
      "name" : "Ng HK",
      "referenceId" : "RGD:A460072"
    }, {
      "firstName" : "C P",
      "lastName" : "Pang",
      "authorRank" : 6,
      "name" : "Pang CP",
      "referenceId" : "RGD:A465315"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13799353"
    } ]
  }, {
    "primaryId" : "PMID:10206308",
    "title" : "E-cadherin and alpha-, beta- and gamma-catenin expression in prostate cancers: correlation with tumour invasion.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Morita N, etal., Br J Cancer. 1999 Apr;79(11-12):1879-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-02T11:44:45.000-05:00",
    "volume" : "79",
    "pages" : "1879-83",
    "abstract" : "The E-cadherin-catenin complex plays an important role in establishing and maintaining intercellular connections and morphogenesis and reduced expression of its constituent molecules is associated with invasion and metastasis. In the present study, we examined E-cadherin and alpha-, beta- and gamma-catenin levels in tumour tissues obtained by radical prostatectomy in order to investigate the relationship with histopathological tumour invasion. Immunohistochemical findings for 45 prostate cancer specimens demonstrated aberrant expression of each molecule to be associated with dedifferentiation and, in addition, alteration of staining patterns for the three types of catenin was significantly correlated with capsular but not lymphatic or vascular invasion. The data thus suggest that three types of catenin may be useful predictive markers for biological aggressiveness of prostate cancer.",
    "issueName" : "11-12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Morita",
      "authorRank" : 1,
      "name" : "Morita N",
      "referenceId" : "RGD:A29005"
    }, {
      "firstName" : "H",
      "lastName" : "Uemura",
      "authorRank" : 2,
      "name" : "Uemura H",
      "referenceId" : "RGD:A53261"
    }, {
      "firstName" : "K",
      "lastName" : "Tsumatani",
      "authorRank" : 3,
      "name" : "Tsumatani K",
      "referenceId" : "RGD:A93733"
    }, {
      "firstName" : "M",
      "lastName" : "Cho",
      "authorRank" : 4,
      "name" : "Cho M",
      "referenceId" : "RGD:A24807"
    }, {
      "firstName" : "Y",
      "lastName" : "Hirao",
      "authorRank" : 5,
      "name" : "Hirao Y",
      "referenceId" : "RGD:A93734"
    }, {
      "firstName" : "E",
      "lastName" : "Okajima",
      "authorRank" : 6,
      "name" : "Okajima E",
      "referenceId" : "RGD:A92715"
    }, {
      "firstName" : "N",
      "lastName" : "Konishi",
      "authorRank" : 7,
      "name" : "Konishi N",
      "referenceId" : "RGD:A38154"
    }, {
      "firstName" : "Y",
      "lastName" : "Hiasa",
      "authorRank" : 8,
      "name" : "Hiasa Y",
      "referenceId" : "RGD:A93735"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2291876"
    } ]
  }, {
    "primaryId" : "PMID:10206335",
    "title" : "The immunohistochemical localization of the interferon-gamma and granulocyte colony-stimulating factor receptors during early amelogenesis in rat molars.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Otsuji W, etal., Arch Oral Biol. 1999 Feb;44(2):173-81.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-06-30T15:04:02.000-05:00",
    "volume" : "44",
    "pages" : "173-81",
    "abstract" : "Previous studies, in which the known janus kinase and signal transducer and activator of transcription (STAT) isoforms were immunohistochemically mapped in developing rat molars, implicated a sizeable list of cytokine superfamily receptor (CSR)/signal-transduction pathway (STP) linkages in the cells of the enamel organ involved in the events leading directly to early amelogenesis. Various combinations of upregulated janus kinases and STATs are known to be linked to single or small groups of CSRs. On the basis of the previous observations it was hypothesized that the interferon-gamma receptor (IFNgamma r) and the granulocyte colony-stimulating factor receptor (G-CSF receptor) would be localized in specific sites in the cells of the enamel organ during early amelogenesis. To verify this, whole-head, freeze-dried sections were here obtained at the level of the mandibular first and second molar from newborn and 5-day-old rats. These sections were not demineralized or fixed, reducing the possibility of false-negative results. Antibodies to the IFNgamma r and the G-CSF receptor were localized using a modification of the avidin-biotin complex method. In the newborn rats, IFNgamma r was localized in the preameloblasts in the cervical loop, the proximal and distal ends of presecretory ameloblasts, the outer enamel epithelium, the dental lamina, and in bone. In 5-day-old rats, it was confined to the proximal ends of the presecretory and secretory ameloblasts. The G-CSF receptor was observed in the molars of newborn rats in the preameloblasts, the proximal and distal ends of the presecretory ameloblasts, outer enamel epithelium, and in bone. In 5-day-old rats, G-CSF receptor was localized in the preameloblasts, the proximal ends of presecretory and secretory ameloblasts, the stellate reticulum, the outer enamel epithelium, and in bone. These findings indicate that the IFNgamma r and the G-CSF receptor, and their downstream STP linkages, are upregulated in the cells of the enamel organ and may be involved in the events leading directly to early enamel formation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Otsuji",
      "authorRank" : 1,
      "name" : "Otsuji W",
      "referenceId" : "RGD:A141124"
    }, {
      "firstName" : "S",
      "lastName" : "Tanase",
      "authorRank" : 2,
      "name" : "Tanase S",
      "referenceId" : "RGD:A19203"
    }, {
      "firstName" : "S",
      "lastName" : "Yoshida",
      "authorRank" : 3,
      "name" : "Yoshida S",
      "referenceId" : "RGD:A4855"
    }, {
      "firstName" : "JW",
      "lastName" : "Bawden",
      "authorRank" : 4,
      "name" : "Bawden JW",
      "referenceId" : "RGD:A141125"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5134351"
    } ]
  }, {
    "primaryId" : "PMID:10206343",
    "title" : "Effect of ageing on the expression of protein kinase C and its activation by 1,25(OH)2-vitamin D3 in rat skeletal muscle.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Facchinetti MM and de Boland AR, Cell Signal. 1999 Jan;11(1):39-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-06-15T14:18:10.000-05:00",
    "volume" : "11",
    "pages" : "39-44",
    "abstract" : "To characterize age-induced effects on muscle protein kinase C (PKC) and its regulation by the steroid hormone 1,25(OH)2-vitamin D3 [1,25(OH)2D3], changes in PKC activity and the expression and translocation of the specific PKC conventional isoforms alpha and beta, novel isoforms delta, epsilon, and theta and atypical isoform zeta were studied in homogenates and subcellular fractions from skeletal muscle of young (3 months) and aged (24 months) rats treated in vitro with 1,25(OH)2D3. The hormone (10(-9) M) increased total and membrane PKC activity, within 1 min, and these effects were completely blunted in muscle from aged rats. The presence of PKC isoenzymes was shown by Western blot analysis with the use of specific antibodies. The expression of PKC alpha, beta and delta was greatly diminished in old rats, whereas age-related changes were less pronounced in the isoforms epsilon, theta and zeta. After a short exposure (1 min) of muscle to 1,25(OH)2D3, increased amounts of PKC alpha and beta in muscle membranes and reverse translocation (from membrane to cytosol) of PKC epsilon were observed only in young animals. The data indicate that, in rat muscle, ageing impairs calcium-dependent PKC (alpha and beta) and calcium-independent PKC (delta, epsilon, theta and zeta) signal transduction pathways under selective regulation by 1,25(OH)2D3.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Facchinetti",
      "authorRank" : 1,
      "name" : "Facchinetti MM",
      "referenceId" : "RGD:A84566"
    }, {
      "firstName" : "AR",
      "lastName" : "De Boland",
      "authorRank" : 2,
      "name" : "De Boland AR",
      "referenceId" : "RGD:A75773"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1625620"
    } ]
  }, {
    "primaryId" : "PMID:10206641",
    "title" : "Exposing the human nude phenotype.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Frank J, etal., Nature. 1999 Apr 8;398(6727):473-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-19T09:30:17.000-06:00",
    "volume" : "398",
    "pages" : "473-4",
    "issueName" : "6727",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Frank",
      "authorRank" : 1,
      "name" : "Frank J",
      "referenceId" : "RGD:A75315"
    }, {
      "firstName" : "C",
      "lastName" : "Pignata",
      "authorRank" : 2,
      "name" : "Pignata C",
      "referenceId" : "RGD:A75316"
    }, {
      "firstName" : "AA",
      "lastName" : "Panteleyev",
      "authorRank" : 3,
      "name" : "Panteleyev AA",
      "referenceId" : "RGD:A42636"
    }, {
      "firstName" : "DM",
      "lastName" : "Prowse",
      "authorRank" : 4,
      "name" : "Prowse DM",
      "referenceId" : "RGD:A75317"
    }, {
      "firstName" : "H",
      "lastName" : "Baden",
      "authorRank" : 5,
      "name" : "Baden H",
      "referenceId" : "RGD:A75318"
    }, {
      "firstName" : "L",
      "lastName" : "Weiner",
      "authorRank" : 6,
      "name" : "Weiner L",
      "referenceId" : "RGD:A75319"
    }, {
      "firstName" : "L",
      "lastName" : "Gaetaniello",
      "authorRank" : 7,
      "name" : "Gaetaniello L",
      "referenceId" : "RGD:A75320"
    }, {
      "firstName" : "W",
      "lastName" : "Ahmad",
      "authorRank" : 8,
      "name" : "Ahmad W",
      "referenceId" : "RGD:A74372"
    }, {
      "firstName" : "N",
      "lastName" : "Pozzi",
      "authorRank" : 9,
      "name" : "Pozzi N",
      "referenceId" : "RGD:A75321"
    }, {
      "firstName" : "PB",
      "lastName" : "Cserhalmi-Friedman",
      "authorRank" : 10,
      "name" : "Cserhalmi-Friedman PB",
      "referenceId" : "RGD:A75322"
    }, {
      "firstName" : "VM",
      "lastName" : "Aita",
      "authorRank" : 11,
      "name" : "Aita VM",
      "referenceId" : "RGD:A75323"
    }, {
      "firstName" : "H",
      "lastName" : "Uyttendaele",
      "authorRank" : 12,
      "name" : "Uyttendaele H",
      "referenceId" : "RGD:A49875"
    }, {
      "firstName" : "D",
      "lastName" : "Gordon",
      "authorRank" : 13,
      "name" : "Gordon D",
      "referenceId" : "RGD:A54562"
    }, {
      "firstName" : "J",
      "lastName" : "Ott",
      "authorRank" : 14,
      "name" : "Ott J",
      "referenceId" : "RGD:A50518"
    }, {
      "firstName" : "JL",
      "lastName" : "Brissette",
      "authorRank" : 15,
      "name" : "Brissette JL",
      "referenceId" : "RGD:A75324"
    }, {
      "firstName" : "AM",
      "lastName" : "Christiano",
      "authorRank" : 16,
      "name" : "Christiano AM",
      "referenceId" : "RGD:A42637"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599846"
    } ]
  }, {
    "primaryId" : "PMID:10206677",
    "title" : "Double mutation (A171T and D444H) is a common cause of profound biotinidase deficiency in children ascertained by newborn screening the the United States. Mutations in brief no. 128. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Norrgard KJ, etal., Hum Mutat. 1998;11(5):410.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:34:50.000-05:00",
    "volume" : "11",
    "pages" : "410",
    "abstract" : "Biotinidase deficiency is inherited as an antosomal recessive trait that, unless  treated with pharmacologic doses of biotin, can result in neurologic and cutaneous symptoms. We have identified two new mutations in exon D of the biotinidase gene of children with profound biotinidase deficiency ascertained by  newborn screening. Transition 511G->A near the 5' end of exon D results in a substitution of threonine for alanine 171 (A171T) and transversion 1330G->C occurs close to the 3' end of exon D causing a substitution of histidine for aspartic acid 444 (D444H). The D444H mutation was detected in four individuals from our normal population whose mean serum biotinidase activity is 5.25 nmol/min/ml, which is significantly lower than the mean normal activity (7.1 nmol/min/ml). We calculated that this mutation causes a 52% loss of activity in the aberrant enzyme. Twenty-three individuals with the D444H mutation were found  by allele specific oligonucleotide analysis of DNA from 296 randomly-selected, anonymous dried-blood spots. We estimate the frequency of this allele in the general population to be 0.039. In contrast, no individuals in 376 have the A171T mutation. Fourteen children (eleven probands and three siblings) out of the 31 enzyme-deficient children have both the A171T and D444H mutations. Both mutations are inherited from a single parent as a double mutation allele. The nine families in which this allele was identified are of mostly European ancestry, although the mutation cannot be attributed to a specific nationality or ethnic group. The serum of a child who is homozygous for the double mutation allele has very little CRM and the aberrant enzyme has very low biotinylhydrolase activity and no botinyl-transferase activity. This double mutation allele (A171T and D444H) is a  common cause of profound biotinidase deficience in children ascertained by newborn screening in the United States.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KJ",
      "lastName" : "Norrgard",
      "authorRank" : 1,
      "name" : "Norrgard",
      "referenceId" : "RGD:A252834"
    }, {
      "firstName" : "RJ",
      "lastName" : "Pomponio",
      "authorRank" : 2,
      "name" : "Pomponio",
      "referenceId" : "RGD:A252835"
    }, {
      "firstName" : "KL",
      "lastName" : "Swango",
      "authorRank" : 3,
      "name" : "Swango",
      "referenceId" : "RGD:A252836"
    }, {
      "firstName" : "J",
      "lastName" : "Hymes",
      "authorRank" : 4,
      "name" : "Hymes",
      "referenceId" : "RGD:A252837"
    }, {
      "firstName" : "T",
      "lastName" : "Reynolds",
      "authorRank" : 5,
      "name" : "Reynolds",
      "referenceId" : "RGD:A282080"
    }, {
      "firstName" : "GA",
      "lastName" : "Buck",
      "authorRank" : 6,
      "name" : "Buck",
      "referenceId" : "RGD:A252839"
    }, {
      "firstName" : "B",
      "lastName" : "Wolf",
      "authorRank" : 7,
      "name" : "Wolf B",
      "referenceId" : "RGD:A47421"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072460"
    } ]
  }, {
    "primaryId" : "PMID:10206683",
    "title" : "Identification of recurrent and novel mutations in the LDL receptor gene in Spanish patients with familial hypercholesterolemia. Mutations in brief no. 135.  Online.",
    "datePublished" : "1000-08-01T00:00:00.000-06:00",
    "citation" : "Cenarro A, etal., Hum Mutat. 1998;11(5):413.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:16:31.000-05:00",
    "volume" : "11",
    "pages" : "413",
    "abstract" : "We used the single strand conformation polymorphism (SSCP) method to investigate  13 apparently unrelated Spanish patients with familial hypercholesterolemia (FH)  for mutations in the promoter region and the 18 exons and their flanking intron sequences of the low density lipoprotein (LDL) receptor gene. We found 16 aberrant SSCP patterns, and the underlying mutations were characterized by DNA sequencing. Five novel missense mutations, Q71E, C74G, C95R, C281Y and D679E, and one nonsense mutation, Q133X, were identified. We also found six missense mutations, S156L, D200Y, D200G, E256K, T413K and C646Y, and one stop codon mutation, W(-18)X, that were previously described in patients from other populations. A new frameshift mutation, 2085del19, was found in one patient. We also identified three splicing mutations; two of them are novel mutations, 1706-10G->A and 2390-1G->A, and the other one has been reported recently, 313+1G->C. Four patients were found to carry two different mutations in the same  allele: Q71E and 313+1G->C; C95R and D679E; W(-18)X and E256K, and C281Y and 1706-10G->A. Our results demonstrate that there is a broad spectrum of mutations  in the LDL receptor gene in the Spanish population.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Cenarro",
      "authorRank" : 1,
      "name" : "Cenarro A",
      "referenceId" : "RGD:A62829"
    }, {
      "firstName" : "HK",
      "lastName" : "Jensen",
      "authorRank" : 2,
      "name" : "Jensen HK",
      "referenceId" : "RGD:A57707"
    }, {
      "firstName" : "E",
      "lastName" : "Casao",
      "authorRank" : 3,
      "name" : "Casao",
      "referenceId" : "RGD:A360534"
    }, {
      "firstName" : "F",
      "lastName" : "Civeira",
      "authorRank" : 4,
      "name" : "Civeira F",
      "referenceId" : "RGD:A62837"
    }, {
      "firstName" : "J",
      "lastName" : "Gonzalez-Bonillo",
      "authorRank" : 5,
      "name" : "Gonzalez-Bonillo",
      "referenceId" : "RGD:A360535"
    }, {
      "firstName" : "JC",
      "lastName" : "Rodriguez-Rey",
      "authorRank" : 6,
      "name" : "Rodriguez-Rey JC",
      "referenceId" : "RGD:A125482"
    }, {
      "firstName" : "N",
      "lastName" : "Gregersen",
      "authorRank" : 7,
      "name" : "Gregersen N",
      "referenceId" : "RGD:A28402"
    }, {
      "firstName" : "M",
      "lastName" : "Pocovi",
      "authorRank" : 8,
      "name" : "Pocovi M",
      "referenceId" : "RGD:A62836"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11526447"
    } ]
  }, {
    "primaryId" : "PMID:10206684",
    "title" : "The identification of five novel mutations in the lysosomal acid a-(1-4) glucosidase gene from patients with glycogen storage disease type II. Mutations in brief no. 134. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Beesley CE, etal., Hum Mutat. 1998;11(5):413.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:44:49.000-05:00",
    "volume" : "11",
    "pages" : "413",
    "abstract" : "The autosomal recessive disorder Glycogen Storage Type II (GSDII) is caused by a  deficiency in the lysosomal enzyme acid alpha-glucosidase. We have optimised a procedure to use fluorescent DNA sequencing technology to screen for mutations within the alpha-glucosidase gene from UK patients with GSDII. Five previously unknown mutations in six patients (4 early onset infantile and 2 late adult) have been found. The mutations are an insertion of a C residue in exon 2 (InsC258), an insertion of a G residue in exon 16 (InsG2242), a deletion of 20 nucleotides in exon 4 delta, and a nonsense mutation in exon 16 (G2237A-Trp746Stop). All will result in the introduction of a premature stop codon in the coding region, predicting a truncated and non-functional protein. The final mutation is a duplication of 18 nucleotides in exon 19 (Ins18nt2776) and will result in the insertion of an additional six amino acids into the protein chain after Asn925 (Gly-Val-Pro-Val-Ser-Asn).",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CE",
      "lastName" : "Beesley",
      "authorRank" : 1,
      "name" : "Beesley",
      "referenceId" : "RGD:A255807"
    }, {
      "firstName" : "AH",
      "lastName" : "Child",
      "authorRank" : 2,
      "name" : "Child AH",
      "referenceId" : "RGD:A80143"
    }, {
      "firstName" : "MH",
      "lastName" : "Yacoub",
      "authorRank" : 3,
      "name" : "Yacoub MH",
      "referenceId" : "RGD:A101124"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071517"
    } ]
  }, {
    "primaryId" : "PMID:10206962",
    "title" : "Dibromopropanone cross-linking of the phosphopantetheine and active-site cysteine thiols of the animal fatty acid synthase can occur both inter- and intrasubunit.  Reevaluation of the side-by-side, antiparallel subunit model.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Witkowski A, etal., J Biol Chem. 1999 Apr 23;274(17):11557-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:45:21.000-05:00",
    "volume" : "274",
    "pages" : "11557-63",
    "abstract" : "The objective of this study was to test a new model for the homodimeric animal FAS which implies that the condensation reaction can be catalyzed by the amino-terminal beta-ketoacyl synthase domain in cooperation with the penultimate  carboxyl-terminal acyl carrier protein domain of either subunit. Treatment of animal fatty acid synthase dimers with dibromopropanone generates three new molecular species with decreased electrophoretic mobilities; none of these species are formed by fatty acid synthase mutant dimers lacking either the active-site cysteine of the beta-ketoacyl synthase domain (C161A) or the phosphopantetheine thiol of the acyl carrier protein domain (S2151A). A double affinity-labeling strategy was used to isolate dimers that carried one or both mutations on one or both subunits; the heterodimers were treated with dibromopropanone and analyzed by a combination of sodium dodecyl sulfate/polyacrylamide gel electrophoresis, Western blotting, gel filtration, and matrix-assisted laser desorption mass spectrometry. Thus the two slowest moving of these species, which accounted for 45 and 15% of the total, were identified as doubly and singly cross-linked dimers, respectively, whereas the fastest moving species, which accounted for 35% of the total, was identified as originating from internally cross-linked subunits. These results show that the two polypeptides of the fatty acid synthase are oriented such that head-to-tail contacts are formed both between and within subunits, and provide the first structural evidence in support of the new model.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Witkowski",
      "authorRank" : 1,
      "name" : "Witkowski A",
      "referenceId" : "RGD:A30640"
    }, {
      "firstName" : "AK",
      "lastName" : "Joshi",
      "authorRank" : 2,
      "name" : "Joshi",
      "referenceId" : "RGD:A185721"
    }, {
      "firstName" : "VS",
      "lastName" : "Rangan",
      "authorRank" : 3,
      "name" : "Rangan",
      "referenceId" : "RGD:A187037"
    }, {
      "firstName" : "AM",
      "lastName" : "Falick",
      "authorRank" : 4,
      "name" : "Falick",
      "referenceId" : "RGD:A187038"
    }, {
      "firstName" : "HE",
      "lastName" : "Witkowska",
      "authorRank" : 5,
      "name" : "Witkowska HE",
      "referenceId" : "RGD:A35788"
    }, {
      "firstName" : "S",
      "lastName" : "Smith",
      "authorRank" : 6,
      "name" : "Smith S",
      "referenceId" : "RGD:A20446"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554616"
    } ]
  }, {
    "primaryId" : "PMID:10206965",
    "title" : "Glu300 of rat carboxypeptidase E is essential for enzymatic activity but not substrate binding or routing to the regulated secretory pathway.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Qian Y, etal., J Biol Chem. 1999 Apr 23;274(17):11582-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-07-23T16:33:09.000-05:00",
    "volume" : "274",
    "pages" : "11582-6",
    "abstract" : "Several recently discovered members of the carboxypeptidase E (CPE) gene family lack critical active site residues that are conserved in other family members. For example, three CPE-like proteins contain a Tyr in place of Glu300 (equivalent to Glu270 of carboxypeptidase A and B). To investigate the importance of this position, Glu300 of rat CPE was converted into Gln, Lys, or Tyr, and the proteins expressed in Sf9 cells using the baculovirus system. All three mutants were secreted from the cells, but the media showed no enzyme activity above background levels. Wild-type CPE and the Gln300 point mutant bound to a p-aminobenzoyl-Arg-Sepharose affinity resin, and this binding was competed by an active site-directed inhibitor, guanidinoethylmercaptosuccinic acid. The affinity purified mutant CPE protein showed no detectable enzyme activity (<0.004% of wild-type CPE) toward dansyl-Phe-Ala-Arg. Expression of the Gln300 and Lys300 mutant CPE proteins in the NIT3 mouse pancreatic beta-cell line showed that these mutants are routed into secretory vesicles and secreted via the regulated pathway. Taken together, these results indicate that Glu300 of CPE is essential for enzyme activity, but not required for substrate binding or for routing into the regulated secretory pathway.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Qian",
      "authorRank" : 1,
      "name" : "Qian Y",
      "referenceId" : "RGD:A7869"
    }, {
      "firstName" : "O",
      "lastName" : "Varlamov",
      "authorRank" : 2,
      "name" : "Varlamov O",
      "referenceId" : "RGD:A41130"
    }, {
      "firstName" : "LD",
      "lastName" : "Fricker",
      "authorRank" : 3,
      "name" : "Fricker LD",
      "referenceId" : "RGD:A7867"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1626217"
    } ]
  }, {
    "primaryId" : "PMID:10207009",
    "title" : "MAGUIN, a novel neuronal membrane-associated guanylate kinase-interacting protein.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Yao I, etal., J Biol Chem 1999 Apr 23;274(17):11889-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T17:21:49.000-05:00",
    "volume" : "274",
    "pages" : "11889-96",
    "abstract" : "Postsynaptic density (PSD)-95/Synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are neuronal membrane-associated guanylate kinases. Because PSD-95/SAP90 and S-SCAM function as synaptic scaffolding proteins, identification of ligands for these proteins is important to elucidate the structure of synaptic junctions. Here, we report a novel protein interacting with the PDZ domains of PSD-95/SAP90 and S-SCAM and named it MAGUIN-1 (membrane-associated guanylate kinase-interacting protein-1). MAGUIN-1 has one sterile alpha motif, one PDZ, and one plekstrin homology domain. MAGUIN-1 is localized at the plasma membrane via the plekstrin homology domain and the C-terminal region and interacts with PSD-95/SAP90 and S-SCAM via a C-terminal PDZ domain-binding motif. MAGUIN-1 has a short isoform, MAGUIN-2, which lacks a PDZ domain-binding motif. MAGUINs are expressed in neurons and localized in the cell body and neurites and are coimmunoprecipitated with PSD-95/SAP90 and S-SCAM from rat crude synaptosome. MAGUIN-1 may play an important role with PSD-95/SAP90 and S-SCAM to assemble the components of synaptic junctions.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Yao",
      "authorRank" : 1,
      "name" : "Yao I",
      "referenceId" : "RGD:A8910"
    }, {
      "firstName" : "Y",
      "lastName" : "Hata",
      "authorRank" : 2,
      "name" : "Hata Y",
      "referenceId" : "RGD:A122620"
    }, {
      "firstName" : "N",
      "lastName" : "Ide",
      "authorRank" : 3,
      "name" : "Ide N",
      "referenceId" : "RGD:A15957"
    }, {
      "firstName" : "K",
      "lastName" : "Hirao",
      "authorRank" : 4,
      "name" : "Hirao K",
      "referenceId" : "RGD:A4762"
    }, {
      "firstName" : "M",
      "lastName" : "Deguchi",
      "authorRank" : 5,
      "name" : "Deguchi M",
      "referenceId" : "RGD:A16949"
    }, {
      "firstName" : "H",
      "lastName" : "Nishioka",
      "authorRank" : 6,
      "name" : "Nishioka H",
      "referenceId" : "RGD:A12325"
    }, {
      "firstName" : "A",
      "lastName" : "Mizoguchi",
      "authorRank" : 7,
      "name" : "Mizoguchi A",
      "referenceId" : "RGD:A12327"
    }, {
      "firstName" : "Y",
      "lastName" : "Takai",
      "authorRank" : 8,
      "name" : "Takai Y",
      "referenceId" : "RGD:A151861"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299456"
    } ]
  }, {
    "primaryId" : "PMID:10207024",
    "title" : "The beta3-adrenergic receptor activates mitogen-activated protein kinase in adipocytes through a Gi-dependent mechanism.",
    "datePublished" : "1999-04-23T00:00:00.000-05:00",
    "citation" : "Soeder KJ, etal., J Biol Chem. 1999 Apr 23;274(17):12017-22. doi: 10.1074/jbc.274.17.12017.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-09-06T06:07:19.000-05:00",
    "volume" : "274",
    "pages" : "12017-22",
    "abstract" : "Promiscuous coupling between G protein-coupled receptors and multiple species of heterotrimeric G proteins provides a potential mechanism for expanding the diversity of G protein-coupled receptor signaling. We have examined the mechanism and functional consequences of dual Gs/Gi protein coupling of the beta3-adrenergic receptor (beta3AR) in 3T3-F442A adipocytes. The beta3AR selective agonist disodium (R, R)-5-[2[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1, 3-benzodioxole-2,2-dicarboxylate (CL316,243) stimulated a dose-dependent increase in cAMP production in adipocyte plasma membrane preparations, and pretreatment of cells with pertussis toxin resulted in a further 2-fold increase in cAMP production by CL316,243. CL316,243 (5 microM) stimulated the incorporation of 8-azido-[32P]GTP into Galphas (1.57 +/- 0.12; n = 3) and Galphai (1. 68 +/- 0.13; n = 4) in adipocyte plasma membranes, directly demonstrating that beta3AR stimulation results in Gi-GTP exchange. The beta3AR-stimulated increase in 8-azido-[32P]GTP labeling of Galphai was equivalent to that obtained with the A1-adenosine receptor agonist N6-cyclopentyladenosine (1.56 +/- 0.07; n = 4), whereas inclusion of unlabeled GTP (100 microM) eliminated all binding. Stimulation of the beta3AR in 3T3-F442A adipocytes led to a 2-3-fold activation of mitogen-activated protein (MAP) kinase, as measured by extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation. Pretreatment of cells with pertussis toxin (PTX) eliminated MAP kinase activation by beta3AR, demonstrating that this response required receptor coupling to Gi. Expression of the human beta3AR in HEK-293 cells reconstituted the PTX-sensitive stimulation of MAP kinase, demonstrating that this phenomenon is not exclusive to adipocytes or to the rodent beta3AR. ERK1/2 activation by the beta3AR was insensitive to the cAMP-dependent protein kinase inhibitor H-89 but was abolished by genistein and AG1478. These data indicate that constitutive beta3AR coupling to Gi proteins serves both to restrain Gs-mediated activation of adenylyl cyclase and to initiate additional signal transduction pathways, including the ERK1/2 MAP kinase cascade.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K J",
      "lastName" : "Soeder",
      "authorRank" : 1,
      "name" : "Soeder KJ",
      "referenceId" : "RGD:A610453"
    }, {
      "firstName" : "S K",
      "lastName" : "Snedden",
      "authorRank" : 2,
      "name" : "Snedden SK",
      "referenceId" : "RGD:A610454"
    }, {
      "firstName" : "W",
      "lastName" : "Cao",
      "authorRank" : 3,
      "name" : "Cao W",
      "referenceId" : "RGD:A96831"
    }, {
      "firstName" : "G J",
      "lastName" : "Della Rocca",
      "authorRank" : 4,
      "name" : "Della Rocca GJ",
      "referenceId" : "RGD:A610455"
    }, {
      "firstName" : "K W",
      "lastName" : "Daniel",
      "authorRank" : 5,
      "name" : "Daniel KW",
      "referenceId" : "RGD:A610456"
    }, {
      "firstName" : "L M",
      "lastName" : "Luttrell",
      "authorRank" : 6,
      "name" : "Luttrell LM",
      "referenceId" : "RGD:A610457"
    }, {
      "firstName" : "S",
      "lastName" : "Collins",
      "authorRank" : 7,
      "name" : "Collins S",
      "referenceId" : "RGD:A39311"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:626467874"
    } ]
  }, {
    "primaryId" : "PMID:10207097",
    "title" : "Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Dörflinger U, etal., Mol Cell Biol. 1999 May;19(5):3736-47.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-02-18T06:19:06.000-06:00",
    "volume" : "19",
    "pages" : "3736-47",
    "abstract" : "Somatostatin receptor type II expression in the mammalian brain displays a spatially and temporally very restricted pattern. In an investigation of the molecular mechanisms controlling these patterns, we have recently shown that binding of the transcription factor SEF-2 to a novel initiator element in the SSTR-2 promoter is essential for SSTR-2 gene expression. Further characterization of the promoter identified a species-conserved TC-rich enhancer element. By screening a mouse brain cDNA expression library, we cloned a cDNA encoding the transcription factor MIBP1. MIBP1 interacts specifically with both the TC box in the SSTR-2 promoter and with the SEF-2 initiator-binding protein to enhance transcription from the basal SSTR-2 promoter. We then investigated SSTR-2, SEF-2, and MIBP1 mRNA expression patterns in the developing and adult murine brain by Northern blotting and in situ hybridization. While SEF-2 is widely expressed in many neuronal and nonneuronal tissues, MIBP1 expression overlapped precisely with expression of SSTR-2 in the frontal cortex and hippocampus. In summary, our data for the first time define a regulatory role for the transcription factor MIBP1 in mediating spatially and temporally regulated SSTR-2 expression in the brain.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "U",
      "lastName" : "Dörflinger",
      "authorRank" : 1,
      "name" : "Dörflinger U",
      "referenceId" : "RGD:A439409"
    }, {
      "firstName" : "A",
      "lastName" : "Pscherer",
      "authorRank" : 2,
      "name" : "Pscherer A",
      "referenceId" : "RGD:A439410"
    }, {
      "firstName" : "M",
      "lastName" : "Moser",
      "authorRank" : 3,
      "name" : "Moser M",
      "referenceId" : "RGD:A29205"
    }, {
      "firstName" : "P",
      "lastName" : "Rümmele",
      "authorRank" : 4,
      "name" : "Rümmele P",
      "referenceId" : "RGD:A439411"
    }, {
      "firstName" : "R",
      "lastName" : "Schüle",
      "authorRank" : 5,
      "name" : "Schüle R",
      "referenceId" : "RGD:A439412"
    }, {
      "firstName" : "R",
      "lastName" : "Buettner",
      "authorRank" : 6,
      "name" : "Buettner R",
      "referenceId" : "RGD:A29209"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12790649"
    } ]
  }, {
    "primaryId" : "PMID:10207099",
    "title" : "ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Foretz M, etal., Mol Cell Biol. 1999 May;19(5):3760-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-06-10T15:26:25.000-05:00",
    "volume" : "19",
    "pages" : "3760-8",
    "abstract" : "The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Foretz",
      "authorRank" : 1,
      "name" : "Foretz M",
      "referenceId" : "RGD:A85035"
    }, {
      "firstName" : "C",
      "lastName" : "Pacot",
      "authorRank" : 2,
      "name" : "Pacot C",
      "referenceId" : "RGD:A108169"
    }, {
      "firstName" : "I",
      "lastName" : "Dugail",
      "authorRank" : 3,
      "name" : "Dugail I",
      "referenceId" : "RGD:A108135"
    }, {
      "firstName" : "P",
      "lastName" : "Lemarchand",
      "authorRank" : 4,
      "name" : "Lemarchand P",
      "referenceId" : "RGD:A108150"
    }, {
      "firstName" : "C",
      "lastName" : "Guichard",
      "authorRank" : 5,
      "name" : "Guichard C",
      "referenceId" : "RGD:A79574"
    }, {
      "firstName" : "X",
      "lastName" : "Le Liepvre",
      "authorRank" : 6,
      "name" : "Le Liepvre X",
      "referenceId" : "RGD:A108134"
    }, {
      "firstName" : "C",
      "lastName" : "Berthelier-Lubrano",
      "authorRank" : 7,
      "name" : "Berthelier-Lubrano C",
      "referenceId" : "RGD:A108170"
    }, {
      "firstName" : "B",
      "lastName" : "Spiegelman",
      "authorRank" : 8,
      "name" : "Spiegelman B",
      "referenceId" : "RGD:A37441"
    }, {
      "firstName" : "JB",
      "lastName" : "Kim",
      "authorRank" : 9,
      "name" : "Kim JB",
      "referenceId" : "RGD:A70355"
    }, {
      "firstName" : "P",
      "lastName" : "Ferre",
      "authorRank" : 10,
      "name" : "Ferre P",
      "referenceId" : "RGD:A11388"
    }, {
      "firstName" : "F",
      "lastName" : "Foufelle",
      "authorRank" : 11,
      "name" : "Foufelle F",
      "referenceId" : "RGD:A34659"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2308847"
    } ]
  }, {
    "primaryId" : "PMID:10207104",
    "title" : "HERF1, a novel hematopoiesis-specific RING finger protein, is required for terminal differentiation of erythroid cells.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Harada H, etal., Mol Cell Biol 1999 May;19(5):3808-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-06T13:37:47.000-05:00",
    "volume" : "19",
    "pages" : "3808-15",
    "abstract" : "The AML1/core binding factor beta (CBFbeta) transcription factor is essential for definitive hematopoiesis; however, the downstream pathways through which it functions remain incompletely defined. Using a differential cloning approach to define components of this pathway, we have identified a novel gene designated HERF1 (for hematopoietic RING finger 1), whose expression during development is dependent on the presence of functional AML1/CBFbeta. HERF1 contains a tripartite RING finger-B box-alpha-helical coiled-coil domain and a C-terminal region homologous to the ret proto-oncogene-encoded finger protein. Expression of HERF1 during embryogenesis coincides with the appearance of definitive erythropoiesis and in adult mice is restricted to erythroid cells, increasing 30-fold during terminal differentiation. Importantly, inhibition of HERF1 expression blocked terminal erythroid differentiation of the murine erythroleukemia cell line MEL, whereas its overexpression induced erythroid maturation. These results suggest an important role for this protein in erythropoiesis.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Harada",
      "authorRank" : 1,
      "name" : "Harada H",
      "referenceId" : "RGD:A55770"
    }, {
      "firstName" : "Y",
      "lastName" : "Harada",
      "authorRank" : 2,
      "name" : "Harada Y",
      "referenceId" : "RGD:A11057"
    }, {
      "firstName" : "DP",
      "lastName" : "O'Brien",
      "authorRank" : 3,
      "name" : "O'Brien DP",
      "referenceId" : "RGD:A55771"
    }, {
      "firstName" : "DS",
      "lastName" : "Rice",
      "authorRank" : 4,
      "name" : "Rice DS",
      "referenceId" : "RGD:A55772"
    }, {
      "firstName" : "CW",
      "lastName" : "Naeve",
      "authorRank" : 5,
      "name" : "Naeve CW",
      "referenceId" : "RGD:A28867"
    }, {
      "firstName" : "JR",
      "lastName" : "Downing",
      "authorRank" : 6,
      "name" : "Downing JR",
      "referenceId" : "RGD:A28875"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549658"
    } ]
  }, {
    "primaryId" : "PMID:10207106",
    "title" : "Isolation of a mammalian homologue of a fission yeast differentiation regulator.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Yamamoto H, etal., Mol Cell Biol 1999 May;19(5):3829-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-18T16:17:29.000-05:00",
    "volume" : "19",
    "pages" : "3829-41",
    "abstract" : "In the fission yeast Schizosaccharomyces pombe the nrd1(+) gene encoding an RNA binding protein negatively regulates the onset of differentiation. Its biological role is to block differentiation by repressing a subset of the Ste11-regulated genes essential for conjugation and meiosis until the cells reach a critical level of nutrient starvation. By using the phenotypic suppression of the S. pombe temperature-sensitive pat1 mutant that commits lethal haploid meiosis at the restrictive temperature, we have cloned ROD1, a functional homologue of nrd1(+), from rat and human cDNA libraries. Like nrd1(+), ROD1 encodes a protein with four repeats of typical RNA binding domains, though its amino acid homology to Nrd1 is limited. When expressed in the fission yeast, ROD1 behaves in a way that is functionally similar to nrd1(+), being able to repress Ste11-regulated genes and to inhibit conjugation upon overexpression. ROD1 is predominantly expressed in hematopoietic cells or organs of adult and embryonic rat. Like nrd1(+) for fission yeast differentiation, overexpressed ROD1 effectively blocks both 12-O-tetradecanoyl phorbol-13-acetate-induced megakaryocytic and sodium butyrate-induced erythroid differentiation of the K562 human leukemia cells without affecting their proliferative ability. These results suggest a role for ROD1 in differentiation control in mammalian cells. We discuss the possibility that a differentiation control system found in the fission yeast might well be conserved in more complex organisms, including mammals.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Yamamoto",
      "authorRank" : 1,
      "name" : "Yamamoto H",
      "referenceId" : "RGD:A158691"
    }, {
      "firstName" : "K",
      "lastName" : "Tsukahara",
      "authorRank" : 2,
      "name" : "Tsukahara K",
      "referenceId" : "RGD:A25702"
    }, {
      "firstName" : "Y",
      "lastName" : "Kanaoka",
      "authorRank" : 3,
      "name" : "Kanaoka Y",
      "referenceId" : "RGD:A4676"
    }, {
      "firstName" : "S",
      "lastName" : "Jinno",
      "authorRank" : 4,
      "name" : "Jinno S",
      "referenceId" : "RGD:A4677"
    }, {
      "firstName" : "H",
      "lastName" : "Okayama",
      "authorRank" : 5,
      "name" : "Okayama H",
      "referenceId" : "RGD:A4683"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:704461"
    } ]
  }, {
    "primaryId" : "PMID:10207168",
    "title" : "Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Chen X, etal., J Clin Invest 1999 Apr;103(8):1159-68.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:01:57.000-05:00",
    "volume" : "103",
    "pages" : "1159-68",
    "abstract" : "Kidney proximal tubule cells take up Krebs cycle intermediates for metabolic purposes and for secretion of organic anions through dicarboxylate/organic anion exchange. Alteration in reabsorption of citrate is closely related to renal stone formation. The presence of distinct types of sodium-coupled dicarboxylate transporters has been postulated on either side of the polarized epithelial membrane in the kidney proximal tubule. Using a PCR-based approach, we isolated a novel member of the sodium-dependent dicarboxylate/sulfate transporter called SDCT2. SDCT2 is a 600-amino acid residue protein that has 47-48% amino acid identity to SDCT1 and NaDC-1, previously identified in kidney and intestine. Northern analysis gave a single band of 3.3 kb for SDCT2 in kidney, liver, and brain. In situ hybridization revealed that SDCT2 is prominently expressed in kidney proximal tubule S3 segments and in perivenous hepatocytes, consistent with the sites of high-affinity dicarboxylate transport identified based on vesicle studies. A signal was also detected in the meningeal layers of the brain. SDCT2 expressed in Xenopus oocytes mediated sodium-dependent transport of di- and tricarboxylates with substrate preference for succinate rather than citrate, but excluding monocarboxylates. SDCT2, unlike SDCT1, displayed a unique pH dependence for succinate transport (optimal pH 7.5-8.5) and showed a high affinity for dimethylsuccinate, two features characteristic of basolateral transport. These data help to interpret the mechanisms of renal citrate transport, their alteration in pathophysiological conditions, and their role in the elimination of organic anions and therapeutic drugs.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Chen",
      "authorRank" : 1,
      "name" : "Chen X",
      "referenceId" : "RGD:A5579"
    }, {
      "firstName" : "H",
      "lastName" : "Tsukaguchi",
      "authorRank" : 2,
      "name" : "Tsukaguchi H",
      "referenceId" : "RGD:A23434"
    }, {
      "firstName" : "XZ",
      "lastName" : "Chen",
      "authorRank" : 3,
      "name" : "Chen XZ",
      "referenceId" : "RGD:A159956"
    }, {
      "firstName" : "UV",
      "lastName" : "Berger",
      "authorRank" : 4,
      "name" : "Berger UV",
      "referenceId" : "RGD:A63295"
    }, {
      "firstName" : "MA",
      "lastName" : "Hediger",
      "authorRank" : 5,
      "name" : "Hediger MA",
      "referenceId" : "RGD:A63297"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634020"
    } ]
  }, {
    "primaryId" : "PMID:10207840",
    "title" : "Expression of transforming growth factor-beta receptors types II and III within various cells in the rat periodontium.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Gao J, etal., J Periodontal Res. 1999 Feb;34(2):113-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-06-02T11:57:43.000-05:00",
    "volume" : "34",
    "pages" : "113-22",
    "abstract" : "This study reports the immunohistochemical localization of TGF-beta receptor type II (T beta R-II) and type III (T beta R-III) in cells of the forming periodontal ligament (PDL) in rat first molar roots. Mandibular periodontium was obtained from 3, 6 and 12-wk-old rats. This represented tissue from the initial, pre-mature and post-mature stages of root and periodontal development, respectively. Mandibular bone chips and molar roots were used to isolate osteoblasts, fibroblasts and cementoblasts. Cells were obtained using a 2-step trypsinization and explant technique, and cultured in Dulbecco's modification of Eagle's medium (DMEM) under routine cell culture conditions. Cells were cultured on coverslips for the purpose of detecting TGF-beta receptors, and compared with whole tissue sections using the same detection method. Cells which stained positively for T beta R-II and T beta R-III on both paraffin sections and cultured cell slides were counted. Both receptors were expressed in the various periodontal tissue compartments. PDL fibroblasts, cementoblasts and osteoblasts were stained positively for T beta R-II and T beta R-III. Endothelial cells were noted to be positive for T beta R-II only. T beta R-II was more widely distributed in cells than T beta R-III, but T beta R-III was extensively localized in the extracellular matrix. Both receptors were expressed on the cell membrane and also localized in the cytoplasm. The findings for paraffin sections were consistent with the immunohistochemical staining of cultured cells. The percentage of cells which stained positively for T beta R-II was greater (approximately 85%) than that for T beta R-III (approximately 60%) in all major types of the PDL cells on both paraffin sections and cultured cell slides. Extensive location of TGF-beta receptors in both cells and extracellular matrix suggests that several binding sites are available for TGF-beta s to interact with target cells during development and following maturation of the periodontium.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Gao",
      "authorRank" : 1,
      "name" : "Gao J",
      "referenceId" : "RGD:A21775"
    }, {
      "firstName" : "AL",
      "lastName" : "Symons",
      "authorRank" : 2,
      "name" : "Symons AL",
      "referenceId" : "RGD:A60389"
    }, {
      "firstName" : "PM",
      "lastName" : "Bartold",
      "authorRank" : 3,
      "name" : "Bartold PM",
      "referenceId" : "RGD:A26330"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1579948"
    } ]
  }, {
    "primaryId" : "PMID:10207942",
    "title" : "Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Baughman RP, etal., Sarcoidosis Vasc Diffuse Lung Dis. 1999 Mar;16(1):57-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-13T10:48:11.000-05:00",
    "volume" : "16",
    "pages" : "57-61",
    "abstract" : "BACKGROUND AND AIM: A recent transgenic mouse model overexpressing transforming growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibrosis. In order to validate this mouse as a model for idiopathic pulmonary fibrosis in humans, we studied the expression of TGF-alpha in lung tissue of patients with idiopathic pulmonary fibrosis compared to control lung tissue. METHODS: Tissue from both groups was obtained from operative specimens and immediately formalin-fixed and paraffin embedded. Contiguous four micron sections were prepared for conventional histochemical staining and staining with antibodies to either TGF-alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immunohistochemistry system. Four cell types were examined (vascular endothelium, bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain activity was scored on a six point scale. RESULTS: Eleven patients with IPF were compared to seven control subjects. TGF-alpha immunoreactivity was significantly higher in the IPF patients than in controls in the vascular endothelium, type 2 pneumocytes, and fibroblasts (P < 0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).] The differences in EGF-R, one of the receptors for TGF-alpha, between these two patient populations were not as striking. There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. CONCLUSIONS: TGF-alpha is overexpressed in patients with IPF, especially in the vascular endothelial cells.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RP",
      "lastName" : "Baughman",
      "authorRank" : 1,
      "name" : "Baughman RP",
      "referenceId" : "RGD:A59495"
    }, {
      "firstName" : "EE",
      "lastName" : "Lower",
      "authorRank" : 2,
      "name" : "Lower EE",
      "referenceId" : "RGD:A59496"
    }, {
      "firstName" : "MA",
      "lastName" : "Miller",
      "authorRank" : 3,
      "name" : "Miller MA",
      "referenceId" : "RGD:A59497"
    }, {
      "firstName" : "PA",
      "lastName" : "Bejarano",
      "authorRank" : 4,
      "name" : "Bejarano PA",
      "referenceId" : "RGD:A59498"
    }, {
      "firstName" : "SC",
      "lastName" : "Heffelfinger",
      "authorRank" : 5,
      "name" : "Heffelfinger SC",
      "referenceId" : "RGD:A59499"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578628"
    } ]
  }, {
    "primaryId" : "PMID:10208466",
    "title" : "Matrix metalloproteinase-1 and -3 in breast cancer: correlation with progesterone receptors and other clinicopathologic features.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Nakopoulou L, etal., Hum Pathol. 1999 Apr;30(4):436-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-01-22T13:50:34.000-06:00",
    "volume" : "30",
    "pages" : "436-42",
    "abstract" : "Although matrix metalloproteinases (MMPs) are implicated in breast cancer progression, the contribution of MMP-1 and MMP-3 to this process, has not been thoroughly investigated. Matrix metalloproteinases (MMPs) are important at several points during multistage neoplastic progression. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1, MMM-3 proteins, and MMP-3 mRNA, respectively, in 77 infiltrative breast carcinomas. MMP-1, MMP-3 protein, and MMP-3 mRNA detection were analyzed in parallel with clinicopathologic features (menopausal status, histological type, nuclear and histological grade, stage) and the immunohistochemical reactivity of  estrogen (ER), progesterone (PR) receptors, and c-erbB-2 oncoprotein in breast carcinomas. Statistical analysis was performed using the multiple linear regression test. Immunoreactivity for MMP-1 and MMP-3 was observed in 59 of 77 (77%) and 22 of 77 (28.5%) breast carcinomas and was evaluated separately in cancer cells and in stromal fibroblasts. MMP-3 mRNA was detected in 72 of 77 (93.5%) carcinomas exclusively in stromal cells within the tumors or in the marginal portion of tumors. MMP-1 protein immunoreactivity in stromal fibroblasts but not in cancer cells showed a statistically significant correlation with tumor stage (P=.04). MMP-1 reactivity either in stromal or in cancer cells showed a statistically significant inverse correlation with PR expression (P=.04 and P=.04, respectively). MMP-3 protein immunoreactivity in cancer or stromal cells and MMP-3 mRNA expression was not associated with the clinicopathologic features  studied. MMP-3 mRNA was detected more often in ductal carcinomas. These results indicate that MMP-1 may contribute to breast cancer invasiveness. Furthermore, they suggest differential functions for MMP-1 and MMP-3 in breast cancer progression.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Nakopoulou",
      "authorRank" : 1,
      "name" : "Nakopoulou L",
      "referenceId" : "RGD:A91725"
    }, {
      "firstName" : "I",
      "lastName" : "Giannopoulou",
      "authorRank" : 2,
      "name" : "Giannopoulou I",
      "referenceId" : "RGD:A91728"
    }, {
      "firstName" : "H",
      "lastName" : "Gakiopoulou",
      "authorRank" : 3,
      "name" : "Gakiopoulou H",
      "referenceId" : "RGD:A118128"
    }, {
      "firstName" : "H",
      "lastName" : "Liapis",
      "authorRank" : 4,
      "name" : "Liapis H",
      "referenceId" : "RGD:A97929"
    }, {
      "firstName" : "A",
      "lastName" : "Tzonou",
      "authorRank" : 5,
      "name" : "Tzonou A",
      "referenceId" : "RGD:A123329"
    }, {
      "firstName" : "PS",
      "lastName" : "Davaris",
      "authorRank" : 6,
      "name" : "Davaris PS",
      "referenceId" : "RGD:A96244"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7207142"
    } ]
  }, {
    "primaryId" : "PMID:10208479",
    "title" : "The type of mutation in the low density lipoprotein receptor gene influences the  cholesterol-lowering response of the HMG-CoA reductase inhibitor simvastatin in patients with heterozygous familial hypercholesterolaemia.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Heath KE, etal., Atherosclerosis. 1999 Mar;143(1):41-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T20:19:48.000-05:00",
    "volume" : "143",
    "pages" : "41-54",
    "abstract" : "In a genetically heterogeneous group of 109 patients with a clinical diagnosis of heterozygous familial hypercholesterolaemia (FH), the influence of gender, apolipoprotein (apo) E genotype and the type of molecular defect in the LDL-receptor (LDLR) gene on the reduction of plasma LDL-cholesterol levels to treatment with a HMG-CoA reductase inhibitor (simvastatin) were studied. Response was determined as the percentage fall in LDL-cholesterol from untreated levels and as the proportion of patients where levels fell below 4.9 or 4.1 mmol/l. Of the patients, 86 individuals had tendon xanthomata (TX+) and a diagnosis of 'definite' FH and these individuals presented with a significantly higher untreated LDL-cholesterol compared to the 23 individuals who did not have xanthomas (TX-) and a diagnosis of 'probable' FH (8.14+/-0.19 vs. 6.81+/-0.25, P= 0.001). Overall, HMG-CoA reductase inhibitor doses of 10, 20 or 40 mg/day resulted in a significant fall of LDL-cholesterol levels of 29, 39 and 49%, but at all doses those with TX had significantly higher levels than those without, and significantly fewer TX + patients achieved LDL-cholesterol levels below 4.9 or 4.1 mmol/l than the TX - group (P < 0.05 at each dose). In the TX+ group the response to treatment was of similar magnitude in men and women and in patients with different apoE genotype. In the 'probable' FH probands only three mutations  were identified (detection rate 13%), one in the LDLR gene and two in the APOB gene, a detection rate significantly lower (P= 0.02) than in the 'definite' FH probands where 28 mutations were detected (detection rate 37%). In the TX + patients where no mutation was detected, treatment resulted in a greater proportion achieving LDL-cholesterol levels below 4.9 and 4.1 mmol/l compared to  those with any LDLR mutation, this difference was close to statistical significance at the 4.9 mmol/l threshold at 10 mg/day (41 vs. 13%, P = 0.058). For the 14 patients with an LDLR mutation that was predicted to be 'severe', fewer achieved LDL-cholesterol levels below 4.9 or 4.1 mmol/l at each dosage compared to the 16 individuals with 'mild' mutations, and this difference was statistically significant at the maximal dosage of 40 mg/day (P = 0.018). Thus although characterisation of the molecular defect in FH patients may not be relevant to their immediate clinical management, those with a particular mutation may need more aggressive lipid-lowering treatment to reach LDL-cholesterol levels recommended to reduce the risk of coronary heart disease (CHD).",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KE",
      "lastName" : "Heath",
      "authorRank" : 1,
      "name" : "Heath",
      "referenceId" : "RGD:A377533"
    }, {
      "firstName" : "V",
      "lastName" : "Gudnason",
      "authorRank" : 2,
      "name" : "Gudnason V",
      "referenceId" : "RGD:A40091"
    }, {
      "firstName" : "SE",
      "lastName" : "Humphries",
      "authorRank" : 3,
      "name" : "Humphries SE",
      "referenceId" : "RGD:A58860"
    }, {
      "firstName" : "M",
      "lastName" : "Seed",
      "authorRank" : 4,
      "name" : "Seed M",
      "referenceId" : "RGD:A110568"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11098540"
    } ]
  }, {
    "primaryId" : "PMID:10208490",
    "title" : "Contribution of receptor negative versus receptor defective mutations in the LDL-receptor gene to angiographically assessed coronary artery disease among young (25-49 years) versus middle-aged (50-64 years) men.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Gaudet D, etal., Atherosclerosis. 1999 Mar;143(1):153-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:48:48.000-05:00",
    "volume" : "143",
    "pages" : "153-61",
    "abstract" : "Elevated plasma LDL-cholesterol (LDL-C) levels are associated with an increased risk of coronary artery disease (CAD). Familial hypercholesterolemia (FH), a monogenic trait due to mutations in the LDL-receptor (R) gene is characterized by raised plasma LDL-C levels and premature CAD. The aim of the present investigation, derived from the study of a population of 1465 unrelated men aged  25 to 64 years, was to compare the expression of CAD assessed by coronary angiography in young (aged 25-49 years) versus middle-aged (50-64 years) heterozygous FH patients of French Canadian descent. Furthermore, the relationship of binding-defective versus receptor negative mutations in the LDL-R to premature CAD ( < 50 years) was examined and compared with men displaying a normal plasma lipoprotein-lipid profile. From the original study sample, a total  of 100 men met the clinical criteria of heterozygous FH. Among them, 30 were carriers of a receptor negative mutation (deletion > 15 kb or point mutations Y468X or R329X) whereas 64 were carriers of a receptor defective mutation (W66G,  E207K or C646Y). As expected, in both age groups (25-49 years vs. 50-64 years), carriers of a receptor negative mutation had higher plasma cholesterol and LDL-C  levels than carriers of a defective allele or men with a normal plasma lipoprotein-lipid profile. In addition, the mean number of diseased vessels (with > 50% stenosis) was higher in men aged 50-64 years compared to those aged 25 49 years. In the two age groups, FH patients were characterized by a higher number of stenosed coronary vessels than the normal phenotype group. Within each group (either receptor negative, receptor defective or normal phenotype) plasma cholesterol, LDL-C, HDL-C, triglyceride and apolipoprotein B levels were similar  irrespective of age (25 49 years vs. 50-64 years). Finally, multiple logistic regression analyses revealed that compared to non-FH men, the relative odds of being affected by CAD before the age of 50 years was 7.3-fold higher for carriers of a receptor negative mutation and 2.7-fold higher for men with a receptor defective mutation at the LDL-R locus. These results suggest that CAD could be an earlier event among heterozygous FH subjects bearing a receptor negative mutation compared to LDL-R defective patients. It also suggest that the selective screening for mutations in the LDL-R gene may allow a better assessment of the individual risk and facilitate the development of family-based preventive strategies or intervention programs in FH.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Gaudet",
      "authorRank" : 1,
      "name" : "Gaudet D",
      "referenceId" : "RGD:A61676"
    }, {
      "firstName" : "MC",
      "lastName" : "Vohl",
      "authorRank" : 2,
      "name" : "Vohl MC",
      "referenceId" : "RGD:A56687"
    }, {
      "firstName" : "P",
      "lastName" : "Couture",
      "authorRank" : 3,
      "name" : "Couture P",
      "referenceId" : "RGD:A65251"
    }, {
      "firstName" : "S",
      "lastName" : "Moorjani",
      "authorRank" : 4,
      "name" : "Moorjani",
      "referenceId" : "RGD:A323068"
    }, {
      "firstName" : "G",
      "lastName" : "Tremblay",
      "authorRank" : 5,
      "name" : "Tremblay G",
      "referenceId" : "RGD:A83089"
    }, {
      "firstName" : "P",
      "lastName" : "Perron",
      "authorRank" : 6,
      "name" : "Perron P",
      "referenceId" : "RGD:A61679"
    }, {
      "firstName" : "C",
      "lastName" : "Gagne",
      "authorRank" : 7,
      "name" : "Gagne C",
      "referenceId" : "RGD:A65257"
    }, {
      "firstName" : "JP",
      "lastName" : "Despres",
      "authorRank" : 8,
      "name" : "Despres JP",
      "referenceId" : "RGD:A50873"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11527933"
    } ]
  }, {
    "primaryId" : "PMID:10208569",
    "title" : "Presence of a voltage-dependent anion channel 1 in the rat postsynaptic density fraction.",
    "datePublished" : "1999-02-25T00:00:00.000-06:00",
    "citation" : "Moon JI, etal., Neuroreport. 1999 Feb 25;10(3):443-7. doi: 10.1097/00001756-199902250-00001.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-09-21T01:58:34.000-05:00",
    "volume" : "10",
    "pages" : "443-7",
    "abstract" : "Little is known about the molecular organization and functions of the postsynaptic density (PSD), a cytoskeletal specialization on the postsynaptic membrane. In an attempt to elucidate the protein composition of PSD, we have sequenced a 35 kDa protein of the rat forebrain PSD fraction. Amino acid sequence information of the tryptic peptides and immunoblot analyses revealed that the protein is a voltage-dependent anion channel 1 (VDAC1). VDAC1 was enriched in the PSD fraction and was partially soluble in 1% n-octyl glucoside (NOG) or Triton X-100. Our data indicate that VDAC1, which is originally found in the outer mitochondrial membrane, is also present in the central nervous system (CNS) synapses in association with the PSD 'core'.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J I",
      "lastName" : "Moon",
      "authorRank" : 1,
      "name" : "Moon JI",
      "referenceId" : "RGD:A521180"
    }, {
      "firstName" : "Y W",
      "lastName" : "Jung",
      "authorRank" : 2,
      "name" : "Jung YW",
      "referenceId" : "RGD:A451292"
    }, {
      "firstName" : "B H",
      "lastName" : "Ko",
      "authorRank" : 3,
      "name" : "Ko BH",
      "referenceId" : "RGD:A451293"
    }, {
      "firstName" : "V",
      "lastName" : "De Pinto",
      "authorRank" : 4,
      "name" : "De Pinto V",
      "referenceId" : "RGD:A521181"
    }, {
      "firstName" : "I",
      "lastName" : "Jin",
      "authorRank" : 5,
      "name" : "Jin I",
      "referenceId" : "RGD:A49364"
    }, {
      "firstName" : "I S",
      "lastName" : "Moon",
      "authorRank" : 6,
      "name" : "Moon IS",
      "referenceId" : "RGD:A451294"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:155230777"
    } ]
  }, {
    "primaryId" : "PMID:10208589",
    "title" : "Reduced expression of brain-derived neurotrophic factor protein in Parkinson's disease substantia nigra.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Parain K, etal., Neuroreport. 1999 Feb 25;10(3):557-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-28T10:21:43.000-05:00",
    "volume" : "10",
    "pages" : "557-61",
    "abstract" : "Several in vitro and in vivo studies have shown that brain-derived neurotrophic factor (BDNF) promotes survival of damaged mesencephalic dopaminergic neurons. Using a specific antibody directed against human recombinant BDNF, we studied the expression of the protein at the cellular level in the post-mortem mesencephalon  of control subjects and patients with Parkinson's disease (PD). In control subjects, BDNF was expressed in all mesencephalic regions containing dopaminergic neurons, and in the substantia nigra pars compacta (SNpc) 65% of the melanized neurons expressed BDNF. In the PD SNpc, the total number of pigmented neurons containing BDNF was reduced to 9.6% of the corresponding control value. In contrast, the number of pigmented neurons non-immunoreactive for BDNF was reduced to 23.9% of the corresponding control value. This result appears to indicate that SNpc melanized neurons not expressing BDNF have a 2.5-fold greater probability of surviving than BDNF-positive melanized neurons. Furthermore, we found that in parkinsonian mesencephalon almost all dopaminergic neurons containing Lewy bodies were immunoreactive for BDNF. These findings demonstrate a reduced expression of  BDNF in PD and suggest that BDNF protein expression does not protect melanized SNpc neurons from the degenerative process in this disease.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Parain",
      "authorRank" : 1,
      "name" : "Parain",
      "referenceId" : "RGD:A188574"
    }, {
      "firstName" : "MG",
      "lastName" : "Murer",
      "authorRank" : 2,
      "name" : "Murer",
      "referenceId" : "RGD:A188575"
    }, {
      "firstName" : "Q",
      "lastName" : "Yan",
      "authorRank" : 3,
      "name" : "Yan Q",
      "referenceId" : "RGD:A4532"
    }, {
      "firstName" : "B",
      "lastName" : "Faucheux",
      "authorRank" : 4,
      "name" : "Faucheux B",
      "referenceId" : "RGD:A60775"
    }, {
      "firstName" : "Y",
      "lastName" : "Agid",
      "authorRank" : 5,
      "name" : "Agid Y",
      "referenceId" : "RGD:A21497"
    }, {
      "firstName" : "E",
      "lastName" : "Hirsch",
      "authorRank" : 6,
      "name" : "Hirsch E",
      "referenceId" : "RGD:A37171"
    }, {
      "firstName" : "R",
      "lastName" : "Raisman-Vozari",
      "authorRank" : 7,
      "name" : "Raisman-Vozari R",
      "referenceId" : "RGD:A21499"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8657025"
    } ]
  }, {
    "primaryId" : "PMID:10208590",
    "title" : "Isolation of human delta-catenin and its binding specificity with presenilin 1.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Tanahashi H and Tabira T, Neuroreport 1999 Feb 25;10(3):563-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:54.000-05:00",
    "volume" : "10",
    "pages" : "563-8",
    "abstract" : "We screened proteins for interaction with presenilin (PS) 1, and cloned the full-length cDNA of human delta-catenin, which encoded 1225 amino acids. Yeast two-hybrid assay, GST binding assay and immunoprecipitation demonstrated that delta-catenin interacted with a hydrophilic loop region in the endoproteolytic C-terminal fragment of PS1, but not with that of PS-2. These results suggest that PS1 and PS2 partly differ in function. PS1 loop fragment containing the pathogenic mutation retained the binding ability. We also found another armadillo-protein, p0071, interacted with PS1.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Tanahashi",
      "authorRank" : 1,
      "name" : "Tanahashi H",
      "referenceId" : "RGD:A45766"
    }, {
      "firstName" : "T",
      "lastName" : "Tabira",
      "authorRank" : 2,
      "name" : "Tabira T",
      "referenceId" : "RGD:A144279"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302245"
    } ]
  }, {
    "primaryId" : "PMID:10208650",
    "title" : "Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H:quinone  oxidoreductase 1.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Siegel D, etal., Pharmacogenetics. 1999 Feb;9(1):113-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T19:31:03.000-05:00",
    "volume" : "9",
    "pages" : "113-21",
    "abstract" : "The NAD(P)H:quinone oxidoreductase 1 (NQO1) genotype-phenotype relationship was examined in individuals with a polymorphism in NQO1. The polymorphism comprises a C to T base change at position 609 of the human NQO1 cDNA (C609T) and codes for a proline to serine substitution in the amino acid structure of the NQO1 protein. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis of genomic DNA. Phenotyping was performed using enzyme activity assays and/or immunoblotting of human tumor cell lines and of saliva and bone marrow samples from healthy donors. Phenotyping of uninvolved lung and lung  tumors from archived biopsy material was performed by immunohistochemistry. NQO1  activity and protein could be detected in wild-type (C/C) human tumor cells (HT-29) under conditions where NQO1 protein could not be detected in cells (BE) homozygous for the C609T change (T/T). Trace levels of NQO1 protein could be detected in BE cells; however, when immunoblots were subjected to chemiluminescence detection for prolonged periods. In saliva samples from 11 individuals carrying the homozygous C609T change (T/T), no NQO1 protein could be  detected even after prolonged chemiluminescence detection. The amount of NQO1 protein present in saliva was quantified and found to be significantly less in heterozygous individuals (C/T) than in wild-type individuals (C/C). In bone marrow stromal cultures, both NQO1 activity and protein could be detected in heterozygotes (C/T) and in wild-type (C/C) samples. In a bone marrow stromal culture from an individual genotyped as T/T at position 609, no NQO1 protein or activity could be detected. NQO1 is elevated in non-small cell lung cancers and could be readily observed as intense immunostaining throughout lung adenocarcinomas genotyped as C/C but no immunostaining could be detected in adenocarcinomas genotyped as T/T at position 609. NQO1 is expressed in normal human lung but is localized to respiratory epithelium and to vascular endothelium. In normal lung tissue from individuals genotyped as T/T, no or faint immunostaining for NQO1 could be detected in either respiratory epithelium or vascular endothelium. These results demonstrate that tissues from individuals homozygous for the C609T change have no detectable or, at best, only trace amounts of NQO1 protein and are devoid of NQO1 activity.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Siegel",
      "authorRank" : 1,
      "name" : "Siegel",
      "referenceId" : "RGD:A315550"
    }, {
      "firstName" : "SM",
      "lastName" : "McGuinness",
      "authorRank" : 2,
      "name" : "McGuinness",
      "referenceId" : "RGD:A315551"
    }, {
      "firstName" : "SL",
      "lastName" : "Winski",
      "authorRank" : 3,
      "name" : "Winski",
      "referenceId" : "RGD:A315552"
    }, {
      "firstName" : "D",
      "lastName" : "Ross",
      "authorRank" : 4,
      "name" : "Ross D",
      "referenceId" : "RGD:A53343"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11096786"
    } ]
  }, {
    "primaryId" : "PMID:10208848",
    "title" : "Fabry disease: identification of novel alpha-galactosidase A mutations and molecular carrier detection by use of fluorescent chemical cleavage of mismatches.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Germain DP and Poenaru L, Biochem Biophys Res Commun. 1999 Apr 21;257(3):708-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:13:23.000-05:00",
    "volume" : "257",
    "pages" : "708-13",
    "abstract" : "Fabry disease (FD) (angiokeratoma corporis diffusum) is an X-linked inborn error  of glycosphingolipid metabolism caused by defects in the lysosomal alpha-galactosidase A gene (GLA). The enzymatic defect leads to the systemic accumulation of neutral glycosphingolipids with terminal alpha-galactosyl moieties. Clinically, affected hemizygous males have angiokeratoma, severe acroparesthesia, renal failure, and vasculopathy of the heart and brain. While demonstration of alpha-galactosidase deficiency in leukocytes is diagnostic in affected males, enzymatic detection of female carriers is often inconclusive, due to random X-chromosomal inactivation, underlining the need of molecular investigations for accurate genetic counseling. By use of chemical cleavage of mismatches adapted to fluorescence-based detection systems, we have characterized the mutations underlying alpha-Gal A deficiency in 16 individuals from six unrelated families with FD. The mutational spectrum included five missense mutations (C202W, C223G, N224D, R301Q, and Q327K) and one splice-site mutation [IVS3 G(-1) --> C]. Studies at the mRNA level showed that the latter led to altered pre-mRNA splicing with consequent alteration of the mRNA translational reading frame and generation of a premature termination codon of translation. By  use of this strategy, carrier status was accurately assessed in all seven at-risk females tested, whereas enzymatic dosages failed to diagnose or exclude heterozygosity.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DP",
      "lastName" : "Germain",
      "authorRank" : 1,
      "name" : "Germain",
      "referenceId" : "RGD:A255530"
    }, {
      "firstName" : "L",
      "lastName" : "Poenaru",
      "authorRank" : 2,
      "name" : "Poenaru",
      "referenceId" : "RGD:A251619"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073148"
    } ]
  }, {
    "primaryId" : "PMID:10209022",
    "title" : "CRM1-mediated recycling of snurportin 1 to the cytoplasm.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Paraskeva E, etal., J Cell Biol 1999 Apr 19;145(2):255-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-01-17T11:22:11.000-06:00",
    "volume" : "145",
    "pages" : "255-64",
    "abstract" : "Importin beta is a major mediator of import into the cell nucleus. Importin beta binds cargo molecules either directly or via two types of adapter molecules, importin alpha, for import of proteins with a classical nuclear localization signal (NLS), or snurportin 1, for import of m3G-capped U snRNPs. Both adapters have an NH2-terminal importin beta-binding domain for binding to, and import by, importin beta, and both need to be returned to the cytoplasm after having delivered their cargoes to the nucleus. We have shown previously that CAS mediates export of importin alpha. Here we show that snurportin 1 is exported by CRM1, the receptor for leucine-rich nuclear export signals (NESs). However, the interaction of CRM1 with snurportin 1 differs from that with previously characterized NESs. First, CRM1 binds snurportin 1 50-fold stronger than the Rev protein and 5,000-fold stronger than the minimum Rev activation domain. Second, snurportin 1 interacts with CRM1 not through a short peptide but rather via a large domain that allows regulation of affinity. Strikingly, snurportin 1 has a low affinity for CRM1 when bound to its m3G-capped import substrate, and a high affinity when substrate-free. This mechanism appears crucial for productive import cycles as it can ensure that CRM1 only exports snurportin 1 that has already released its import substrate in the nucleus.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Paraskeva",
      "authorRank" : 1,
      "name" : "Paraskeva E",
      "referenceId" : "RGD:A50221"
    }, {
      "firstName" : "E",
      "lastName" : "Izaurralde",
      "authorRank" : 2,
      "name" : "Izaurralde E",
      "referenceId" : "RGD:A50222"
    }, {
      "firstName" : "FR",
      "lastName" : "Bischoff",
      "authorRank" : 3,
      "name" : "Bischoff FR",
      "referenceId" : "RGD:A50223"
    }, {
      "firstName" : "J",
      "lastName" : "Huber",
      "authorRank" : 4,
      "name" : "Huber J",
      "referenceId" : "RGD:A50224"
    }, {
      "firstName" : "U",
      "lastName" : "Kutay",
      "authorRank" : 5,
      "name" : "Kutay U",
      "referenceId" : "RGD:A50225"
    }, {
      "firstName" : "E",
      "lastName" : "Hartmann",
      "authorRank" : 6,
      "name" : "Hartmann E",
      "referenceId" : "RGD:A72123"
    }, {
      "firstName" : "R",
      "lastName" : "Luhrmann",
      "authorRank" : 7,
      "name" : "Luhrmann R",
      "referenceId" : "RGD:A50227"
    }, {
      "firstName" : "D",
      "lastName" : "Gorlich",
      "authorRank" : 8,
      "name" : "Gorlich D",
      "referenceId" : "RGD:A56503"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1331354"
    } ]
  }, {
    "primaryId" : "PMID:10209024",
    "title" : "Overexpression of CALNUC (nucleobindin) increases agonist and thapsigargin releasable Ca2+ storage in the Golgi.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Lin P, etal., J Cell Biol. 1999 Apr 19;145(2):279-89.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-02-25T12:28:07.000-06:00",
    "volume" : "145",
    "pages" : "279-89",
    "abstract" : "We previously demonstrated that CALNUC, a Ca2+-binding protein with two EF-hands, is the major Ca2+-binding protein in the Golgi by 45Ca2+ overlay (Lin, P., H. Le-Niculescu, R. Hofmeister, J.M. McCaffery, M. Jin, H. Henneman, T. McQuistan, L. De Vries, and M. Farquhar. 1998. J. Cell Biol. 141:1515-1527). In this study we investigated CALNUC's properties and the Golgi Ca2+ storage pool in vivo. CALNUC was found to be a highly abundant Golgi protein (3.8 microg CALNUC/mg Golgi protein, 2.5 x 10(5) CALNUC molecules/NRK cell) and to have a single high affinity, low capacity Ca2+-binding site (Kd = 6.6 microM, binding capacity = 1.1 micromol Ca2+/micromol CALNUC). 45Ca2+ storage was increased by 2.5- and 3-fold,  respectively, in HeLa cells transiently overexpressing CALNUC-GFP and in EcR-CHO  cells stably overexpressing CALNUC. Deletion of the first EF-hand alpha helix from CALNUC completely abolished its Ca2+-binding capability. CALNUC was correctly targeted to the Golgi in transfected cells as it colocalized and cosedimented with the Golgi marker, alpha-mannosidase II (Man II). Approximately  70% of the 45Ca2+ taken up by HeLa and CHO cells overexpressing CALNUC was released by treatment with thapsigargin, a sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) (Ca2+ pump) blocker. Stimulation of transfected cells with the agonist ATP or IP3 alone (permeabilized cells) also resulted in a significant increase in Ca2+ release from Golgi stores. By immunofluorescence, the IP3 receptor type 1 (IP3R-1) was distributed over the endoplasmic reticulum and codistributed with CALNUC in the Golgi. These results provide direct evidence that CALNUC binds Ca2+ in vivo and together with SERCA and IP3R is involved in establishment of the agonist-mobilizable Golgi Ca2+ store.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Lin",
      "authorRank" : 1,
      "name" : "Lin P",
      "referenceId" : "RGD:A25590"
    }, {
      "firstName" : "Y",
      "lastName" : "Yao",
      "authorRank" : 2,
      "name" : "Yao Y",
      "referenceId" : "RGD:A69835"
    }, {
      "firstName" : "R",
      "lastName" : "Hofmeister",
      "authorRank" : 3,
      "name" : "Hofmeister",
      "referenceId" : "RGD:A199526"
    }, {
      "firstName" : "RY",
      "lastName" : "Tsien",
      "authorRank" : 4,
      "name" : "Tsien",
      "referenceId" : "RGD:A199527"
    }, {
      "firstName" : "MG",
      "lastName" : "Farquhar",
      "authorRank" : 5,
      "name" : "Farquhar",
      "referenceId" : "RGD:A206703"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9831124"
    } ]
  }, {
    "primaryId" : "PMID:10209028",
    "title" : "Relationship between Arp2/3 complex and the barbed ends of actin filaments at the leading edge of carcinoma cells after epidermal growth factor stimulation.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Bailly M, etal., J Cell Biol. 1999 Apr 19;145(2):331-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-03-25T15:39:08.000-05:00",
    "volume" : "145",
    "pages" : "331-45",
    "abstract" : "Using both light and high resolution electron microscopy, we analyzed the spatial and temporal relationships between the Arp2/3 complex and the nucleation activity that is required for lamellipod extension in mammary carcinoma cells after epidermal growth factor stimulation. A rapid two- to fourfold increase in filament barbed end number occurs transiently after stimulation and remains confined almost exclusively to the extreme outer edge of the extending lamellipod (within 100-200 nm of the plasma membrane). This is accompanied by an increase in filament density at the leading edge and a general decrease in filament length, with a specific loss of long filaments. Concomitantly, the Arp2/3 complex is recruited with a 1.5-fold increase throughout the entire cortical filament network extending 1-1.5 microm in depth from the membrane at the leading edge. The recruitment of the Arp2/3 complex at the membrane of the extending lamellipod indicates that Arp2/3 may be involved in initial generation of growing filaments. However, only a small subset of the complex present in the cortical network colocalizes near free barbed ends. This suggests that the 100-200-nm submembraneous compartment at the leading edge of the extending lamellipod constitutes a special biochemical microenvironment that favors the generation and maintenance of free barbed ends, possibly through the locally active Arp2/3 complex, severing or decreasing the on-rate of capping protein. Our results are inconsistent with the hypothesis suggesting uncapping is the dominant mechanism responsible for the generation of nucleation activity. However, they support the hypothesis of an Arp2/3-mediated capture of actin oligomers that formed close to the membrane by other mechanisms such as severing. They also support pointed-end capping by the Arp2/3 complex, accounting for its wide distribution at the leading edge.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Bailly",
      "authorRank" : 1,
      "name" : "Bailly M",
      "referenceId" : "RGD:A58751"
    }, {
      "firstName" : "F",
      "lastName" : "Macaluso",
      "authorRank" : 2,
      "name" : "Macaluso F",
      "referenceId" : "RGD:A105122"
    }, {
      "firstName" : "M",
      "lastName" : "Cammer",
      "authorRank" : 3,
      "name" : "Cammer M",
      "referenceId" : "RGD:A67838"
    }, {
      "firstName" : "A",
      "lastName" : "Chan",
      "authorRank" : 4,
      "name" : "Chan A",
      "referenceId" : "RGD:A61639"
    }, {
      "firstName" : "JE",
      "lastName" : "Segall",
      "authorRank" : 5,
      "name" : "Segall JE",
      "referenceId" : "RGD:A67840"
    }, {
      "firstName" : "JS",
      "lastName" : "Condeelis",
      "authorRank" : 6,
      "name" : "Condeelis JS",
      "referenceId" : "RGD:A105123"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306208"
    } ]
  }, {
    "primaryId" : "PMID:10209101",
    "title" : "Association of the type 1 protein phosphatase PP1 with the A-kinase anchoring protein AKAP220.",
    "datePublished" : "1999-03-25T00:00:00.000-06:00",
    "citation" : "Schillace RV and Scott JD, Curr Biol. 1999 Mar 25;9(6):321-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-02-06T10:01:35.000-06:00",
    "volume" : "9",
    "pages" : "321-4",
    "abstract" : "The cyclic AMP (cAMP)-dependent protein kinase (PKA) and the type 1 protein phosphatase (PP1) are broad-specificity signaling enzymes with opposing actions that catalyze changes in the phosphorylation state of cellular proteins. Subcellular targeting to the vicinity of preferred substrates is a means of restricting the specificity of each enzyme [1] [2]. Compartmentalization of the PKA holoenzyme is mediated through association of the regulatory subunits with A-kinase anchoring proteins (AKAPs), whereas a diverse family of phosphatase-targeting subunits directs the location of the PP1 catalytic subunit (PP1c) [3] [4]. Here, we demonstrate that the PKA-anchoring protein, AKAP220, binds PP1c with a dissociation constant (KD) of 12.1 +/- 4 nM in vitro. Immunoprecipitation of PP1 from cell extracts resulted in a 10.4 +/- 3.8-fold enrichment of PKA activity. AKAP220 co-purified with PP1c by affinity chromatography on microcystin sepharos Immunocytochemical analysis demonstrated that the kinase, the phosphatase and the anchoring protein had distinct but overlapping staining patterns in rat hippocampal neurons. Collectively, these results provide the first evidence that AKAP220 is a multivalent anchoring protein that maintains a signaling scaffold of PP1 and the PKA holoenzyme.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R V",
      "lastName" : "Schillace",
      "authorRank" : 1,
      "name" : "Schillace RV",
      "referenceId" : "RGD:A467715"
    }, {
      "firstName" : "J D",
      "lastName" : "Scott",
      "authorRank" : 2,
      "name" : "Scott JD",
      "referenceId" : "RGD:A467716"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14349025"
    } ]
  }, {
    "primaryId" : "PMID:10209122",
    "title" : "Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Giroux S, etal., Curr Biol 1999 Apr 8;9(7):369-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-10-13T11:44:57.000-05:00",
    "volume" : "9",
    "pages" : "369-72",
    "abstract" : "Mek is a dual-specificity kinase that activates the extracellular-signal-regulated (Erk) mitogen-activated protein (MAP) kinases upon agonist binding to receptors. The Erk MAP kinase cascade is involved in cell-fate determination in many organisms. In mammals, this pathway is proposed to regulate cell growth and differentiation. Genetic studies have shown that although a single mek gene is present in Caenorhabditis elegans, Drosophila and Xenopus, two mek homologs, Mek1 and Mek2, are present in the mammalian cascade. In the present study, we describe a mutant mouse line in which the mek1 gene has been disrupted by insertional mutagenesis. The null mutation was recessive lethal, as the homozygous mutant embryos died at 10.5 days of gestation. Histopathological analyses revealed a reduction in vascularization of the placenta that was due to a marked decrease of vascular endothelial cells in the labyrinthine region. The failure to establish a functional placenta probably explains the death of the mek1-/- embryos. Cell-migration assays indicated that mek1-/- fibroblasts could not be induced to migrate by fibronectin, although the levels of Mek2 protein and Erk activation were normal. Re-expression of Mek1 in the mutant mouse embryonic fibroblasts (MEFs) restored their ability to migrate. Our findings provide genetic evidence that establishes the unique role played by Mek1 in signal transduction. They also suggest that mek1 function is required for normal response to angiogenic signals that might promote vascularization of the labyrinthine region of the placenta.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Giroux",
      "authorRank" : 1,
      "name" : "Giroux S",
      "referenceId" : "RGD:A46618"
    }, {
      "firstName" : "M",
      "lastName" : "Tremblay",
      "authorRank" : 2,
      "name" : "Tremblay M",
      "referenceId" : "RGD:A46619"
    }, {
      "firstName" : "D",
      "lastName" : "Bernard",
      "authorRank" : 3,
      "name" : "Bernard D",
      "referenceId" : "RGD:A46359"
    }, {
      "firstName" : "JF",
      "lastName" : "Cardin-Girard",
      "authorRank" : 4,
      "name" : "Cardin-Girard JF",
      "referenceId" : "RGD:A46620"
    }, {
      "firstName" : "S",
      "lastName" : "Aubry",
      "authorRank" : 5,
      "name" : "Aubry S",
      "referenceId" : "RGD:A46621"
    }, {
      "firstName" : "L",
      "lastName" : "Larouche",
      "authorRank" : 6,
      "name" : "Larouche L",
      "referenceId" : "RGD:A46622"
    }, {
      "firstName" : "S",
      "lastName" : "Rousseau",
      "authorRank" : 7,
      "name" : "Rousseau S",
      "referenceId" : "RGD:A46623"
    }, {
      "firstName" : "J",
      "lastName" : "Huot",
      "authorRank" : 8,
      "name" : "Huot J",
      "referenceId" : "RGD:A46624"
    }, {
      "firstName" : "J",
      "lastName" : "Landry",
      "authorRank" : 9,
      "name" : "Landry J",
      "referenceId" : "RGD:A46625"
    }, {
      "firstName" : "L",
      "lastName" : "Jeannotte",
      "authorRank" : 10,
      "name" : "Jeannotte L",
      "referenceId" : "RGD:A46626"
    }, {
      "firstName" : "J",
      "lastName" : "Charron",
      "authorRank" : 11,
      "name" : "Charron J",
      "referenceId" : "RGD:A46627"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302505"
    } ]
  }, {
    "primaryId" : "PMID:10209294",
    "title" : "Structural characterization, stability and fatty acid-binding properties of two French genetic variants of human serum albumin.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Minchiotti L, etal., Biochim Biophys Acta. 1999 Apr 12;1431(1):223-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:50:04.000-05:00",
    "volume" : "1431",
    "pages" : "223-31",
    "abstract" : "Four bisalbuminemic, unrelated persons were found in Bretagne, France, and their  variant and normal albumins were isolated by DEAE ion exchange chromatography, reduced, carboxymethylated and treated with CNBr. Comparative two-dimensional electrophoresis of the CNBr digests showed that three of the variants were modified in fragment CB4, whereas the fourth had an abnormal fragment CB1. These  fragments were isolated, digested with trypsin and mapped by reverse-phase HPLC.  Sequencing of altered tryptic peptides showed that the three variants modified in CB4 were caused by the same, previously unreported, amino acid substitution: Asp314-->Val (albumin Brest). The fourth, however, was a proalbumin variant with  the change Arg-2-->Cys (albumin Ildut). Both amino acid substitutions can be explained by point mutations in the structural gene: GAT-->GTT (albumin Brest) and CGT-->TGT (albumin Ildut). The proalbumin Ildut is very unstable and already  in vivo it is to a large extent cleaved posttranslationally to Arg-Albumin and normal albumin. Furthermore, we observed that during a lengthy isolation procedure the remaining proalbumin was changed to Arg-Albumin or proalbumin lacking Arg-6. In addition, part of normal albumin had lost Asp1. Gas chromatographic investigations using isolated proteins indicated that albumin Brest has improved in vivo fatty acid-binding properties, whereas the structural  modification(s) of albumin Ildut does not affect fatty acid binding.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Minchiotti",
      "authorRank" : 1,
      "name" : "Minchiotti L",
      "referenceId" : "RGD:A72210"
    }, {
      "firstName" : "U",
      "lastName" : "Kragh-Hansen",
      "authorRank" : 2,
      "name" : "Kragh-Hansen",
      "referenceId" : "RGD:A259128"
    }, {
      "firstName" : "H",
      "lastName" : "Nielsen",
      "authorRank" : 3,
      "name" : "Nielsen H",
      "referenceId" : "RGD:A128168"
    }, {
      "firstName" : "E",
      "lastName" : "Hardy",
      "authorRank" : 4,
      "name" : "Hardy E",
      "referenceId" : "RGD:A73187"
    }, {
      "firstName" : "AY",
      "lastName" : "Mercier",
      "authorRank" : 5,
      "name" : "Mercier",
      "referenceId" : "RGD:A279945"
    }, {
      "firstName" : "M",
      "lastName" : "Galliano",
      "authorRank" : 6,
      "name" : "Galliano M",
      "referenceId" : "RGD:A72209"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071607"
    } ]
  }, {
    "primaryId" : "PMID:10209489",
    "title" : "The MUC6 secretory mucin gene is expressed in a wide variety of epithelial tissues.",
    "datePublished" : "1998-05-01T00:00:00.000-05:00",
    "citation" : "Bartman AE, etal., J Pathol. 1998 Dec;186(4):398-405.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-05-21T13:34:39.000-05:00",
    "volume" : "186",
    "pages" : "398-405",
    "abstract" : "Secretory mucins play an important role in the cytoprotection of epithelial surfaces and are used as tumour markers in a variety of cancers. The MUC6 secretory mucin was originally isolated from a gastric cDNA library. The aim was to determine the specific type and location of MUC6 mucin gene expression in a wide range of human adult and fetal epithelial tissues. In situ hybridization, RNA analysis, and immunohistochemistry were used to quantify and localize mucin gene expression. The data obtained show that MUC6 is highly expressed in gastric mucosa, duodenal Brunner's glands, gall bladder, seminal vesicle, pancreatic centroacinar cells and ducts, and periductal glands of the common bile duct; focal expression is seen in basal endometrial and endocervical glands. MUC6 epitopes were also highly expressed in 7/10 pancreatic cancers and 7/10 cholangiocarcinomas and focally expressed in 4/10 endocervical adenocarcinomas. Expression of MUC6 occurs early in fetal development and was observed in Brunner's glands and pancreatic ducts at 18-19 weeks and in gastric glands at 20 weeks' gestation. The tissue distribution of the MUC6 secretory mucin indicates that it may function to protect epithelial tissues from a wide range of substances. Expression of MUC6 is frequently preserved in pancreatic and bile duct adenocarcinomas, but it is only sparsely expressed in endocervical carcinomas.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AE",
      "lastName" : "Bartman",
      "authorRank" : 1,
      "name" : "Bartman AE",
      "referenceId" : "RGD:A123661"
    }, {
      "firstName" : "MP",
      "lastName" : "Buisine",
      "authorRank" : 2,
      "name" : "Buisine MP",
      "referenceId" : "RGD:A123662"
    }, {
      "firstName" : "JP",
      "lastName" : "Aubert",
      "authorRank" : 3,
      "name" : "Aubert JP",
      "referenceId" : "RGD:A123184"
    }, {
      "firstName" : "GA",
      "lastName" : "Niehans",
      "authorRank" : 4,
      "name" : "Niehans GA",
      "referenceId" : "RGD:A117913"
    }, {
      "firstName" : "NW",
      "lastName" : "Toribara",
      "authorRank" : 5,
      "name" : "Toribara NW",
      "referenceId" : "RGD:A20859"
    }, {
      "firstName" : "YS",
      "lastName" : "Kim",
      "authorRank" : 6,
      "name" : "Kim YS",
      "referenceId" : "RGD:A20087"
    }, {
      "firstName" : "EJ",
      "lastName" : "Kelly",
      "authorRank" : 7,
      "name" : "Kelly EJ",
      "referenceId" : "RGD:A123663"
    }, {
      "firstName" : "JE",
      "lastName" : "Crabtree",
      "authorRank" : 8,
      "name" : "Crabtree JE",
      "referenceId" : "RGD:A123664"
    }, {
      "firstName" : "SB",
      "lastName" : "Ho",
      "authorRank" : 9,
      "name" : "Ho SB",
      "referenceId" : "RGD:A25972"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2325167"
    } ]
  }, {
    "primaryId" : "PMID:10209957",
    "title" : "Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma: expression patterns and effects on in vitro invasive behavior.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Miknyoczki SJ, etal., Int J Cancer. 1999 May 5;81(3):417-27.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-04T13:06:27.000-05:00",
    "volume" : "81",
    "pages" : "417-27",
    "abstract" : "The aggressive and highly metastatic behavior observed in pancreatic ductal adenocarcinoma (PDAC) may be due to autocrine and/or paracrine interactions (tumor/stromal) involving altered expression of peptide growth factors and their corresponding receptors. The neurotrophin (NT) growth factor family and their cognate receptors have been demonstrated to play a role in the invasiveness, chemotactic behavior and tumor cell survival of both neuronal and non-neuronal cancers. We hypothesized that aberrant expression of the NTs and/or the Trk receptors may contribute to the malignant phenotype of PDAC, specifically tumor cell invasiveness, through autocrine and/or paracrine interactions. In this study, we examined the expression of NTs, Trks and p75NGFR by immunohistochemical and in situ hybridization analyses in both normal (n=14) and neoplastic pancreas (n=47) and PDAC-derived cell lines (n=6). Further, we evaluated the effects of various NTs on the in vitro invasive and chemotactic behavior on 6 human PDAC-derived cell lines in a modified Boyden chamber assay. Brain-derived nerve growth factor (BDNF), NT-3, NT-4/5 and Trks A, B and C exhibited diffuse cytoplasmic and membranous immunostaining patterns in both the ducts and the acini of the exocrine pancreas and the islets of the endocrine pancreas of both normal and PDAC specimens. NT expression was primarily within the stromal compartment of the tumor, while Trk expression was weak or absent. We observed a 68%, 64% and 66% increase in the expression of Trks A, B and C, respectively, in the ductal elements of the PDAC samples examined compared with the normal adjacent tissue. Invasiveness of 4 of 6 PDAC cell lines was significantly inhibited (p<0.05) when the cells were incubated with 100 ng/ml NT. However, when select cell lines were incubated with lower concentrations of NT-3 and BDNF (0, 1, 5, 25 and 50 ng/ml), invasiveness was significantly stimulated (p<0.05) through the Matrigel matrix. Collectively, our data suggest the possibility that paracrine and/or autocrine NT-Trk interactions may influence the phenotype (possibly the invasive behavior) of PDAC.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SJ",
      "lastName" : "Miknyoczki",
      "authorRank" : 1,
      "name" : "Miknyoczki SJ",
      "referenceId" : "RGD:A124229"
    }, {
      "firstName" : "D",
      "lastName" : "Lang",
      "authorRank" : 2,
      "name" : "Lang D",
      "referenceId" : "RGD:A39724"
    }, {
      "firstName" : "L",
      "lastName" : "Huang",
      "authorRank" : 3,
      "name" : "Huang L",
      "referenceId" : "RGD:A4095"
    }, {
      "firstName" : "AJ",
      "lastName" : "Klein-Szanto",
      "authorRank" : 4,
      "name" : "Klein-Szanto AJ",
      "referenceId" : "RGD:A12647"
    }, {
      "firstName" : "CA",
      "lastName" : "Dionne",
      "authorRank" : 5,
      "name" : "Dionne CA",
      "referenceId" : "RGD:A96328"
    }, {
      "firstName" : "BA",
      "lastName" : "Ruggeri",
      "authorRank" : 6,
      "name" : "Ruggeri BA",
      "referenceId" : "RGD:A121379"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2325663"
    } ]
  }, {
    "primaryId" : "PMID:10210204",
    "title" : "Comparison of anionic and cationic trypsinogens: the anionic activation domain is more flexible in solution and differs in its mode of BPTI binding in the crystal structure.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Pasternak A, etal., Protein Sci. 1999 Jan;8(1):253-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-22T09:37:24.000-06:00",
    "volume" : "8",
    "pages" : "253-8",
    "abstract" : "Unlike bovine cationic trypsin, rat anionic trypsin retains activity at high pH. This alkaline stability has been attributed to stabilization of the salt bridge between the N-terminal Ile16 and Asp194 by the surface negative charge (Soman K, Yang A-S, Honig B, Fletterick R., 1989, Biochemistry 28:9918-9926). The formation of this salt bridge controls the conformation of the activation domain in trypsin. In this work we probe the structure of rat trypsinogen to determine the effects of the surface negative charge on the activation domain in the absence of the Ile16-Asp194 salt bridge. We determined the crystal structures of the rat trypsin-BPTI complex and the rat trypsinogen-BPTI complex at 1.8 and 2.2 A, respectively. The BPTI complex of rat trypsinogen resembles that of rat trypsin. Surprisingly, the side chain of Ile16 is found in a similar position in both the rat trypsin and trypsinogen complexes, although it is not the N-terminal residue and cannot form the salt bridge in trypsinogen. The resulting position of the activation peptide alters the conformation of the adjacent autolysis loop (residues 142-153). While bovine trypsinogen and trypsin have similar CD spectra, the CD spectrum of rat trypsinogen has only 60% of the intensity of rat trypsin. This lower intensity most likely results from increased flexibility around two conserved tryptophans, which are adjacent to the activation domain. The NMR spectrum of rat trypsinogen contains high field methyl signals as observed in bovine trypsinogen. It is concluded that the activation domain of rat trypsinogen is more flexible than that of bovine trypsinogen, but does not extend further into the protein core.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Pasternak",
      "authorRank" : 1,
      "name" : "Pasternak A",
      "referenceId" : "RGD:A75739"
    }, {
      "firstName" : "D",
      "lastName" : "Ringe",
      "authorRank" : 2,
      "name" : "Ringe D",
      "referenceId" : "RGD:A75740"
    }, {
      "firstName" : "L",
      "lastName" : "Hedstrom",
      "authorRank" : 3,
      "name" : "Hedstrom L",
      "referenceId" : "RGD:A75741"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599969"
    } ]
  }, {
    "primaryId" : "PMID:10210776",
    "title" : "Duration of STAT5 activation influences the response of interleukin-2 receptor alpha gene to different cytokines.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Imbert V and Renauld PR, Eur Cytokine Netw. 1999 Mar;10(1):71-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-28T13:31:28.000-06:00",
    "volume" : "10",
    "pages" : "71-8",
    "abstract" : "Cytokines and growth factors regulate expression of their target genes via the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) signaling pathway. One of the best characterized targets of STAT is the interleukin-2 receptor-alpha (IL-2Ralpha) gene. Its transcription is controlled by interleukin 2 (IL-2) through STAT5 activation. Using the PC60 cell line, in which the role of STAT5 in the regulation of the murine IL-2Ralpha gene by IL-2 has been elucidated, we have compared the response of this gene to IL-2, interleukin-9 (IL-9) and erythropoietin (Epo). IL-2 and IL-9, but not Epo, stimulate cell surface expression of IL-2Ralpha. This correlates with the fact that IL-2 and IL-9 support long-term STAT5 activation whereas Epo only induces transient activation. In cells treated with vanadate, a protein tyrosine phosphatase (PTP) inhibitor, Epo induces prolonged STAT5 activation and strongly stimulates IL-2Ralpha expression. Our study suggests that by controlling the duration of the STAT activation signal, PTP influences the specificity of cytokine signaling.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Imbert",
      "authorRank" : 1,
      "name" : "Imbert V",
      "referenceId" : "RGD:A76279"
    }, {
      "firstName" : "PR",
      "lastName" : "Renauld",
      "authorRank" : 2,
      "name" : "Renauld PR",
      "referenceId" : "RGD:A76280"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600126"
    } ]
  }, {
    "primaryId" : "PMID:10210891",
    "title" : "High levels of hippocampal cholinergic neurostimulating peptide (HCNP) in the CSF of some patients with Alzheimer's disease.",
    "datePublished" : "1998-01-01T00:00:00.000-06:00",
    "citation" : "Tsugu Y, etal., Eur J Neurol. 1998 Nov;5(6):561-569.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-01-20T16:10:56.000-06:00",
    "volume" : "5",
    "pages" : "561-569",
    "abstract" : "Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from the hippocampus of young rats, enhances the cholinergic development of rat medial septal nuclei in vitro. This report concerns the determination of the HCNP content of the cerebrospinal fluid (CSF) of 173 clinically, and of 22 clinico-pathologically defined patients. A radioimmunoassay was used throughout. The HCNP level was relatively uniform among the clinically defined patients; for almost all non-Alzheimer's patients, the level fell within the range delimited by +/- 2 SD of the mean for all patients taken together, and none of them had a level above this range. By contrast, the early-onset Alzheimer's disease patients could be divided on the basis of their HCNP level into two groups, one with high levels (markedly above the mean +/- 2SD range), and the other with levels similar to those of the other patients. The analysis of the CSF samples obtained postmortem revealed that Group I Alzheimer-type dementia (ATD) patients with clinico-pathologically established diagnoses had a strikingly higher level of HCNP than patients with either Group II ATD or cerebral vascular disease. These results suggest that HCNP is involved in certain pathophysiological alterations associated with dementia, and that its determination may be useful in patient evaluation. Copyright 1998 Lippincott Williams & Wilkins",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Tsugu",
      "authorRank" : 1,
      "name" : "Tsugu Y",
      "referenceId" : "RGD:A102859"
    }, {
      "firstName" : "K",
      "lastName" : "Ojika",
      "authorRank" : 2,
      "name" : "Ojika K",
      "referenceId" : "RGD:A32953"
    }, {
      "firstName" : "N",
      "lastName" : "Matsukawa",
      "authorRank" : 3,
      "name" : "Matsukawa N",
      "referenceId" : "RGD:A28389"
    }, {
      "firstName" : "T",
      "lastName" : "Iwase",
      "authorRank" : 4,
      "name" : "Iwase T",
      "referenceId" : "RGD:A14155"
    }, {
      "firstName" : "Y",
      "lastName" : "Otsuka",
      "authorRank" : 5,
      "name" : "Otsuka Y",
      "referenceId" : "RGD:A32949"
    }, {
      "firstName" : "E",
      "lastName" : "Katada",
      "authorRank" : 6,
      "name" : "Katada E",
      "referenceId" : "RGD:A102790"
    }, {
      "firstName" : "S",
      "lastName" : "Mitake",
      "authorRank" : 7,
      "name" : "Mitake S",
      "referenceId" : "RGD:A65489"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2302864"
    } ]
  }, {
    "primaryId" : "PMID:10212000",
    "title" : "Mutation of p53 and K-ras, and loss of heterozygosity of APC in intrahepatic cholangiocarcinoma.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kang YK, etal., Lab Invest. 1999 Apr;79(4):477-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-19T13:37:47.000-05:00",
    "volume" : "79",
    "pages" : "477-83",
    "abstract" : "Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor in liver; however, the carcinogenic mechanism of ICC is poorly understood. To analyze the molecular carcinogenesis of ICC, we examined the alterations of the p53, APC, and K-ras genes in 40 surgically resected ICC cases. The single-strand conformation polymorphism/sequencing revealed a p53 mutation in 12 cases (30%). An immunohistochemical overexpression of the p53 gene was detected in 10 cases (25%). The PCR/RFLP showed loss of heterozygosity of APC in 4 of 17 informative cases (23.5%). And the PCR/RFLP assay of K-ras codon 12 revealed the mutation in nine cases (22.5%). Twenty-one cases (52.5%) showed an alteration of at least one of the examined genes, and six (15%) carried an abnormality in more than two genes. The analysis of the clinicopathologic findings disclosed a significant relationship between the genetic alteration and gross type of the tumor: the p53 mutation was prominent in the ICC of mass-forming type, and K-ras mutation occurred more frequently in the ICC of periductal extension type (p < 0.05). These data suggest that each of the examined genes is involved in the development of ICC and that the p53 and K-ras mutation may play a role in the tumor growth pattern.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YK",
      "lastName" : "Kang",
      "authorRank" : 1,
      "name" : "Kang YK",
      "referenceId" : "RGD:A13046"
    }, {
      "firstName" : "WH",
      "lastName" : "Kim",
      "authorRank" : 2,
      "name" : "Kim WH",
      "referenceId" : "RGD:A120671"
    }, {
      "firstName" : "HW",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee HW",
      "referenceId" : "RGD:A109929"
    }, {
      "firstName" : "HK",
      "lastName" : "Lee",
      "authorRank" : 4,
      "name" : "Lee HK",
      "referenceId" : "RGD:A8669"
    }, {
      "firstName" : "YI",
      "lastName" : "Kim",
      "authorRank" : 5,
      "name" : "Kim YI",
      "referenceId" : "RGD:A47111"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317205"
    } ]
  }, {
    "primaryId" : "PMID:10212142",
    "title" : "The Sec61 complex is located in both the ER and the ER-Golgi intermediate compartment.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Greenfield JJ and High S, J Cell Sci 1999 May;112 ( Pt 10):1477-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-31T14:26:02.000-05:00",
    "volume" : "112 ( Pt 10)",
    "pages" : "1477-86",
    "abstract" : "The heteromeric Sec61 complex is composed of (alpha), beta and (gamma) subunits and forms the core of the mammalian ER translocon. Oligomers of the Sec61 complex form a transmembrane channel where proteins are translocated across and integrated into the ER membrane. We have studied the subcellular localisation of the Sec61 complex using both wild-type COS1 cells and cells transfected with GFP-tagged Sec61(alpha). By double labelling immunofluorescence microscopy the GFP-tagged Sec61(alpha) was found in both the ER and the ER-Golgi intermediate compartment (ERGIC) but not in the trans-Golgi network. Immunofluorescence studies of endogenous Sec61beta and Sec61(gamma) showed that these proteins are also located in both the ER and the ERGIC. Using the alternative strategy of subcellular fractionation, we have shown that wild-type Sec61(alpha), beta and (gamma), and GFP-tagged Sec61(alpha), are all present in both the ER and the ERGIC/Golgi fractions of the gradient. The presence of the Sec61 subunits in a post-ER compartment suggests that these proteins can escape the ER and be recycled back, despite the fact that none of them contain any known membrane protein retrieval signals such as cytosolic di-lysine or di-arginine motifs. We also found that another translocon component, the glycoprotein TRAM, was present in post-ER compartments as demonstrated by subcellular fractionation. Our data indicate that the core components of the mammalian ER translocon are not permanently resident in the ER, but rather that they are maintained in the ER by a specific retrieval mechanism.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JJ",
      "lastName" : "Greenfield",
      "authorRank" : 1,
      "name" : "Greenfield JJ",
      "referenceId" : "RGD:A55101"
    }, {
      "firstName" : "S",
      "lastName" : "High",
      "authorRank" : 2,
      "name" : "High S",
      "referenceId" : "RGD:A55102"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549467"
    } ]
  }, {
    "primaryId" : "PMID:10212192",
    "title" : "Expression and functional role of the gamma subunit of the Na, K-ATPase in mammalian cells.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Therien AG, etal., J Biol Chem 1999 Apr 30;274(18):12252-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-04T10:09:09.000-05:00",
    "volume" : "274",
    "pages" : "12252-6",
    "abstract" : "The functional role of the gamma subunit of the Na,K-ATPase was studied using rat gamma cDNA-transfected HEK-293 cells and an antiserum (gammaC33) specific for gamma. Although the sequence for gamma was verified and shown to be larger (7237 Da) than first reported, it still comprises a single initiator methionine despite the expression of a gammaC33-reactive doublet on immunoblots. Kinetic analysis of the enzyme of transfected compared with control cells and of gammaC33-treated kidney pumps shows that gamma regulates the apparent affinity for ATP. Thus, gamma-transfected cells have a decreased K'ATP as shown in measurements of (i) K'ATP of Na,K-ATPase activity and (ii) K+ inhibition of Na-ATPase at 1 microM ATP. Consistent with the behavior of gamma-transfected cells, gammaC33 pretreatment increases K'ATP of the kidney enzyme and K+ inhibition (1 microM ATP) of both kidney and gamma-transfected cells. These results are consistent with previous findings that an antiserum raised against the pig gamma subunit stabilizes the E2(K) form of the enzyme (Therien, A. G., Goldshleger, R., Karlish, S. J., and Blostein, R. (1997) J. Biol. Chem. 272, 32628-32634). Overall, our data demonstrate that gamma is a tissue (kidney)-specific regulator of the Na,K-ATPase that can increase the apparent affinity of the enzyme for ATP in a manner that is reversible by anti-gamma antiserum.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AG",
      "lastName" : "Therien",
      "authorRank" : 1,
      "name" : "Therien AG",
      "referenceId" : "RGD:A43766"
    }, {
      "firstName" : "SJ",
      "lastName" : "Karlish",
      "authorRank" : 2,
      "name" : "Karlish SJ",
      "referenceId" : "RGD:A43767"
    }, {
      "firstName" : "R",
      "lastName" : "Blostein",
      "authorRank" : 3,
      "name" : "Blostein R",
      "referenceId" : "RGD:A43768"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299857"
    } ]
  }, {
    "primaryId" : "PMID:10212223",
    "title" : "A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a heparin-binding growth factor midkine. Involvement of arginine 78 of midkine in the high affinity binding to PTPzeta.",
    "datePublished" : "1999-04-30T00:00:00.000-05:00",
    "citation" : "Maeda N, etal., J Biol Chem. 1999 Apr 30;274(18):12474-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-04-10T03:02:01.000-05:00",
    "volume" : "274",
    "pages" : "12474-9",
    "abstract" : "Midkine is a 13-kDa heparin-binding growth factor with 45% sequence identity to pleiotrophin. Pleiotrophin has been demonstrated to bind to protein-tyrosine phosphatase zeta (PTPzeta) with high affinity. In this study, we examined the binding of midkine to PTPzeta by solid-phase binding assay. Midkine and pleiotrophin binding to PTPzeta were equally inhibited by soluble pleiotrophin and also by some specific glycosaminoglycans. For both bindings, Scatchard analysis revealed low (3.0 nM) and high (0.58 nM) affinity binding sites. These results suggested that PTPzeta is a common receptor for midkine and pleiotrophin. Midkine is structurally divided into the N- and C-terminal halves, and the latter exhibited full activity for PTPzeta binding and neuronal migration induction. The C-terminal half contains two heparin-binding sites consisting of clusters of basic amino acids, Clusters I and II. A mutation at Arg78 in Cluster I resulted in loss of the high affinity binding and reduced neuronal migration-inducing activity, while mutations at Lys83 and Lys84 in Cluster II showed almost no effect on either activity. Chondroitinase ABC-treated PTPzeta exhibited similar low affinity binding both to the native midkine and midkine mutants at Arg78. These results suggested that Arg78 in midkine plays an essential role in high affinity binding to PTPzeta by interacting with the chondroitin sulfate portion of this receptor.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Maeda",
      "authorRank" : 1,
      "name" : "Maeda N",
      "referenceId" : "RGD:A7278"
    }, {
      "firstName" : "K",
      "lastName" : "Ichihara-Tanaka",
      "authorRank" : 2,
      "name" : "Ichihara-Tanaka K",
      "referenceId" : "RGD:A69094"
    }, {
      "firstName" : "T",
      "lastName" : "Kimura",
      "authorRank" : 3,
      "name" : "Kimura T",
      "referenceId" : "RGD:A6130"
    }, {
      "firstName" : "K",
      "lastName" : "Kadomatsu",
      "authorRank" : 4,
      "name" : "Kadomatsu K",
      "referenceId" : "RGD:A24932"
    }, {
      "firstName" : "T",
      "lastName" : "Muramatsu",
      "authorRank" : 5,
      "name" : "Muramatsu T",
      "referenceId" : "RGD:A22404"
    }, {
      "firstName" : "M",
      "lastName" : "Noda",
      "authorRank" : 6,
      "name" : "Noda M",
      "referenceId" : "RGD:A6115"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14397575"
    } ]
  }, {
    "primaryId" : "PMID:10212238",
    "title" : "The peroxin Pex14p. cDNA cloning by functional complementation on a Chinese hamster ovary cell mutant, characterization, and functional analysis.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Shimizu N, etal., J Biol Chem 1999 Apr 30;274(18):12593-604.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-07-31T12:14:23.000-05:00",
    "volume" : "274",
    "pages" : "12593-604",
    "abstract" : "Rat cDNA encoding a 376-amino acid peroxin was isolated by functional complementation of a peroxisome-deficient Chinese hamster ovary cell mutant, ZP110, of complementation group 14 (CG14). The primary sequence showed 28 and 24% amino acid identity with the yeast Pex14p from Hansenula polymorpha and Saccharomyces cerevisiae, respectively; therefore, we termed this cDNA rat PEX14 (RnPEX14). Human and Chinese hamster Pex14p showed 96 and 94% identity to rat Pex14p, except that both Pex14p comprised 377 amino acids. Pex14p was characterized as an integral membrane protein of peroxisomes, exposing its N- and C-terminal parts to the cytosol. Pex14p interacts with both Pex5p and Pex7p, the receptors for peroxisome targeting signal type 1 (PTS1) and PTS2, respectively, together with the receptors' cargoes, PTS1 and PTS2 proteins. Mutation in PEX14 from ZP161, the same CG as ZP110, was determined by reverse transcription-PCR as follows. A 133-base pair deletion at nucleotide residues 37-169 in one allele created a termination codon at 40-42; in addition to this mutation, 103 base pairs were deleted at positions 385-487, resulting in the second termination immediately downstream the second deletion site in the other allele. Neither of these two mutant forms of Pex14p restored peroxisome biogenesis in ZP110 and ZP161, thereby demonstrating PEX14 to be responsible for peroxisome deficiency in CG14.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Shimizu",
      "authorRank" : 1,
      "name" : "Shimizu N",
      "referenceId" : "RGD:A5024"
    }, {
      "firstName" : "R",
      "lastName" : "Itoh",
      "authorRank" : 2,
      "name" : "Itoh R",
      "referenceId" : "RGD:A5025"
    }, {
      "firstName" : "Y",
      "lastName" : "Hirono",
      "authorRank" : 3,
      "name" : "Hirono Y",
      "referenceId" : "RGD:A5026"
    }, {
      "firstName" : "H",
      "lastName" : "Otera",
      "authorRank" : 4,
      "name" : "Otera H",
      "referenceId" : "RGD:A5027"
    }, {
      "firstName" : "K",
      "lastName" : "Ghaedi",
      "authorRank" : 5,
      "name" : "Ghaedi K",
      "referenceId" : "RGD:A5028"
    }, {
      "firstName" : "K",
      "lastName" : "Tateishi",
      "authorRank" : 6,
      "name" : "Tateishi K",
      "referenceId" : "RGD:A5029"
    }, {
      "firstName" : "S",
      "lastName" : "Tamura",
      "authorRank" : 7,
      "name" : "Tamura S",
      "referenceId" : "RGD:A5030"
    }, {
      "firstName" : "K",
      "lastName" : "Okumoto",
      "authorRank" : 8,
      "name" : "Okumoto K",
      "referenceId" : "RGD:A5031"
    }, {
      "firstName" : "T",
      "lastName" : "Harano",
      "authorRank" : 9,
      "name" : "Harano T",
      "referenceId" : "RGD:A5032"
    }, {
      "firstName" : "S",
      "lastName" : "Mukai",
      "authorRank" : 10,
      "name" : "Mukai S",
      "referenceId" : "RGD:A5033"
    }, {
      "firstName" : "Y",
      "lastName" : "Fujiki",
      "authorRank" : 11,
      "name" : "Fujiki Y",
      "referenceId" : "RGD:A161490"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68287"
    } ]
  }, {
    "primaryId" : "PMID:10212242",
    "title" : "Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Hasegawa M, etal., J Biol Chem. 1999 Apr 30;274(18):12626-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:39:30.000-05:00",
    "volume" : "274",
    "pages" : "12626-31",
    "abstract" : "Mechanisms for selective targeting to unique subcellular sites play an important  role in determining the substrate specificities of protein kinases. Here we show  that stress-activated protein kinase-3 (SAPK3, also called ERK6 and p38gamma), a  member of the mitogen-activated protein kinase family that is abundantly expressed in skeletal muscle, binds through its carboxyl-terminal sequence -KETXL to the PDZ domain of alpha1-syntrophin. SAPK3 phosphorylates alpha1-syntrophin at serine residues 193 and 201 in vitro and phosphorylation is dependent on binding  to the PDZ domain of alpha1-syntrophin. In skeletal muscle SAPK3 and alpha1-syntrophin co-localize at the neuromuscular junction, and both proteins can be co-immunoprecipitated from transfected COS cell lysates. Phosphorylation of a PDZ domain-containing protein by an associated protein kinase is a novel mechanism for determining both the localization and the substrate specificity of  a protein kinase.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Hasegawa",
      "authorRank" : 1,
      "name" : "Hasegawa M",
      "referenceId" : "RGD:A9017"
    }, {
      "firstName" : "A",
      "lastName" : "Cuenda",
      "authorRank" : 2,
      "name" : "Cuenda A",
      "referenceId" : "RGD:A53698"
    }, {
      "firstName" : "MG",
      "lastName" : "Spillantini",
      "authorRank" : 3,
      "name" : "Spillantini MG",
      "referenceId" : "RGD:A30936"
    }, {
      "firstName" : "GM",
      "lastName" : "Thomas",
      "authorRank" : 4,
      "name" : "Thomas GM",
      "referenceId" : "RGD:A53693"
    }, {
      "firstName" : "V",
      "lastName" : "Buee-Scherrer",
      "authorRank" : 5,
      "name" : "Buee-Scherrer V",
      "referenceId" : "RGD:A87527"
    }, {
      "firstName" : "P",
      "lastName" : "Cohen",
      "authorRank" : 6,
      "name" : "Cohen P",
      "referenceId" : "RGD:A20611"
    }, {
      "firstName" : "M",
      "lastName" : "Goedert",
      "authorRank" : 7,
      "name" : "Goedert M",
      "referenceId" : "RGD:A8105"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554048"
    } ]
  }, {
    "primaryId" : "PMID:10212299",
    "title" : "Peripheral myelin protein 22 and protein zero: a novel association in peripheral  nervous system myelin.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "D'Urso D, etal., J Neurosci. 1999 May 1;19(9):3396-403.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-07-11T08:16:57.000-05:00",
    "volume" : "19",
    "pages" : "3396-403",
    "abstract" : "Mutations found in the two major glycosylated transmembrane proteins of the PNS myelin, the peripheral myelin protein zero (P0) and peripheral myelin protein 22  (PMP22), have been independently associated with the most common hereditary demyelinating peripheral neuropathies. Genotype-phenotype correlations in humans  and transgenic animals have provided functional evidence that P0 and PMP22 are involved in formation and maintenance of compact myelin. Here, we demonstrate for the first time that P0 and PMP22 proteins form complexes in the myelin membrane,  as shown by coimmunoprecipitation experiments, and that glycosylation is not involved in mediating these interactions. Complex formation was also detected when the two proteins were coexpressed in heterologous cells. In transfected cells, P0 and PMP22 are recruited and colocalize at the apposed plasma membranes  of expressors as shown by confocal microscopy. These findings provide a new basis for a better understanding of myelin assembly and of the pathomechanisms involved in demyelinating peripheral neuropathies. Furthermore, these results propose a possible explanation why alterations in either of these molecules are sufficient  to destabilize the myelin structure and cause a similar disease phenotype.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "D'Urso",
      "authorRank" : 1,
      "name" : "D'Urso D",
      "referenceId" : "RGD:A54054"
    }, {
      "firstName" : "P",
      "lastName" : "Ehrhardt",
      "authorRank" : 2,
      "name" : "Ehrhardt",
      "referenceId" : "RGD:A203754"
    }, {
      "firstName" : "HW",
      "lastName" : "Muller",
      "authorRank" : 3,
      "name" : "Muller HW",
      "referenceId" : "RGD:A12451"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10047163"
    } ]
  }, {
    "primaryId" : "PMID:10212300",
    "title" : "Insertion of a retrotransposon in Mbp disrupts mRNA splicing and myelination in a new mutant rat.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "O'Connor LT, etal., J Neurosci 1999 May 1;19(9):3404-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-27T17:29:53.000-05:00",
    "volume" : "19",
    "pages" : "3404-13",
    "abstract" : "Our understanding of myelination has been greatly enhanced via the study of spontaneous mutants that harbor a defect in a gene encoding one of the major myelin proteins (myelin mutants). In this study, we describe a unique genetic defect in a new myelin mutant called the Long Evans shaker (les) rat that causes severe dysmyelination of the CNS. Myelin deficits result from disruption of the myelin basic protein (Mbp) gene caused by the insertion of an endogenous retrotransposon [early transposons (ETn) element] into a noncoding region (intron 3) of the gene. The ETn element alters the normal splicing dynamics of MBP mRNA, leading to a dramatic reduction in the levels of full-length isoforms (<5% of normal) and the appearance of improperly spliced, chimeric transcripts. Although these aberrant transcripts contain proximal coding regions of the MBP gene (exons 1-3), they are unable to encode functional proteins required to maintain the structural integrity of the myelin sheath. These chimeric transcripts seem capable, however, of producing the necessary signal to initiate and coordinate myelin gene expression because normal numbers of mature oligodendrocytes synthesizing abundant levels of other myelin proteins are present in the mutant CNS. The les rat is thus an excellent model to study alternative functions of MBP beyond its well characterized role in myelin compaction.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LT",
      "lastName" : "O'Connor",
      "authorRank" : 1,
      "name" : "O'Connor LT",
      "referenceId" : "RGD:A54006"
    }, {
      "firstName" : "BD",
      "lastName" : "Goetz",
      "authorRank" : 2,
      "name" : "Goetz BD",
      "referenceId" : "RGD:A54007"
    }, {
      "firstName" : "JM",
      "lastName" : "Kwiecien",
      "authorRank" : 3,
      "name" : "Kwiecien JM",
      "referenceId" : "RGD:A54004"
    }, {
      "firstName" : "KH",
      "lastName" : "Delaney",
      "authorRank" : 4,
      "name" : "Delaney KH",
      "referenceId" : "RGD:A54008"
    }, {
      "firstName" : "AL",
      "lastName" : "Fletch",
      "authorRank" : 5,
      "name" : "Fletch AL",
      "referenceId" : "RGD:A54009"
    }, {
      "firstName" : "ID",
      "lastName" : "Duncan",
      "authorRank" : 6,
      "name" : "Duncan ID",
      "referenceId" : "RGD:A54010"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358763"
    } ]
  }, {
    "primaryId" : "PMID:10212301",
    "title" : "Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Fujimura M, etal., J Neurosci. 1999 May 1;19(9):3414-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-06-21T13:53:47.000-05:00",
    "volume" : "19",
    "pages" : "3414-22",
    "abstract" : "Recent studies have shown that release of mitochondrial cytochrome c is a critical step in the apoptosis process. We have reported that cytosolic redistribution of cytochrome c in vivo occurred after transient focal cerebral ischemia (FCI) in rats and preceded the peak of DNA fragmentation. Although the involvement of reactive oxygen species in the cytosolic redistribution of cytochrome c in vitro has been suggested, the detailed mechanism by which cytochrome c release is mediated in vivo has not yet been established. Also, the role of mitochondrial oxidative stress in cytochrome c release is unknown. These issues can be addressed using knock-out mutants that are deficient in the level of the mitochondrial antioxidant manganese superoxide dismutase (Mn-SOD). In this study we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and heterozygous knock-outs of the Mn-SOD gene (Sod2 -/+) after permanent FCI, in which apoptosis is assumed to participate. Cytosolic cytochrome c was detected as early as 1 hr after ischemia, and correspondingly, mitochondrial cytochrome c showed a significant reduction 2 hr after ischemia (p < 0.01). Cytosolic accumulation of cytochrome c was significantly higher in Sod2 -/+ mice compared with wild-type animals (p < 0.05). N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone (z-VAD.FMK), a nonselective caspase inhibitor, did not affect cytochrome c release after ischemia. A significant amount of DNA laddering was detected 24 hr after ischemia and increased in Sod2 -/+ mice. These data suggest that Mn-SOD blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after permanent FCI.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Fujimura",
      "authorRank" : 1,
      "name" : "Fujimura M",
      "referenceId" : "RGD:A9382"
    }, {
      "firstName" : "Y",
      "lastName" : "Morita-Fujimura",
      "authorRank" : 2,
      "name" : "Morita-Fujimura Y",
      "referenceId" : "RGD:A84794"
    }, {
      "firstName" : "M",
      "lastName" : "Kawase",
      "authorRank" : 3,
      "name" : "Kawase M",
      "referenceId" : "RGD:A76043"
    }, {
      "firstName" : "JC",
      "lastName" : "Copin",
      "authorRank" : 4,
      "name" : "Copin JC",
      "referenceId" : "RGD:A84795"
    }, {
      "firstName" : "B",
      "lastName" : "Calagui",
      "authorRank" : 5,
      "name" : "Calagui B",
      "referenceId" : "RGD:A84796"
    }, {
      "firstName" : "CJ",
      "lastName" : "Epstein",
      "authorRank" : 6,
      "name" : "Epstein CJ",
      "referenceId" : "RGD:A36066"
    }, {
      "firstName" : "PH",
      "lastName" : "Chan",
      "authorRank" : 7,
      "name" : "Chan PH",
      "referenceId" : "RGD:A65437"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1625695"
    } ]
  }, {
    "primaryId" : "PMID:10212487",
    "title" : "Norepinephrine exocytosis stimulated by alpha-latrotoxin requires both external and stored Ca2+ and is mediated by latrophilin, G proteins and phospholipase C.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Rahman MA, etal., Philos Trans R Soc Lond B Biol Sci. 1999 Feb 28;354(1381):379-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-11-14T10:34:37.000-06:00",
    "volume" : "354",
    "pages" : "379-86",
    "abstract" : "alpha-latrotoxin (LTX) stimulates massive release of neurotransmitters by binding to a heptahelical transmembrane protein, latrophilin. Our experiments demonstrate that latrophilin is a G-protein-coupled receptor that specifically associates with heterotrimeric G proteins. The latrophilin-G protein complex is very stable in the presence of GDP but dissociates when incubated with GTP, suggesting a functional interaction. As revealed by immunostaining, latrophilin interacts with G alpha q/11 and G alpha o but not with G alpha s, G alpha i or G alpha z, indicating that this receptor may couple to several G proteins but it is not promiscuous. The mechanisms underlying LTX-evoked norepinephrine secretion from rat brain nerve terminals were also studied. In the presence of extracellular Ca2+, LTX triggers vesicular exocytosis because botulinum neurotoxins E, Cl or tetanus toxin inhibit the Ca(2+)-dependent component of the toxin-evoked release. Based on (i) the known involvement of G alpha q in the regulation of inositol-1,4,5-triphosphate generation and (ii) the requirement for Ca2+ in LTX action, we tested the effect of inhibitors of Ca2+ mobilization on the toxin-evoked norepinephrine release. It was found that aminosteroid U73122, which inhibits the coupling of G proteins to phospholipase C, blocks the Ca(2+)-dependent toxin's action. Thapsigargin, which depletes intracellular Ca2+ stores, also potently decreases the effect of LTX in the presence of extracellular Ca2+. On the other hand, clostridial neurotoxins or drugs interfering with Ca2+ metabolism do not inhibit the Ca2(+)-independent component of LTX-stimulated release. In the absence of Ca2+, the toxin induces in the presynaptic membrane non-selective pores permeable to small fluorescent dyes; these pores may allow efflux of neurotransmitters from the cytoplasm. Our results suggest that LTX stimulates norepinephrine exocytosis only in the presence of external Ca2+ provided intracellular Ca2+ stores are unperturbed and that latrophilin, G proteins and phospholipase C may mediate the mobilization of stored Ca2+, which then triggers secretion.",
    "issueName" : "1381",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MA",
      "lastName" : "Rahman",
      "authorRank" : 1,
      "name" : "Rahman MA",
      "referenceId" : "RGD:A17287"
    }, {
      "firstName" : "AC",
      "lastName" : "Ashton",
      "authorRank" : 2,
      "name" : "Ashton AC",
      "referenceId" : "RGD:A101842"
    }, {
      "firstName" : "FA",
      "lastName" : "Meunier",
      "authorRank" : 3,
      "name" : "Meunier FA",
      "referenceId" : "RGD:A101843"
    }, {
      "firstName" : "BA",
      "lastName" : "Davletov",
      "authorRank" : 4,
      "name" : "Davletov BA",
      "referenceId" : "RGD:A17281"
    }, {
      "firstName" : "JO",
      "lastName" : "Dolly",
      "authorRank" : 5,
      "name" : "Dolly JO",
      "referenceId" : "RGD:A101844"
    }, {
      "firstName" : "YA",
      "lastName" : "Ushkaryov",
      "authorRank" : 6,
      "name" : "Ushkaryov YA",
      "referenceId" : "RGD:A101845"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2302006"
    } ]
  }, {
    "primaryId" : "PMID:10212842",
    "title" : "Genetic models for non insulin dependent diabetes mellitus in rodents.",
    "datePublished" : "1998-08-01T00:00:00.000-05:00",
    "citation" : "Kim JH, etal., J Basic Clin Physiol Pharmacol 1998;9(2-4):325-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-05T14:22:50.000-05:00",
    "volume" : "9",
    "pages" : "325-45",
    "abstract" : "Efforts to identify human genes with major effects on insulin resistance and type II diabetes have yet to be successful because of the technical difficulties associated with the analysis of complex traits in humans. Animal models, particularly the rodent models with their well developed genetic tools, and their genetic similarity to humans, offer an alternate approach to access genes important in the etiology of diabetes. This approach is validated by the remarkable progress that has been made in the identification and characterization of the genes mutated in five monogenic mouse models of obesity. Identification of these genes has led to new insights into the etiology of obesity and provided promising targets for therapeutic intervention. Arguably, genetic animal models could do the same for our understanding of diabetes. In this brief review, we introduce rodent models of type II diabetes and report on the state of their genetic analyses.",
    "issueName" : "2-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JH",
      "lastName" : "Kim",
      "authorRank" : 1,
      "name" : "Kim JH",
      "referenceId" : "RGD:A157311"
    }, {
      "firstName" : "PM",
      "lastName" : "Nishina",
      "authorRank" : 2,
      "name" : "Nishina PM",
      "referenceId" : "RGD:A11080"
    }, {
      "firstName" : "JK",
      "lastName" : "Naggert",
      "authorRank" : 3,
      "name" : "Naggert JK",
      "referenceId" : "RGD:A11081"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619673"
    } ]
  }, {
    "primaryId" : "PMID:1021286",
    "title" : "Spectrophotometric determination of quinine, emethine and ephedrine in pharmaceutical preparations with tetrabromophenolphthalein ethyl ester by solvent extraction.",
    "datePublished" : "1976-04-01T00:00:00.000-06:00",
    "citation" : "Sakai T, etal., Chem Pharm Bull (Tokyo). 1976 Jun;24(6):1254-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:30:03.000-05:00",
    "volume" : "24",
    "pages" : "1254-9",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Sakai",
      "authorRank" : 1,
      "name" : "Sakai T",
      "referenceId" : "RGD:A21002"
    }, {
      "firstName" : "I",
      "lastName" : "Hara",
      "authorRank" : 2,
      "name" : "Hara I",
      "referenceId" : "RGD:A48626"
    }, {
      "firstName" : "M",
      "lastName" : "Tsubouchi",
      "authorRank" : 3,
      "name" : "Tsubouchi",
      "referenceId" : "RGD:A284522"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073432"
    } ]
  }, {
    "primaryId" : "PMID:10213452",
    "title" : "Kainate-elicited seizures induce mRNA encoding a CaMK-related peptide: a putative modulator of kinase activity in rat hippocampus.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Vreugdenhil E, etal., J Neurobiol 1999 Apr;39(1):41-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-21T16:23:20.000-05:00",
    "volume" : "39",
    "pages" : "41-50",
    "abstract" : "By means of differential display techniques, we have previously identified an mRNA transcript whose expression is highly induced in the rat hippocampus by kainate-elicited seizures. Here, we report the cloning of a corresponding cDNA encoding a 55-amino-acid, serine-rich peptide which contains four predicted phosphorylation sites. The peptide was designated CaMK-related peptide (CARP) as it shares significant amino acid sequence identity with part of a novel putative calcium/calmodulin-dependent kinase (CaMK-VI) that was also cloned in this study. It appears that CARP and CaMK-VI are derived from the same gene through differential splicing. Intriguingly, CARP also exhibits 64% amino acid sequence identity with the C-terminal part of human doublecortin, encoded by a recently identified gene which is mutated in patients with X-linked lissencephaly and the double-cortex syndrome. In addition, the structure of CARP resembles the autoinhibitory, serine-rich N-terminal domain of CaMK-IV, suggesting a possible modulatory role of CARP with respect to CaMK activity. Northern blot analysis and in situ hybridization experiments showed that CARP mRNA is specifically induced by kainate-elicited seizures in the dentate gyrus and in the pyramidal layers CA1 and CA2, but not in CA3. In contrast, kainate-induced seizures did not change the level of expression of the CaMK-VI gene. We propose that CARP induction leads to the modulation of kinase activity in specific subregions of the rat hippocampus, providing a negative feedback mechanism for seizure-induced kinases.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Vreugdenhil",
      "authorRank" : 1,
      "name" : "Vreugdenhil E",
      "referenceId" : "RGD:A15924"
    }, {
      "firstName" : "N",
      "lastName" : "Datson",
      "authorRank" : 2,
      "name" : "Datson N",
      "referenceId" : "RGD:A15925"
    }, {
      "firstName" : "B",
      "lastName" : "Engels",
      "authorRank" : 3,
      "name" : "Engels B",
      "referenceId" : "RGD:A15926"
    }, {
      "firstName" : "J",
      "lastName" : "De Jong",
      "authorRank" : 4,
      "name" : "De Jong J",
      "referenceId" : "RGD:A15927"
    }, {
      "firstName" : "S",
      "lastName" : "Van Koningsbruggen",
      "authorRank" : 5,
      "name" : "Van Koningsbruggen S",
      "referenceId" : "RGD:A15928"
    }, {
      "firstName" : "M",
      "lastName" : "Schaaf",
      "authorRank" : 6,
      "name" : "Schaaf M",
      "referenceId" : "RGD:A15929"
    }, {
      "firstName" : "ER",
      "lastName" : "De Kloet",
      "authorRank" : 7,
      "name" : "De Kloet ER",
      "referenceId" : "RGD:A15930"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:631963"
    } ]
  }, {
    "primaryId" : "PMID:10213492",
    "title" : "Dominant negative effect of the APC1309 mutation: a possible explanation for genotype-phenotype correlations in familial adenomatous polyposis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Dihlmann S, etal., Cancer Res. 1999 Apr 15;59(8):1857-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:43:55.000-05:00",
    "volume" : "59",
    "pages" : "1857-60",
    "abstract" : "Inactivation of the adenomatous polyposis coli (APC) gene product initiates colorectal tumorigenesis. Patients with familial APC (FAP) carry germ-line mutations in the APC gene and develop multiple colorectal adenomas and subsequent carcinomas early in life. The severity of the disease correlates with the position of the inherited APC mutation (genotype-phenotype correlation). Together with the fact that both germ-line and sporadic APC mutations cluster in the central region of the APC gene, this points to a dominant negative effect of certain APC mutants. Loss of APC function was recently shown to result in enhanced beta-catenin-/Tcf-mediated transcription in colon epithelial cells. Here, we provide experimental evidence for a dominant negative effect of APC gene products associated with severe polyposis. Wild-type APC activity in beta-catenin-/Tcf-mediated transcription was strongly inhibited by a mutant APC that is truncated at codon 1309. In contrast, mutant APC gene products that are associated with attenuated polyposis (codon 386 or 1465) interfered only weakly with wild-type APC activity. These results suggest a molecular explanation for the genotype-phenotype correlation in FAP patients and support the idea that colorectal tumor growth might be, in part, driven by selection for a mutation in  the mutation cluster region.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Dihlmann",
      "authorRank" : 1,
      "name" : "Dihlmann",
      "referenceId" : "RGD:A264959"
    }, {
      "firstName" : "J",
      "lastName" : "Gebert",
      "authorRank" : 2,
      "name" : "Gebert",
      "referenceId" : "RGD:A251604"
    }, {
      "firstName" : "A",
      "lastName" : "Siermann",
      "authorRank" : 3,
      "name" : "Siermann",
      "referenceId" : "RGD:A264960"
    }, {
      "firstName" : "C",
      "lastName" : "Herfarth",
      "authorRank" : 4,
      "name" : "Herfarth",
      "referenceId" : "RGD:A264961"
    }, {
      "firstName" : "M",
      "lastName" : "Von Knebel Doeberitz",
      "authorRank" : 5,
      "name" : "Von Knebel Doeberitz M",
      "referenceId" : "RGD:A93649"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066451"
    } ]
  }, {
    "primaryId" : "PMID:10213691",
    "title" : "Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Kamura T, etal., Science. 1999 Apr 23;284(5414):657-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-09-23T16:59:23.000-05:00",
    "volume" : "284",
    "pages" : "657-61",
    "abstract" : "The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G1 to S cell cycle transition. These findings provide a further link between VHL and the cellular ubiquitination machinery.",
    "issueName" : "5414",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kamura",
      "authorRank" : 1,
      "name" : "Kamura T",
      "referenceId" : "RGD:A35495"
    }, {
      "firstName" : "DM",
      "lastName" : "Koepp",
      "authorRank" : 2,
      "name" : "Koepp DM",
      "referenceId" : "RGD:A55905"
    }, {
      "firstName" : "MN",
      "lastName" : "Conrad",
      "authorRank" : 3,
      "name" : "Conrad MN",
      "referenceId" : "RGD:A100303"
    }, {
      "firstName" : "D",
      "lastName" : "Skowyra",
      "authorRank" : 4,
      "name" : "Skowyra D",
      "referenceId" : "RGD:A100304"
    }, {
      "firstName" : "RJ",
      "lastName" : "Moreland",
      "authorRank" : 5,
      "name" : "Moreland RJ",
      "referenceId" : "RGD:A18874"
    }, {
      "firstName" : "O",
      "lastName" : "Iliopoulos",
      "authorRank" : 6,
      "name" : "Iliopoulos O",
      "referenceId" : "RGD:A100305"
    }, {
      "firstName" : "WS",
      "lastName" : "Lane",
      "authorRank" : 7,
      "name" : "Lane WS",
      "referenceId" : "RGD:A104579"
    }, {
      "firstName" : "JR",
      "lastName" : "Kaelin WG",
      "authorRank" : 8,
      "name" : "Kaelin WG JR",
      "referenceId" : "RGD:A44549"
    }, {
      "firstName" : "SJ",
      "lastName" : "Elledge",
      "authorRank" : 9,
      "name" : "Elledge SJ",
      "referenceId" : "RGD:A20045"
    }, {
      "firstName" : "RC",
      "lastName" : "Conaway",
      "authorRank" : 10,
      "name" : "Conaway RC",
      "referenceId" : "RGD:A19251"
    }, {
      "firstName" : "JW",
      "lastName" : "Harper",
      "authorRank" : 11,
      "name" : "Harper JW",
      "referenceId" : "RGD:A46013"
    }, {
      "firstName" : "JW",
      "lastName" : "Conaway",
      "authorRank" : 12,
      "name" : "Conaway JW",
      "referenceId" : "RGD:A19252"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301042"
    } ]
  }, {
    "primaryId" : "PMID:10213993",
    "title" : "[A study of human beta-defensin-1 and human beta-defensin-2 in airway mucosal defense].",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hiratsuka T, etal., Kansenshogaku Zasshi. 1999 Feb;73(2):156-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-02-16T11:38:43.000-06:00",
    "volume" : "73",
    "pages" : "156-62",
    "abstract" : "Human beta-defensin-1 (hBD-1) and human beta-defensin-2 (hBD-2) are new members of the defensin family. In this study, we investigated their gene expressions in the respiratory epithelial surface of the human lung and their bactericidal activities against Escherichia coli. Both hBD-1 and hBD-2 gene transcripts were detected in human lung tissue and cellular component of bronchoalveolar lavage fluid by reverse transcription-polymerase chain reaction. Synthetic hBD-1 and hBD-2 had dose-dependent bactericidal activities against E. coli. The concentration for the 50% colony reduction of hBD-2 was 0.46 nmol/ml, that for HNP-1 2.15 nmol/ml, and hBD-1 99.3 nmol/ml under conditions nearly the same as in human bronchial airway surface liquid. We prepared an antiserum against hBD-2 and established a highly sensitive radioimmunoassay and quantified plasma hBD-2 concentrations in normal subjects and patients with pneumonia. The plasma concentration of hBD-2 in normal individuals was 8.3 +/- 0.9 fmol/ml (mean +/- SE). The mean hBD-2 plasma concentration for the 12 patients with bacterial pneumonia in the acute stage was 34.2 +/- 3.4 fmol/ml, significantly higher than normal individuals, and returned to the normal range after recovery. The presence of hBD-1 and hBD-2 in the airway tract and their bactericidal activity suggest that they function in innate airway mucosal defense.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Hiratsuka",
      "authorRank" : 1,
      "name" : "Hiratsuka T",
      "referenceId" : "RGD:A134801"
    }, {
      "firstName" : "M",
      "lastName" : "Nakazato",
      "authorRank" : 2,
      "name" : "Nakazato M",
      "referenceId" : "RGD:A11949"
    }, {
      "firstName" : "J",
      "lastName" : "Ashitani",
      "authorRank" : 3,
      "name" : "Ashitani J",
      "referenceId" : "RGD:A128427"
    }, {
      "firstName" : "S",
      "lastName" : "Matsukura",
      "authorRank" : 4,
      "name" : "Matsukura S",
      "referenceId" : "RGD:A30260"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892266"
    } ]
  }, {
    "primaryId" : "PMID:10214861",
    "title" : "Endogenous FLT-3 ligand serum levels are associated with disease stage in patients with myelodysplastic syndromes.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Zwierzina H, etal., Leukemia. 1999 Apr;13(4):553-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-06T15:36:42.000-05:00",
    "volume" : "13",
    "pages" : "553-7",
    "abstract" : "Myelodysplastic syndromes (MDS) caused by a clonal hematopoietic stem cell disorder progress to either overt leukemia or cytopenia, which leads to lethal infection or bleeding. Although several clinical trials have attempted to reverse cytopenia by using hematopoietic growth factors (HGF), success has been limited due in part to a limited understanding of the role of HGF in MDS progression. The FLT3 ligand, which binds to and activates the FLT3 receptor, does not have a stimulatory effect on hematopoietic cells, but can synergize with other HGF to support the expansion of both immature and committed progenitors. Using ELISA technology we measured endogenous serum levels in 93 patients with MDS: 29 RA, 1  RARS, 31 RAEB, 23 RAEBt, 9 CMML. 48.3% of RA patients' sera had significantly elevated FLT3 ligand levels ranging from 404 to 5735 pg/ml, whereas none of the RAEB, RAEBt, or CMML patients sera had levels different from controls. No significant correlation was found between FLT3 ligand levels and peripheral blood counts, bone marrow cellularity, age, cytogenetic abnormalities, or survival. Our data suggest that FLT3 ligand levels can be upregulated early in the course of MDS, which may represent an appropriate response to a decreased number of normal  progenitors, or alternatively a dysregulated HGF system.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Zwierzina",
      "authorRank" : 1,
      "name" : "Zwierzina",
      "referenceId" : "RGD:A215614"
    }, {
      "firstName" : "JE",
      "lastName" : "Anderson",
      "authorRank" : 2,
      "name" : "Anderson JE",
      "referenceId" : "RGD:A30843"
    }, {
      "firstName" : "I",
      "lastName" : "Rollinger-Holzinger",
      "authorRank" : 3,
      "name" : "Rollinger-Holzinger",
      "referenceId" : "RGD:A215615"
    }, {
      "firstName" : "B",
      "lastName" : "Torok-Storb",
      "authorRank" : 4,
      "name" : "Torok-Storb",
      "referenceId" : "RGD:A215616"
    }, {
      "firstName" : "V",
      "lastName" : "Nuessler",
      "authorRank" : 5,
      "name" : "Nuessler V",
      "referenceId" : "RGD:A121161"
    }, {
      "firstName" : "SD",
      "lastName" : "Lyman",
      "authorRank" : 6,
      "name" : "Lyman",
      "referenceId" : "RGD:A215617"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11049479"
    } ]
  }, {
    "primaryId" : "PMID:10214941",
    "title" : "p24 and p23, the major transmembrane proteins of COPI-coated transport vesicles, form hetero-oligomeric complexes and cycle between the organelles of the early secretory pathway.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Gommel D, etal., FEBS Lett. 1999 Mar 26;447(2-3):179-85.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-25T12:24:23.000-05:00",
    "volume" : "447",
    "pages" : "179-85",
    "abstract" : "COPI-coated vesicles that bud off the Golgi complex contain two major transmembrane proteins, p23 and p24. We have localized the protein at the Golgi complex and at COPI-coated vesicles. Transport from the intermediate compartment (IC) to the Golgi can be blocked at 15 degrees C, and under these conditions p24 accumulates in peripheral punctated structures identified as IC. Release from the temperature block leads to a redistribution of p24 to the Golgi, showing that p24, similar to p23, cycles between the IC and Golgi complex. Immunoprecipitations of p24 from cell lysates and from detergent-solubilized Golgi membranes and COPI-coated vesicles show that p24 and p23 interact with each other to form a complex. Transient transfection of p23 in HeLa cells shows that p23 and p24 colocalize in structures induced by the overexpression of p23. Taken together p24 interacts with p23 and constitutively cycles between the organelles of the early secretory pathway.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Gommel",
      "authorRank" : 1,
      "name" : "Gommel D",
      "referenceId" : "RGD:A120892"
    }, {
      "firstName" : "L",
      "lastName" : "Orci",
      "authorRank" : 2,
      "name" : "Orci L",
      "referenceId" : "RGD:A31199"
    }, {
      "firstName" : "EM",
      "lastName" : "Emig",
      "authorRank" : 3,
      "name" : "Emig EM",
      "referenceId" : "RGD:A120893"
    }, {
      "firstName" : "MJ",
      "lastName" : "Hannah",
      "authorRank" : 4,
      "name" : "Hannah MJ",
      "referenceId" : "RGD:A120894"
    }, {
      "firstName" : "M",
      "lastName" : "Ravazzola",
      "authorRank" : 5,
      "name" : "Ravazzola M",
      "referenceId" : "RGD:A56420"
    }, {
      "firstName" : "W",
      "lastName" : "Nickel",
      "authorRank" : 6,
      "name" : "Nickel W",
      "referenceId" : "RGD:A120895"
    }, {
      "firstName" : "JB",
      "lastName" : "Helms",
      "authorRank" : 7,
      "name" : "Helms JB",
      "referenceId" : "RGD:A120896"
    }, {
      "firstName" : "FT",
      "lastName" : "Wieland",
      "authorRank" : 8,
      "name" : "Wieland FT",
      "referenceId" : "RGD:A120897"
    }, {
      "firstName" : "K",
      "lastName" : "Sohn",
      "authorRank" : 9,
      "name" : "Sohn K",
      "referenceId" : "RGD:A120898"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317280"
    } ]
  }, {
    "primaryId" : "PMID:10215039",
    "title" : "Purification and identification of an estrogen binding protein from rat brain: oligomycin sensitivity-conferring protein (OSCP), a subunit of mitochondrial F0F1-ATP synthase/ATPase.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Zheng J and Ramirez VD, J Steroid Biochem Mol Biol 1999 Jan;68(1-2):65-75.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-14T13:10:31.000-06:00",
    "volume" : "68",
    "pages" : "65-75",
    "abstract" : "Early studies have suggested the presence in the central nervous system of possible estrogen binding sites/proteins other than classical nuclear estrogen receptors (nER). We report here the isolation and identification of a 23 kDa membrane protein from digitonin-solubilized rat brain mitochondrial fractions that binds 17beta-estradiol conjugated to bovine serum albumin at C-6 position (17beta-E-6-BSA), a ligand that also specifically binds nER. This protein was partially purified using affinity columns coupled with 17beta-E-6-BSA and was recognized by the iodinated 17beta-E-6-BSA (17beta-E-6-[125I]BSA) in a ligand blotting assay. The binding of 17beta-E-6-BSA to this protein was specific for the 17beta-estradiol portion of the conjugate, not BSA. Using N-terminal sequencing and immunoblotting, this 23 kDa protein was identified as the oligomycin-sensitivity conferring protein (OSCP). This protein is a subunit of the FOF1 (F-type) mitochondrial ATP synthase/ATPase required for the coupling of a proton gradient across the F0 sector of the enzyme in the mitochondrial membrane to ATP synthesis in the F1 sector of the enzyme. Studies using recombinant bovine OSCP (rbOSCP) in ligand blotting revealed that rbOSCP bound 17beta-E-6-[125I]BSA with the same specificity as the purified 23 kDa protein. Further, in a ligand binding assay, 17beta-E-6-[125I]BSA also bound rbOSCP and it was displaced by both 17beta-E-6-BSA and 17alpha-E-6-BSA as well as partially by 17beta-estradiol and diethylstilbestrol (DES), but not by BSA. This finding opens up the possibility that estradiol, and probably other compounds with similar structures, in addition to their classical genomic mechanism, may interact with ATP synthase/ATPase by binding to OSCP, and thereby modulating cellular energy metabolism. Current experiments are addressing such an issue.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Zheng",
      "authorRank" : 1,
      "name" : "Zheng J",
      "referenceId" : "RGD:A29377"
    }, {
      "firstName" : "VD",
      "lastName" : "Ramirez",
      "authorRank" : 2,
      "name" : "Ramirez VD",
      "referenceId" : "RGD:A29378"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:728365"
    } ]
  }, {
    "primaryId" : "PMID:10215103",
    "title" : "Determination of glutathione S-transferase mu and theta polymorphisms in neurological disease.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Stroombergen MC and Waring RH, Hum Exp Toxicol. 1999 Mar;18(3):141-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-09-08T09:19:55.000-05:00",
    "volume" : "18",
    "pages" : "141-5",
    "abstract" : "1. Correlations between deletions in two glutathione S-transferase (GST) genes, GSTM1 and GSTT1 and susceptibility to Alzheimer's disease (AD), motor neuron disease (MND) and Parkinson's disease (PD) have been investigated by PCR, using primers specific for both genes. 2. It was found that males with a deletion of the GSTM1 gene were more susceptible to PD and males with a deletion of the GSTT1 gene more susceptible to MND and PD, possibly implying that environmental factors which specifically target men may be involved. Furthermore, subjects with a deletion of the GSTT1 gene were more susceptible to AD.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MC",
      "lastName" : "Stroombergen",
      "authorRank" : 1,
      "name" : "Stroombergen MC",
      "referenceId" : "RGD:A144465"
    }, {
      "firstName" : "RH",
      "lastName" : "Waring",
      "authorRank" : 2,
      "name" : "Waring RH",
      "referenceId" : "RGD:A144466"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5490213"
    } ]
  }, {
    "primaryId" : "PMID:10215164",
    "title" : "Alteration in expression of G-protein-activated inward rectifier K+-channel subunits GIRK1 and GIRK2 in the rat brain following electroconvulsive shock.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Pei Q, etal., Neuroscience. 1999 May;90(2):621-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-15T09:59:27.000-06:00",
    "volume" : "90",
    "pages" : "621-7",
    "abstract" : "G-protein-activated inward rectifier potassium channels are coupled to a number of neurotransmitter receptors, including some monoamine receptors. In the present study we have investigated the effect of electroconvulsive shock on gene expression of the G-protein-activated inward rectifier potassium channel subunits G-protein-coupled inward rectifier K+-channel (GIRK1) and GIRK2 in the rat brain using in situ hybridization and immunocytochemistry. Acute electroconvulsive shock (a single shock) increased GIRK2 expression while causing a transient reduction of the messenger RNA abundance of GIRK1 in granule cells of the dentate gyrus. Chronic electroconvulsive shock (five shocks over 10 days) caused a larger increase in GIRK2 messenger RNA abundance, which was accompanied by an increase in GIRK2 immunoreactivity in the molecular layer of the dentate gyrus. Unlike for acute electroconvulsive shock, GIRK1 messenger RNA abundance in the dentate gyrus was significantly increased after chronic electroconvulsive shock. No significant alterations in GIRK1 and GIRK2 messenger RNA abundance were detected in the other brain regions studied, including the CA1 and CA3 subfields of the hippocampus, the frontal-parietal cortex and piriform cortex. The neuroanatomically specific changes in expression of the potassium channel subunits may directly influence neuronal excitability as well as the functions of G-protein-coupled neurotransmitter receptors.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Pei",
      "authorRank" : 1,
      "name" : "Pei Q",
      "referenceId" : "RGD:A119147"
    }, {
      "firstName" : "L",
      "lastName" : "Lewis",
      "authorRank" : 2,
      "name" : "Lewis L",
      "referenceId" : "RGD:A47966"
    }, {
      "firstName" : "DG",
      "lastName" : "Grahame-Smith",
      "authorRank" : 3,
      "name" : "Grahame-Smith DG",
      "referenceId" : "RGD:A119148"
    }, {
      "firstName" : "TS",
      "lastName" : "Zetterstrom",
      "authorRank" : 4,
      "name" : "Zetterstrom TS",
      "referenceId" : "RGD:A77732"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316513"
    } ]
  }, {
    "primaryId" : "PMID:10215166",
    "title" : "Expression of platelet-derived growth factor B-chain and beta-receptor in hypoxic/ischemic encephalopathy of neonatal rats.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Ohno M, etal., Neuroscience. 1999 May;90(2):643-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-07T14:47:15.000-06:00",
    "volume" : "90",
    "pages" : "643-51",
    "abstract" : "Expression of platelet-derived growth factor B-chain and of its specific receptor (beta-receptor) was investigated in immature brains with hypoxic/ischemic injury. After the left common carotid arteries of seven-day-old rats were ligated and pups were placed in a hypoxic chamber, the protein and messenger RNA of both B-chain and beta-receptor were assessed using immunocytochemistry and northern analysis, respectively. Transcripts for B-chain were localized by in situ hybridization. Faint but definite expression of B-chain and beta-receptor was seen in the brains of untreated neonatal controls. Three to 48 h after hypoxia B-chain protein was generally increased above control levels, but focally decreased expression was seen in infarcted areas. Enhanced induction of messenger RNA of B-chain was seen in the both sides of cerebral cortices and hippocampi at  3 h. Strongly increased positivity for B-chain protein and mRNA occurred in the neurons surrounding the infarct. In situ hybridization still showed this up-regulation seven days after hypoxia. Beta-receptor protein expression was enhanced in some neurons immediately surrounding the infarct at 3 h of hypoxia, and marked up-regulation was seen at 16 h. Beta-receptor messenger RNA remained at control levels. Immunocytochemistry showed strong immunoreactivity for the beta-receptor on the neurons surrounding the infarct at 72 h. These results indicate that a neonatal hypoxic/ischemic insult induces neuronal up-regulation of the platelet-derived growth factor B-chain as well as beta-receptor immediately after hypoxia. While this up-regulation is relatively transient in most neurons, sublethal damage to neurons immediately surrounding an infarct induces sustained up-regulation. Through autocrine and paracrine mechanisms, platelet-derived growth factor B-chain molecules may act as a neuroprotective factor in immature brain experiencing with hypoxic/ischemic injury.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Ohno",
      "authorRank" : 1,
      "name" : "Ohno M",
      "referenceId" : "RGD:A9173"
    }, {
      "firstName" : "M",
      "lastName" : "Sasahara",
      "authorRank" : 2,
      "name" : "Sasahara M",
      "referenceId" : "RGD:A5414"
    }, {
      "firstName" : "S",
      "lastName" : "Narumiya",
      "authorRank" : 3,
      "name" : "Narumiya S",
      "referenceId" : "RGD:A39091"
    }, {
      "firstName" : "N",
      "lastName" : "Tanaka",
      "authorRank" : 4,
      "name" : "Tanaka N",
      "referenceId" : "RGD:A8912"
    }, {
      "firstName" : "T",
      "lastName" : "Yamano",
      "authorRank" : 5,
      "name" : "Yamano T",
      "referenceId" : "RGD:A80712"
    }, {
      "firstName" : "M",
      "lastName" : "Shimada",
      "authorRank" : 6,
      "name" : "Shimada",
      "referenceId" : "RGD:A397574"
    }, {
      "firstName" : "F",
      "lastName" : "Hazama",
      "authorRank" : 7,
      "name" : "Hazama F",
      "referenceId" : "RGD:A5418"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10449494"
    } ]
  }, {
    "primaryId" : "PMID:10215321",
    "title" : "Cloning and characterization of two new isoforms of the rat kidney urea transporter: UT-A3 and UT-A4.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Karakashian A, etal., J Am Soc Nephrol 1999 Feb;10(2):230-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-15T16:18:59.000-05:00",
    "volume" : "10",
    "pages" : "230-7",
    "abstract" : "Urea transport in the kidney is important for the production of concentrated urine and is mediated by a family of transporter proteins, identified from erythropoietic tissue (UT-B) and from kidney (UT-A). Two isoforms of the renal urea transporter (UT-A) have been cloned so far: UT-A1 and UT-A2. We used rapid amplification of cDNA ends to clone two new isoforms of the rat UT-A transporter: UT-A3 and UT-A4. UT-A3 and UT-A4 are 87% homologous. The UT-A3 cDNA encodes a peptide of 460 amino acids, which corresponds to the amino-terminal half of the UT-A1 peptide and is 62% identical to UT-A2. The UT-A4 cDNA encodes a peptide of 466 amino acids, which is 84% identical to UT-A2. Transient transfection of HEK-293 cells with the UT-A3 or UT-A4 cDNA results in phloretin-inhibitable urea uptake, which is increased by forskolin. Thus, both new isoforms encode functional urea transporters that may be vasopressin-regulated. UT-A3 and UT-A4 mRNA are expressed in the renal outer and inner medulla but not in the cortex; unidentified UT-A isoforms similar to UT-A3 may also be expressed in the testis. It is concluded that there are at least four different rat UT-A urea transporters.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Karakashian",
      "authorRank" : 1,
      "name" : "Karakashian A",
      "referenceId" : "RGD:A6399"
    }, {
      "firstName" : "RT",
      "lastName" : "Timmer",
      "authorRank" : 2,
      "name" : "Timmer RT",
      "referenceId" : "RGD:A6400"
    }, {
      "firstName" : "JD",
      "lastName" : "Klein",
      "authorRank" : 3,
      "name" : "Klein JD",
      "referenceId" : "RGD:A6401"
    }, {
      "firstName" : "RB",
      "lastName" : "Gunn",
      "authorRank" : 4,
      "name" : "Gunn RB",
      "referenceId" : "RGD:A6402"
    }, {
      "firstName" : "JM",
      "lastName" : "Sands",
      "authorRank" : 5,
      "name" : "Sands JM",
      "referenceId" : "RGD:A6346"
    }, {
      "firstName" : "SM",
      "lastName" : "Bagnasco",
      "authorRank" : 6,
      "name" : "Bagnasco SM",
      "referenceId" : "RGD:A6403"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68904"
    } ]
  }, {
    "primaryId" : "PMID:10215407",
    "title" : "Identification of a large insertion and two novel point mutations (3671del8 and S1221X) in tuberous sclerosis complex (TSC) patients. Mutations in brief no. 119. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Wang Q, etal., Hum Mutat. 1998;11(4):331-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:06:18.000-05:00",
    "volume" : "11",
    "pages" : "331-2",
    "abstract" : "Important symptoms of tuberous sclerosis complex (TSC), an autosomal dominant disorder, are hamartomata in several organs, mental retardation and epilepsy. Either one of two loci can be involved (TSC1 and TSC2), of which the TSC2 gene has been cloned. To date, only 35 mutations in the TSC2 gene have been described  ranging from large deletions to point mutations. Southern blot analysis using cDNA clones of the TSC2 gene was performed on a cohort of 160 unrelated TSC patients and revealed a 10 kb insertion. The insertion was also present in DNA of the affected father. Both patients showed renal angiomyolipoma, hypomelanotic macules and epilepsy. SSCP analysis of exons 1,2,3,9,12,14,30a and 36 identified  two mutations in exon 30a: 3671del8 and S1221X. Symptoms of the sporadic patient  with the 3671del8 mutation are cortical tubers, subependymal nodules, facial angiofibroma, ungual fibroma, renal angiomyolipoma, hypomelanotic macules, epilepsy and mental retardation. Clinical symptoms of the patient with the S1221X mutation are facial angiofibroma, ungual fibroma, hypomelanotic macules, epilepsy and mental retardation. His parents were negative for the S1221X mutation, although a germline mosaicism can not be excluded. Besides the previously described polymorphism 1596C->T, two rare variants were observed, a substitution  of C->T at position 1294 and at position 1299 C->A.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang",
      "referenceId" : "RGD:A415158"
    }, {
      "firstName" : "S",
      "lastName" : "Verhoef",
      "authorRank" : 2,
      "name" : "Verhoef S",
      "referenceId" : "RGD:A81999"
    }, {
      "firstName" : "AM",
      "lastName" : "Tempelaars",
      "authorRank" : 3,
      "name" : "Tempelaars",
      "referenceId" : "RGD:A254327"
    }, {
      "firstName" : "PL",
      "lastName" : "Bakker",
      "authorRank" : 4,
      "name" : "Bakker",
      "referenceId" : "RGD:A255128"
    }, {
      "firstName" : "R",
      "lastName" : "Vrtel",
      "authorRank" : 5,
      "name" : "Vrtel",
      "referenceId" : "RGD:A236194"
    }, {
      "firstName" : "AL",
      "lastName" : "Hesseling-Janssen",
      "authorRank" : 6,
      "name" : "Hesseling-Janssen",
      "referenceId" : "RGD:A254328"
    }, {
      "firstName" : "M",
      "lastName" : "Nellist",
      "authorRank" : 7,
      "name" : "Nellist M",
      "referenceId" : "RGD:A81998"
    }, {
      "firstName" : "AP",
      "lastName" : "Oranje",
      "authorRank" : 8,
      "name" : "Oranje",
      "referenceId" : "RGD:A255129"
    }, {
      "firstName" : "H",
      "lastName" : "Stroink",
      "authorRank" : 9,
      "name" : "Stroink",
      "referenceId" : "RGD:A255130"
    }, {
      "firstName" : "D",
      "lastName" : "Lindhout",
      "authorRank" : 10,
      "name" : "Lindhout D",
      "referenceId" : "RGD:A81725"
    }, {
      "firstName" : "DJ",
      "lastName" : "Halley",
      "authorRank" : 11,
      "name" : "Halley DJ",
      "referenceId" : "RGD:A126470"
    }, {
      "firstName" : "AM",
      "lastName" : "Van den Ouweland",
      "authorRank" : 12,
      "name" : "Van den Ouweland AM",
      "referenceId" : "RGD:A101725"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063439"
    } ]
  }, {
    "primaryId" : "PMID:10215408",
    "title" : "Mutational analysis of the cystathionine beta-synthase gene: a splicing mutation, two missense mutations and an insertion in patients with homocystinuria. Mutations in brief no. 120. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Gordon RB, etal., Hum Mutat. 1998;11(4):332.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:41:37.000-05:00",
    "volume" : "11",
    "pages" : "332",
    "abstract" : "RT-PCR and direct sequence analyses were used to define mutations in the cystathionine beta-synthase (CBS) gene in two unrelated male patients with vitamin B6 nonresponsive homocystinuria. Both patients were compound heterozygotes for CBS alleles containing point mutations. One patient had a maternally derived G->A transition in the splice-donor site of intron 1, resulting in aberrant splicing of CBS mRNA. The other allele contained a missense mutation resulting in the previously reported E144K mutant CBS protein. The second patient had a maternally derived 4 bp insertion in exon 17, predicted to cause a CBS peptide of altered amino acid sequence. A 494G->A transition was found in exon 4 of the other allele, predicting a C165Y substitution. Expression  of recombinant CBS protein, containing the C165Y mutation, had no detectable catalytic activity. Each mutation was confirmed in genomic DNA.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RB",
      "lastName" : "Gordon",
      "authorRank" : 1,
      "name" : "Gordon",
      "referenceId" : "RGD:A278010"
    }, {
      "firstName" : "AJ",
      "lastName" : "Cox",
      "authorRank" : 2,
      "name" : "Cox AJ",
      "referenceId" : "RGD:A21014"
    }, {
      "firstName" : "PA",
      "lastName" : "Dawson",
      "authorRank" : 3,
      "name" : "Dawson PA",
      "referenceId" : "RGD:A4425"
    }, {
      "firstName" : "BT",
      "lastName" : "Emmerson",
      "authorRank" : 4,
      "name" : "Emmerson",
      "referenceId" : "RGD:A282361"
    }, {
      "firstName" : "JP",
      "lastName" : "Kraus",
      "authorRank" : 5,
      "name" : "Kraus JP",
      "referenceId" : "RGD:A15066"
    }, {
      "firstName" : "NP",
      "lastName" : "Dudman",
      "authorRank" : 6,
      "name" : "Dudman",
      "referenceId" : "RGD:A282362"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072581"
    } ]
  }, {
    "primaryId" : "PMID:10215409",
    "title" : "Analysis of five mutations in 20 mucopolysaccharidois type 1 patients: high prevalence of the W402X mutation. Mutations in brief no. 121. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Gort L, etal., Hum Mutat. 1998;11(4):332-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:23:48.000-05:00",
    "volume" : "11",
    "pages" : "332-3",
    "abstract" : "Mucopolysaccharidosis type 1 is a lysosomal storage disease due to a L-Iduroniase deficiency. Three main phenotypes have been reported: Hurler (severe), Scheie (mild) and Hurler/Scheie (intermediate). High prevalence of mutations W402X and Q70X has been described. We studied these two mutations in 20 unrelated MPSI Spanish patients. In addition we have also analysed the P533R mutation because of its frequency in the close Mediterranean country Italy and mutations R89Q and 678-7g->a because of its prevalence in European Scheie syndrome. We found that 60% (24/40) mutated alleles carried the W402X mutation, 40% of them in homozygosity. Such a high prevalence of this mutation has not been described so far. Patients who carry this mutation in both alleles or in combination with Q70X and P533R have a severe phenotyoe. Mutation Q70X was found in 10% (4/40) of the alleles, two of them in heterozygosity with W402X. Patient with Q70X/Q70X genotype had a severe Hurler phenotype. The P533R mutation accounts for 10% (4/40) of the alleles. One Hurler phenotype patient was homozygous for this mutation. No patient presented the R89Q or 678-7g->a mutations. In conclusion, screening of Spanish patients for mutations W402X, Q70X and P533R allowed identification of 80% of the mutant alleles and genotyping of 70% of patients.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Gort",
      "authorRank" : 1,
      "name" : "Gort",
      "referenceId" : "RGD:A253722"
    }, {
      "firstName" : "A",
      "lastName" : "Chabas",
      "authorRank" : 2,
      "name" : "Chabas A",
      "referenceId" : "RGD:A44117"
    }, {
      "firstName" : "MJ",
      "lastName" : "Coll",
      "authorRank" : 3,
      "name" : "Coll MJ",
      "referenceId" : "RGD:A44116"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064041"
    } ]
  }, {
    "primaryId" : "PMID:10215585",
    "title" : "Aminopeptidase B is structurally related to leukotriene-A4 hydrolase but is not a bifunctional enzyme with epoxide hydrolase activity.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Fukasawa KM, etal., Biochem J 1999 May 1;339 ( Pt 3):497-502.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:40.000-05:00",
    "volume" : "339 ( Pt 3)",
    "pages" : "497-502",
    "abstract" : "Aminopeptidase B (Ap B; EC 3.4.11.6) is a zinc-binding protein that contains the consensus sequence HEXXHX18E (324-347), conserved among the M1 family of metallopeptidases. To determine if these putative zinc-binding residues (His324, His328 and Glu347) and the active-site Glu325 are essential for the enzyme activity, we replaced the histidines with tyrosines and the glutamic acid residues with alanines using site-directed mutagenesis. The cDNAs were expressed in Escherichia coli, and the resulting recombinant proteins, named H324Y, E325A, H328Y and E347A, were purified to apparent homogeneity. None of the expressed mutated proteins showed aminopeptidase activity. The E325A enzyme contained 1 mol of zinc per mol of protein, and the other three mutants, H324Y, H328Y and E347A, did not contain significant amounts of zinc, as determined by atomic absorption spectrometry. From sequence-homology searches, Ap B is known to be closely related to leukotriene (LT)-A4 hydrolase (EC 3.3.2.6). We examined human placental Ap B and recombinant rat Ap B, both of which had been purified previously [Fukasawa, Fukasawa, Kanai, Fujii and Harada (1996) J. Biol. Chem. 271, 30731-30735], to determine whether or not they had epoxide hydrolase activities. However, neither enzyme hydrolysed LTA4 into LTB4. We then replaced some amino acids in the domain of the rat enzyme similar to the LTA4-binding site of LTA4 hydrolase. However, these mutants, Y408F, N409S and NE409-410SS also did not possess any epoxide hydrolase activity. We concluded that Ap B is an M1-family zinc metallopeptidase without epoxide hydrolase activity.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KM",
      "lastName" : "Fukasawa",
      "authorRank" : 1,
      "name" : "Fukasawa KM",
      "referenceId" : "RGD:A9424"
    }, {
      "firstName" : "K",
      "lastName" : "Fukasawa",
      "authorRank" : 2,
      "name" : "Fukasawa K",
      "referenceId" : "RGD:A9425"
    }, {
      "firstName" : "M",
      "lastName" : "Harada",
      "authorRank" : 3,
      "name" : "Harada M",
      "referenceId" : "RGD:A314640"
    }, {
      "firstName" : "J",
      "lastName" : "Hirose",
      "authorRank" : 4,
      "name" : "Hirose J",
      "referenceId" : "RGD:A29615"
    }, {
      "firstName" : "T",
      "lastName" : "Izumi",
      "authorRank" : 5,
      "name" : "Izumi T",
      "referenceId" : "RGD:A20114"
    }, {
      "firstName" : "T",
      "lastName" : "Shimizu",
      "authorRank" : 6,
      "name" : "Shimizu T",
      "referenceId" : "RGD:A161715"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:729754"
    } ]
  }, {
    "primaryId" : "PMID:10215608",
    "title" : "Genomic cloning and characterization of the rat glutathione S-transferase-A3-subunit gene.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Fotouhi-Ardakani N and Batist G, Biochem J 1999 May 1;339 ( Pt 3):685-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:01.000-05:00",
    "volume" : "339 ( Pt 3)",
    "pages" : "685-93",
    "abstract" : "The rat glutathione S-transferase-A3-subunit (GSTA3) gene is a member of the class Alpha GSTs, which we have previously reported to be overexpressed in anti-cancer-drug-resistant cells. In this study, we report the isolation and characterization of the entire rat GSTA3 (rGST Yc1) subunit gene. The rat GSTA3 subunit gene is approximately 15 kb in length and consists of seven exons interrupted by introns of different lengths. Exon 1, with a length of 219 bp, contains only the 5'-untranslated region of the gene. Each exon-intron splicing junction exhibited the consensus sequence for a mammalian splice site. The transcription start site and exon 1 of rat GSTA3 were characterized by a combination of primer extension and rapid amplification of the cDNA ends. Position +1 was identified 219 bp upstream of the first exon-intron splicing junction. The proximal promoter region of the rat GSTA3 subunit gene does not contain typical TATA or CAAT boxes. A computer-based search for potential transcription-factor binding sites revealed the existence of a number of motifs such as anti-oxidant-responsive element, ras-response element, activator protein-1, nuclear factor-kappaB, cAMP-response-element-binding protein, Barbie box and E box. The functional activity of the regulatory region of the rat GSTA3 subunit gene was shown by its ability to drive the expression of a chloramphenicol acetyltransferase reporter gene in rat mammary carcinoma cells, and its activity was greater in melphalan-resistant cells known to have transcriptional activation of this gene by previous studies. The structure of the gene, with a large intron upstream of the translation-initiation site, may explain why the isolation of this promoter has been so elusive. This information will provide the opportunity to examine the involvement of the rat GSTA3 subunit gene in drug resistance and carcinogenesis.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Fotouhi-Ardakani",
      "authorRank" : 1,
      "name" : "Fotouhi-Ardakani N",
      "referenceId" : "RGD:A19465"
    }, {
      "firstName" : "G",
      "lastName" : "Batist",
      "authorRank" : 2,
      "name" : "Batist G",
      "referenceId" : "RGD:A19466"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633003"
    } ]
  }, {
    "primaryId" : "PMID:10215863",
    "title" : "Identification of a novel human adenylate kinase. cDNA cloning, expression analysis, chromosome localization and characterization of the recombinant protein.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Van Rompay AR, etal., Eur J Biochem. 1999 Apr;261(2):509-17.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-20T17:45:27.000-05:00",
    "volume" : "261",
    "pages" : "509-17",
    "abstract" : "Adenylate kinases have an important role in the synthesis of adenine nucleotides  that are required for cellular metabolism. We report the cDNA cloning of a novel  22-kDa human enzyme that is sequence related to the human adenylate kinases and to UMP/CMP kinase of several species. The enzyme was expressed in Escherichia coli and shown to catalyse phosphorylation of AMP and dAMP with ATP as phosphate  donor. When GTP was used as phosphate donor, the enzyme phosphorylated AMP, CMP,  and to a small extent dCMP. Expression as a fusion protein with the green fluorescent protein showed that the enzyme is located in the cytosol. Northern blot analysis with mRNA from eight different human tissues demonstrated that the  enzyme was expressed exclusively in brain, with two mRNA isoforms of 2.4 and 4.0  kb. The gene that encoded the enzyme was localized to chromosome 1p31. Based on the substrate specificity and the sequence similarity with the previously identified human adenylate kinases, we have named this novel enzyme adenylate kinase 5.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AR",
      "lastName" : "Van Rompay",
      "authorRank" : 1,
      "name" : "Van Rompay",
      "referenceId" : "RGD:A246786"
    }, {
      "firstName" : "M",
      "lastName" : "Johansson",
      "authorRank" : 2,
      "name" : "Johansson M",
      "referenceId" : "RGD:A75501"
    }, {
      "firstName" : "A",
      "lastName" : "Karlsson",
      "authorRank" : 3,
      "name" : "Karlsson A",
      "referenceId" : "RGD:A17649"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11061148"
    } ]
  }, {
    "primaryId" : "PMID:10215998",
    "title" : "Differential downregulation of vascular endothelial growth factor by dexamethasone in normoxic and hypoxic rat glioma cells.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Machein MR, etal., Neuropathol Appl Neurobiol. 1999 Apr;25(2):104-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-12-02T10:27:11.000-06:00",
    "volume" : "25",
    "pages" : "104-12",
    "abstract" : "Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is a mitogen and chemotactic factor for endothelial cells in vitro and an angiogenesis and vascular permeability factor in vivo. Due to its properties, VEGF is a candidate for both angiogenesis and vascular permeability/oedema induction which  typically occur in glioblastomas. In this study we test the hypothesis that the antioedema effect of dexamethasone is mediated by downregulation of VEGF or VEGF  receptor expression. VEGF mRNA and protein levels of two rat glioma cells lines,  C6 and GS-9L, were determined after incubation with dexamethasone under normoxic  and hypoxic conditions. In normoxic C6 and GS9L cells, we observed 50-60% downregulation of VEGF mRNA by dexamethasone (P=0.015 and P=0. 01, respectively). This effect was dependent on glucocorticoid-receptor (GR) function. The inhibitory effect of dexamethasone on VEGF gene expression by tumour cells was markedly reduced by hypoxia which suggests that the upregulation of VEGF driven by hypoxia overcomes the effect of the dexamethasone. Dexamethasone did not alter VEGFR-2 mRNA levels in human umbilical endothelial cells. In a subcutaneous glioma tumour model, we observed only a 15% decrease in VEGF mRNA expression in dexamethasone treated animals (n = 12) compared with controls animals (P = 0.24). We conclude that dexamethasone may decrease brain tumour-associated oedema by reduction of VEGF expression in tumour cells. However, the highly reduced activity on hypoxic tumour cells suggests that dexamethasone efficacy may be limited by hypoxia in rapidly growing tumours.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MR",
      "lastName" : "Machein",
      "authorRank" : 1,
      "name" : "Machein MR",
      "referenceId" : "RGD:A52015"
    }, {
      "firstName" : "J",
      "lastName" : "Kullmer",
      "authorRank" : 2,
      "name" : "Kullmer",
      "referenceId" : "RGD:A176169"
    }, {
      "firstName" : "V",
      "lastName" : "Ronicke",
      "authorRank" : 3,
      "name" : "Ronicke",
      "referenceId" : "RGD:A176170"
    }, {
      "firstName" : "U",
      "lastName" : "Machein",
      "authorRank" : 4,
      "name" : "Machein",
      "referenceId" : "RGD:A176171"
    }, {
      "firstName" : "M",
      "lastName" : "Krieg",
      "authorRank" : 5,
      "name" : "Krieg",
      "referenceId" : "RGD:A176172"
    }, {
      "firstName" : "A",
      "lastName" : "Damert",
      "authorRank" : 6,
      "name" : "Damert",
      "referenceId" : "RGD:A176173"
    }, {
      "firstName" : "G",
      "lastName" : "Breier",
      "authorRank" : 7,
      "name" : "Breier G",
      "referenceId" : "RGD:A12807"
    }, {
      "firstName" : "W",
      "lastName" : "Risau",
      "authorRank" : 8,
      "name" : "Risau",
      "referenceId" : "RGD:A176174"
    }, {
      "firstName" : "KH",
      "lastName" : "Plate",
      "authorRank" : 9,
      "name" : "Plate KH",
      "referenceId" : "RGD:A52019"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7483563"
    } ]
  }, {
    "primaryId" : "PMID:10216127",
    "title" : "A fresh look at augmenter of liver regeneration in rats.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Gandhi CR, etal., Hepatology. 1999 May;29(5):1435-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-26T08:59:45.000-06:00",
    "volume" : "29",
    "pages" : "1435-45",
    "abstract" : "Augmenter of liver regeneration (ALR) is a hepatotrophic protein originally identified by bioassay in regenerating rat and canine livers following partial hepatectomy and in the hyperplastic livers of weanling rats, but not in resting adult livers. The ALR gene and gene product were subsequently described, but little is known about the cellular/subcellular sites of ALR synthesis in the liver, or about the release and dissemination of the peptide. To obtain this information in rats, we raised antibodies in rabbits against rat ALR for development of an enzyme-linked immunosorbent assay (ELISA). ALR concentrations were then determined in intact livers of unaltered weanling and adult rats; in regenerating residual liver after partial hepatectomy; in cultured hepatocytes and nonparenchymal cells (NPCs); and in culture medium and serum. ALR in the various liver cells was localized with immunohistochemistry. In addition, hepatic ALR and ALR mRNA were assayed with Western blotting and reverse-transcriptase polymerase chain reaction (RT-PCR), respectively. The hepatocyte was the predominant liver cell in which ALR was synthesized and stored; the cultured hepatocytes secreted ALR into the medium in a time-dependent fashion. Contrary to previous belief, the ALR peptide and ALR mRNA were present in comparable concentrations in the hepatocytes of both weanling and resting adult livers, as well as in cultured hepatocytes. A further unexpected finding was that hepatic ALR levels decreased for 12 hours after 70% hepatectomy in adult rats and then rose with no corresponding change in mRNA transcripts. In the meantime, circulating (serum) ALR levels increased up to 12 hours and declined thereafter.  Thus, ALR appears to be constitutively expressed in hepatocytes in an inactive form, and released from the cells in an active form by unknown means in response  to partial hepatectomy and under other circumstances of liver maturation (as in weanling rats) or regeneration.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CR",
      "lastName" : "Gandhi",
      "authorRank" : 1,
      "name" : "Gandhi CR",
      "referenceId" : "RGD:A106582"
    }, {
      "firstName" : "R",
      "lastName" : "Kuddus",
      "authorRank" : 2,
      "name" : "Kuddus",
      "referenceId" : "RGD:A198557"
    }, {
      "firstName" : "VM",
      "lastName" : "Subbotin",
      "authorRank" : 3,
      "name" : "Subbotin",
      "referenceId" : "RGD:A198558"
    }, {
      "firstName" : "J",
      "lastName" : "Prelich",
      "authorRank" : 4,
      "name" : "Prelich",
      "referenceId" : "RGD:A198551"
    }, {
      "firstName" : "N",
      "lastName" : "Murase",
      "authorRank" : 5,
      "name" : "Murase N",
      "referenceId" : "RGD:A68232"
    }, {
      "firstName" : "AS",
      "lastName" : "Rao",
      "authorRank" : 6,
      "name" : "Rao",
      "referenceId" : "RGD:A198559"
    }, {
      "firstName" : "MA",
      "lastName" : "Nalesnik",
      "authorRank" : 7,
      "name" : "Nalesnik",
      "referenceId" : "RGD:A198560"
    }, {
      "firstName" : "SC",
      "lastName" : "Watkins",
      "authorRank" : 8,
      "name" : "Watkins SC",
      "referenceId" : "RGD:A8579"
    }, {
      "firstName" : "A",
      "lastName" : "DeLeo",
      "authorRank" : 9,
      "name" : "DeLeo",
      "referenceId" : "RGD:A198561"
    }, {
      "firstName" : "M",
      "lastName" : "Trucco",
      "authorRank" : 10,
      "name" : "Trucco M",
      "referenceId" : "RGD:A30234"
    }, {
      "firstName" : "TE",
      "lastName" : "Starzl",
      "authorRank" : 11,
      "name" : "Starzl",
      "referenceId" : "RGD:A198598"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685731"
    } ]
  }, {
    "primaryId" : "PMID:10216139",
    "title" : "Deranged blood coagulation equilibrium as a factor of massive liver necrosis following endotoxin administration in partially hepatectomized rats.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mochida S, etal., Hepatology. 1999 May;29(5):1532-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-30T11:46:30.000-05:00",
    "volume" : "29",
    "pages" : "1532-40",
    "abstract" : "Activated Kupffer cells provoke massive liver necrosis after endotoxin stimulation through microcirculatory disturbance caused by sinusoidal fibrin deposition in rats undergoing 70% hepatectomy. In these rats, serum activities of purine nucleoside phosphorylase (PNP) and alanine transaminase (ALT) were increased at 1 and 5 hours, respectively, following endotoxin administration. When 70% resected liver was perfused with Dulbecco's modified Eagle medium (DMEM) containing heat-inactivated fetal calf serum, the increase in both enzyme activities was not affected by addition of endotoxin during perfusion, suggesting that activated Kupffer cells injured neither sinusoidal endothelial cells nor hepatocytes. The activity of tissue factor, an initiator of blood coagulation cascade, was much higher in Kupffer cells isolated from partially hepatectomized  rats than in those from normal rats. In contrast, mRNA expressions of tissue factor pathway inhibitor (TFPI) as well as thrombomodulin were almost undetectable in normal and partially resected livers. When recombinant human TFPI was injected intravenously in 70% hepatectomized rats, TFPI was markedly stained  on the surfaces of sinusoidal endothelial cells and microvilli of hepatocytes on  immunohistochemistry. In these rats, endotoxin-induced liver injury was significantly attenuated compared with rats given no TFPI. Similar attenuation was also found in rats receiving recombinant human thrombomodulin. These results  suggest that fibrin deposition developing in 70% hepatectomized rats after endotoxin administration may be caused by deranged blood coagulation in the hepatic sinusoids through increasing tissue factor activity in Kupffer cells and  minimal TFPI and thrombomodulin in endothelial cells. The destruction of sinusoidal endothelial cells as well as hepatocytes may occur as a result of microcirculatory disturbance caused by such sinusoidal fibrin deposition.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Mochida",
      "authorRank" : 1,
      "name" : "Mochida S",
      "referenceId" : "RGD:A12716"
    }, {
      "firstName" : "M",
      "lastName" : "Arai",
      "authorRank" : 2,
      "name" : "Arai M",
      "referenceId" : "RGD:A5879"
    }, {
      "firstName" : "A",
      "lastName" : "Ohno",
      "authorRank" : 3,
      "name" : "Ohno",
      "referenceId" : "RGD:A212720"
    }, {
      "firstName" : "F",
      "lastName" : "Yamanobe",
      "authorRank" : 4,
      "name" : "Yamanobe",
      "referenceId" : "RGD:A334114"
    }, {
      "firstName" : "K",
      "lastName" : "Ishikawa",
      "authorRank" : 5,
      "name" : "Ishikawa K",
      "referenceId" : "RGD:A16618"
    }, {
      "firstName" : "A",
      "lastName" : "Matsui",
      "authorRank" : 6,
      "name" : "Matsui A",
      "referenceId" : "RGD:A27427"
    }, {
      "firstName" : "I",
      "lastName" : "Maruyama",
      "authorRank" : 7,
      "name" : "Maruyama I",
      "referenceId" : "RGD:A75843"
    }, {
      "firstName" : "H",
      "lastName" : "Kato",
      "authorRank" : 8,
      "name" : "Kato",
      "referenceId" : "RGD:A405894"
    }, {
      "firstName" : "K",
      "lastName" : "Fujiwara",
      "authorRank" : 9,
      "name" : "Fujiwara K",
      "referenceId" : "RGD:A16347"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11341667"
    } ]
  }, {
    "primaryId" : "PMID:10216252",
    "title" : "Isolation, sequencing and expression of RED, a novel human gene encoding an acidic-basic dipeptide repeat.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Assier E, etal., Gene 1999 Apr 16;230(2):145-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-18T10:22:04.000-06:00",
    "volume" : "230",
    "pages" : "145-54",
    "abstract" : "A novel human gene RED, and the murine homologue, MuRED, were cloned. These genes were named after the extensive stretch of alternating arginine (R) and glutamic acid (E) or aspartic acid (D) residues that they contain. We term this the 'RED' repeat. The genes of both species were expressed in a wide range of tissues and we have mapped the human gene to chromosome 5q22-24. MuRED and RED shared 98% sequence identity at the amino acid level. The open reading frame of both genes encodes a 557 amino acid protein. RED fused to a fluorescent tag was expressed in nuclei of transfected cells and localised to nuclear dots. Co-localisation studies showed that these nuclear dots did not contain either PML or Coilin, which are commonly found in the POD or coiled body nuclear compartments. Deletion of the amino terminal 265 amino acids resulted in a failure to sort efficiently to the nucleus, though nuclear dots were formed. Deletion of a further 50 amino acids from the amino terminus generates a protein that can sort to the nucleus but is unable to generate nuclear dots. Neither construct localised to the nucleolus. The characteristics of RED and its nuclear localisation implicate it as a regulatory protein, possibly involved in transcription.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Assier",
      "authorRank" : 1,
      "name" : "Assier E",
      "referenceId" : "RGD:A56343"
    }, {
      "firstName" : "H",
      "lastName" : "Bouzinba-Segard",
      "authorRank" : 2,
      "name" : "Bouzinba-Segard H",
      "referenceId" : "RGD:A57401"
    }, {
      "firstName" : "MC",
      "lastName" : "Stolzenberg",
      "authorRank" : 3,
      "name" : "Stolzenberg MC",
      "referenceId" : "RGD:A57402"
    }, {
      "firstName" : "R",
      "lastName" : "Stephens",
      "authorRank" : 4,
      "name" : "Stephens R",
      "referenceId" : "RGD:A57403"
    }, {
      "firstName" : "J",
      "lastName" : "Bardos",
      "authorRank" : 5,
      "name" : "Bardos J",
      "referenceId" : "RGD:A57404"
    }, {
      "firstName" : "P",
      "lastName" : "Freemont",
      "authorRank" : 6,
      "name" : "Freemont P",
      "referenceId" : "RGD:A21048"
    }, {
      "firstName" : "D",
      "lastName" : "Charron",
      "authorRank" : 7,
      "name" : "Charron D",
      "referenceId" : "RGD:A36571"
    }, {
      "firstName" : "J",
      "lastName" : "Trowsdale",
      "authorRank" : 8,
      "name" : "Trowsdale J",
      "referenceId" : "RGD:A23053"
    }, {
      "firstName" : "T",
      "lastName" : "Rich",
      "authorRank" : 9,
      "name" : "Rich T",
      "referenceId" : "RGD:A57405"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556805"
    } ]
  }, {
    "primaryId" : "PMID:10216485",
    "title" : "Investigation of the Mek-MAP kinase-Rsk pathway in human breast cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Salh B, etal., Anticancer Res. 1999 Jan-Feb;19(1B):731-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-28T10:08:37.000-05:00",
    "volume" : "19",
    "pages" : "731-40",
    "abstract" : "BACKGROUND: Mitogenic signaling through the principal growth factor receptor tyrosine kinase (RTK) pathway, i.e. RTK-->Ras-->Raf-->Mek-->MAPK has been implicated in the pathogenesis of human cancer. However, biochemical characterization of this has not been adequately assessed in human cancers. MATERIALS AND METHODS: Using extracts from 23 human breast cancers and control tissue from the same resected specimens, the protein levels, phosphotransferase activities and subcellular locations of the mitogen-activated protein (MAP) kinase isoforms p42 Erk2 and p44 Erk1 were examined, together with their phosphotransferase activities towards myelin basic protein (MBP) and a peptide substrate patterned after the Thr-669 site in the epidermal growth factor receptor (EGFR T669) that is phosphorylated by MAP kinase. RESULTS: Overexpression of both Erk2 and Erk1 isoforms was evident using specific antibodies. A universal activation of MBP and EGFR T669 peptide phosphotransferase activities was also found (up to 3-fold). MonoQ fractionation resolved the bulk of the EGFR T669 peptide phosphorylation from elution of the MAP kinase protein. Erk1 and Erk2 activities determined by specific immunoprecipitation were increased by up to only 2.5-fold in only 50% of tumors overall. Immunohistochemical studies, using a monoclonal antibody specific for Erk2 demonstrated that the cellular distribution of this MAP kinase was similar in both control and tumor tissues, and Erk2 was largely confined to normal and malignant acini, whilst the intensity of staining was actually reduced in the tumor tissue. Mek1 and especially Mek2 protein expression, as well as MAP kinase kinase activity as determined by phosphorylation of kinase-inactive Erk [GST-K71A] were increased in cancer samples. CONCLUSIONS: a) This confirms that MAP kinase activity is increased in human breast cancer. However, the frequency and magnitude of this change is dependent upon the chosen methodology (i.e. crude lysate assays versus specific immunoprecipitation). b) A MAP-kinase-independent source of increased EGFR T669 phosphotransferase activity in tumor extracts has been demonstrated for the first time in human breast cancer. c) By immunohistochemistry, Erk2 protein was actually found to exhibit lower intensity in tumor samples; the increased expression was most likely due to its increased distribution. d) Increased Mek protein expression and activation have been demonstrated for the first time in human breast tumors.",
    "issueName" : "1B",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Salh",
      "authorRank" : 1,
      "name" : "Salh B",
      "referenceId" : "RGD:A95475"
    }, {
      "firstName" : "A",
      "lastName" : "Marotta",
      "authorRank" : 2,
      "name" : "Marotta A",
      "referenceId" : "RGD:A95476"
    }, {
      "firstName" : "C",
      "lastName" : "Matthewson",
      "authorRank" : 3,
      "name" : "Matthewson C",
      "referenceId" : "RGD:A95477"
    }, {
      "firstName" : "M",
      "lastName" : "Ahluwalia",
      "authorRank" : 4,
      "name" : "Ahluwalia M",
      "referenceId" : "RGD:A95478"
    }, {
      "firstName" : "J",
      "lastName" : "Flint",
      "authorRank" : 5,
      "name" : "Flint J",
      "referenceId" : "RGD:A152380"
    }, {
      "firstName" : "D",
      "lastName" : "Owen",
      "authorRank" : 6,
      "name" : "Owen D",
      "referenceId" : "RGD:A15751"
    }, {
      "firstName" : "S",
      "lastName" : "Pelech",
      "authorRank" : 7,
      "name" : "Pelech S",
      "referenceId" : "RGD:A95480"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292627"
    } ]
  }, {
    "primaryId" : "PMID:10217146",
    "title" : "Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "van der Horst GT, etal., Nature 1999 Apr 15;398(6728):627-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-04T12:09:23.000-06:00",
    "volume" : "398",
    "pages" : "627-30",
    "abstract" : "Many biochemical, physiological and behavioural processes show circadian rhythms which are generated by an internal time-keeping mechanism referred to as the biological clock. According to rapidly developing models, the core oscillator driving this clock is composed of an autoregulatory transcription-(post) translation-based feedback loop involving a set of 'dock' genes. Molecular clocks do not oscillate with an exact 24-hour rhythmicity but are entrained to solar day/night rhythms by light. The mammalian proteins Cryl and Cry2, which are members of the family of plant blue-light receptors (cryptochromes) and photolyases, have been proposed as candidate light receptors for photoentrainment of the biological clock. Here we show that mice lacking the Cryl or Cry2 protein display accelerated and delayed free-running periodicity of locomotor activity, respectively. Strikingly, in the absence of both proteins, an instantaneous and complete loss of free-running rhythmicity is observed. This suggests that, in addition to a possible photoreceptor and antagonistic clock-adjusting function, both proteins are essential for the maintenance of circadian rhythmicity.",
    "issueName" : "6728",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GT",
      "lastName" : "Van der Horst",
      "authorRank" : 1,
      "name" : "Van der Horst GT",
      "referenceId" : "RGD:A38513"
    }, {
      "firstName" : "M",
      "lastName" : "Muijtjens",
      "authorRank" : 2,
      "name" : "Muijtjens M",
      "referenceId" : "RGD:A38514"
    }, {
      "firstName" : "K",
      "lastName" : "Kobayashi",
      "authorRank" : 3,
      "name" : "Kobayashi K",
      "referenceId" : "RGD:A314641"
    }, {
      "firstName" : "R",
      "lastName" : "Takano",
      "authorRank" : 4,
      "name" : "Takano R",
      "referenceId" : "RGD:A38516"
    }, {
      "firstName" : "S",
      "lastName" : "Kanno",
      "authorRank" : 5,
      "name" : "Kanno S",
      "referenceId" : "RGD:A17000"
    }, {
      "firstName" : "M",
      "lastName" : "Takao",
      "authorRank" : 6,
      "name" : "Takao M",
      "referenceId" : "RGD:A15341"
    }, {
      "firstName" : "J",
      "lastName" : "De Wit",
      "authorRank" : 7,
      "name" : "De Wit J",
      "referenceId" : "RGD:A38517"
    }, {
      "firstName" : "A",
      "lastName" : "Verkerk",
      "authorRank" : 8,
      "name" : "Verkerk A",
      "referenceId" : "RGD:A38518"
    }, {
      "firstName" : "AP",
      "lastName" : "Eker",
      "authorRank" : 9,
      "name" : "Eker AP",
      "referenceId" : "RGD:A38519"
    }, {
      "firstName" : "D",
      "lastName" : "Van Leenen",
      "authorRank" : 10,
      "name" : "Van Leenen D",
      "referenceId" : "RGD:A38520"
    }, {
      "firstName" : "R",
      "lastName" : "Buijs",
      "authorRank" : 11,
      "name" : "Buijs R",
      "referenceId" : "RGD:A38521"
    }, {
      "firstName" : "D",
      "lastName" : "Bootsma",
      "authorRank" : 12,
      "name" : "Bootsma D",
      "referenceId" : "RGD:A38522"
    }, {
      "firstName" : "JH",
      "lastName" : "Hoeijmakers",
      "authorRank" : 13,
      "name" : "Hoeijmakers JH",
      "referenceId" : "RGD:A38523"
    }, {
      "firstName" : "A",
      "lastName" : "Yasui",
      "authorRank" : 14,
      "name" : "Yasui A",
      "referenceId" : "RGD:A7602"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734990"
    } ]
  }, {
    "primaryId" : "PMID:10217258",
    "title" : "Synthesis degradation, and subcellular localization of synaptotagmin IV, a neuronal immediate early gene product.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Ferguson GD, etal., J Neurochem. 1999 May;72(5):1821-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-09-21T00:01:50.000-05:00",
    "volume" : "72",
    "pages" : "1821-31",
    "abstract" : "Synaptotagmin IV (Syt IV) is an immediate early gene induced by depolarization in rat PC12 cells and in rat hippocampus. We prepared an antiserum to Syt IV protein. The 46-kDa Syt IV protein is nearly undetectable by western blotting in  unstimulated PC12 cells. After depolarization, Syt IV increases rapidly, peaks at 4 h, and decays to near baseline levels by 12 h. Forskolin stimulation also leads to rapid Syt IV protein accumulation. The rate of Syt IV protein synthesis, determined by labeling with radioactive amino acids and immunoprecipitation, is low in unstimulated PC12 cells, but increases over the first 3 h after forskolin  stimulation and remains elevated for several hours. Syt IV protein is relatively  labile; metabolically labeled Syt IV has a half-life of approximately 2 h in PC12 cells. Sucrose density gradient fractionation and vesicle immunoisolation experiments suggest that Syt IV protein is present in both synaptic-like microvesicles and secretory granules. Vesicles immunoisolated from forskolin-treated PC12 cells with anti-Syt I antibody contain radioactively labeled Syt IV, demonstrating that Syt I and Syt IV colocalize in common vesicles. These results suggest that Syt IV protein, after its stimulation-induced synthesis, is rapidly transported to secretory vesicles where it may transiently modulate the exocytotic machinery.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GD",
      "lastName" : "Ferguson",
      "authorRank" : 1,
      "name" : "Ferguson",
      "referenceId" : "RGD:A384534"
    }, {
      "firstName" : "DM",
      "lastName" : "Thomas",
      "authorRank" : 2,
      "name" : "Thomas",
      "referenceId" : "RGD:A320094"
    }, {
      "firstName" : "LA",
      "lastName" : "Elferink",
      "authorRank" : 3,
      "name" : "Elferink LA",
      "referenceId" : "RGD:A5179"
    }, {
      "firstName" : "HR",
      "lastName" : "Herschman",
      "authorRank" : 4,
      "name" : "Herschman",
      "referenceId" : "RGD:A384573"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11535095"
    } ]
  }, {
    "primaryId" : "PMID:10217661",
    "title" : "Vascular endothelin-1 gene expression and synthesis and effect on renal type I collagen synthesis and nephroangiosclerosis during nitric oxide synthase inhibition in rats.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Tharaux PL, etal., Circulation. 1999 Apr 27;99(16):2185-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-19T13:03:55.000-05:00",
    "volume" : "99",
    "pages" : "2185-91",
    "abstract" : "BACKGROUND: The progression of hypertension during NO deficiency is associated with renal vascular fibrosis due to increased extracellular matrix (mainly collagen I) formation. The purpose of the present study was to investigate whether endothelin-1 (ET-1) is involved in this pathophysiological process. METHODS AND RESULTS: Treatment of rats for 4 weeks with the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) 50 mg. kg-1. d-1 increased systolic blood pressure to 159+/-12 mm Hg. In animals treated with L-NAME, histological evaluation of renal sections revealed an increased formation of extracellular matrix (Masson's trichrome), and specifically of collagens (Sirius red). A part of this fibrosis was attributed to abnormal collagen I presence, because mRNA expression of the collagen I alpha1 chain (reverse transcription-polymerase chain reaction) and procollagen I formation (radioimmunoassay) were increased 3- and 2.5-fold, respectively, in the renal resistance vessels of hypertensive animals.  In subsequent experiments, we examined whether ET-1 was involved in activation of collagen I formation. mRNA expression (RNase protection assay) of preproET-1 and  ET-1 content (radioimmunoassay) were 10-fold and 3-fold increased, respectively,  in renal microvessels of rats treated with L-NAME. Interestingly, in these vessels, ET-1 (immunostaining) was colocalized with sudanophilic lesions. Bosentan, an ET receptor antagonist (20 mg. kg-1. d-1), coadministered with L-NAME canceled the increased mRNA expression and synthesis of collagen I and attenuated the severity of renal vascular lesions without affecting L-NAME-induced high blood pressure. CONCLUSIONS: These data demonstrate that ET-1 synthesis is increased in renal microvessels when NO production is suppressed. In this model of hypertension, ET-1 is a major activator of collagen I formation in  renal resistance vessels and participates in the development of renal fibrosis without affecting systolic blood pressure.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PL",
      "lastName" : "Tharaux",
      "authorRank" : 1,
      "name" : "Tharaux PL",
      "referenceId" : "RGD:A67805"
    }, {
      "firstName" : "C",
      "lastName" : "Chatziantoniou",
      "authorRank" : 2,
      "name" : "Chatziantoniou C",
      "referenceId" : "RGD:A67807"
    }, {
      "firstName" : "D",
      "lastName" : "Casellas",
      "authorRank" : 3,
      "name" : "Casellas",
      "referenceId" : "RGD:A183227"
    }, {
      "firstName" : "L",
      "lastName" : "Fouassier",
      "authorRank" : 4,
      "name" : "Fouassier L",
      "referenceId" : "RGD:A23385"
    }, {
      "firstName" : "R",
      "lastName" : "Ardaillou",
      "authorRank" : 5,
      "name" : "Ardaillou R",
      "referenceId" : "RGD:A67653"
    }, {
      "firstName" : "JC",
      "lastName" : "Dussaule",
      "authorRank" : 6,
      "name" : "Dussaule JC",
      "referenceId" : "RGD:A67806"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662320"
    } ]
  }, {
    "primaryId" : "PMID:10218106",
    "title" : "Adenylosuccinate synthetase: recent developments.",
    "datePublished" : "1000-07-01T00:00:00.000-06:00",
    "citation" : "Honzatko RB, etal., Adv Enzymol Relat Areas Mol Biol. 1999;73:57-102, ix-x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-07-27T12:39:24.000-05:00",
    "volume" : "73",
    "pages" : "57-102, ix-x",
    "abstract" : "By exerting strategic control on purine nucleotide biosynthesis, and by engaging GTP-dependent transphosphorylation of IMP to activate loss of an oxygen atom during catalysis, adenylosuccinate synthetase remains as enzyme that justifiably fascinates students of enzyme catalysis. This review describes how the balanced application of X-ray crystallography and enzyme kinetics has advanced the comprehension of the catalytic and regulatory properties of adenylosuccinate synthetase. Detailed analysis has demonstrated the formation of 6-phosphoryl-IMP, an intermediate originally postulated over 40 years ago on the basis of oxygen-18 exchange experiments showing that position-6 oxygen of IMP becomes incorporated into phosphate. Inferences about the participation of amino acid side-chains that stabilize 6-P-IMP during catalysis have also been confirmed by site-directed mutagenesis and examination of such mutations on various kinetic parameters. Moreover, the action of certain regulatory ligands have also been viewed at atomic level resolution. For example, magnesium ion and GDP can induce conformational changes linked to the stabilization of one of two known conformations of the so-called 40s loop. Another significant finding is that two magnesium ions play fundamental roles: one binding with high affinity to the substrate GTP, and a second binding with lower affinity to the co-substrate aspartate. These structural and kinetic studies have also formed the basis for clarifying the action of various inhibitors and potentially important pharmacologic agents with this key regulatory enzyme. Finally, this review explores the current status of investigations on gene structure and gene expression in a number of organisms.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RB",
      "lastName" : "Honzatko",
      "authorRank" : 1,
      "name" : "Honzatko RB",
      "referenceId" : "RGD:A142025"
    }, {
      "firstName" : "MM",
      "lastName" : "Stayton",
      "authorRank" : 2,
      "name" : "Stayton MM",
      "referenceId" : "RGD:A142026"
    }, {
      "firstName" : "HJ",
      "lastName" : "Fromm",
      "authorRank" : 3,
      "name" : "Fromm HJ",
      "referenceId" : "RGD:A102772"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5143930"
    } ]
  }, {
    "primaryId" : "PMID:10218444",
    "title" : "Identification of possible quantitative trait loci responsible for hyperglycaemia after 70% pancreatectomy using a spontaneously diabetogenic rat.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Ogino T, etal., Genet Res 1999 Feb;73(1):29-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-05T14:27:09.000-05:00",
    "volume" : "73",
    "pages" : "29-36",
    "abstract" : "The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat exhibits sustained hyperglycaemia after partial pancreatectomy, while the normal control rat does not. This difference is thought to be genetically determined and to be caused by impairment of beta-cell regrowth, a possible event involved in the pathogenesis of NIDDM. Our investigation was designed to identify quantitative trait loci (QTL) responsible for post-pancreatectomy hyperglycaemia by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and Fischer-344 (F344) rats. We have identified three possible QTL on rat chromosomes (Chrs) 3, 14 and 19 that account for a total of approximately 75% of the genetic variance in the F2. For the QTL on Chr 14, the OLETF allele corresponds with increased glucose levels, as expected. Surprisingly, for the QTL on Chr 19, the F344 allele corresponds with increased glucose levels. The Chr 3 QTL exhibits heterosis, heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) between the QTL on Chrs 14 and 19.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Ogino",
      "authorRank" : 1,
      "name" : "Ogino T",
      "referenceId" : "RGD:A137306"
    }, {
      "firstName" : "DH",
      "lastName" : "Moralejo",
      "authorRank" : 2,
      "name" : "Moralejo DH",
      "referenceId" : "RGD:A157573"
    }, {
      "firstName" : "M",
      "lastName" : "Zhu",
      "authorRank" : 3,
      "name" : "Zhu M",
      "referenceId" : "RGD:A6904"
    }, {
      "firstName" : "K",
      "lastName" : "Toide",
      "authorRank" : 4,
      "name" : "Toide K",
      "referenceId" : "RGD:A6905"
    }, {
      "firstName" : "S",
      "lastName" : "Wei",
      "authorRank" : 5,
      "name" : "Wei S",
      "referenceId" : "RGD:A152512"
    }, {
      "firstName" : "K",
      "lastName" : "Wei",
      "authorRank" : 6,
      "name" : "Wei K",
      "referenceId" : "RGD:A128356"
    }, {
      "firstName" : "T",
      "lastName" : "Yamada",
      "authorRank" : 7,
      "name" : "Yamada T",
      "referenceId" : "RGD:A159941"
    }, {
      "firstName" : "A",
      "lastName" : "Mizuno",
      "authorRank" : 8,
      "name" : "Mizuno A",
      "referenceId" : "RGD:A6906"
    }, {
      "firstName" : "K",
      "lastName" : "Matsumoto",
      "authorRank" : 9,
      "name" : "Matsumoto K",
      "referenceId" : "RGD:A159245"
    }, {
      "firstName" : "K",
      "lastName" : "Shima",
      "authorRank" : 10,
      "name" : "Shima K",
      "referenceId" : "RGD:A6907"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619676"
    } ]
  }, {
    "primaryId" : "PMID:10218527",
    "title" : "Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Denoyelle F, etal., Lancet. 1999 Apr 17;353(9161):1298-303.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:26:53.000-05:00",
    "volume" : "353",
    "pages" : "1298-303",
    "abstract" : "BACKGROUND: DFNB1, the locus of an autosomal recessive form of deafness due to mutations in the connexin-26 gene (CX26 or GJB2) is one of the most frequent hereditary defects in human beings. To date, no clinical characterisation of the  DFNB1 inner-ear defects has been reported, which precludes the provision of prognostic information and genetic counselling. METHODS: We enrolled, in a prospective study, 140 children from 104 families affected by sensorineural deafness with various degrees of hearing loss. The children either belonged to a  family affected by autosomal recessive deafness (DFNB family) or represented sporadic cases. We searched for mutations in the 5' non-coding exon and in the coding region of CX26. Audiometric and radiological features were investigated and compared in deaf children with and without CX26 mutations. FINDINGS: CX26 mutations were present in 43 (49%) of the 88 families with cases of prelingual deafness versus none of the 16 families with postlingual forms of deafness (p<0.01). The inner-ear defects of 54 prelingually deaf children with biallelic CX26 mutations were compared with the defects in 57 prelingually deaf children without CX26 mutations. DFNB1 deafness varied from mild to profound, associated with sloping or flat audiometric curves and a radiologically normal inner ear. Hearing loss was not progressive in 11 of 16 cases tested, and variations in the  severity of deafness between siblings were common. INTERPRETATION: The characteristic audiometric and radiological features of DFNB1 should be the reference used to guide the investigation, by CX26 molecular diagnostic tests, of deaf children with a compatible phenotype. Prognostic information can now be given to families: the hearing loss in DFNB1 deafness is non-progressive in most  cases, at least up to young adulthood. An important element for genetic counselling is that the severity of hearing loss due to DFNB1 is extremely variable and cannot be predicted, even within families.",
    "issueName" : "9161",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Denoyelle",
      "authorRank" : 1,
      "name" : "Denoyelle F",
      "referenceId" : "RGD:A72965"
    }, {
      "firstName" : "S",
      "lastName" : "Marlin",
      "authorRank" : 2,
      "name" : "Marlin S",
      "referenceId" : "RGD:A72964"
    }, {
      "firstName" : "D",
      "lastName" : "Weil",
      "authorRank" : 3,
      "name" : "Weil D",
      "referenceId" : "RGD:A52734"
    }, {
      "firstName" : "L",
      "lastName" : "Moatti",
      "authorRank" : 4,
      "name" : "Moatti",
      "referenceId" : "RGD:A252378"
    }, {
      "firstName" : "P",
      "lastName" : "Chauvin",
      "authorRank" : 5,
      "name" : "Chauvin P",
      "referenceId" : "RGD:A72944"
    }, {
      "firstName" : "EN",
      "lastName" : "Garabedian",
      "authorRank" : 6,
      "name" : "Garabedian EN",
      "referenceId" : "RGD:A72962"
    }, {
      "firstName" : "C",
      "lastName" : "Petit",
      "authorRank" : 7,
      "name" : "Petit C",
      "referenceId" : "RGD:A38761"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067397"
    } ]
  }, {
    "primaryId" : "PMID:10218634",
    "title" : "Expression of growth inhibitory factor (metallothionein-III) mRNA and protein following excitotoxic immature brain injury.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Acarin L, etal., J Neuropathol Exp Neurol. 1999 Apr;58(4):389-97.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-27T14:44:26.000-06:00",
    "volume" : "58",
    "pages" : "389-97",
    "abstract" : "The balance between trophic factors and inhibitory molecules is likely to determine the outcome of neural tissue damage. The growth inhibitory factor (GIF), a member of the metallothionein family of proteins named metallothionein-III (MT-III), has been suggested to play an important role in tissue repair after adult brain injury. Because no information is available on this factor in relation to immature brain damage, we examined the chronological changes of GIF (MT-III) mRNA and protein following excitotoxic lesions to the postnatal day 9 brain using in situ hybridization and immunocytochemical techniques. We observed a significant decrease of neuronal GIF (MT-III) mRNA and  protein levels between 4 and 24 hours postinjury and an increase in glial GIF (MT-III) levels. Double immunocytochemical techniques showed GIF (MT-III) and GFAP positive astrocytes from 2-4 hours postinjury. From 3 days postinjury strongly reactive astrocytes expressed strong levels of both GIF (MT-III) mRNA and protein, which were maintained in the glial scar formed at longer times. These results show the expression of an inhibitory molecule by postnatal reactive astrocytes. Glial GIF (MT-III) expression may play an important role in the tissue reconstruction after immature brain damage.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Acarin",
      "authorRank" : 1,
      "name" : "Acarin L",
      "referenceId" : "RGD:A152822"
    }, {
      "firstName" : "J",
      "lastName" : "Carrasco",
      "authorRank" : 2,
      "name" : "Carrasco",
      "referenceId" : "RGD:A198610"
    }, {
      "firstName" : "B",
      "lastName" : "Gonzalez",
      "authorRank" : 3,
      "name" : "Gonzalez B",
      "referenceId" : "RGD:A26343"
    }, {
      "firstName" : "J",
      "lastName" : "Hidalgo",
      "authorRank" : 4,
      "name" : "Hidalgo",
      "referenceId" : "RGD:A196830"
    }, {
      "firstName" : "B",
      "lastName" : "Castellano",
      "authorRank" : 5,
      "name" : "Castellano B",
      "referenceId" : "RGD:A93691"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685803"
    } ]
  }, {
    "primaryId" : "PMID:10218646",
    "title" : "Stimulation of respiratory burst by cyclocommunin in rat neutrophils is associated with the increase in cellular Ca2+ and protein kinase C activity.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Wang JP, etal., Free Radic Biol Med. 1999 Mar;26(5-6):580-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-06-15T14:09:19.000-05:00",
    "volume" : "26",
    "pages" : "580-8",
    "abstract" : "In this study, the underlying mechanisms of stimulation by cyclocommunin, a natural pyranoflavonoid, of respiratory burst in rat neutrophils was investigated. Cyclocommunin evoked a concentration-dependent stimulation of superoxide anion (O2*-) generation with a slow onset and long lasting profile. The maximum response (16.4+/-2.3 nmol O2*-/10 min per 10(6) cells) was observed at 3-10 microM cyclocommunin. Cyclocommunin did not activate NADPH oxidase in a cell-free system. Cells pretreated with pertussis toxin or n-butanol did not affect the cyclocommunin-induced O2*- generation. However, a protein kinase inhibitor staurosporine and EGTA greatly reduced the O2*-generation caused by cyclocommunin. Treatment of neutrophils with phorbol 12-myristate 13-acetate (PMA), but not with formylmethionyl-leucyl-phenylalanine (fMLP), for 20 min significantly reduced the O2*- generation following the subsequent stimulation of cells with cyclocommunin. Cyclocommunin did not affect the cellular mass of phosphatidic acid (PA). Neither the tyrosine kinase inhibitor, genistein, nor the p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, affected cyclocommunin-induced O2*- generation. The enzyme activities of neutrophil cytosolic and membrane-associated protein kinase C (PKC) were both increased significantly with 100 microM cyclocommunin. The membrane-associated PKC-theta and PKC-beta were increased following the stimulation of neutrophils with 30 and 100 microM cyclocommunin, respectively. Cyclocommunin reduced the [3H]phorbol 12,13-dibutyrate ([3H]PDB) binding to cytosolic PKC in a concentration-dependent manner. Cyclocommunin (> or =3 microM) significantly evoked a slow and long lasting [Ca2+]i elevation in neutrophils, and a phospholipase C (PLC) inhibitor U73122 greatly inhibited these Ca2+ responses. Moreover, the increase in cellular inositol bis- and trisphosphate (IP2 and IP3) levels were observed in neutrophils stimulated with 30 microM cyclocommunin for 3 min. Collectively, these results indicate that the stimulation of respiratory burst by cyclocommunin is probably mediated by the synergism of PKC activation and [Ca2+]i elevation in rat neutrophils.",
    "issueName" : "5-6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JP",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang JP",
      "referenceId" : "RGD:A1234"
    }, {
      "firstName" : "LT",
      "lastName" : "Tsao",
      "authorRank" : 2,
      "name" : "Tsao LT",
      "referenceId" : "RGD:A84562"
    }, {
      "firstName" : "SL",
      "lastName" : "Raung",
      "authorRank" : 3,
      "name" : "Raung SL",
      "referenceId" : "RGD:A84563"
    }, {
      "firstName" : "PL",
      "lastName" : "Lin",
      "authorRank" : 4,
      "name" : "Lin PL",
      "referenceId" : "RGD:A84564"
    }, {
      "firstName" : "CN",
      "lastName" : "Lin",
      "authorRank" : 5,
      "name" : "Lin CN",
      "referenceId" : "RGD:A84565"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1625619"
    } ]
  }, {
    "primaryId" : "PMID:10218712",
    "title" : "Plasminogen activator inhibitor 1 in central serous chorioretinopathy.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Iijima H, etal., Am J Ophthalmol. 1999 Apr;127(4):477-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-20T13:56:06.000-06:00",
    "volume" : "127",
    "pages" : "477-8",
    "abstract" : "PURPOSE: To describe the plasma level of plasminogen activator inhibitor 1, the major antifibrinolytic agent, in eyes with central serous chorioretinopathy, in which choroidal thrombosis is suspected as the underlying condition based on the  findings of choroidal hyperpermeability in indocyanine green angiograms. METHODS: Plasminogen activator inhibitor 1 concentrations in the plasma of 17 patients with central serous chorioretinopathy were measured by enzyme-linked immunosorbent assay and compared with those in 12 age-matched normal volunteers.  RESULTS: The plasma levels of plasminogen activator inhibitor 1 in patients with  central serous chorioretinopathy (range, 25 to 439 ng/ml; median, 87 ng/ml) were  significantly increased compared with those in normal volunteers (range, 7 to 84  ng/ml; median, 36 ng/ml) (P = .0013, Mann-Whitney U test). CONCLUSION: Increased  plasminogen activator inhibitor 1 concentrations in patients with central serous  chorioretinopathy support the hypothesis that the choroidal hyperpermeability disclosed by indocyanine green angiography is caused from impaired fibrinolysis and the resulting thrombotic occlusion in the choroidal veins.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Iijima",
      "authorRank" : 1,
      "name" : "Iijima H",
      "referenceId" : "RGD:A6514"
    }, {
      "firstName" : "T",
      "lastName" : "Iida",
      "authorRank" : 2,
      "name" : "Iida T",
      "referenceId" : "RGD:A38563"
    }, {
      "firstName" : "K",
      "lastName" : "Murayama",
      "authorRank" : 3,
      "name" : "Murayama K",
      "referenceId" : "RGD:A55860"
    }, {
      "firstName" : "M",
      "lastName" : "Imai",
      "authorRank" : 4,
      "name" : "Imai",
      "referenceId" : "RGD:A325770"
    }, {
      "firstName" : "T",
      "lastName" : "Gohdo",
      "authorRank" : 5,
      "name" : "Gohdo",
      "referenceId" : "RGD:A179808"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547738"
    } ]
  }, {
    "primaryId" : "PMID:10218791",
    "title" : "Apolipoprotein D gene expression in the rat brain and light and electron microscopic immunocytochemistry of apolipoprotein D expression in the cerebellum of neonatal, immature and adult rats.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Ong WY, etal., Neuroscience. 1999 Mar;90(3):913-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-06-29T16:10:18.000-05:00",
    "volume" : "90",
    "pages" : "913-22",
    "abstract" : "Apolipoprotein D gene and protein expression were investigated in the rat brain and cerebellum, respectively, during development. Apolipoprotein D gene expression was first observed in embryonic day 12 rat brain, with a moderate increase in apolipoprotein D messenger RNA levels towards the later part (embryonic days 15-17) of gestation. In the postnatal rat brain, a marked induction of apolipoprotein D messenger RNA occurred at postnatal day 10, with progressively higher levels of apolipoprotein D messenger RNA observed up to postnatal day 20. Somewhat lower, but none the less high, levels of apolipoprotein D messenger RNA continued to be present in brains of adult animals. In the immature cerebellum (day 3 up to one- to two-week-old rats), there were many densely labeled apolipoprotein D-immunoreactive cells that had features of oligodendrocyte precursors. Purkinje neurons showed apolipoprotein D immunoreactivity in one- to two-week-old animals, after which there appeared to be some decrease in staining. Oligodendrocytes in the cerebella of two-week-old animals were strongly apolipoprotein D positive, with immunoreactivity declining in older animals. These results reveal a maturation-associated induction of apolipoprotein D gene expression in the rat brain, and expression of apolipoprotein D in glial (immature oligodendrocyte) cells in the immature cerebellum, followed by specific expression of apolipoprotein D in Purkinje neurons.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WY",
      "lastName" : "Ong",
      "authorRank" : 1,
      "name" : "Ong WY",
      "referenceId" : "RGD:A41859"
    }, {
      "firstName" : "CP",
      "lastName" : "Lau",
      "authorRank" : 2,
      "name" : "Lau CP",
      "referenceId" : "RGD:A60897"
    }, {
      "firstName" : "SK",
      "lastName" : "Leong",
      "authorRank" : 3,
      "name" : "Leong SK",
      "referenceId" : "RGD:A108874"
    }, {
      "firstName" : "U",
      "lastName" : "Kumar",
      "authorRank" : 4,
      "name" : "Kumar U",
      "referenceId" : "RGD:A52221"
    }, {
      "firstName" : "S",
      "lastName" : "Suresh",
      "authorRank" : 5,
      "name" : "Suresh S",
      "referenceId" : "RGD:A108875"
    }, {
      "firstName" : "SC",
      "lastName" : "Patel",
      "authorRank" : 6,
      "name" : "Patel SC",
      "referenceId" : "RGD:A108860"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311208"
    } ]
  }, {
    "primaryId" : "PMID:10218947",
    "title" : "Parathyroid hormone increases mac25/insulin-like growth factor-binding protein-related protein-1 expression in cultured osteoblasts.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Pereira RC and Canalis E, Endocrinology. 1999 May;140(5):1998-2003.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-08-10T18:01:21.000-05:00",
    "volume" : "140",
    "pages" : "1998-2003",
    "abstract" : "PTH induces the synthesis of insulin-like growth factor I (IGF-I) and regulates the expression of IGF-binding proteins (IGFBP) in osteoblast cultures. IGFBP-related protein-1 (IGFBP-RP-1), the product of the mac25 gene, binds IGF-I, IGF-II, and insulin. We tested the actions of PTH on the expression of mac25/IGFBP-RP-1 in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). PTH at 0.1-10 nM for 6-48 h increased mac25/IGFBP-RP-1 messenger RNA (mRNA) levels in Ob cells, an effect not altered by cycloheximide. PGE2 increased mac25/IGFBP-RP-1 mRNA levels, but indomethacin did not modify basal or PTH-stimulated mac25/IGFBP-RP-1 expression. The decay of mac25/IGFBP-RP-1 mRNA in transcriptionally arrested Ob cells was not modified by PTH, and PTH increased the rate of IGFBP-RP-1 transcription. GH, insulin, bone morphogenetic protein-2, fibroblast growth factor-2, platelet-derived growth factor BB, IGF-I, and IGF-II did not modify mac25/IGFBP-RP-1 expression, whereas transforming growth factor-beta1 was modestly stimulatory. In conclusion, PTH stimulates mac25/IGFBP-RP-1 transcription in osteoblasts, an effect that could be relevant to the actions of PTH in bone.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RC",
      "lastName" : "Pereira",
      "authorRank" : 1,
      "name" : "Pereira RC",
      "referenceId" : "RGD:A86449"
    }, {
      "firstName" : "E",
      "lastName" : "Canalis",
      "authorRank" : 2,
      "name" : "Canalis E",
      "referenceId" : "RGD:A69195"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1626572"
    } ]
  }, {
    "primaryId" : "PMID:10219239",
    "title" : "MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Abbott GW, etal., Cell 1999 Apr 16;97(2):175-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:08.000-05:00",
    "volume" : "97",
    "pages" : "175-87",
    "abstract" : "A novel potassium channel gene has been cloned, characterized, and associated with cardiac arrhythmia. The gene encodes MinK-related peptide 1 (MiRP1), a small integral membrane subunit that assembles with HERG, a pore-forming protein, to alter its function. Unlike channels formed only with HERG, mixed complexes resemble native cardiac IKr channels in their gating, unitary conductance, regulation by potassium, and distinctive biphasic inhibition by the class III antiarrhythmic E-4031. Three missense mutations associated with long QT syndrome and ventricular fibrillation are identified in the gene for MiRP1. Mutants form channels that open slowly and close rapidly, thereby diminishing potassium currents. One variant, associated with clarithromycin-induced arrhythmia, increases channel blockade by the antibiotic. A mechanism for acquired arrhythmia is revealed: genetically based reduction in potassium currents that remains clinically silent until combined with additional stressors.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GW",
      "lastName" : "Abbott",
      "authorRank" : 1,
      "name" : "Abbott GW",
      "referenceId" : "RGD:A19585"
    }, {
      "firstName" : "F",
      "lastName" : "Sesti",
      "authorRank" : 2,
      "name" : "Sesti F",
      "referenceId" : "RGD:A17158"
    }, {
      "firstName" : "I",
      "lastName" : "Splawski",
      "authorRank" : 3,
      "name" : "Splawski I",
      "referenceId" : "RGD:A19586"
    }, {
      "firstName" : "ME",
      "lastName" : "Buck",
      "authorRank" : 4,
      "name" : "Buck ME",
      "referenceId" : "RGD:A19587"
    }, {
      "firstName" : "MH",
      "lastName" : "Lehmann",
      "authorRank" : 5,
      "name" : "Lehmann MH",
      "referenceId" : "RGD:A19588"
    }, {
      "firstName" : "KW",
      "lastName" : "Timothy",
      "authorRank" : 6,
      "name" : "Timothy KW",
      "referenceId" : "RGD:A19589"
    }, {
      "firstName" : "MT",
      "lastName" : "Keating",
      "authorRank" : 7,
      "name" : "Keating MT",
      "referenceId" : "RGD:A18685"
    }, {
      "firstName" : "SA",
      "lastName" : "Goldstein",
      "authorRank" : 8,
      "name" : "Goldstein SA",
      "referenceId" : "RGD:A19590"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633041"
    } ]
  }, {
    "primaryId" : "PMID:10219240",
    "title" : "Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hirota H, etal., Cell 1999 Apr 16;97(2):189-98.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-26T10:55:21.000-06:00",
    "volume" : "97",
    "pages" : "189-98",
    "abstract" : "Biomechanical stress is a major stimulus for cardiac hypertrophy and the transition to heart failure. By generating mice that harbor a ventricular restricted knockout of the gp130 cytokine receptor via Cre-IoxP-mediated recombination, we demonstrate a critical role for a gp130-dependent myocyte survival pathway in the transition to heart failure. Such conditional mutant mice have normal cardiac structure and function, but during aortic pressure overload, these mice display rapid onset of dilated cardiomyopathy and massive induction of myocyte apoptosis versus the control mice that exhibit compensatory hypertrophy. Thus, cardiac myocyte apoptosis is a critical point in the transition between compensatory cardiac hypertrophy and heart failure. gp130-dependent cytokines may represent a novel therapeutic strategy for preventing in vivo heart failure.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Hirota",
      "authorRank" : 1,
      "name" : "Hirota H",
      "referenceId" : "RGD:A39256"
    }, {
      "firstName" : "J",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen J",
      "referenceId" : "RGD:A161502"
    }, {
      "firstName" : "UA",
      "lastName" : "Betz",
      "authorRank" : 3,
      "name" : "Betz UA",
      "referenceId" : "RGD:A39258"
    }, {
      "firstName" : "K",
      "lastName" : "Rajewsky",
      "authorRank" : 4,
      "name" : "Rajewsky K",
      "referenceId" : "RGD:A16503"
    }, {
      "firstName" : "Y",
      "lastName" : "Gu",
      "authorRank" : 5,
      "name" : "Gu Y",
      "referenceId" : "RGD:A7018"
    }, {
      "firstName" : "JR",
      "lastName" : "Ross J",
      "authorRank" : 6,
      "name" : "Ross J JR",
      "referenceId" : "RGD:A35771"
    }, {
      "firstName" : "W",
      "lastName" : "Muller",
      "authorRank" : 7,
      "name" : "Muller W",
      "referenceId" : "RGD:A39259"
    }, {
      "firstName" : "KR",
      "lastName" : "Chien",
      "authorRank" : 8,
      "name" : "Chien KR",
      "referenceId" : "RGD:A7326"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:737751"
    } ]
  }, {
    "primaryId" : "PMID:10219263",
    "title" : "Characterization of seizures in the flathead rat: a new genetic model of epilepsy in early postnatal development.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Sarkisian MR, etal., Epilepsia. 1999 Apr;40(4):394-400.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-07-21T11:53:13.000-05:00",
    "volume" : "40",
    "pages" : "394-400",
    "abstract" : "<br><b>PURPOSE: </b>Disorders in normal central nervous system (CNS) development are often associated with epilepsy. This report characterizes seizures in a novel genetic model of developmental epilepsy, the Flathead (FH) rat.<br><b>METHODS: </b>Animals (n = 76) ages P0-22 were monitored for clinical and electrographic seizure activity. The effects of various AEDs on seizure frequency and duration also were assessed: phenobarbital (PB; 40 mg/kg), valproate (VPA; 400 mg/kg), or ethosuximide (ESM; 600 mg/kg).<br><b>RESULTS: </b>FHs display episodes of behavior characterized by whole-body tremor, strub tail, alternating forelimb clonus, and complete tonus. EEG recordings from neocortex reveal that FH seizures are bilateral and begin around P7. Seizures occur at a frequency of approximately six per hour from P7 to P18 and the average duration of seizures increases through development. PB, VPA, and ESM failed to prevent seizures; however, PB significantly increased the interval of seizures but had no effects on the duration of seizures, whereas VPA decreased the duration of seizures and not the interval.<br><b>CONCLUSIONS: </b>Seizures in FH rats occur at a constant and high frequency through a defined period in early postnatal development, and these seizures are not completely blocked by high doses of PB, VPA, or ESM. Because FH is a single-locus mutant displaying a highly regular pattern of seizure activity, it is an ideal model for examining the process of epileptogenesis in the developing brain, evaluating new AED therapies, and determining the identity of a gene essential to the normal development of cortical excitability.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M R",
      "lastName" : "Sarkisian",
      "authorRank" : 1,
      "name" : "Sarkisian MR",
      "referenceId" : "RGD:A447846"
    }, {
      "firstName" : "S",
      "lastName" : "Rattan",
      "authorRank" : 2,
      "name" : "Rattan S",
      "referenceId" : "RGD:A76203"
    }, {
      "firstName" : "S R",
      "lastName" : "D'Mello",
      "authorRank" : 3,
      "name" : "D'Mello SR",
      "referenceId" : "RGD:A447847"
    }, {
      "firstName" : "J J",
      "lastName" : "LoTurco",
      "authorRank" : 4,
      "name" : "LoTurco JJ",
      "referenceId" : "RGD:A446473"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13204836"
    } ]
  }, {
    "primaryId" : "PMID:10219625",
    "title" : "Expression of tenascin-C and the integrin alpha 9 subunit in regeneration of rat nasal mucosa after chemical injury: involvement in migration and proliferation of epithelial cells.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Yoshimura E, etal., Histochem Cell Biol. 1999 Apr;111(4):259-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-04-29T10:26:56.000-05:00",
    "volume" : "111",
    "pages" : "259-64",
    "abstract" : "Nasal mucosa covered by pseudostratified ciliated epithelia can be injured by microbial infection and physical and chemical agents. To elucidate mechanisms of regeneration, erosion of rat nasal mucosa was produced by intranasal instillation of trichloroacetic acid, and tissue specimens were then sequentially obtained after 1-14 days. Since tenascin-C (TN-C) and its receptor, alpha 9 beta 1 integrin, are assumed to play important roles in regeneration of stratified squamous epithelia, their expression was evaluated by immunohistochemistry and in situ hybridization. Three to five days after the injury, TN-C mRNA was found in epithelial cells of migrating fronts and in epithelial sheets recovering ulcerated surfaces between the fronts and normal regions. TN-C deposition was increased under such sheets. Enhanced alpha 9 staining was also evident in the involved epithelium. 5-Bromo-2'-deoxyuridine incorporation assays revealed significant increase in proliferating cells in cell sheets over TN-C deposits at 3-7 days. Therefore, we conclude that regenerating epithelial cells produce and secrete TN-C, associated with an increase in alpha 9 expression, and that interactions between these molecules could regulate migration and proliferation of the epithelial cells in an autocrine manner.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Yoshimura",
      "authorRank" : 1,
      "name" : "Yoshimura E",
      "referenceId" : "RGD:A122550"
    }, {
      "firstName" : "A",
      "lastName" : "Majima",
      "authorRank" : 2,
      "name" : "Majima A",
      "referenceId" : "RGD:A122551"
    }, {
      "firstName" : "Y",
      "lastName" : "Sakakura",
      "authorRank" : 3,
      "name" : "Sakakura Y",
      "referenceId" : "RGD:A122552"
    }, {
      "firstName" : "T",
      "lastName" : "Sakakura",
      "authorRank" : 4,
      "name" : "Sakakura T",
      "referenceId" : "RGD:A122553"
    }, {
      "firstName" : "T",
      "lastName" : "Yoshida",
      "authorRank" : 5,
      "name" : "Yoshida T",
      "referenceId" : "RGD:A160470"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317877"
    } ]
  }, {
    "primaryId" : "PMID:10219846",
    "title" : "Keratinocyte growth factor ameliorates dextran sodium sulfate colitis in mice.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Egger B, etal., Dig Dis Sci. 1999 Apr;44(4):836-44. doi: 10.1023/a:1026642715764.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-05-27T16:22:45.000-05:00",
    "volume" : "44",
    "pages" : "836-44",
    "abstract" : "Keratinocyte growth factor (KGF) is emerging as an important mediator of mucosal defense and repair in the colon. The aim of the present study was to evaluate and further characterize the effects of exogenous KGF administration utilizing the dextran sodium sulfate (DSS) model of colitis in mice. Colitis was induced via oral administration of DSS (5 g/100 ml) to Balb/c mice for eight days. Intraperitoneal administration of KGF (5 mg/kg, once daily) or vehicle (VEH) was initiated 1 hr prior to the induction of the colitis (N = 10, each group). Mucosal injury of the entire colon was histologically assessed and graded. An approximately fourfold reduction in the crypt damage score was noted in the KGF group when compared to controls (VEH) (2.8 +/- 1.03 and 11.4 +/- 0.78, respectively). The significant reduction of mucosal injury in KGF treated mice confirms that KGF is a key mediator maintaining the integrity of the colonic mucosa.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Egger",
      "authorRank" : 1,
      "name" : "Egger B",
      "referenceId" : "RGD:A500026"
    }, {
      "firstName" : "F",
      "lastName" : "Procaccino",
      "authorRank" : 2,
      "name" : "Procaccino F",
      "referenceId" : "RGD:A500027"
    }, {
      "firstName" : "I",
      "lastName" : "Sarosi",
      "authorRank" : 3,
      "name" : "Sarosi I",
      "referenceId" : "RGD:A39299"
    }, {
      "firstName" : "J",
      "lastName" : "Tolmos",
      "authorRank" : 4,
      "name" : "Tolmos J",
      "referenceId" : "RGD:A500028"
    }, {
      "firstName" : "M W",
      "lastName" : "Büchler",
      "authorRank" : 5,
      "name" : "Büchler MW",
      "referenceId" : "RGD:A468573"
    }, {
      "firstName" : "V E",
      "lastName" : "Eysselein",
      "authorRank" : 6,
      "name" : "Eysselein VE",
      "referenceId" : "RGD:A500029"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:126928136"
    } ]
  }, {
    "primaryId" : "PMID:10220139",
    "title" : "WRN mutations in Werner syndrome.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Moser MJ, etal., Hum Mutat. 1999;13(4):271-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-01T16:50:48.000-06:00",
    "volume" : "13",
    "pages" : "271-9",
    "abstract" : "Werner syndrome (WS) is one of a group of human genetic diseases that have recently been linked to deficits in cellular helicase function. We review the spectrum of WS-associated WRN mutations, the organization and potential functions of the WRN protein, and potential mechanistic links between the loss of WRN function and pathogenesis of the WS clinical and cellular phenotypes.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MJ",
      "lastName" : "Moser",
      "authorRank" : 1,
      "name" : "Moser MJ",
      "referenceId" : "RGD:A73764"
    }, {
      "firstName" : "J",
      "lastName" : "Oshima",
      "authorRank" : 2,
      "name" : "Oshima J",
      "referenceId" : "RGD:A64171"
    }, {
      "firstName" : "JR",
      "lastName" : "Monnat RJ",
      "authorRank" : 3,
      "name" : "Monnat RJ JR",
      "referenceId" : "RGD:A19395"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599418"
    } ]
  }, {
    "primaryId" : "PMID:10220144",
    "title" : "Novel KCNQ1 and HERG missense mutations in Dutch long-QT families.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Jongbloed RJ, etal., Hum Mutat. 1999;13(4):301-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:19:32.000-05:00",
    "volume" : "13",
    "pages" : "301-10",
    "abstract" : "Congenital long QT syndrome (cLQTS) is electrocardiographically characterized by  a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncopes, seizure, or sudden death. LQTS can occur either as an autosomal dominant (Romano Ward) or as  an autosomal recessive disorder (Jervell and Lange-Nielsen syndrome). Mutations in at least five genes have been associated with the LQTS. Four genes, encoding cardiac ion channels, have been identified. The most common forms of LQTS are due to mutations in the potassium-channel genes KCNQ1 and HERG. We have screened 24 Dutch LQTS families for mutations in KCNQ1 and HERG. Fourteen missense mutations  were identified. Eight of these missense mutations were novel: three in KCNQ1 and five in HERG. Novel missense mutations in KCNQ1 were Y184S, S373P, and W392R and  novel missense mutations in HERG were A558P, R582C, G604S, T613M, and F640L. The  KCNQ1 mutation G189R and the HERG mutation R582C were detected in two families. The pathogenicity of the mutations was based on segregation in families, absence  in control individuals, the nature of the amino acid substitution, and localization in the protein. Genotype-phenotype studies indicated that auditory stimuli as trigger of cardiac events differentiate LQTS2 and LQTS1. In LQTS1, exercise was the predominant trigger. In addition, a number of asymptomatic gene  defect carriers were identified. Asymptomatic carriers are still at risk of the development of life-threatening arrhythmias, underlining the importance of DNA analyses for unequivocal diagnosis of patients with LQTS.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RJ",
      "lastName" : "Jongbloed",
      "authorRank" : 1,
      "name" : "Jongbloed",
      "referenceId" : "RGD:A251979"
    }, {
      "firstName" : "AA",
      "lastName" : "Wilde",
      "authorRank" : 2,
      "name" : "Wilde AA",
      "referenceId" : "RGD:A60672"
    }, {
      "firstName" : "JL",
      "lastName" : "Geelen",
      "authorRank" : 3,
      "name" : "Geelen",
      "referenceId" : "RGD:A256826"
    }, {
      "firstName" : "P",
      "lastName" : "Doevendans",
      "authorRank" : 4,
      "name" : "Doevendans",
      "referenceId" : "RGD:A252533"
    }, {
      "firstName" : "C",
      "lastName" : "Schaap",
      "authorRank" : 5,
      "name" : "Schaap",
      "referenceId" : "RGD:A256827"
    }, {
      "firstName" : "I",
      "lastName" : "Van Langen",
      "authorRank" : 6,
      "name" : "Van Langen",
      "referenceId" : "RGD:A256828"
    }, {
      "firstName" : "JP",
      "lastName" : "Van Tintelen",
      "authorRank" : 7,
      "name" : "Van Tintelen JP",
      "referenceId" : "RGD:A64445"
    }, {
      "firstName" : "JM",
      "lastName" : "Cobben",
      "authorRank" : 8,
      "name" : "Cobben JM",
      "referenceId" : "RGD:A152892"
    }, {
      "firstName" : "GC",
      "lastName" : "Beaufort-Krol",
      "authorRank" : 9,
      "name" : "Beaufort-Krol",
      "referenceId" : "RGD:A256829"
    }, {
      "firstName" : "JP",
      "lastName" : "Geraedts",
      "authorRank" : 10,
      "name" : "Geraedts JP",
      "referenceId" : "RGD:A108726"
    }, {
      "firstName" : "HJ",
      "lastName" : "Smeets",
      "authorRank" : 11,
      "name" : "Smeets HJ",
      "referenceId" : "RGD:A54243"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063922"
    } ]
  }, {
    "primaryId" : "PMID:10220146",
    "title" : "High-throughput single-strand conformation polymorphism analysis by automated capillary electrophoresis: robust multiplex analysis and pattern-based identification of allelic variants.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Larsen LA, etal., Hum Mutat. 1999;13(4):318-27.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:04:50.000-05:00",
    "volume" : "13",
    "pages" : "318-27",
    "abstract" : "Genetic diagnosis of an inherited disease or cancer often involves analysis for unknown point mutations in several genes; therefore, rapid and automated techniques that can process a large number of samples are needed. We describe a method for high-throughput single-strand conformation polymorphism (SSCP) analysis using automated capillary electrophoresis. The operating temperature of  a commercially available capillary electrophoresis instrument (ABI PRISM 310) was expanded by installation of a cheap in-house designed cooling system, thereby allowing us to perform automated SSCP analysis at 14-45 degrees C. We have used the method for detection of point mutations associated with the inherited cardiac disorders long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM). The sensitivity of the method was 100% when 34 different point mutations were analyzed, including two previously unpublished LQTS-associated mutations (F157C in KVLQT1 and G572R in HERG), as well as eight novel normal variants in HERG and  MYH7. The analyzed polymerase chain reaction (PCR) fragments ranged in size from  166 to 1,223 bp. Seventeen different sequence contexts were analyzed. Three different electrophoresis temperatures were used to obtain 100% sensitivity. Two  mutants could not be detected at temperatures greater than 20 degrees C. The method has a high resolution and good reproducibility and is very robust, making  multiplex SSCP analysis and pattern-based identification of known allelic variants as single nucleotide polymorphisms (SNPs) possible. These possibilities, combined with automation and short analysis time, make the method suitable for high-throughput tasks, such as genetic screening.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LA",
      "lastName" : "Larsen",
      "authorRank" : 1,
      "name" : "Larsen LA",
      "referenceId" : "RGD:A61734"
    }, {
      "firstName" : "M",
      "lastName" : "Christiansen",
      "authorRank" : 2,
      "name" : "Christiansen M",
      "referenceId" : "RGD:A61739"
    }, {
      "firstName" : "J",
      "lastName" : "Vuust",
      "authorRank" : 3,
      "name" : "Vuust J",
      "referenceId" : "RGD:A61738"
    }, {
      "firstName" : "PS",
      "lastName" : "Andersen",
      "authorRank" : 4,
      "name" : "Andersen PS",
      "referenceId" : "RGD:A61730"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069690"
    } ]
  }, {
    "primaryId" : "PMID:10220149",
    "title" : "A novel mutation L1425P in the GAP-region of the NF1 gene detected by temperature gradient gel electrophoresis (TGGE). Mutation in brief no. 230. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Peters H, etal., Hum Mutat. 1999;13(4):337.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:55:27.000-05:00",
    "volume" : "13",
    "pages" : "337",
    "abstract" : "Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an incidence of between 1: 3000 and 1: 4000. Common clinical signs include more than six cafe-au-lait spots, multiple cutaneous neurofibromas and iris Lisch nodules.  Rarer are skeletal anomalies, learning disabilities and an increased risk of malignancy. The NF1 gene contains at least 60 exons with intron sizes ranging from 60 bp to more than 40 kb. Despite using different techniques including PTT,  SSCP heteroduplex analyses and direct sequencing, only a relatively small number  of mutations have been reported world-wide. Using the more sensitive technique of temperature gradient gel electrophoresis (TGGE), we analysed a part of the NF1-GAP-region, namely exon 25, in DNA samples from 131 unrelated patients. We have identified a novel mutation L1425P in exon 25 of the NF1 gene in a 12-year-old boy (clinically diagnosed with NF1 at the age of 7). In contrast to those cases diagnosed with having both GAP-region mutations and malignant tumours, neither the proband nor four clinically affected family members with this mutation showed any evidence of malignancies.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Peters",
      "authorRank" : 1,
      "name" : "Peters H",
      "referenceId" : "RGD:A46918"
    }, {
      "firstName" : "D",
      "lastName" : "Hess",
      "authorRank" : 2,
      "name" : "Hess D",
      "referenceId" : "RGD:A25785"
    }, {
      "firstName" : "R",
      "lastName" : "Fahsold",
      "authorRank" : 3,
      "name" : "Fahsold",
      "referenceId" : "RGD:A267522"
    }, {
      "firstName" : "M",
      "lastName" : "Schulke",
      "authorRank" : 4,
      "name" : "Schulke",
      "referenceId" : "RGD:A280225"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071708"
    } ]
  }, {
    "primaryId" : "PMID:10220153",
    "title" : "Identification of four novel mutations of the XLRS1 gene in Japanese patients with X-linked juvenile retinoschisis. Mutation in brief no. 234. Online.",
    "datePublished" : "1000-10-01T00:00:00.000-06:00",
    "citation" : "Mashima Y, etal., Hum Mutat. 1999;13(4):338.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-10-20T15:22:41.000-05:00",
    "volume" : "13",
    "pages" : "338",
    "abstract" : "The XLRS1 gene (HUGO-approved symbol, RS1) has been found to cause X-linked recessive retinoschisis (RS) which is characterized by splitting of the superficial layer of the retina. Recent mutation analysis of this gene revealed 82 different mutations in 214 patients with RS. We have now identified 10 mutations of the XLRS1 gene in 11 unrelated Japanese males with RS. Mutations found in these patients were; 1) a 20-kb deletion in exon 1 region; 2) mutations  in the initiation sequence (M1V); 3) mutations in the splice donor site (IVS1 + 1 g-->a); 4) two nonsense mutations (Q88X, W163X); and 5) five missense mutations (E72K, Y89C, R182C, G109E, P203L). Four (M1V, Q88X, G109E, and W163X) of the 10 mutations were novel. The R182C mutation was identified in 2 unrelated patients.  The 3 mutations found between exons 1 and 3 cause premature translation termination in the XLRS1 protein. The rest of the 7 mutations were clustered between exons 4 and 6. This region of the protein is homologous to the proteins implicated in cell-cell adhesion.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Mashima",
      "authorRank" : 1,
      "name" : "Mashima Y",
      "referenceId" : "RGD:A113715"
    }, {
      "firstName" : "K",
      "lastName" : "Shinoda",
      "authorRank" : 2,
      "name" : "Shinoda K",
      "referenceId" : "RGD:A4199"
    }, {
      "firstName" : "S",
      "lastName" : "Ishida",
      "authorRank" : 3,
      "name" : "Ishida S",
      "referenceId" : "RGD:A39621"
    }, {
      "firstName" : "Y",
      "lastName" : "Ozawa",
      "authorRank" : 4,
      "name" : "Ozawa Y",
      "referenceId" : "RGD:A20769"
    }, {
      "firstName" : "J",
      "lastName" : "Kudoh",
      "authorRank" : 5,
      "name" : "Kudoh J",
      "referenceId" : "RGD:A73864"
    }, {
      "firstName" : "T",
      "lastName" : "Iwata",
      "authorRank" : 6,
      "name" : "Iwata T",
      "referenceId" : "RGD:A123124"
    }, {
      "firstName" : "Y",
      "lastName" : "Oguchi",
      "authorRank" : 7,
      "name" : "Oguchi Y",
      "referenceId" : "RGD:A35510"
    }, {
      "firstName" : "N",
      "lastName" : "Shimizu",
      "authorRank" : 8,
      "name" : "Shimizu N",
      "referenceId" : "RGD:A5024"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9587805"
    } ]
  }, {
    "primaryId" : "PMID:10220377",
    "title" : "Mitochondrial disease in mouse results in increased oxidative stress.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Esposito LA, etal., Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4820-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-09-23T17:03:59.000-05:00",
    "volume" : "96",
    "pages" : "4820-5",
    "abstract" : "It has been hypothesized that a major factor in the progression of mitochondrial disease resulting from defects in oxidative phosphorylation (OXPHOS) is the stimulation of the mitochondrial production of reactive oxygen species (ROS) and the resulting damage to the mtDNA. To test this hypothesis, we examined the mitochondria from mice lacking the heart/muscle isoform of the adenine nucleotide translocator (Ant1), designated Ant1(tm2Mgr) (-/-) mice. The absence of Ant1 blocks the exchange of ADP and ATP across the mitochondrial inner membrane, thus inhibiting OXPHOS. Consistent with Ant1 expression, mitochondria isolated from skeletal muscle, heart, and brain of the Ant1-deficient mice produced markedly increased amounts of the ROS hydrogen peroxide, whereas liver mitochondria, which express a different Ant isoform, produced normally low levels of hydrogen peroxide. The increased production of ROS by the skeletal muscle and heart was associated with a dramatic increase in the ROS detoxification enzyme manganese superoxide dismutase (Sod2, also known as MnSod) in muscle tissue and muscle mitochondria, a modest increase in Sod2 in heart tissue, and no increase in heart mitochondria. The level of glutathione peroxidase-1 (Gpx1), a second ROS detoxifying enzyme, was increased moderately in the mitochondria of both tissues. Consistent with the lower antioxidant defenses in heart, the heart mtDNAs of the Ant1-deficient mice showed a striking increase in the accumulation of mtDNA rearrangements, whereas skeletal muscle, with higher antioxidant defenses, had fewer mtDNA rearrangements. Hence, inhibition of OXPHOS does increase mitochondrial ROS production, eliciting antioxidant defenses. If the antioxidant defenses are insufficient to detoxify the ROS, then an increased mtDNA mutation rate can result.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LA",
      "lastName" : "Esposito",
      "authorRank" : 1,
      "name" : "Esposito LA",
      "referenceId" : "RGD:A66061"
    }, {
      "firstName" : "S",
      "lastName" : "Melov",
      "authorRank" : 2,
      "name" : "Melov S",
      "referenceId" : "RGD:A66062"
    }, {
      "firstName" : "A",
      "lastName" : "Panov",
      "authorRank" : 3,
      "name" : "Panov A",
      "referenceId" : "RGD:A66063"
    }, {
      "firstName" : "BA",
      "lastName" : "Cottrell",
      "authorRank" : 4,
      "name" : "Cottrell BA",
      "referenceId" : "RGD:A66064"
    }, {
      "firstName" : "DC",
      "lastName" : "Wallace",
      "authorRank" : 5,
      "name" : "Wallace DC",
      "referenceId" : "RGD:A63312"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581261"
    } ]
  }, {
    "primaryId" : "PMID:10220438",
    "title" : "Association of a missense change in the D2 dopamine receptor with myoclonus dystonia.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Klein C, etal., Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5173-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-30T11:03:40.000-05:00",
    "volume" : "96",
    "pages" : "5173-6",
    "abstract" : "Hereditary autosomal dominant myoclonus dystonia (MD) is a movement disorder characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Although various large families with MD have been described, no positive linkage has been found to a chromosomal location. We report a family with eight members with MD. Linkage analysis identified a 23-centimorgan region on chromosome 11q23 that cosegregates with the disease state (maximum multipoint logarithm of odds score = 2.96 at D11S897). This region contains an excellent candidate gene for involvement in the etiology of MD, the D2 dopamine receptor (DRD2) gene. Neurotransmission mediated by DRD2 is known to have a key role in the control of movement and also has been implicated in reward and reinforcement mechanisms and psychiatric disorders. Sequencing of the coding region of DRD2 indicated that all affected and obligate carriers were heterozygous for a Val154Ile change in exon 3 of the protein, which is highly conserved across species. This change was found neither in other unaffected members of the pedigree nor in 250 control chromosomes. Our finding provides evidence for the involvement of DRD2 in a disorder of the central nervous system and should lead to further insight into the function of the dopaminergic system in dystonia and other movement and mood disorders.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Klein",
      "authorRank" : 1,
      "name" : "Klein C",
      "referenceId" : "RGD:A9584"
    }, {
      "firstName" : "MF",
      "lastName" : "Brin",
      "authorRank" : 2,
      "name" : "Brin MF",
      "referenceId" : "RGD:A56356"
    }, {
      "firstName" : "P",
      "lastName" : "Kramer",
      "authorRank" : 3,
      "name" : "Kramer P",
      "referenceId" : "RGD:A37498"
    }, {
      "firstName" : "M",
      "lastName" : "Sena-Esteves",
      "authorRank" : 4,
      "name" : "Sena-Esteves M",
      "referenceId" : "RGD:A78868"
    }, {
      "firstName" : "D",
      "lastName" : "De Leon",
      "authorRank" : 5,
      "name" : "De Leon D",
      "referenceId" : "RGD:A56355"
    }, {
      "firstName" : "D",
      "lastName" : "Doheny",
      "authorRank" : 6,
      "name" : "Doheny D",
      "referenceId" : "RGD:A78869"
    }, {
      "firstName" : "S",
      "lastName" : "Bressman",
      "authorRank" : 7,
      "name" : "Bressman S",
      "referenceId" : "RGD:A78870"
    }, {
      "firstName" : "S",
      "lastName" : "Fahn",
      "authorRank" : 8,
      "name" : "Fahn S",
      "referenceId" : "RGD:A162070"
    }, {
      "firstName" : "XO",
      "lastName" : "Breakefield",
      "authorRank" : 9,
      "name" : "Breakefield XO",
      "referenceId" : "RGD:A24901"
    }, {
      "firstName" : "LJ",
      "lastName" : "Ozelius",
      "authorRank" : 10,
      "name" : "Ozelius LJ",
      "referenceId" : "RGD:A24900"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600903"
    } ]
  }, {
    "primaryId" : "PMID:10220506",
    "title" : "Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Crosnier C, etal., Gastroenterology. 1999 May;116(5):1141-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:43:34.000-05:00",
    "volume" : "116",
    "pages" : "1141-8",
    "abstract" : "BACKGROUNDS & AIMS: Mutations in the JAGGED1 gene are responsible for the Alagille syndrome, an autosomal dominant disorder characterized by neonatal jaundice, intrahepatic cholestasis, and developmental disorders affecting the liver, heart, vertebrae, eyes, and face. We screened a large group of patients for mutations in JAGGED1 and studied transmission of the mutations. METHODS: The  coding sequence of the JAGGED1 gene was searched by single-strand conformation polymorphism and sequence analysis for mutations in 109 unrelated patients with the Alagille syndrome and their family if available. RESULTS: Sixty-nine patients (63%) had intragenic mutations, including 14 nonsense mutations, 31 frameshifts,  11 splice site mutations, and 13 missense mutations. We identified 59 different types of mutation of which 54 were previously undescribed; 8 were observed more than once. Mutations were de novo in 40 of 57 probands. CONCLUSIONS: Most of the  observed mutations other than the missense mutations in JAGGED1 are expected to give rise to truncated and unanchored proteins. All mutations mapped to the extracellular domain of the protein, and there appeared to be regional hot spots, although no clustering was observed. Thus, the sequencing of 7 exons of JAGGED1 would detect 51% of the mutations. Transmission analysis showed a high frequency  of sporadic cases (70%).",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Crosnier",
      "authorRank" : 1,
      "name" : "Crosnier",
      "referenceId" : "RGD:A259732"
    }, {
      "firstName" : "C",
      "lastName" : "Driancourt",
      "authorRank" : 2,
      "name" : "Driancourt",
      "referenceId" : "RGD:A259733"
    }, {
      "firstName" : "N",
      "lastName" : "Raynaud",
      "authorRank" : 3,
      "name" : "Raynaud",
      "referenceId" : "RGD:A259734"
    }, {
      "firstName" : "S",
      "lastName" : "Dhorne-Pollet",
      "authorRank" : 4,
      "name" : "Dhorne-Pollet",
      "referenceId" : "RGD:A259735"
    }, {
      "firstName" : "N",
      "lastName" : "Pollet",
      "authorRank" : 5,
      "name" : "Pollet",
      "referenceId" : "RGD:A259736"
    }, {
      "firstName" : "O",
      "lastName" : "Bernard",
      "authorRank" : 6,
      "name" : "Bernard O",
      "referenceId" : "RGD:A44665"
    }, {
      "firstName" : "M",
      "lastName" : "Hadchouel",
      "authorRank" : 7,
      "name" : "Hadchouel M",
      "referenceId" : "RGD:A44666"
    }, {
      "firstName" : "M",
      "lastName" : "Meunier-Rotival",
      "authorRank" : 8,
      "name" : "Meunier-Rotival M",
      "referenceId" : "RGD:A34765"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064752"
    } ]
  }, {
    "primaryId" : "PMID:10220555",
    "title" : "Combined aortic and mitral stenosis in mucopolysaccharidosis type I-S (Ullrich-Scheie syndrome).",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Fischer TA, etal., Heart. 1999 Jan;81(1):97-9. doi: 10.1136/hrt.81.1.97.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:39:07.000-05:00",
    "volume" : "81",
    "pages" : "97-9",
    "abstract" : "The genetic mucopolysaccharidosis syndromes (MPS) are autosomal recessive inborn errors of metabolism. Heart valve involvement in MPS is not uncommon but only a few case reports of successful cardiac surgery are available. In particular, reports of combined aortic and mitral stenosis associated with MPS type I-S are very rare. Both type I and type VI MPS are associated with significant left sided valvar heart disease that requires surgical valve replacement because of irregular valve thickening, fibrosis, and calcification. A 35 year old man had severe mitral valve stenosis after successful surgical replacement of a stenotic aortic valve. Valvar heart disease was investigated by cardiac ultrasound and left heart catheterisation. Histomorphological characterisation of the affected mitral valve was performed. The case illustrates typically associated clinical features of cardiac and extracardiac abnormalities found in MPS type I-S.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T A",
      "lastName" : "Fischer",
      "authorRank" : 1,
      "name" : "Fischer TA",
      "referenceId" : "RGD:A568887"
    }, {
      "firstName" : "H A",
      "lastName" : "Lehr",
      "authorRank" : 2,
      "name" : "Lehr HA",
      "referenceId" : "RGD:A568888"
    }, {
      "firstName" : "U",
      "lastName" : "Nixdorff",
      "authorRank" : 3,
      "name" : "Nixdorff U",
      "referenceId" : "RGD:A568889"
    }, {
      "firstName" : "J",
      "lastName" : "Meyer",
      "authorRank" : 4,
      "name" : "Meyer J",
      "referenceId" : "RGD:A37905"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598114959"
    } ]
  }, {
    "primaryId" : "PMID:10220556",
    "title" : "Transduction of intracellular calcium signals through G protein-mediated activation of phospholipase C by recombinant sphingosine 1-phosphate receptors.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "An S, etal., Mol Pharmacol 1999 May;55(5):787-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-03-29T10:32:19.000-06:00",
    "volume" : "55",
    "pages" : "787-94",
    "abstract" : "Sphingosine 1-phosphate (S1P) increases intracellular Ca2+ concentration in many cell types, but the signaling mechanism remains uncertain. The recent identification of three closely related seven-transmembrane domain receptors for S1P, termed Edg1, H218, and Edg3, support the extracellular ligand role of S1P and allowed examination of Ca2+ responses mediated specifically by each receptor subtype. To substantiate each subtype in S1P-induced Ca2+ responses and to study the transductional mechanisms, we applied the aequorin luminescence method and the fura-2 fluorescence method in two transfected mammalian cell systems. We showed that H218 and Edg3 were capable of mediating S1P-induced mobilization of intracellular Ca2+ when transiently transfected in human TAg-Jurkat T cells. Ca2+ responses mediated by Edg1 in TAg-Jurkat cells required coexpression of the Gqi5 chimeric G protein that links Gi-coupled receptors to Gq. When H218 and Edg3 were stably expressed in rat HTC4 hepatoma cells, S1P induced Ca2+ responses with nanomolar EC50 values. Edg3, but not H218, elicited a sustained influx of extracellular Ca2+. The coincident formation of inositol phosphates and the complete inhibition of Ca2+ responses by the phospholipase C inhibitor U73122 indicated that H218 and Edg3 mobilized Ca2+ through activation of phospholipase C. Partial inhibition of Ca2+ responses and inositol phosphates formation by pertussis toxin implied that H218 and Edg3 transduce phospholipase C activation and Ca2+ responses only partially through Gi proteins. Although these results did not dismiss that S1P may function as an intracellular second messenger in other settings, they definitively proved that S1P can mobilize Ca2+ as an extracellular ligand for G protein-coupled receptors.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "An",
      "authorRank" : 1,
      "name" : "An S",
      "referenceId" : "RGD:A17664"
    }, {
      "firstName" : "T",
      "lastName" : "Bleu",
      "authorRank" : 2,
      "name" : "Bleu T",
      "referenceId" : "RGD:A17665"
    }, {
      "firstName" : "Y",
      "lastName" : "Zheng",
      "authorRank" : 3,
      "name" : "Zheng Y",
      "referenceId" : "RGD:A12561"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1357202"
    } ]
  }, {
    "primaryId" : "PMID:10220558",
    "title" : "Gene for pain modulatory neuropeptide NPFF: induction in spinal cord by noxious stimuli.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Vilim FS, etal., Mol Pharmacol 1999 May;55(5):804-11.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-10T11:27:24.000-05:00",
    "volume" : "55",
    "pages" : "804-11",
    "abstract" : "Neuropeptides FF (NPFF), AF (NPAF), and SF (NPSF) are homologous amidated peptides that were originally identified on the basis of similarity to the molluscan neuropeptide FMRF-amide. They have been hypothesized to have wide-ranging functions in the mammalian central nervous system, including pain modulation, opiate function, cardiovascular regulation, and neuroendocrine function. We have cloned the NPFF gene from human, bovine, rat, and mouse, and show that the precursor mRNA encodes for all three of the biochemically identified peptides (NPFF, NPAF, and NPSF). We demonstrate that NPFF precursor mRNA expression by Northern analysis and map sites of expression by in situ hybridization. We confirm the validity of the in situ hybridization by showing that its distribution in the brain and spinal cord matches the distribution of NPFF and NPSF immunoreactivity. We go on to show that the mRNA levels (as measured by in situ hybridization) in the spinal cord can be up-regulated by a model for inflammatory pain (carrageenan injection), but not by a model for neuropathic pain (lumbar nerve ligation). Our results confirm the evolutionary conservation of NPFF, NPAF, and NPSF neuropeptide expression in mammalian brain. They also provide a context for the interpretation of the pain-sensitizing effects of injections of these peptides that have been previously reported. Our results support a model for the role of these peptides in pain regulation at the level of the spinal cord.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FS",
      "lastName" : "Vilim",
      "authorRank" : 1,
      "name" : "Vilim FS",
      "referenceId" : "RGD:A19295"
    }, {
      "firstName" : "AA",
      "lastName" : "Aarnisalo",
      "authorRank" : 2,
      "name" : "Aarnisalo AA",
      "referenceId" : "RGD:A3449"
    }, {
      "firstName" : "ML",
      "lastName" : "Nieminen",
      "authorRank" : 3,
      "name" : "Nieminen ML",
      "referenceId" : "RGD:A42794"
    }, {
      "firstName" : "M",
      "lastName" : "Lintunen",
      "authorRank" : 4,
      "name" : "Lintunen M",
      "referenceId" : "RGD:A119307"
    }, {
      "firstName" : "K",
      "lastName" : "Karlstedt",
      "authorRank" : 5,
      "name" : "Karlstedt K",
      "referenceId" : "RGD:A86166"
    }, {
      "firstName" : "VK",
      "lastName" : "Kontinen",
      "authorRank" : 6,
      "name" : "Kontinen VK",
      "referenceId" : "RGD:A119310"
    }, {
      "firstName" : "E",
      "lastName" : "Kalso",
      "authorRank" : 7,
      "name" : "Kalso E",
      "referenceId" : "RGD:A119311"
    }, {
      "firstName" : "B",
      "lastName" : "States",
      "authorRank" : 8,
      "name" : "States B",
      "referenceId" : "RGD:A19298"
    }, {
      "firstName" : "P",
      "lastName" : "Panula",
      "authorRank" : 9,
      "name" : "Panula P",
      "referenceId" : "RGD:A119312"
    }, {
      "firstName" : "E",
      "lastName" : "Ziff",
      "authorRank" : 10,
      "name" : "Ziff E",
      "referenceId" : "RGD:A41040"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61673"
    } ]
  }, {
    "primaryId" : "PMID:10220570",
    "title" : "Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Claeysen S, etal., Mol Pharmacol 1999 May;55(5):910-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-25T10:40:03.000-06:00",
    "volume" : "55",
    "pages" : "910-20",
    "abstract" : "We have cloned new 5-Hydroxytryptamine 4 (5-HT4) receptor splice variants from mouse (m5-HT4(e)R and m5-HT4(f)R), rat (r5-HT4(e)R), and human brain tissue (h5-HT4(e)R) which differ, as do the previously described 5-HT4 receptor variants, in the length and composition of their intracellular C termini after the common splicing site (L358). These new variants have a unique C-terminal sequence made of two PV repeats and are only expressed in brain tissue. All of the 5-HT4 receptor splice variants have a high constitutive activity when expressed at low and physiological densities (<500 fmol/mg protein). At similar density, they showed a much higher constitutive activity than the native and the mutated beta2-adrenergic receptors. The constitutive activity of the new splice variants with short C-terminal sequences (m5-HT4(e)R and m5-HT4(f)R) was higher than that of the long C-terminal sequence variants (m5-HT4(a)R and m5-HT4(b)R). This may indicate that the short variants have a higher capacity for isomerization from the inactive to the active conformation. Moreover, we further identified a sequence within the C-terminal tail upstream of L358, rich in serine and threonine residues, that played a crucial role in maintaining 5-HT4R under its inactive conformation.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Claeysen",
      "authorRank" : 1,
      "name" : "Claeysen S",
      "referenceId" : "RGD:A31881"
    }, {
      "firstName" : "M",
      "lastName" : "Sebben",
      "authorRank" : 2,
      "name" : "Sebben M",
      "referenceId" : "RGD:A31882"
    }, {
      "firstName" : "C",
      "lastName" : "Becamel",
      "authorRank" : 3,
      "name" : "Becamel C",
      "referenceId" : "RGD:A31883"
    }, {
      "firstName" : "J",
      "lastName" : "Bockaert",
      "authorRank" : 4,
      "name" : "Bockaert J",
      "referenceId" : "RGD:A15096"
    }, {
      "firstName" : "A",
      "lastName" : "Dumuis",
      "authorRank" : 5,
      "name" : "Dumuis A",
      "referenceId" : "RGD:A31884"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:729213"
    } ]
  }, {
    "primaryId" : "PMID:10220572",
    "title" : "Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Cui Y, etal., Mol Pharmacol. 1999 May;55(5):929-37.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-02-27T06:06:08.000-06:00",
    "volume" : "55",
    "pages" : "929-37",
    "abstract" : "The multidrug resistance protein MRP1 functions as an ATP-dependent conjugate export pump and confers multidrug resistance. We cloned MRP2 (symbol ABCC2), a MRP family member localized to the apical membrane of polarized cells. Stable expression of MRP2 in transfected human embryonic kidney (HEK-293) and Madin-Darby canine kidney (MDCK) cells was enhanced by inhibitors of histone deacetylase. In polarized MDCK cells, both rat and human MRP2 were sorted to the apical plasma membrane. An antibody raised against the amino terminus of rat MRP2 recognized the recombinant protein on the apical surface of nonpermeabilized cells, providing direct evidence for the extracellular localization of the amino terminus of MRP2. ATP-dependent transport by recombinant human and rat MRP2 was measured with membrane vesicles from stably transfected cells. The Km value of human MRP2 was 1.0 +/- 0.1 microM for leukotriene C4 and 7.2 +/- 0.7 microM for 17beta-glucuronosyl estradiol; the Km values of human MRP1 were 0.1 +/- 0.02 microM for leukotriene C4 and 1.5 +/- 0.3 microM for 17beta-glucoronosyl estradiol. Thus, the conjugate-transporting ATPases MRP2 and MRP1 differ not only by their domain-specific localization but also by their kinetic properties. Drug resistance conferred by recombinant MRP2 was studied in MDCK and HEK-293 cells using cell viability assays. Expression of human and rat MRP2 enhanced the resistance of MDCK cells to etoposide 5.0-fold and 3.8-fold and to vincristine 2.3- and 6.0-fold, respectively. Buthionine sulfoximine reduced resistance to these drugs. Human MRP2 overexpressed in HEK-293 cells enhanced the resistance to etoposide (4-fold), cisplatin (10-fold), doxorubicin (7.8-fold), and epirubicin (5-fold). These results demonstrate that MRP2 confers resistance to cytotoxic drugs.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Cui",
      "authorRank" : 1,
      "name" : "Cui Y",
      "referenceId" : "RGD:A44680"
    }, {
      "firstName" : "J",
      "lastName" : "König",
      "authorRank" : 2,
      "name" : "König J",
      "referenceId" : "RGD:A495274"
    }, {
      "firstName" : "J K",
      "lastName" : "Buchholz",
      "authorRank" : 3,
      "name" : "Buchholz JK",
      "referenceId" : "RGD:A495277"
    }, {
      "firstName" : "H",
      "lastName" : "Spring",
      "authorRank" : 4,
      "name" : "Spring H",
      "referenceId" : "RGD:A15695"
    }, {
      "firstName" : "I",
      "lastName" : "Leier",
      "authorRank" : 5,
      "name" : "Leier I",
      "referenceId" : "RGD:A495273"
    }, {
      "firstName" : "D",
      "lastName" : "Keppler",
      "authorRank" : 6,
      "name" : "Keppler D",
      "referenceId" : "RGD:A15689"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:42721988"
    } ]
  }, {
    "primaryId" : "PMID:10220582",
    "title" : "Nucleolar protein B23.1 binds to retinoblastoma protein and synergistically stimulates DNA polymerase alpha activity.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Takemura M, etal., J Biochem. 1999 May;125(5):904-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-09-19T13:01:32.000-05:00",
    "volume" : "125",
    "pages" : "904-9",
    "abstract" : "Phosphorylated retinoblastoma protein and nucleolar protein B23 are putative stimulatory factors for DNA polymerase alpha. We showed that these two factors interacted with each other and stimulated the activity of DNA polymerase alpha synergistically. B23 exists in two isoforms designated as B23.1 and B23.2. While  B23.1 bound to a retinoblastoma protein-conjugated column, B23.2 did not. These results indicate that B23.1 can directly bind to retinoblastoma protein. It was also shown that B23 was co-immunoprecipitated with both retinoblastoma protein and DNA polymerase alpha from a HeLa cell extract by monoclonal antibodies raised against these components. These results suggest that these three proteins exist as a complex in cells, at least in part. The simultaneous addition of both B23.1  and retinoblastoma protein caused stimulation of DNA polymerase alpha activity that is much higher than the sum of the stimulation by retinoblastoma protein and B23.1 alone. The maximal stimulation was attained at the molar ratio of DNA polymerase alpha/retinoblastoma protein/B23.1 = 1:1:12. Since B23 exists as a hexamer in solution, it may act as a stimulator of DNA polymerase alpha in a form of double-hexamer, in concert with the phosphorylated retinoblastoma protein.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Takemura",
      "authorRank" : 1,
      "name" : "Takemura M",
      "referenceId" : "RGD:A10100"
    }, {
      "firstName" : "K",
      "lastName" : "Sato",
      "authorRank" : 2,
      "name" : "Sato",
      "referenceId" : "RGD:A415987"
    }, {
      "firstName" : "M",
      "lastName" : "Nishio",
      "authorRank" : 3,
      "name" : "Nishio M",
      "referenceId" : "RGD:A6315"
    }, {
      "firstName" : "T",
      "lastName" : "Akiyama",
      "authorRank" : 4,
      "name" : "Akiyama",
      "referenceId" : "RGD:A414093"
    }, {
      "firstName" : "H",
      "lastName" : "Umekawa",
      "authorRank" : 5,
      "name" : "Umekawa H",
      "referenceId" : "RGD:A48182"
    }, {
      "firstName" : "S",
      "lastName" : "Yoshida",
      "authorRank" : 6,
      "name" : "Yoshida S",
      "referenceId" : "RGD:A4855"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11535024"
    } ]
  }, {
    "primaryId" : "PMID:10220587",
    "title" : "Molecular cloning of mouse p47, a second group mammalian RuvB DNA helicase-like protein: homology with those from human and Saccharomyces cerevisiae.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Gohshi T, etal., J Biochem. 1999 May;125(5):939-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-05-13T10:08:55.000-05:00",
    "volume" : "125",
    "pages" : "939-46",
    "abstract" : "A 47k protein (p47) in a high-salt buffer extract of a rat liver nuclear matrix fraction was purified by means of a wheat germ agglutinin affinity column, reversed phase HPLC, and SDS-PAGE, and partial amino acid sequences were analyzed. Based on these sequences, the mouse cDNA of the protein was cloned and  sequenced, and its amino acid sequence was deduced. Mouse p47 consists of 463 amino acid residues with a molecular weight of 51,112. The amino acid sequences of human and Saccharomyces cerevisiae p47s were also deduced from the nucleotide  sequences of \"expressed sequence tag\" fragments and genomic DNA, respectively. These sequences contain helicase motifs and show homology to bacterial RuvB DNA helicases acting in homologous recombination. They also show homology with the putative mammalian helicases p50/TIP49 and RUVBL1. Comparison of the amino acid sequences of p47 group proteins and those of p50/TIP49 group proteins revealed the p47 group proteins to comprise a group distinct from the p50/TIP49 proteins.  Ultracentrifugation and gel filtration analyses showed that p47 in the rat liver  cytosol fraction exists as large complexes of 697k.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Gohshi",
      "authorRank" : 1,
      "name" : "Gohshi T",
      "referenceId" : "RGD:A5114"
    }, {
      "firstName" : "M",
      "lastName" : "Shimada",
      "authorRank" : 2,
      "name" : "Shimada",
      "referenceId" : "RGD:A397574"
    }, {
      "firstName" : "S",
      "lastName" : "Kawahire",
      "authorRank" : 3,
      "name" : "Kawahire S",
      "referenceId" : "RGD:A5115"
    }, {
      "firstName" : "N",
      "lastName" : "Imai",
      "authorRank" : 4,
      "name" : "Imai N",
      "referenceId" : "RGD:A85503"
    }, {
      "firstName" : "T",
      "lastName" : "Ichimura",
      "authorRank" : 5,
      "name" : "Ichimura",
      "referenceId" : "RGD:A214100"
    }, {
      "firstName" : "S",
      "lastName" : "Omata",
      "authorRank" : 6,
      "name" : "Omata S",
      "referenceId" : "RGD:A5122"
    }, {
      "firstName" : "T",
      "lastName" : "Horigome",
      "authorRank" : 7,
      "name" : "Horigome T",
      "referenceId" : "RGD:A5123"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10043092"
    } ]
  }, {
    "primaryId" : "PMID:10220857",
    "title" : "Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: antioxidant defense system.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Rybak LP, etal., Toxicol Sci. 1999 Feb;47(2):195-202.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-08-25T15:38:27.000-05:00",
    "volume" : "47",
    "pages" : "195-202",
    "abstract" : "This study investigated the alterations that occur in auditory brainstem-evoked responses (ABRs) concurrent with changes in cochlear concentrations of glutathione (GSH), lipid peroxidation, and antioxidant enzyme activity in cisplatin-induced ototoxicity and in dose-dependent otoprotection by an antioxidant lipoate. Male Wistar rats were divided into different groups and were treated as follows, with: (1) vehicle (saline) control; (2) cisplatin (16 mg/kg,  i.p.); (3) lipoate (100 mg/kg, i.p.) plus saline; (4) cisplatin plus lipoate (25  mg/kg); (5) cisplatin plus lipoate (50 mg/kg), and (6) cisplatin plus lipoate (100 mg/kg). Post-treatment ABRs were evaluated after three days, the rats were sacrificed, and cochleae were harvested and analyzed. The cisplatin-injected rats showed ABR threshold elevations above the pre-treatment thresholds. Rats treated  with lipoate plus cisplatin did not show significant elevation of hearing thresholds. Cisplatin administration resulted in a depletion of cochlear GSH concentration (69% of control), whereas, cisplatin-plus-lipoate treatment increased GSH concentration close to control value. Cisplatin-treated rats showed a decrease in cochlear superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities (57, 78, 59, and 58% of control, respectively), and an increase in malondialdehyde (MDA) concentration (196% of control). Cochlear SOD, CAT, GSH-Px, and GR activities and MDA concentrations were restored in the rats injected with cisplatin plus graded  doses of lipoate than those with cisplatin alone. It is concluded that cisplatin-induced ototoxicity is related to impairment of the cochlear antioxidant defense system, and the dose-dependent otoprotection conferred by an  antioxidant lipoate against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant defense system.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LP",
      "lastName" : "Rybak",
      "authorRank" : 1,
      "name" : "Rybak",
      "referenceId" : "RGD:A179376"
    }, {
      "firstName" : "K",
      "lastName" : "Husain",
      "authorRank" : 2,
      "name" : "Husain K",
      "referenceId" : "RGD:A12246"
    }, {
      "firstName" : "C",
      "lastName" : "Whitworth",
      "authorRank" : 3,
      "name" : "Whitworth",
      "referenceId" : "RGD:A179375"
    }, {
      "firstName" : "SM",
      "lastName" : "Somani",
      "authorRank" : 4,
      "name" : "Somani",
      "referenceId" : "RGD:A193258"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9197256"
    } ]
  }, {
    "primaryId" : "PMID:10220866",
    "title" : "Emerin and cardiomyopathy in Emery-Dreifuss muscular dystrophy.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Funakoshi M, etal., Neuromuscul Disord. 1999 Mar;9(2):108-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:32:26.000-05:00",
    "volume" : "9",
    "pages" : "108-14",
    "abstract" : "Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder characterized by the clinical triad of life-threatening progressive cardiomyopathy with conduction defect, early onset joint contractures and slow progressive muscle weakness in scapulo-humero-peroneal distribution. Cardiomyopathy in EDMD is usually noticed after the second to third decade of life, and becomes worse with  age. Permanent auricular paralysis occurs frequently and is considered a hallmark of EDMD cardiomyopathy. Cardiac involvement may also occur in female carriers. In autopsy cases, enlargement of the atria with remarkable thinning have been observed. Identification of the gene responsible for X-linked EDMD (X-EDMD) and the protein product, emerin, provided a diagnostic clue for EDMD. Since the emerin gene is rather small, the entire sequence can easily be surveyed. Western  blot and immunohistochemistry show an absence of emerin in muscle and skin tissues and oral exfoliating cells in male patients with X-EDMD, and a reduction  of the protein content with a mosaic expression pattern in female carriers. Emerin anchors at the inner nuclear membrane of cardiac, skeletal and smooth muscles, and interacts with lamins and nucleoplasm, thereby possibly maintaining  the mechanical stability of the nuclear membrane of muscle cells that shows rigorous contraction/relaxation. More recently, positive emerin staining at the cardiac demosomes and fasciae adherentes was noticed in addition to the specific  localization at the inner nuclear membrane. This localization implies a physiological role for the protein in cardiac conduction.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Funakoshi",
      "authorRank" : 1,
      "name" : "Funakoshi",
      "referenceId" : "RGD:A253669"
    }, {
      "firstName" : "Y",
      "lastName" : "Tsuchiya",
      "authorRank" : 2,
      "name" : "Tsuchiya Y",
      "referenceId" : "RGD:A40391"
    }, {
      "firstName" : "K",
      "lastName" : "Arahata",
      "authorRank" : 3,
      "name" : "Arahata K",
      "referenceId" : "RGD:A36680"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066157"
    } ]
  }, {
    "primaryId" : "PMID:10221589",
    "title" : "Expression and hormonal regulation of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I messenger ribonucleic acid in the rat ovary.",
    "datePublished" : "1998-12-01T00:00:00.000-06:00",
    "citation" : "McLean MP and Sandhoff TW, Endocrine 1998 Dec;9(3):243-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-12-22T09:53:42.000-06:00",
    "volume" : "9",
    "pages" : "243-52",
    "abstract" : "Since cholesterol delivery to the ovary is an essential regulated step in steroidogenesis, mRNA levels for the Scavenger Receptor Class B Type I (SR-BI), a putative high-density lipoprotein receptor (HDL-R), were examined in response to tropic hormones and the luteolytic agent prostaglandin F2alpha (PGF2alpha). For this, the rat SR-BI cDNA was isolated and cloned. The results of this investigation revealed that a single SR-BI mRNA transcript of 2.4 kb was highly expressed in the rat adrenal, ovary, and testis. The SR-BI transcript was increased (twofold) in the immature rat ovary following pregnant mare's serum gonadotropin (PMSG) administration and in the ovary, 8 d after ovulation, in response to stimulation by human chorionic gonadotropin (hCG). In the ovary 8 d following ovulation, basal ovarian SR-BI mRNA levels were elevated up to sixfold relative to the preovulatory SR-BI mRNA levels. Even with the enhanced basal level of SR-BI mRNA within the ovary, hCG administration still resulted in a 2.5- (p < 0.025) and sevenfold (p < 0.01) increase in the 2.4-kb transcript, 3 and 6 h postinjection, respectively. This increase corresponded to a 58% increase in serum progesterone. In contrast, when PGF2alpha was administered, SR-BI mRNA levels were significantly reduced (3.5-fold; p < 0.01) in concert with a fourfold reduction (p < 0.001) in serum progesterone secretion. Furthermore, PGF2alpha blocked the hCG-induced increase in SR-BI mRNA levels when administered 30 min prior to hCG injection. The results of this study demonstrate that SR-BI mRNA levels are dramatically increased following exposure to gonadotropins in the ovary, whereas PGF2alpha exposure significantly reduced SR-BI mRNA levels.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MP",
      "lastName" : "McLean",
      "authorRank" : 1,
      "name" : "McLean MP",
      "referenceId" : "RGD:A24220"
    }, {
      "firstName" : "TW",
      "lastName" : "Sandhoff",
      "authorRank" : 2,
      "name" : "Sandhoff TW",
      "referenceId" : "RGD:A48958"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1304219"
    } ]
  }, {
    "primaryId" : "PMID:10223461",
    "title" : "Polymorphism of the endoglin gene in patients with intracranial saccular aneurysms.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Takenaka K, etal., J Neurosurg. 1999 May;90(5):935-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-09-06T17:24:55.000-05:00",
    "volume" : "90",
    "pages" : "935-8",
    "abstract" : "OBJECT: Endoglin, a transforming growth factor beta-binding protein, is a glycoprotein expressed on the surface of human vascular endothelial cells. Mutations of this gene are responsible for hereditary hemorrhagic telangiectasis and are associated with sporadic intracerebral hemorrhage as a risk factor. The purpose of this study was to examine the polymorphism of this gene in patients with intracranial aneurysms. METHODS: The authors identified the mutations and insertion polymorphism around exon 7 of the endoglin gene in 82 patients with intracranial saccular aneurysms (aneurysm group) and 114 control volunteers (control group). A 6-base insertion (GGGGGA) was found in intron 7 at 26 bases beyond the 3' end of exon 7. The homozygous insertion of intron 7 of the gene was present in 20.7% of the aneurysm group compared with 6.1% of the control group (chi2 = 9.837, p = 0.0073). The insertion allele frequency was significantly higher in the aneurysm group (67 [40.8%] of 164) than that in the control group (63 [27.6%] of 228) (chi2 = 7.48, p = 0.0062). The most notable clinical characteristic of the 17 patients with homozygous insertion in the aneurysm group was the relatively high percentage of patients with hypertension and of those with multiple aneurysms. CONCLUSIONS: The data provide evidence of an association between aneurysm development and a polymorphism at a genetic variant of endoglin in patients with these lesions.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Takenaka",
      "authorRank" : 1,
      "name" : "Takenaka K",
      "referenceId" : "RGD:A21182"
    }, {
      "firstName" : "H",
      "lastName" : "Sakai",
      "authorRank" : 2,
      "name" : "Sakai H",
      "referenceId" : "RGD:A160193"
    }, {
      "firstName" : "H",
      "lastName" : "Yamakawa",
      "authorRank" : 3,
      "name" : "Yamakawa H",
      "referenceId" : "RGD:A8060"
    }, {
      "firstName" : "S",
      "lastName" : "Yoshimura",
      "authorRank" : 4,
      "name" : "Yoshimura S",
      "referenceId" : "RGD:A5864"
    }, {
      "firstName" : "M",
      "lastName" : "Kumagai",
      "authorRank" : 5,
      "name" : "Kumagai M",
      "referenceId" : "RGD:A64908"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580964"
    } ]
  }, {
    "primaryId" : "PMID:10224071",
    "title" : "Inhibition of transcription by the trimeric cyclin-dependent kinase 7 complex.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Bochar DA, etal., J Biol Chem 1999 May 7;274(19):13162-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-09-10T15:24:21.000-05:00",
    "volume" : "274",
    "pages" : "13162-6",
    "abstract" : "Cyclin-dependent kinase 7 (CDK7) can be isolated as a subunit of a trimeric kinase complex functional in activation of the mitotic promoting factor. In this study, we demonstrate that the trimeric cdk-activating kinase (CAK) acts as a transcriptional repressor of class II promoters and show that repression results from CAK impeding the entry of RNA polymerase II and basal transcription factor IIF into a competent preinitiation complex. This repression is independent of CDK7 kinase activity. We find that the p36/MAT1 subunit of CAK is required for transcriptional repression and the repression is independent of the promoter used. Our results demonstrate a central role for CAK in regulation of messenger RNA synthesis by either inhibition of RNA polymerase II-catalyzed transcription or stimulation of transcription through association with basal transcription repair factor IIH.",
    "issueName" : "19",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DA",
      "lastName" : "Bochar",
      "authorRank" : 1,
      "name" : "Bochar DA",
      "referenceId" : "RGD:A45932"
    }, {
      "firstName" : "ZQ",
      "lastName" : "Pan",
      "authorRank" : 2,
      "name" : "Pan ZQ",
      "referenceId" : "RGD:A22461"
    }, {
      "firstName" : "R",
      "lastName" : "Knights",
      "authorRank" : 3,
      "name" : "Knights R",
      "referenceId" : "RGD:A45933"
    }, {
      "firstName" : "RP",
      "lastName" : "Fisher",
      "authorRank" : 4,
      "name" : "Fisher RP",
      "referenceId" : "RGD:A45934"
    }, {
      "firstName" : "A",
      "lastName" : "Shilatifard",
      "authorRank" : 5,
      "name" : "Shilatifard A",
      "referenceId" : "RGD:A45935"
    }, {
      "firstName" : "R",
      "lastName" : "Shiekhattar",
      "authorRank" : 6,
      "name" : "Shiekhattar R",
      "referenceId" : "RGD:A45936"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302291"
    } ]
  }, {
    "primaryId" : "PMID:10224102",
    "title" : "Molecular cloning of a lipolysis-stimulated remnant receptor expressed in the liver.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Yen FT, etal., J Biol Chem 1999 May 7;274(19):13390-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:55.000-05:00",
    "volume" : "274",
    "pages" : "13390-8",
    "abstract" : "The lipolysis-stimulated receptor (LSR) is a lipoprotein receptor primarily expressed in the liver and activated by free fatty acids. Antibodies inhibiting LSR functions showed that the receptor is a heterotrimer or tetramer consisting of 68-kDa (alpha) and 56-kDa (beta) subunits associated through disulfide bridges. Screening of expression libraries with these antibodies led to identification of mRNAs derived by alternate splicing from a single gene and coding for proteins with molecular masses matching that of LSR alpha and beta. Antibodies directed against a synthetic peptide of LSR alpha and beta putative ligand binding domains inhibited LSR activity. Western blotting identified two liver proteins with the same apparent molecular mass as that of LSR alpha and beta. Transient transfections of LSR alpha alone in Chinese hamster ovary cells increased oleate-induced binding and uptake of lipoproteins, while cotransfection of both LSR alpha and beta increased oleate-induced proteolytic degradation of the particles. The ligand specificity of LSR expressed in cotransfected Chinese hamster ovary cells closely matched that previously described using fibroblasts from subjects lacking the low density lipoprotein receptor. LSR affinity is highest for the triglyceride-rich lipoproteins, chylomicrons, and very low density lipoprotein. We speculate that LSR is a rate-limiting step for the clearance of dietary triglycerides and plays a role in determining their partitioning between the liver and peripheral tissues.",
    "issueName" : "19",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FT",
      "lastName" : "Yen",
      "authorRank" : 1,
      "name" : "Yen FT",
      "referenceId" : "RGD:A5958"
    }, {
      "firstName" : "M",
      "lastName" : "Masson",
      "authorRank" : 2,
      "name" : "Masson M",
      "referenceId" : "RGD:A5959"
    }, {
      "firstName" : "N",
      "lastName" : "Clossais-Besnard",
      "authorRank" : 3,
      "name" : "Clossais-Besnard N",
      "referenceId" : "RGD:A5960"
    }, {
      "firstName" : "P",
      "lastName" : "Andre",
      "authorRank" : 4,
      "name" : "Andre P",
      "referenceId" : "RGD:A5961"
    }, {
      "firstName" : "JM",
      "lastName" : "Grosset",
      "authorRank" : 5,
      "name" : "Grosset JM",
      "referenceId" : "RGD:A5962"
    }, {
      "firstName" : "L",
      "lastName" : "Bougueleret",
      "authorRank" : 6,
      "name" : "Bougueleret L",
      "referenceId" : "RGD:A5963"
    }, {
      "firstName" : "JB",
      "lastName" : "Dumas",
      "authorRank" : 7,
      "name" : "Dumas JB",
      "referenceId" : "RGD:A5964"
    }, {
      "firstName" : "O",
      "lastName" : "Guerassimenko",
      "authorRank" : 8,
      "name" : "Guerassimenko O",
      "referenceId" : "RGD:A5965"
    }, {
      "firstName" : "BE",
      "lastName" : "Bihain",
      "authorRank" : 9,
      "name" : "Bihain BE",
      "referenceId" : "RGD:A5966"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68812"
    } ]
  }, {
    "primaryId" : "PMID:10224108",
    "title" : "Insulin inhibits growth hormone signaling via the growth hormone receptor/JAK2/STAT5B pathway.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ji S, etal., J Biol Chem. 1999 May 7;274(19):13434-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-18T09:21:17.000-05:00",
    "volume" : "274",
    "pages" : "13434-42",
    "abstract" : "Insulin is important for maintaining the responsiveness of the liver to growth hormone (GH). Insulin deficiency results in a decrease in liver GH receptor (GHR) expression, which can be reversed by insulin administration. In osteoblasts, continuous insulin treatment decreases the fraction of cellular GHR localized to the plasma membrane. Thus, it is not clear whether hyperinsulinemia results in an enhancement or inhibition of GH action. We asked whether continuous insulin stimulation, similar to what occurs in hyperinsulinemic states, results in GH resistance. Our present studies suggest that insulin treatment of hepatoma cells results in a time-dependent inhibition of acute GH-induced phosphorylation of STAT5B. Whereas total protein levels of JAK2 were not reduced after insulin pretreatment for 16 h, GH-induced JAK2 phosphorylation was inhibited. There was a concomitant decrease in GH binding and a reduction in immunoreactive GHR levels following pretreatment with insulin for 8-24 h. In summary, continuous insulin treatment in rat H4 hepatoma cells reduces GH binding, immunoreactive GHR, GH-induced phosphorylation of JAK2, and GH-induced tyrosine phosphorylation of STAT5B. These findings suggest that hepatic GH resistance may develop when a patient exhibits chronic hyperinsulinemia, a condition often observed in patients with obesity and in the early stage of Type 2 diabetes.",
    "issueName" : "19",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Ji",
      "authorRank" : 1,
      "name" : "Ji S",
      "referenceId" : "RGD:A11890"
    }, {
      "firstName" : "R",
      "lastName" : "Guan",
      "authorRank" : 2,
      "name" : "Guan R",
      "referenceId" : "RGD:A80765"
    }, {
      "firstName" : "SJ",
      "lastName" : "Frank",
      "authorRank" : 3,
      "name" : "Frank SJ",
      "referenceId" : "RGD:A11891"
    }, {
      "firstName" : "JL",
      "lastName" : "Messina",
      "authorRank" : 4,
      "name" : "Messina JL",
      "referenceId" : "RGD:A11892"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601382"
    } ]
  }, {
    "primaryId" : "PMID:10224140",
    "title" : "Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kusuhara H, etal., J Biol Chem 1999 May 7;274(19):13675-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-05-10T13:46:06.000-05:00",
    "volume" : "274",
    "pages" : "13675-80",
    "abstract" : "A cDNA encoding the new member of the multispecific organic anion transporter family, OAT3, was isolated by the reverse transcription-polymerase chain reaction cloning method. Degenerate primers were designed based on the sequences conserved among OAT1, OAT2, and organic cation transporter 1 (OCT1), and reverse transcription-polymerase chain reaction was performed using rat brain poly(A)+ RNA. The 536-amino acid protein sequence encoded by OAT3 showed 49, 39, and 36% identity to those of OAT1, OAT2, and OCT1, respectively. Northern blot analysis revealed that rat OAT3 mRNA is expressed in the liver, brain, kidney, and eye. When expressed in Xenopus laevis oocytes, OAT3 mediated the uptake of organic anions, such as p-aminohippurate (Km = 65 microM), ochratoxin A (Km = 0.74 microM), and estrone sulfate (Km = 2.3 microM) and a cationic compound, cimetidine. OAT3-mediated uptake of [3H]estrone sulfate was sodium-independent. para-Aminohippuric acid, estrone sulfate or ochratoxin A did not show any trans-stimulatory effect on either influx or efflux of [3H]estrone sulfate via OAT3. Organic anions such as sulfobromophthalein, probenecid, indocyanine green, bumetanide, piroxicam, furosemide, azidodeoxythymidine, 4, 4'-diisothiocyanostilbene-3,3'-disulfonic acid, and benzylpenicillin inhibited OAT3-mediated estrone sulfate uptake, while ouabain and digoxin did not. Organic cations such as tetraethylammonium, guanidine, verapamil, and quinidine did not interact with OAT3. Acidic metabolites of neurotransmitters derived from dopamine, epinephrine, norepinephrine, and serotonin inhibited the uptake of estrone sulfate via OAT3. These results suggest an important role of OAT3 in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain.",
    "issueName" : "19",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Kusuhara",
      "authorRank" : 1,
      "name" : "Kusuhara H",
      "referenceId" : "RGD:A9063"
    }, {
      "firstName" : "T",
      "lastName" : "Sekine",
      "authorRank" : 2,
      "name" : "Sekine T",
      "referenceId" : "RGD:A4123"
    }, {
      "firstName" : "N",
      "lastName" : "Utsunomiya-Tate",
      "authorRank" : 3,
      "name" : "Utsunomiya-Tate N",
      "referenceId" : "RGD:A9064"
    }, {
      "firstName" : "M",
      "lastName" : "Tsuda",
      "authorRank" : 4,
      "name" : "Tsuda M",
      "referenceId" : "RGD:A8703"
    }, {
      "firstName" : "R",
      "lastName" : "Kojima",
      "authorRank" : 5,
      "name" : "Kojima R",
      "referenceId" : "RGD:A6105"
    }, {
      "firstName" : "SH",
      "lastName" : "Cha",
      "authorRank" : 6,
      "name" : "Cha SH",
      "referenceId" : "RGD:A121442"
    }, {
      "firstName" : "Y",
      "lastName" : "Sugiyama",
      "authorRank" : 7,
      "name" : "Sugiyama Y",
      "referenceId" : "RGD:A9066"
    }, {
      "firstName" : "Y",
      "lastName" : "Kanai",
      "authorRank" : 8,
      "name" : "Kanai Y",
      "referenceId" : "RGD:A122459"
    }, {
      "firstName" : "H",
      "lastName" : "Endou",
      "authorRank" : 9,
      "name" : "Endou H",
      "referenceId" : "RGD:A121444"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70523"
    } ]
  }, {
    "primaryId" : "PMID:10224316",
    "title" : "Accelerated release and production of orphanin FQ in brain of chronic morphine tolerant rats.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Yuan L, etal., Brain Res. 1999 May 1;826(2):330-4. doi: 10.1016/s0006-8993(99)01337-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-06-24T10:54:59.000-05:00",
    "volume" : "826",
    "pages" : "330-4",
    "abstract" : "Orphanin FQ has been shown to possess anti-opioid activity at supraspinal level. Our previous work revealed that chronic morphine tolerance could be reversed by intracerebroventricular (i.c.v.) injection of OFQ IgG to rats. In this study, we used radioimmunoassay (RIA) to assess the changes of Orphanin FQ immunoreactivity (OFQ-ir) in cerebroventricular perfusate, periaqueductal gray (PAG) and amygdala of rats made tolerance to morphine (10-60 mg/kg, s.c., t.i.d., for 5 days). The results indicated that: (1) In rats administrated with morphine for 3 and 5 days, the content of OFQ-ir in cerebroventricular perfusate increased by 25% and 52% over the NS control group. (2) The content of OFQ-ir in PAG of rats receiving 1d, 3d and 5d injections of morphine showed an increase of 17%, 48% and 81% respectively over NS group. (3) The content of OFQ-ir in amygdala of rats given 3d and 5d of morphine showed a 36% and 55% increase compared with corresponding control group. It is suggested that continuous use of high doses of morphine accelerated the release and biosynthesis of OFQ in rat brain to antagonize the effect of opioids, which may play a role in the development of morphine tolerance, and that brain OFQ may serve as a delayed negative feedback control on opioid analgesia.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Yuan",
      "authorRank" : 1,
      "name" : "Yuan L",
      "referenceId" : "RGD:A32200"
    }, {
      "firstName" : "Z",
      "lastName" : "Han",
      "authorRank" : 2,
      "name" : "Han Z",
      "referenceId" : "RGD:A68540"
    }, {
      "firstName" : "J K",
      "lastName" : "Chang",
      "authorRank" : 3,
      "name" : "Chang JK",
      "referenceId" : "RGD:A465825"
    }, {
      "firstName" : "J S",
      "lastName" : "Han",
      "authorRank" : 4,
      "name" : "Han JS",
      "referenceId" : "RGD:A455258"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:616926596"
    } ]
  }, {
    "primaryId" : "PMID:10224351",
    "title" : "Regulation of IL-5 and IL-5 receptor expression in the bone marrow of allergic asthmatics.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Denburg JA, etal., Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):101-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-03-14T13:15:17.000-05:00",
    "volume" : "118",
    "pages" : "101-3",
    "abstract" : "BACKGROUND: Following consistent demonstrations of the clinical relevance of fluctuations in eosinophil-basophil (Eo-B) progenitors in the blood of patients with a variety of allergic airway disorders, we have turned our attention recently to hemopoietic events occurring in the bone marrow of allergic asthmatic subjects, utilizing a model of airway allergen challenge. METHODS: Flow-cytometric analyses of CD34/45+ progenitors for coexpression of surface alpha-receptor subunits for IL-3, IL-5 and GM-CSF, as well as in situ hybridization and in situ PCR methodologies to detect mRNA for IL-5 and GM-CSF in developing Eo-B in colony and liquid culture assays were employed before and after in vivo allergen challenge. RESULTS: An early, specific upregulation of IL-5R alpha expression on CD34/45 progenitors was observed after allergen challenge, concomitant with the development of the late-phase asthmatic response. Protein and mRNA for both GM-CSF and IL-5 were expressed in a time-dependent manner ex vivo, in developing (beta 7-integrin-positive), colony-derived Eo-B after allergen challenge in vivo. Both retinoic acid and corticosteroids were able to downregulate IL-3- and IL-5-induced expression of IL-5R on cord-blood-derived as well as HL-60 cloned Eo-B progenitors. CONCLUSION: These studies indicate the critical involvement of IL-5 and IL-5R in the induction of Eo-B differentiation and eosinophilic airway inflammation in allergic asthmatics, and point to these events as potential targets for long-term therapy of atopic disease.",
    "issueName" : "2-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Denburg",
      "authorRank" : 1,
      "name" : "Denburg JA",
      "referenceId" : "RGD:A130937"
    }, {
      "firstName" : "R",
      "lastName" : "Sehmi",
      "authorRank" : 2,
      "name" : "Sehmi R",
      "referenceId" : "RGD:A136041"
    }, {
      "firstName" : "J",
      "lastName" : "Upham",
      "authorRank" : 3,
      "name" : "Upham J",
      "referenceId" : "RGD:A129119"
    }, {
      "firstName" : "L",
      "lastName" : "Wood",
      "authorRank" : 4,
      "name" : "Wood L",
      "referenceId" : "RGD:A24082"
    }, {
      "firstName" : "G",
      "lastName" : "Gauvreau",
      "authorRank" : 5,
      "name" : "Gauvreau G",
      "referenceId" : "RGD:A136042"
    }, {
      "firstName" : "P",
      "lastName" : "O'Byrne",
      "authorRank" : 6,
      "name" : "O'Byrne P",
      "referenceId" : "RGD:A136043"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5128623"
    } ]
  }, {
    "primaryId" : "PMID:10224365",
    "title" : "Neural hyperresponsiveness and nerve growth factor in allergic rhinitis.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Sanico AM, etal., Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):154-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-05T16:00:02.000-06:00",
    "volume" : "118",
    "pages" : "154-8",
    "abstract" : "BACKGROUND: In allergic rhinitis, symptoms are triggered not only by allergens but also by environmental irritants. Hereinafter we address the hypothesis that this is reflective of increased responsiveness of the neural apparatus which, in turn, may be attributable to upregulation of nerve growth factor (NGF) in this disease. METHODS: We compared subjects with active allergic rhinitis and healthy volunteers in terms of sensitivity and/or magnitude of three nerve-mediated responses, namely (1) the sneezing reflex induced by histamine, (2) the central or nasonasal reflex depicted by contralateral secretions induced by unilateral nasal challenge with capsaicin, and (3) the axonal reflex depicted by plasma extravasation upon capsaicin challenge. We have also measured NGF levels in nasal lavage fluids at baseline and with allergen provocation in rhinitis and healthy subjects. RESULTS: Compared to healthy individuals, subjects with active allergic rhinitis were found to have (1) significantly greater sensitivity and reactivity of the sneezing reflex, (2) significantly greater secretory responsiveness to sensory nerve stimulation, and (3) significantly greater plasma extravasation indicated by albumin leakage following capsaicin nasal challenge. We also found that subjects with active allergic rhinitis have significantly greater baseline levels of NGF in nasal lavage fluids compared to their healthy counterparts, and that these levels can be increased by allergen nasal provocation. CONCLUSION: The responsiveness of the neural apparatus of the nose is significantly greater in patients with active allergic rhinitis. The increased presence of NGF in the nasal mucosa of these patients supports the hypothesis that this neurotrophin may be implicated in neural hyperresponsiveness.",
    "issueName" : "2-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AM",
      "lastName" : "Sanico",
      "authorRank" : 1,
      "name" : "Sanico AM",
      "referenceId" : "RGD:A133180"
    }, {
      "firstName" : "VE",
      "lastName" : "Koliatsos",
      "authorRank" : 2,
      "name" : "Koliatsos VE",
      "referenceId" : "RGD:A133181"
    }, {
      "firstName" : "AM",
      "lastName" : "Stanisz",
      "authorRank" : 3,
      "name" : "Stanisz AM",
      "referenceId" : "RGD:A133182"
    }, {
      "firstName" : "J",
      "lastName" : "Bienenstock",
      "authorRank" : 4,
      "name" : "Bienenstock J",
      "referenceId" : "RGD:A133183"
    }, {
      "firstName" : "A",
      "lastName" : "Togias",
      "authorRank" : 5,
      "name" : "Togias A",
      "referenceId" : "RGD:A162566"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4891115"
    } ]
  }, {
    "primaryId" : "PMID:10224452",
    "title" : "Regulation of proinflammatory cytokines in seasonal allergic rhinitis.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Bachert C, etal., Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):375-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-20T13:11:47.000-05:00",
    "volume" : "118",
    "pages" : "375-9",
    "abstract" : "BACKGROUND: Mediators and cytokines have been demonstrated to be released due to nasal allergen exposure in sensitized subjects, but little is known about the release of cytokines and their antagonists under natural conditions. METHODS: Mediators - histamine, eosinophilic cationic protein (ECP), leukotrienes (LT) C4/ D4/E4 - and cytokines - interleukin (IL)-1beta, IL-8, IL-1 receptor antagonist (ra) - were measured in nasal secretions throughout the grass pollen season (6 visits) and for 6 weeks thereafter (3 visits) in patients with seasonal allergic rhinitis (n = 13) and compared to controls (n = 12). A second study was performed comparing nasal secretions of 13 subjects allergic to house dust mite to 8 controls. RESULTS: Compared to controls, leukotrienes and ECP were significantly elevated at nearly all time points in and postseason in the allergic group. Whereas IL-1beta was significantly elevated throughout the study period, IL-1ra was significantly decreased from visit 1 to 3. IL-8 showed no increase compared to controls. Data from subjects with perennial allergic rhinitis supported these findings and additionally demonstrated decreased concentrations of IL-8 and myeloperoxidase in secretions compared to controls. CONCLUSION: Allergic rhinitis represents a persistent inflammation in terms of an activation of eosinophils and constant upregulation of the proinflammatory cytokine IL-1beta in the pollen season and thereafter. We additionally could demonstrate a dysfunction of the anti-inflammatory capacity, i.e. IL-1ra, a naturally occurring antagonist. Persistent inflammation may furthermore lead to the dysregulation of local cellular immunity by reducing the number and activity of neutrophils on the mucosal surface.",
    "issueName" : "2-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Bachert",
      "authorRank" : 1,
      "name" : "Bachert C",
      "referenceId" : "RGD:A127673"
    }, {
      "firstName" : "M",
      "lastName" : "Van Kempen",
      "authorRank" : 2,
      "name" : "Van Kempen M",
      "referenceId" : "RGD:A127674"
    }, {
      "firstName" : "P",
      "lastName" : "Van Cauwenberge",
      "authorRank" : 3,
      "name" : "Van Cauwenberge P",
      "referenceId" : "RGD:A127675"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4143227"
    } ]
  }, {
    "primaryId" : "PMID:10224671",
    "title" : "Delta aminolevulinate dehydratase (ALA-D) activity in human and experimental diabetes mellitus.",
    "datePublished" : "0001-12-01T00:00:00.000-06:00",
    "citation" : "Fernández-Cuartero B, etal., Int J Biochem Cell Biol. 1999 Mar-Apr;31(3-4):479-88. doi: 10.1016/s1357-2725(98)00145-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-12-05T11:56:59.000-06:00",
    "volume" : "31",
    "pages" : "479-88",
    "abstract" : "The haem pathway is impaired in porphyrias and a frequent coexistence of diabetes mellitus and porphyria disease has been reported. We have therefore decided to investigate delta-aminolevulinate dehydratase, one of the more sensitive enzymes in the haem pathway, in both human diabetic patients and diabetic rats. We have studied 131 diabetes mellitus patients, 32 insulin dependent and 99 non-insulin dependent. The latter group was further subdivided according to treatment: diet alone (n = 24), diet plus oral hypoglycemic agents (n = 28) and diet plus insulin (n = 47). We have also performed similar studies in the rat model of diabetes mellitus, induced in 11 Wistar rats by streptozotocin. Control groups of both humans and animals were used. Erythrocytic aminolevulinate dehydratase activity was reduced in both insulin dependent and non-insulin dependent diabetic patients as compared to their controls (p < 0.001). This activity was only partially restored by addition of zinc and thiols to the incubation media. In insulin-dependent diabetes mellitus, reduction of enzyme activity was related to the glycosilated hemoglobin concentration (p < 0.05) and in non-insulin dependent diabetes mellitus to the glycemia (p < 0.01). In the diabetic rat, aminolevulinate dehydratase activity was diminished on both erythrocytes (p < 0.01) and hepatic tissue (p < 0.01) when compared to the control group. The decrease in activity of erythrocyte aminolevulinate dehydratase observed in diabetic patients, may represent an additional and useful parameter for the assessment of the severity of carbohydrate metabolism impairment.",
    "issueName" : "3-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Fernández-Cuartero",
      "authorRank" : 1,
      "name" : "Fernández-Cuartero B",
      "referenceId" : "RGD:A476976"
    }, {
      "firstName" : "J L",
      "lastName" : "Rebollar",
      "authorRank" : 2,
      "name" : "Rebollar JL",
      "referenceId" : "RGD:A476977"
    }, {
      "firstName" : "A",
      "lastName" : "Batlle",
      "authorRank" : 3,
      "name" : "Batlle A",
      "referenceId" : "RGD:A101145"
    }, {
      "firstName" : "R",
      "lastName" : "Enriquez de Salamanca",
      "authorRank" : 4,
      "name" : "Enriquez de Salamanca R",
      "referenceId" : "RGD:A476978"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:15039405"
    } ]
  }, {
    "primaryId" : "PMID:10225449",
    "title" : "Preneoplastic mammary tumor markers: Cripto and Amphiregulin are overexpressed in hyperplastic stages of tumor progression in transgenic mice.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Niemeyer CC, etal., Int J Cancer. 1999 May 17;81(4):588-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-30T14:50:10.000-05:00",
    "volume" : "81",
    "pages" : "588-91",
    "abstract" : "Amphiregulin (Ar) and Cripto (Cr) are autocrine growth factors for mammary cells and both have been observed to exhibit high expression in human mammary tumors, in contrast with adjacent tissues. To investigate whether Ar and Cr play roles in the progression of mammary cell proliferation to unregulated growth and tumor formation, the levels of expression were examined in transgenic mice (TGM) that over-express several different oncogenes: MMTV-Polyoma virus middle T antigen (MMTV-PyMT), MMTV-c-ErbB2 (c-neu, HER2) and MT-hTGF alpha. These transgenic mice all produce mammary tumors but with different rates of progression. The levels of Ar were induced up to 10-fold in association with hyperplasia in 2 of the TGM. Cr overexpression was consistently observed in hyperplastic mammary glands in all the animal models, decreasing in overt tumors in 2 of the TGM models. In MMTV-PyMT mammary glands, the levels of Cr expression rose 7- to 10-fold in hyperplastic tissue and 25-fold the levels in tumors compared to age-matched transgene negative mice. Ar and especially Cr thus should have potential value as markers of preneoplastic change in mammary tissue.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CC",
      "lastName" : "Niemeyer",
      "authorRank" : 1,
      "name" : "Niemeyer CC",
      "referenceId" : "RGD:A95593"
    }, {
      "firstName" : "B",
      "lastName" : "Spencer-Dene",
      "authorRank" : 2,
      "name" : "Spencer-Dene B",
      "referenceId" : "RGD:A95594"
    }, {
      "firstName" : "JX",
      "lastName" : "Wu",
      "authorRank" : 3,
      "name" : "Wu JX",
      "referenceId" : "RGD:A95595"
    }, {
      "firstName" : "ED",
      "lastName" : "Adamson",
      "authorRank" : 4,
      "name" : "Adamson ED",
      "referenceId" : "RGD:A95596"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292663"
    } ]
  }, {
    "primaryId" : "PMID:10225458",
    "title" : "Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Kleeff J, etal., Int J Cancer. 1999 May 17;81(4):650-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-12-03T16:03:29.000-06:00",
    "volume" : "81",
    "pages" : "650-7",
    "abstract" : "Macrophage Proinflammatory Human Chemokine-3alpha (Mip-3alpha/LARC/Exodus) belongs to a large family of chemotactic cytokines, which participate in directing inflammatory cell migration and in modulating angiogenesis. Mip-3alpha  signals through a recently identified G-protein linked 7-transmembrane receptor,  CCR6. In this study, we have characterized the expression of Mip-3alpha and CCR6  in 12 normal and 16 cancerous human pancreatic tissues and in 4 cultured pancreatic cancer cell lines, and assessed the effects of Mip-3alpha on growth and invasion of these cell lines. Pancreatic cancer tissues markedly overexpressed Mip-3alpha in comparison with normal pancreatic samples. By in situ hybridization Mip-3alpha and CCR6 mRNA moieties were present in cancer cells within the tumors. In addition, Mip-3alpha was abundant in the macrophages infiltrating the tumor mass. Mip-3alpha and its receptor CCR6 were expressed in all 4 tested pancreatic cancer cell lines. Mip-3alpha stimulated the growth of one cell line, enhanced the migration of another cell line, and was without effect in the other 2 cell lines. Together, our findings suggest that Mip-3alpha  has the potential to act via autocrine and paracrine mechanisms to contribute to  the pathobiology of human pancreatic cancer.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Kleeff",
      "authorRank" : 1,
      "name" : "Kleeff J",
      "referenceId" : "RGD:A66462"
    }, {
      "firstName" : "T",
      "lastName" : "Kusama",
      "authorRank" : 2,
      "name" : "Kusama T",
      "referenceId" : "RGD:A148441"
    }, {
      "firstName" : "DL",
      "lastName" : "Rossi",
      "authorRank" : 3,
      "name" : "Rossi",
      "referenceId" : "RGD:A176416"
    }, {
      "firstName" : "T",
      "lastName" : "Ishiwata",
      "authorRank" : 4,
      "name" : "Ishiwata T",
      "referenceId" : "RGD:A26091"
    }, {
      "firstName" : "H",
      "lastName" : "Maruyama",
      "authorRank" : 5,
      "name" : "Maruyama H",
      "referenceId" : "RGD:A7548"
    }, {
      "firstName" : "H",
      "lastName" : "Friess",
      "authorRank" : 6,
      "name" : "Friess H",
      "referenceId" : "RGD:A66470"
    }, {
      "firstName" : "MW",
      "lastName" : "Buchler",
      "authorRank" : 7,
      "name" : "Buchler MW",
      "referenceId" : "RGD:A66468"
    }, {
      "firstName" : "A",
      "lastName" : "Zlotnik",
      "authorRank" : 8,
      "name" : "Zlotnik A",
      "referenceId" : "RGD:A18043"
    }, {
      "firstName" : "M",
      "lastName" : "Korc",
      "authorRank" : 9,
      "name" : "Korc M",
      "referenceId" : "RGD:A120705"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7483623"
    } ]
  }, {
    "primaryId" : "PMID:10225952",
    "title" : "Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Pekny M, etal., J Cell Biol. 1999 May 3;145(3):503-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-03-23T09:31:49.000-05:00",
    "volume" : "145",
    "pages" : "503-14",
    "abstract" : "In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin. We have shown that astrocytes in mice deficient for both GFAP and vimentin (GFAP-/-vim-/-) cannot form IFs even when nestin is expressed and are thus devoid of IFs in their reactive state. Here, we have studied the reaction to injury in the central nervous system in GFAP-/-, vimentin-/-, or GFAP-/-vim-/- mice. Glial scar formation appeared normal after spinal cord or brain lesions in GFAP-/- or vimentin-/- mice, but was impaired in GFAP-/-vim-/- mice that developed less dense scars frequently accompanied by bleeding. These results show that GFAP and  vimentin are required for proper glial scar formation in the injured central nervous system and that some degree of functional overlap exists between these IF proteins.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Pekny",
      "authorRank" : 1,
      "name" : "Pekny M",
      "referenceId" : "RGD:A152657"
    }, {
      "firstName" : "CB",
      "lastName" : "Johansson",
      "authorRank" : 2,
      "name" : "Johansson CB",
      "referenceId" : "RGD:A152658"
    }, {
      "firstName" : "C",
      "lastName" : "Eliasson",
      "authorRank" : 3,
      "name" : "Eliasson C",
      "referenceId" : "RGD:A152659"
    }, {
      "firstName" : "J",
      "lastName" : "Stakeberg",
      "authorRank" : 4,
      "name" : "Stakeberg J",
      "referenceId" : "RGD:A152660"
    }, {
      "firstName" : "A",
      "lastName" : "Wallen",
      "authorRank" : 5,
      "name" : "Wallen A",
      "referenceId" : "RGD:A152661"
    }, {
      "firstName" : "T",
      "lastName" : "Perlmann",
      "authorRank" : 6,
      "name" : "Perlmann T",
      "referenceId" : "RGD:A161505"
    }, {
      "firstName" : "U",
      "lastName" : "Lendahl",
      "authorRank" : 7,
      "name" : "Lendahl U",
      "referenceId" : "RGD:A21177"
    }, {
      "firstName" : "C",
      "lastName" : "Betsholtz",
      "authorRank" : 8,
      "name" : "Betsholtz C",
      "referenceId" : "RGD:A39566"
    }, {
      "firstName" : "CH",
      "lastName" : "Berthold",
      "authorRank" : 9,
      "name" : "Berthold CH",
      "referenceId" : "RGD:A152662"
    }, {
      "firstName" : "J",
      "lastName" : "Frisen",
      "authorRank" : 10,
      "name" : "Frisen J",
      "referenceId" : "RGD:A24917"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6480471"
    } ]
  }, {
    "primaryId" : "PMID:10225955",
    "title" : "Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Takahashi K, etal., J Cell Biol. 1999 May 3;145(3):539-49.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-03T20:35:00.000-05:00",
    "volume" : "145",
    "pages" : "539-49",
    "abstract" : "We have isolated a novel actin filament-binding protein, named afadin, localized  at cadherin-based cell-cell adherens junctions (AJs) in various tissues and cell  lines. Afadin has one PDZ domain, three proline-rich regions, and one actin filament-binding domain. We found here that afadin directly interacted with a family of the immunoglobulin superfamily, which was isolated originally as the poliovirus receptor-related protein (PRR) family consisting of PRR1 and -2, and has been identified recently to be the alphaherpes virus receptor. PRR has a COOH-terminal consensus motif to which the PDZ domain of afadin binds. PRR and afadin were colocalized at cadherin-based cell-cell AJs in various tissues and cell lines. In E-cadherin-expressing EL cells, PRR was recruited to cadherin-based cell-cell AJs through interaction with afadin. PRR showed Ca2+-independent cell-cell adhesion activity. These results indicate that PRR is  a cell-cell adhesion molecule of the immunoglobulin superfamily which is recruited to cadherin-based cell-cell AJs through interaction with afadin. We rename PRR as nectin (taken from the Latin word \"necto\" meaning \"to connect\").",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Takahashi",
      "authorRank" : 1,
      "name" : "Takahashi",
      "referenceId" : "RGD:A410401"
    }, {
      "firstName" : "H",
      "lastName" : "Nakanishi",
      "authorRank" : 2,
      "name" : "Nakanishi H",
      "referenceId" : "RGD:A12322"
    }, {
      "firstName" : "M",
      "lastName" : "Miyahara",
      "authorRank" : 3,
      "name" : "Miyahara M",
      "referenceId" : "RGD:A42926"
    }, {
      "firstName" : "K",
      "lastName" : "Mandai",
      "authorRank" : 4,
      "name" : "Mandai K",
      "referenceId" : "RGD:A12329"
    }, {
      "firstName" : "K",
      "lastName" : "Satoh",
      "authorRank" : 5,
      "name" : "Satoh K",
      "referenceId" : "RGD:A8355"
    }, {
      "firstName" : "A",
      "lastName" : "Satoh",
      "authorRank" : 6,
      "name" : "Satoh A",
      "referenceId" : "RGD:A12321"
    }, {
      "firstName" : "H",
      "lastName" : "Nishioka",
      "authorRank" : 7,
      "name" : "Nishioka H",
      "referenceId" : "RGD:A12325"
    }, {
      "firstName" : "J",
      "lastName" : "Aoki",
      "authorRank" : 8,
      "name" : "Aoki J",
      "referenceId" : "RGD:A9495"
    }, {
      "firstName" : "A",
      "lastName" : "Nomoto",
      "authorRank" : 9,
      "name" : "Nomoto A",
      "referenceId" : "RGD:A60638"
    }, {
      "firstName" : "A",
      "lastName" : "Mizoguchi",
      "authorRank" : 10,
      "name" : "Mizoguchi A",
      "referenceId" : "RGD:A12327"
    }, {
      "firstName" : "Y",
      "lastName" : "Takai",
      "authorRank" : 11,
      "name" : "Takai",
      "referenceId" : "RGD:A403509"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11522311"
    } ]
  }, {
    "primaryId" : "PMID:10225962",
    "title" : "Myogenin induces a shift of enzyme activity from glycolytic to oxidative metabolism in muscles of transgenic mice.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hughes SM, etal., J Cell Biol. 1999 May 3;145(3):633-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-02-02T17:35:49.000-06:00",
    "volume" : "145",
    "pages" : "633-42",
    "abstract" : "Physical training regulates muscle metabolic and contractile properties by altering gene expression. Electrical activity evoked in muscle fiber membrane during physical activity is crucial for such regulation, but the subsequent intracellular pathway is virtually unmapped. Here we investigate the ability of myogenin, a muscle-specific transcription factor strongly regulated by electrical activity, to alter muscle phenotype. Myogenin was overexpressed in transgenic mice using regulatory elements that confer strong expression confined to differentiated post-mitotic fast muscle fibers. In fast muscles from such mice, the activity levels of oxidative mitochondrial enzymes were elevated two- to threefold, whereas levels of glycolytic enzymes were reduced to levels 0.3-0.6 times those found in wild-type mice. Histochemical analysis shows widespread increases in mitochondrial components and glycogen accumulation. The changes in enzyme content were accompanied by a reduction in fiber size, such that many fibers acquired a size typical of oxidative fibers. No change in fiber type-specific myosin heavy chain isoform expression was observed. Changes in metabolic properties without changes in myosins are observed after moderate endurance training in mammals, including humans. Our data suggest that myogenin regulated by electrical activity may mediate effects of physical training on metabolic capacity in muscle.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SM",
      "lastName" : "Hughes",
      "authorRank" : 1,
      "name" : "Hughes SM",
      "referenceId" : "RGD:A29131"
    }, {
      "firstName" : "MM",
      "lastName" : "Chi",
      "authorRank" : 2,
      "name" : "Chi",
      "referenceId" : "RGD:A198775"
    }, {
      "firstName" : "OH",
      "lastName" : "Lowry",
      "authorRank" : 3,
      "name" : "Lowry",
      "referenceId" : "RGD:A198776"
    }, {
      "firstName" : "K",
      "lastName" : "Gundersen",
      "authorRank" : 4,
      "name" : "Gundersen",
      "referenceId" : "RGD:A198777"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9686132"
    } ]
  }, {
    "primaryId" : "PMID:10225970",
    "title" : "Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Johnston B, etal., J Clin Invest. 1999 May;103(9):1269-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-04-04T12:40:37.000-05:00",
    "volume" : "103",
    "pages" : "1269-76",
    "abstract" : "Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that stimulates monocyte recruitment when injected into tissues of healthy animals. However, the  function of this chemokine in models with preexisting inflammation is not known.  Therefore, MCP-1 was superfused over the mesentery of naive rats or rats with chronic adjuvant-induced vasculitis. MCP-1 elicited increased leukocyte transendothelial migration in adjuvant-immunized rats compared with naive animals. Surprisingly, histology revealed that neutrophils constituted the majority of leukocytes recruited in adjuvant-immunized animals. In vitro, MCP-1 was also able to induce chemotaxis of neutrophils isolated from adjuvant-immunized rats but not from naive rats. Flow cytometry revealed novel expression of the CC chemokine receptors CCR1 and CCR2 on neutrophils from adjuvant-immunized animals. In naive animals, an antibody against CD18 blocked leukocyte adhesion and emigration in response to MCP-1. In adjuvant-immunized animals, leukocyte adhesion was reduced by antibodies against the alpha4-integrin but not by antibodies against CD18. However, the CD18 antibody did block emigration. To our knowledge, this study is the first to show increased sensitivity to a CC chemokine in a model with preexisting inflammation, and altered leukocyte recruitment profiles in response to MCP-1. It also demonstrates that CD18 is required for chemokine-induced leukocyte transendothelial migration, independent of its known role in mediating firm adhesion. J. Clin. Invest. 103:1269-1276 (1999).",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Johnston",
      "authorRank" : 1,
      "name" : "Johnston B",
      "referenceId" : "RGD:A26421"
    }, {
      "firstName" : "AR",
      "lastName" : "Burns",
      "authorRank" : 2,
      "name" : "Burns",
      "referenceId" : "RGD:A182176"
    }, {
      "firstName" : "M",
      "lastName" : "Suematsu",
      "authorRank" : 3,
      "name" : "Suematsu M",
      "referenceId" : "RGD:A12816"
    }, {
      "firstName" : "TB",
      "lastName" : "Issekutz",
      "authorRank" : 4,
      "name" : "Issekutz TB",
      "referenceId" : "RGD:A1165"
    }, {
      "firstName" : "RC",
      "lastName" : "Woodman",
      "authorRank" : 5,
      "name" : "Woodman",
      "referenceId" : "RGD:A182177"
    }, {
      "firstName" : "P",
      "lastName" : "Kubes",
      "authorRank" : 6,
      "name" : "Kubes P",
      "referenceId" : "RGD:A66056"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8549768"
    } ]
  }, {
    "primaryId" : "PMID:10225979",
    "title" : "Constitutive activation of an epithelial signal transducer and activator of transcription (STAT) pathway in asthma.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Sampath D, etal., J Clin Invest. 1999 May;103(9):1353-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-03-15T16:46:59.000-05:00",
    "volume" : "103",
    "pages" : "1353-61",
    "abstract" : "Cytokine effects on immunity and inflammation often depend on the transcription factors termed signal transducers and activators of transcription (STATs), so STAT signaling pathways are candidates for influencing inflammatory disease. We reasoned that selective IFN responsiveness of the first STAT family member (Stat1) and Stat1-dependent immune-response genes such as intercellular adhesion molecule-1 (ICAM-1), IFN regulatory factor-1 (IRF-1), and Stat1 itself in airway epithelial cells provides a basis for detecting cytokine signaling abnormalities in inflammatory airway disease. On the basis of nuclear localization and phosphorylation, we found that epithelial Stat1 (but not other control transcription factors) was invariably activated in asthmatic compared with normal control or chronic bronchitis subjects. Furthermore, epithelial levels of activated Stat1 correlated with levels of expression for epithelial ICAM-1, IRF-1, and Stat1, and in turn, ICAM-1 levels correlated with T-cell accumulation in tissue. However, only low levels of IFN-gamma or IFN-gamma-producing cells were detected in airway tissue in all subjects. The results therefore provide initial evidence linking abnormal behavior of STAT pathways for cytokine signaling to the development of an inflammatory disease. In that context, the results also change the current scheme for asthma pathogenesis to one that must include a localized gain in transcriptional signal ordinarily used for a T helper 1-type cytokine (IFN-gamma) in combination with allergy-driven overproduction of T helper 2-type cytokines.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Sampath",
      "authorRank" : 1,
      "name" : "Sampath D",
      "referenceId" : "RGD:A45753"
    }, {
      "firstName" : "M",
      "lastName" : "Castro",
      "authorRank" : 2,
      "name" : "Castro M",
      "referenceId" : "RGD:A88409"
    }, {
      "firstName" : "DC",
      "lastName" : "Look",
      "authorRank" : 3,
      "name" : "Look DC",
      "referenceId" : "RGD:A136281"
    }, {
      "firstName" : "MJ",
      "lastName" : "Holtzman",
      "authorRank" : 4,
      "name" : "Holtzman MJ",
      "referenceId" : "RGD:A132392"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5128723"
    } ]
  }, {
    "primaryId" : "PMID:10226074",
    "title" : "Structure and hormone responsiveness of the gene encoding the alpha-subunit of the rat amiloride-sensitive epithelial sodium channel.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Otulakowski G, etal., Am J Respir Cell Mol Biol 1999 May;20(5):1028-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:33.000-05:00",
    "volume" : "20",
    "pages" : "1028-40",
    "abstract" : "The rat amiloride-sensitive epithelial sodium channel (rENaC) is the rate-limiting step for vectorial transport of Na+ across tight epithelia. The complex is composed of three subunits, alpha, beta, and gamma. Expression of the subunits has been shown to be tissue-specific and developmentally and hormonally regulated. To study mechanisms involved in transcriptional regulation of alpharENaC, we determined the genomic organization of the alpharENaC gene. By 5' rapid amplification of cDNA ends and primer extension, two transcriptional start sites were detected 453 base pairs (bp) apart, resulting in alternative 5' untranslated region (UTR) lengths of 515 or 62 bp. The longer 5' UTR is more prevalent in fetal lung than in adult lung or kidney. The 5' untranslated and coding regions are contained within 12 exons, with the translation start site located within the first exon. Sequence analysis of approximately 1,500 bp of 5' flanking DNA identified putative binding sites for transcription factors PEA3, SP1, AP-1, nuclear factor-kappaB, and thyroid and glucocorticoid receptors. alpharENaC promoter-reporter gene constructs produced low levels of reporter gene activity in transiently transfected cells, which could be increased by dexamethasone (DEX) treatment. Tri-iodothyronine treatment alone had no effect but potentiated stimulation by DEX.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Otulakowski",
      "authorRank" : 1,
      "name" : "Otulakowski G",
      "referenceId" : "RGD:A9910"
    }, {
      "firstName" : "B",
      "lastName" : "Rafii",
      "authorRank" : 2,
      "name" : "Rafii B",
      "referenceId" : "RGD:A33576"
    }, {
      "firstName" : "HR",
      "lastName" : "Bremner",
      "authorRank" : 3,
      "name" : "Bremner HR",
      "referenceId" : "RGD:A9907"
    }, {
      "firstName" : "H",
      "lastName" : "O'Brodovich",
      "authorRank" : 4,
      "name" : "O'Brodovich H",
      "referenceId" : "RGD:A33577"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:729755"
    } ]
  }, {
    "primaryId" : "PMID:10226095",
    "title" : "Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant HERG (G601S) potassium channel.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Furutani M, etal., Circulation. 1999 May 4;99(17):2290-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:17:07.000-05:00",
    "volume" : "99",
    "pages" : "2290-4",
    "abstract" : "BACKGROUND: The congenital long-QT syndrome (LQTS) is an inherited disorder characterized by a prolonged cardiac action potential and a QT interval that leads to arrhythmia. Mutations in the human ether-a-go-go-related gene (HERG), which encodes the rapidly activating component of the delayed rectifier current (IKr), cause chromosome 7-linked LQTS (LQT2). Studies of mutant HERG channels in  heterologous systems indicate that the mechanisms mediating LQT2 are varied and include mutant subunits that form channels with altered kinetic properties or nonfunctional mutant subunits. We recently reported a novel missense mutation of  HERG (G601S) in an LQTS family that we have characterized in the present work. METHODS AND RESULTS: To elucidate the electrophysiological properties of the G601S mutant channels, we expressed these channels in mammalian cells and Xenopus oocytes. The G601S mutant produced less current than wild-type channels but exhibited no change in kinetic properties or dominant-negative suppression when coexpressed with wild-type subunits. To examine the cellular trafficking of mutant HERG channel subunits, enhanced green fluorescent protein tagging and Western blot analyses were performed. These showed deficient protein trafficking  of the G601S mutant to the plasma membrane. CONCLUSIONS: Our results from both the Xenopus oocyte and HEK293 cell expression systems and green fluorescent protein tagging and Western blot analyses support the conclusion that the G601S mutant is a hypomorphic mutation, resulting in a reduced current amplitude. Thus, it represents a novel mechanism underlying LQT2.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Furutani",
      "authorRank" : 1,
      "name" : "Furutani M",
      "referenceId" : "RGD:A7051"
    }, {
      "firstName" : "MC",
      "lastName" : "Trudeau",
      "authorRank" : 2,
      "name" : "Trudeau",
      "referenceId" : "RGD:A255937"
    }, {
      "firstName" : "N",
      "lastName" : "Hagiwara",
      "authorRank" : 3,
      "name" : "Hagiwara N",
      "referenceId" : "RGD:A64380"
    }, {
      "firstName" : "A",
      "lastName" : "Seki",
      "authorRank" : 4,
      "name" : "Seki",
      "referenceId" : "RGD:A243618"
    }, {
      "firstName" : "Q",
      "lastName" : "Gong",
      "authorRank" : 5,
      "name" : "Gong Q",
      "referenceId" : "RGD:A123800"
    }, {
      "firstName" : "Z",
      "lastName" : "Zhou",
      "authorRank" : 6,
      "name" : "Zhou Z",
      "referenceId" : "RGD:A27436"
    }, {
      "firstName" : "S",
      "lastName" : "Imamura",
      "authorRank" : 7,
      "name" : "Imamura S",
      "referenceId" : "RGD:A33356"
    }, {
      "firstName" : "H",
      "lastName" : "Nagashima",
      "authorRank" : 8,
      "name" : "Nagashima",
      "referenceId" : "RGD:A205651"
    }, {
      "firstName" : "H",
      "lastName" : "Kasanuki",
      "authorRank" : 9,
      "name" : "Kasanuki H",
      "referenceId" : "RGD:A65044"
    }, {
      "firstName" : "A",
      "lastName" : "Takao",
      "authorRank" : 10,
      "name" : "Takao",
      "referenceId" : "RGD:A256529"
    }, {
      "firstName" : "K",
      "lastName" : "Momma",
      "authorRank" : 11,
      "name" : "Momma",
      "referenceId" : "RGD:A201222"
    }, {
      "firstName" : "CT",
      "lastName" : "January",
      "authorRank" : 12,
      "name" : "January CT",
      "referenceId" : "RGD:A156859"
    }, {
      "firstName" : "GA",
      "lastName" : "Robertson",
      "authorRank" : 13,
      "name" : "Robertson",
      "referenceId" : "RGD:A256530"
    }, {
      "firstName" : "R",
      "lastName" : "Matsuoka",
      "authorRank" : 14,
      "name" : "Matsuoka R",
      "referenceId" : "RGD:A62346"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063834"
    } ]
  }, {
    "primaryId" : "PMID:10226549",
    "title" : "Effects of 5-fluorouracil derivative UFT on thymidylate synthetase and thymidine kinase in rat colorectal tumors.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Sakamoto S, etal., Anticancer Res. 1999 Jan-Feb;19(1A):245-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-04-05T13:19:13.000-05:00",
    "volume" : "19",
    "pages" : "245-50",
    "abstract" : "BACKGROUND: Thymidylate synthetase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. MATERIALS AND METHODS: Weekly injections of 1,2-dimethyl-hydrazine induced high incidence of colorectal adenocarcinomas in rats. RESULTS: An increased activity of thymidylate synthetase was found in the poorly differentiated adenocarcinomas of the chemically induced rat colorectal tumors. Six-week oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) reduced the total number of colorectal tumors, with the reduction of thymidylate synthetase activity in the poorly-differentiated type, though the mRNA expression of thymidylate synthetase and thymidine kinase differed little between the groups with or without UFT treatment. CONCLUSIONS: These results indicate that the long-term oral administration using UFT suppresses colorectal carcinogenesis and the growth of the poorly-differentiated type tumors.",
    "issueName" : "1A",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Sakamoto",
      "authorRank" : 1,
      "name" : "Sakamoto S",
      "referenceId" : "RGD:A81563"
    }, {
      "firstName" : "Y",
      "lastName" : "Kawachi",
      "authorRank" : 2,
      "name" : "Kawachi Y",
      "referenceId" : "RGD:A121374"
    }, {
      "firstName" : "T",
      "lastName" : "Iwama",
      "authorRank" : 3,
      "name" : "Iwama T",
      "referenceId" : "RGD:A17034"
    }, {
      "firstName" : "K",
      "lastName" : "Kuwa",
      "authorRank" : 4,
      "name" : "Kuwa K",
      "referenceId" : "RGD:A117623"
    }, {
      "firstName" : "T",
      "lastName" : "Suzuki",
      "authorRank" : 5,
      "name" : "Suzuki T",
      "referenceId" : "RGD:A4733"
    }, {
      "firstName" : "T",
      "lastName" : "Mitamura",
      "authorRank" : 6,
      "name" : "Mitamura T",
      "referenceId" : "RGD:A117622"
    }, {
      "firstName" : "H",
      "lastName" : "Kudo",
      "authorRank" : 7,
      "name" : "Kudo H",
      "referenceId" : "RGD:A30706"
    }, {
      "firstName" : "S",
      "lastName" : "Sassa",
      "authorRank" : 8,
      "name" : "Sassa S",
      "referenceId" : "RGD:A28351"
    }, {
      "firstName" : "S",
      "lastName" : "Yoshimura",
      "authorRank" : 9,
      "name" : "Yoshimura S",
      "referenceId" : "RGD:A5864"
    }, {
      "firstName" : "T",
      "lastName" : "Maemura",
      "authorRank" : 10,
      "name" : "Maemura T",
      "referenceId" : "RGD:A121375"
    }, {
      "firstName" : "T",
      "lastName" : "Nakayama",
      "authorRank" : 11,
      "name" : "Nakayama T",
      "referenceId" : "RGD:A140893"
    }, {
      "firstName" : "M",
      "lastName" : "Ohsawa",
      "authorRank" : 12,
      "name" : "Ohsawa M",
      "referenceId" : "RGD:A121377"
    }, {
      "firstName" : "Y",
      "lastName" : "Hara",
      "authorRank" : 13,
      "name" : "Hara Y",
      "referenceId" : "RGD:A22080"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317418"
    } ]
  }, {
    "primaryId" : "PMID:10226800",
    "title" : "The absence of 150-kDa insulin-like growth factor complexes in fetal rat serum is not due to a lack of functional acid-labile subunit.",
    "datePublished" : "0001-12-01T00:00:00.000-06:00",
    "citation" : "Lee CY, etal., Horm Metab Res. 1999 Feb-Mar;31(2-3):182-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-06-27T15:54:30.000-05:00",
    "volume" : "31",
    "pages" : "182-5",
    "abstract" : "Most of the insulin-like growth factors (IGFs) in adult rat or human plasma circulate in 150-kDa heterotrimeric complexes with IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS). These 150-kDa complexes are not present, however, in rat serum at birth. As ALS is the critical determinant in the formation of the 150-kDa complexes in adult rat serum, the present study asks whether the absence of 150-kDa complexes in fetal rat serum results from a low abundance of ALS. We report that ALS mRNA is expressed in term fetal rat liver at 30% of the levels in adult liver, that radioiodinated rat ALS is not proteolyzed by incubation with fetal rat serum, and that sufficient functional ALS is present in fetal rat serum to form 150-kDa complexes with recombinant human IGFBP-3. These results indicate that the low levels of 150-kDa complexes in perinatal rat serum are not due to low circulating levels of ALS.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C Y",
      "lastName" : "Lee",
      "authorRank" : 1,
      "name" : "Lee CY",
      "referenceId" : "RGD:A446155"
    }, {
      "firstName" : "F J",
      "lastName" : "Cohen",
      "authorRank" : 2,
      "name" : "Cohen FJ",
      "referenceId" : "RGD:A446156"
    }, {
      "firstName" : "H B",
      "lastName" : "Wu",
      "authorRank" : 3,
      "name" : "Wu HB",
      "referenceId" : "RGD:A446157"
    }, {
      "firstName" : "G T",
      "lastName" : "Ooi",
      "authorRank" : 4,
      "name" : "Ooi GT",
      "referenceId" : "RGD:A446158"
    }, {
      "firstName" : "M M",
      "lastName" : "Rechler",
      "authorRank" : 5,
      "name" : "Rechler MM",
      "referenceId" : "RGD:A446159"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12910864"
    } ]
  }, {
    "primaryId" : "PMID:10227394",
    "title" : "Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "van Slegtenhorst M, etal., J Med Genet. 1999 Apr;36(4):285-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:45:18.000-05:00",
    "volume" : "36",
    "pages" : "285-9",
    "abstract" : "Tuberous sclerosis complex is an inherited tumour suppressor syndrome, caused by  a mutation in either the TSC1 or TSC2 gene. The disease is characterised by a broad phenotypic spectrum that can include seizures, mental retardation, renal dysfunction, and dermatological abnormalities. The TSC1 gene was recently identified and has 23 exons, spanning 45 kb of genomic DNA, and encoding an 8.6 kb mRNA. After screening all 21 coding exons in our collection of 225 unrelated patients, only 29 small mutations were detected, suggesting that TSC1 mutations are under-represented among TSC patients. Almost all TSC1 mutations were small changes leading to a truncated protein, except for a splice site mutation and two in frame deletions in exon 7 and exon 15. No clear difference was observed in the clinical phenotype of patients with an in frame deletion or a frameshift or nonsense mutation. We found the disease causing mutation in 13% of our unrelated  set of TSC patients, with more than half of the mutations clustered in exons 15 and 17, and no obvious under-representation of mutations among sporadic cases. In conclusion, we find no support for a genotype-phenotype correlation for the group of TSC1 patients compared to the overall population of TSC patients.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Van Slegtenhorst",
      "authorRank" : 1,
      "name" : "Van Slegtenhorst M",
      "referenceId" : "RGD:A32167"
    }, {
      "firstName" : "S",
      "lastName" : "Verhoef",
      "authorRank" : 2,
      "name" : "Verhoef S",
      "referenceId" : "RGD:A81999"
    }, {
      "firstName" : "A",
      "lastName" : "Tempelaars",
      "authorRank" : 3,
      "name" : "Tempelaars",
      "referenceId" : "RGD:A251808"
    }, {
      "firstName" : "L",
      "lastName" : "Bakker",
      "authorRank" : 4,
      "name" : "Bakker",
      "referenceId" : "RGD:A251809"
    }, {
      "firstName" : "Q",
      "lastName" : "Wang",
      "authorRank" : 5,
      "name" : "Wang",
      "referenceId" : "RGD:A415158"
    }, {
      "firstName" : "M",
      "lastName" : "Wessels",
      "authorRank" : 6,
      "name" : "Wessels",
      "referenceId" : "RGD:A251811"
    }, {
      "firstName" : "R",
      "lastName" : "Bakker",
      "authorRank" : 7,
      "name" : "Bakker",
      "referenceId" : "RGD:A251812"
    }, {
      "firstName" : "M",
      "lastName" : "Nellist",
      "authorRank" : 8,
      "name" : "Nellist M",
      "referenceId" : "RGD:A81998"
    }, {
      "firstName" : "D",
      "lastName" : "Lindhout",
      "authorRank" : 9,
      "name" : "Lindhout D",
      "referenceId" : "RGD:A81725"
    }, {
      "firstName" : "D",
      "lastName" : "Halley",
      "authorRank" : 10,
      "name" : "Halley D",
      "referenceId" : "RGD:A79346"
    }, {
      "firstName" : "A",
      "lastName" : "Van den Ouweland",
      "authorRank" : 11,
      "name" : "Van den Ouweland A",
      "referenceId" : "RGD:A37090"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062617"
    } ]
  }, {
    "primaryId" : "PMID:10227395",
    "title" : "Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Plasilova M, etal., J Med Genet. 1999 Apr;36(4):290-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-15T12:27:43.000-06:00",
    "volume" : "36",
    "pages" : "290-4",
    "abstract" : "Primary congenital glaucoma (PCG) is an autosomal recessive eye disease that occurs at an unusually high frequency in the ethnic isolate of Roms (Gypsies) in  Slovakia. Recently, we linked the disease in this population to the GLC3A locus on 2p21. At this locus, mutations in the cytochrome P4501B1 (CYP1B1) gene have been identified as a molecular basis for this condition. Here, we report the results of CYP1B1 mutation screening of 43 PCG patients from 26 Slovak Rom families. A homozygous G-->A transition at nucleotide 1505 in the highly conserved region of exon 3 was detected in all families. This mutation results in the E387K substitution, which affects the conserved K helix region of the cytochrome P450 molecule. Determination of the CYP1B1 polymorphic background showed a common DNA haplotype in all patients, thus indicating that the E387K mutation in Roms has originated from a single ancestral mutational event. The Slovak Roms represent the first population in which PCG is found to result from a single mutation in the CYP1B1 gene, so that a founder effect is the most plausible explanation of its increased incidence. An ARMS-PCR assay has been developed for fast detection of this mutation, thus allowing direct DNA based prenatal diagnosis as well as gene carrier detection in this particular population. Screening of 158 healthy Roms identified 17 (10.8%) mutation carriers, indicating that the frequency of PCG in this population may be even higher than originally estimated.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Plasilova",
      "authorRank" : 1,
      "name" : "Plasilova",
      "referenceId" : "RGD:A178056"
    }, {
      "firstName" : "I",
      "lastName" : "Stoilov",
      "authorRank" : 2,
      "name" : "Stoilov I",
      "referenceId" : "RGD:A74221"
    }, {
      "firstName" : "M",
      "lastName" : "Sarfarazi",
      "authorRank" : 3,
      "name" : "Sarfarazi M",
      "referenceId" : "RGD:A37170"
    }, {
      "firstName" : "L",
      "lastName" : "Kadasi",
      "authorRank" : 4,
      "name" : "Kadasi L",
      "referenceId" : "RGD:A126387"
    }, {
      "firstName" : "E",
      "lastName" : "Ferakova",
      "authorRank" : 5,
      "name" : "Ferakova",
      "referenceId" : "RGD:A178057"
    }, {
      "firstName" : "V",
      "lastName" : "Ferak",
      "authorRank" : 6,
      "name" : "Ferak",
      "referenceId" : "RGD:A178058"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7800670"
    } ]
  }, {
    "primaryId" : "PMID:10227398",
    "title" : "High frequency of BRCA1/2 germline mutations in 42 Belgian families with a small  number of symptomatic subjects.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Goelen G, etal., J Med Genet. 1999 Apr;36(4):304-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:59:20.000-05:00",
    "volume" : "36",
    "pages" : "304-8",
    "abstract" : "AIM: The initial risk assessments for BRCA1/2 mutation carriers and estimates of  carrier frequencies were based on extended pedigrees with a large number of symptomatic subjects. When counselling based on BRCA gene mutation analysis was initiated, we faced requests for counselling mostly from members of small families with only two or three affected members. We report on the likelihood of  finding a BRCA mutation in such small families. METHODS: In the first 100 families that came for oncogenetic counselling since September 1994, a BRCA1/2 gene mutation screen was initiated if there were two or more symptomatic first degree relatives, if one of them had ovarian cancer, or if one breast cancer was  diagnosed before the age of 50 years. RESULTS: BRCA gene mutations were found and confirmed by sequencing in 14 out of 42 families (33%); 10 mutations were in the  BRCA1 gene and four in the BRCA2 gene. Our findings indicate an increased probability of detecting a BRCA gene mutation when ovarian cancer occurred in the family. There is no increased probability of detecting a mutation with increasing numbers of breast cancers. Only 22% of the eligible presymptomatic family members opted for testing. The presymptomatic female carriers currently prefer breast surveillance rather than prophylactic surgery. CONCLUSION: BRCA1/2 gene mutation  testing can be done with reasonable efficiency in the Belgian population when there are two symptomatic family members. The availability of testing does not lead to a high frequency of requests for testing by presymptomatic family members.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Goelen",
      "authorRank" : 1,
      "name" : "Goelen",
      "referenceId" : "RGD:A363519"
    }, {
      "firstName" : "E",
      "lastName" : "Teugels",
      "authorRank" : 2,
      "name" : "Teugels",
      "referenceId" : "RGD:A258038"
    }, {
      "firstName" : "M",
      "lastName" : "Bonduelle",
      "authorRank" : 3,
      "name" : "Bonduelle M",
      "referenceId" : "RGD:A79224"
    }, {
      "firstName" : "B",
      "lastName" : "Neyns",
      "authorRank" : 4,
      "name" : "Neyns",
      "referenceId" : "RGD:A366031"
    }, {
      "firstName" : "J",
      "lastName" : "De Greve",
      "authorRank" : 5,
      "name" : "De Greve",
      "referenceId" : "RGD:A258039"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11528326"
    } ]
  }, {
    "primaryId" : "PMID:10227647",
    "title" : "A DLST genotype associated with reduced risk for Alzheimer's disease.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Sheu KF, etal., Neurology 1999 Apr 22;52(7):1505-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-16T16:46:55.000-05:00",
    "volume" : "52",
    "pages" : "1505-7",
    "abstract" : "Recent studies suggest that variants of the DLST gene alter the risk of AD. DLST encodes the core subunit of the mitochondrial alpha-ketoglutarate dehydrogenase complex, which is deficient in AD. The authors report that in 247 US white subjects, homozygosity for DLST A19,117, T19,183 was associated with a reduced risk of AD (odds ratio [OR] = 0.35, p = 0.018). The reduced risk was marked in subjects who did not carry the apolipoprotein (APOE)-4 allele (OR = 0.16, p = 0.014). Further study of DLST in AD appears warranted.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KF",
      "lastName" : "Sheu",
      "authorRank" : 1,
      "name" : "Sheu KF",
      "referenceId" : "RGD:A53185"
    }, {
      "firstName" : "AM",
      "lastName" : "Brown",
      "authorRank" : 2,
      "name" : "Brown AM",
      "referenceId" : "RGD:A31063"
    }, {
      "firstName" : "BS",
      "lastName" : "Kristal",
      "authorRank" : 3,
      "name" : "Kristal BS",
      "referenceId" : "RGD:A53186"
    }, {
      "firstName" : "RN",
      "lastName" : "Kalaria",
      "authorRank" : 4,
      "name" : "Kalaria RN",
      "referenceId" : "RGD:A53187"
    }, {
      "firstName" : "L",
      "lastName" : "Lilius",
      "authorRank" : 5,
      "name" : "Lilius L",
      "referenceId" : "RGD:A53188"
    }, {
      "firstName" : "L",
      "lastName" : "Lannfelt",
      "authorRank" : 6,
      "name" : "Lannfelt L",
      "referenceId" : "RGD:A162068"
    }, {
      "firstName" : "JP",
      "lastName" : "Blass",
      "authorRank" : 7,
      "name" : "Blass JP",
      "referenceId" : "RGD:A53190"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358587"
    } ]
  }, {
    "primaryId" : "PMID:10227685",
    "title" : "X-linked adrenoleukodystrophy: genes, mutations, and phenotypes.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Smith KD, etal., Neurochem Res. 1999 Apr;24(4):521-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:51:18.000-05:00",
    "volume" : "24",
    "pages" : "521-35",
    "abstract" : "X-linked adrenoleukodystrophy (X-ALD) is a complex and perplexing neurodegenerative disorder. The metabolic abnormality, elevated levels of very long-chain fatty acids in tissues and plasma, and the biochemical defect, reduced peroxisomal very long-chain acyl-CoA synthetase (VLCS) activity, are ubiquitous features of the disease. However, clinical manifestations are highly variable with regard to time of onset, site of initial pathology and rate of progression.  In addition, the abnormal gene in X-ALD is not the gene for VLCS. Rather, it encodes a peroxisomal membrane protein with homology to the ATP-binding cassette  (ABC) transmembrane transporter superfamily of proteins. The X-ALD protein (ALDP) is closely related to three other peroxisomal membrane ABC proteins. In this report we summarize all known X-ALD mutations and establish the lack of an X-ALD  genotype/phenotype correlation. We compare the evolutionary relationships among peroxisomal ABC proteins, demonstrate that ALDP forms homodimers with itself and  heterodimers with other peroxisomal ABC proteins and present cDNA complementation studies suggesting that the peroxisomal ABC proteins have overlapping functions.  We also establish that there are at least two peroxisomal VLCS activities, one that is ALDP dependent and one that is ALDP independent. Finally, we discuss variable expression of the peroxisomal ABC proteins and ALDP independent VLCS in  relation to the variable clinical presentations of X-ALD.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KD",
      "lastName" : "Smith",
      "authorRank" : 1,
      "name" : "Smith KD",
      "referenceId" : "RGD:A137236"
    }, {
      "firstName" : "S",
      "lastName" : "Kemp",
      "authorRank" : 2,
      "name" : "Kemp S",
      "referenceId" : "RGD:A71092"
    }, {
      "firstName" : "LT",
      "lastName" : "Braiterman",
      "authorRank" : 3,
      "name" : "Braiterman LT",
      "referenceId" : "RGD:A67531"
    }, {
      "firstName" : "JF",
      "lastName" : "Lu",
      "authorRank" : 4,
      "name" : "Lu",
      "referenceId" : "RGD:A225516"
    }, {
      "firstName" : "HM",
      "lastName" : "Wei",
      "authorRank" : 5,
      "name" : "Wei",
      "referenceId" : "RGD:A191100"
    }, {
      "firstName" : "M",
      "lastName" : "Geraghty",
      "authorRank" : 6,
      "name" : "Geraghty",
      "referenceId" : "RGD:A252916"
    }, {
      "firstName" : "G",
      "lastName" : "Stetten",
      "authorRank" : 7,
      "name" : "Stetten",
      "referenceId" : "RGD:A252917"
    }, {
      "firstName" : "JS",
      "lastName" : "Bergin",
      "authorRank" : 8,
      "name" : "Bergin",
      "referenceId" : "RGD:A252918"
    }, {
      "firstName" : "J",
      "lastName" : "Pevsner",
      "authorRank" : 9,
      "name" : "Pevsner J",
      "referenceId" : "RGD:A9666"
    }, {
      "firstName" : "PA",
      "lastName" : "Watkins",
      "authorRank" : 10,
      "name" : "Watkins PA",
      "referenceId" : "RGD:A121851"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062888"
    } ]
  }, {
    "primaryId" : "PMID:10227724",
    "title" : "Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Yonezawa S, etal., Pathol Int. 1999 Jan;49(1):45-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-05-14T13:03:00.000-05:00",
    "volume" : "49",
    "pages" : "45-54",
    "abstract" : "Previously it has been found that the MUC2 gene for intestinal type secretory mucin is highly expressed in intraductal papillary mucinous tumors (IPMT), which are characterized by non-invasive growth and a favorable outcome. In contrast, MUC2 mRNA is rarely expressed in invasive ductal carcinomas (IDC), which have poor outcomes. The gastric type secretory mucin, MUC5AC, is strongly expressed in the surface mucous cells of gastric mucosa. As both MUC2 and MUC5AC mucins share the characteristics of forming highly viscous gels, it is expected that not only MUC2 mucin expression but also MUC5AC mucin expression may be associated with a favorable prognosis in patients with pancreatic tumors. MUC5AC mucin gene expression was examined in 24 cases of IPMT and 38 cases of IDC by in situ hybridization using a digoxigenin-labeled oligonucleotide. The results were compared with MUC2 mucin gene expression. Neither MUC5AC mRNA nor MUC2 mRNA was detected in normal pancreatic tissues. MUC5AC mRNA was expressed in 20 of 24 cases of IPMT (83%) and in five of 38 cases of IDC (13%). In contrast, MUC2 mRNA was expressed in 14 of 24 cases of IPMT (58%) and in none of the 38 cases of IDC (0%). The expression rates of MUC5AC mRNA and MUC2 mRNA in IPMT were significantly higher than those in IDC (P< 0.001, respectively). Intraductal papillary mucinous tumors are characterized by three histological types: (i) villous dark cell type; (ii) papillary clear cell type; and (iii) compact cell type. The villous dark cell type generally expressed both MUC5AC+ and MUC2+ genes. Alternatively, the papillary clear cell type and the compact cell type usually showed MUC5AC+ and MUC2- expression. Patients with MUC5AC mRNA expression had a significantly better survival prognosis than those with no MUC5AC mRNA expression (P< 0.005). In conclusion, MUC5AC gene expression occurs in a majority of IPMT cases, even in those with no MUC2 production. MUC5AC expression can be",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Yonezawa",
      "authorRank" : 1,
      "name" : "Yonezawa S",
      "referenceId" : "RGD:A21718"
    }, {
      "firstName" : "M",
      "lastName" : "Horinouchi",
      "authorRank" : 2,
      "name" : "Horinouchi M",
      "referenceId" : "RGD:A123214"
    }, {
      "firstName" : "M",
      "lastName" : "Osako",
      "authorRank" : 3,
      "name" : "Osako M",
      "referenceId" : "RGD:A66399"
    }, {
      "firstName" : "M",
      "lastName" : "Kubo",
      "authorRank" : 4,
      "name" : "Kubo M",
      "referenceId" : "RGD:A60217"
    }, {
      "firstName" : "S",
      "lastName" : "Takao",
      "authorRank" : 5,
      "name" : "Takao S",
      "referenceId" : "RGD:A123215"
    }, {
      "firstName" : "Y",
      "lastName" : "Arimura",
      "authorRank" : 6,
      "name" : "Arimura Y",
      "referenceId" : "RGD:A123112"
    }, {
      "firstName" : "K",
      "lastName" : "Nagata",
      "authorRank" : 7,
      "name" : "Nagata K",
      "referenceId" : "RGD:A5190"
    }, {
      "firstName" : "S",
      "lastName" : "Tanaka",
      "authorRank" : 8,
      "name" : "Tanaka S",
      "referenceId" : "RGD:A161408"
    }, {
      "firstName" : "K",
      "lastName" : "Sakoda",
      "authorRank" : 9,
      "name" : "Sakoda K",
      "referenceId" : "RGD:A123216"
    }, {
      "firstName" : "T",
      "lastName" : "Aikou",
      "authorRank" : 10,
      "name" : "Aikou T",
      "referenceId" : "RGD:A123217"
    }, {
      "firstName" : "E",
      "lastName" : "Sato",
      "authorRank" : 11,
      "name" : "Sato E",
      "referenceId" : "RGD:A23141"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2324907"
    } ]
  }, {
    "primaryId" : "PMID:10227812",
    "title" : "Expression of interferon-gamma in the lens exacerbates anterior uveitis and induces retinal degenerative changes in transgenic Lewis rats.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Egwuagu CE, etal., Clin Immunol. 1999 May;91(2):196-205.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-03T15:06:53.000-06:00",
    "volume" : "91",
    "pages" : "196-205",
    "abstract" : "Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that has been implicated in immunopathogenic mechanisms of a number of inflammatory diseases of autoimmune or infectious disease etiology. However, its exact role is still a matter of debate. In experimental mouse models, IFN-gamma has been shown to exacerbate autoimmune thyroiditis, insulin-dependent diabetes mellitus, and autoimmune neuritis while it confers protection against experimental allergic encephalomyelitis and experimental uveitis. In this study, we generated transgenic rats with constitutive expression of IFN-gamma in the eye to study its paracrine effects and to investigate whether local production of IFN-gamma also confers protection against uveitis in the rat species. We show here that chronic  exposure of ocular cells to IFN-gamma results in apoptotic death of retinal ganglion cells, development of chronic choroiditis, formation of retinal in-foldings, and activation of proinflammatory genes. In contrast to its protective systemic effect in the mouse, constitutive secretion of IFN-gamma in the rat eye was found to predispose the development of severe anterior uveitis and induction of retinal degenerative processes that impair visual acuity. Our data underscore the danger in extrapolation of cytokine effects in the mouse to humans without corroborating evidence in other species.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CE",
      "lastName" : "Egwuagu",
      "authorRank" : 1,
      "name" : "Egwuagu CE",
      "referenceId" : "RGD:A98602"
    }, {
      "firstName" : "RM",
      "lastName" : "Mahdi",
      "authorRank" : 2,
      "name" : "Mahdi",
      "referenceId" : "RGD:A178950"
    }, {
      "firstName" : "CC",
      "lastName" : "Chan",
      "authorRank" : 3,
      "name" : "Chan",
      "referenceId" : "RGD:A410074"
    }, {
      "firstName" : "J",
      "lastName" : "Sztein",
      "authorRank" : 4,
      "name" : "Sztein",
      "referenceId" : "RGD:A178952"
    }, {
      "firstName" : "W",
      "lastName" : "Li",
      "authorRank" : 5,
      "name" : "Li W",
      "referenceId" : "RGD:A16573"
    }, {
      "firstName" : "JA",
      "lastName" : "Smith",
      "authorRank" : 6,
      "name" : "Smith JA",
      "referenceId" : "RGD:A24599"
    }, {
      "firstName" : "AB",
      "lastName" : "Chepelinsky",
      "authorRank" : 7,
      "name" : "Chepelinsky AB",
      "referenceId" : "RGD:A49002"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8157614"
    } ]
  }, {
    "primaryId" : "PMID:10227984",
    "title" : "T cell reconstitution of BB/W rats after the initiation of insulitis precipitates the onset of diabetes.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ramanathan S and Poussier P, J Immunol 1999 May 1;162(9):5134-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-03-28T14:34:57.000-06:00",
    "volume" : "162",
    "pages" : "5134-42",
    "abstract" : "One of the diabetes susceptibility genes of the BB/W (Biobreeding/Worcester) rat maps to the lyp locus on chromosome 4. The BB/W lyp allele is responsible for a severe peripheral T lymphopenia. Correction of this lymphopenia by transfer of normal, histocompatible T cells prevents diabetes, providing T cell reconstitution is initiated before insulitis. We have analyzed this time-dependent regulation of the diabetogenic process by normal T cells. We demonstrate that T cell reconstitution after the initiation of insulitis precipitates the onset of diabetes through the recruitment of donor T cells to the autoimmune process. This inability of normal T cells to regulate primed diabetogenic BB/W T cells and their own autoreactive potential were observed when normal T cells outnumbered pathogenic T cells by approximately 1000-fold. Analysis of donor-derived T cells recovered from BB/W rats that were reconstituted before insulitis, and hence protected from diabetes, demonstrates that early T cell reconstitution of BB/W rats does not result in a long term physical or functional depletion of islet cell-specific T cell precursors among donor cells or in the expansion of T cells that can regulate the activation and expansion of diabetogenic T cells.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Ramanathan",
      "authorRank" : 1,
      "name" : "Ramanathan S",
      "referenceId" : "RGD:A12420"
    }, {
      "firstName" : "P",
      "lastName" : "Poussier",
      "authorRank" : 2,
      "name" : "Poussier P",
      "referenceId" : "RGD:A12422"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:629469"
    } ]
  }, {
    "primaryId" : "PMID:10228098",
    "title" : "G-CSF during Escherichia coli versus Staphylococcus aureus pneumonia in rats has  fundamentally different and opposite effects.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Karzai W, etal., Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1377-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-04T15:04:24.000-06:00",
    "volume" : "159",
    "pages" : "1377-82",
    "abstract" : "We investigated if bacteria type alters outcome with prophylactic granulocyte colony stimulating factor (G-CSF) therapy during pneumonia. Rats received G-CSF or placebo daily for 6 d and after the third dose were intrabronchially inoculated with either Escherichia coli or Staphylococcus aureus. Without G-CSF,  E. coli and S. aureus produced similar (p = NS) mortality rates (36 versus 38%) and serial changes in mean circulating neutrophil counts (CNC), but differing mean (+/- SE) tumor necrosis factor (TNF) levels (E. coli, 259 +/- 104 versus S.  aureus, 51 +/- 17 pg/ml, p = 0.01). G-CSF prior to bacteria increased mean CNC more than six times compared with placebo (p = 0.001). However, with G-CSF in the first 6 h after E. coli, there was a greater than 20-fold decrease in mean (+/- SE) CNC (x 10(3)/ mm3) to below placebo (0.5 +/- 0.1 versus 0.8 +/- 0.1), whereas with G-CSF after S. aureus, there was only a fivefold decrease in mean CNC and CNC were greater than placebo (1.8 +/- 0.2 versus 0.8 +/- 0.1) (E. coli versus S. aureus decrease in CNC with G-CSF, p = 0.001). With E. coli, G-CSF worsened oxygenation and increased bacteremia and mortality, whereas with S. aureus, G-CSF improved oxygenation and decreased bacteremia and mortality (G-CSF therapy, E. coli versus S. aureus, p = 0.03, 0.05, and 0.001, respectively). Thus, during S.  aureus pneumonia with low TNF levels, G-CSF increased CNC and bacterial clearance, resulting in less pulmonary injury and decreased death. During E. coli pneumonia with high TNF levels, G-CSF paradoxically decreased CNC, resulting in impaired bacterial clearance and worsened pulmonary injury and death. Bacterial species and the associated inflammatory mediator response can alter outcome with  prophylactic G-CSF therapy during pneumonia.",
    "issueName" : "5 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Karzai",
      "authorRank" : 1,
      "name" : "Karzai",
      "referenceId" : "RGD:A213314"
    }, {
      "firstName" : "BU",
      "lastName" : "Von Specht",
      "authorRank" : 2,
      "name" : "Von Specht",
      "referenceId" : "RGD:A213315"
    }, {
      "firstName" : "C",
      "lastName" : "Parent",
      "authorRank" : 3,
      "name" : "Parent C",
      "referenceId" : "RGD:A149647"
    }, {
      "firstName" : "J",
      "lastName" : "Haberstroh",
      "authorRank" : 4,
      "name" : "Haberstroh",
      "referenceId" : "RGD:A213316"
    }, {
      "firstName" : "K",
      "lastName" : "Wollersen",
      "authorRank" : 5,
      "name" : "Wollersen",
      "referenceId" : "RGD:A213317"
    }, {
      "firstName" : "C",
      "lastName" : "Natanson",
      "authorRank" : 6,
      "name" : "Natanson C",
      "referenceId" : "RGD:A149651"
    }, {
      "firstName" : "SM",
      "lastName" : "Banks",
      "authorRank" : 7,
      "name" : "Banks SM",
      "referenceId" : "RGD:A149653"
    }, {
      "firstName" : "PQ",
      "lastName" : "Eichacker",
      "authorRank" : 8,
      "name" : "Eichacker PQ",
      "referenceId" : "RGD:A149654"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11039478"
    } ]
  }, {
    "primaryId" : "PMID:10228112",
    "title" : "HLA class II polymorphism in cystic fibrosis. A possible modifier of pulmonary phenotype.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Aron Y, etal., Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1464-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-08-25T15:54:36.000-05:00",
    "volume" : "159",
    "pages" : "1464-8",
    "abstract" : "Evolution of lung damage is highly variable in cystic fibrosis (CF) even in patients with the same cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The analysis of genetic factors other than CFTR may help our understanding of genotype-phenotype relationships in CF. As human leukocyte antigen (HLA) class II polymorphism has been associated with a number of diseases including autoimmune and inflammatory diseases, asthma, and allergy, we investigated the possibility that HLA polymorphism contributes to CF-associated pulmonary inflammation. Among the 98 adult CF patients tested, the genotypic frequencies of DR4 and DR7 alleles (serologic group DR53) and DR7/ DQA*0201 haplotype were higher than in 39 selected control subjects without atopy (p </= 10(-)6, relative risk [RR] = 22, and p </= 5.10(-)4, RR = 27, respectively) and in a random population. No significant difference of these allelic distributions was found according to the CFTR genotype. In the CF patients, the DR7 allele was significantly associated with an increase in total IgE and with chronic Pseudomonas aeruginosa colonization (100% of DR7 versus 83% of non-DR7 patients being colonized, p < 0.05). Our results suggest that genetic factors known to modulate the immune response might contribute to chronic infection with Pseudomonas, increased total IgE, and pulmonary outcome in CF.",
    "issueName" : "5 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Aron",
      "authorRank" : 1,
      "name" : "Aron Y",
      "referenceId" : "RGD:A143848"
    }, {
      "firstName" : "BS",
      "lastName" : "Polla",
      "authorRank" : 2,
      "name" : "Polla BS",
      "referenceId" : "RGD:A19999"
    }, {
      "firstName" : "T",
      "lastName" : "Bienvenu",
      "authorRank" : 3,
      "name" : "Bienvenu T",
      "referenceId" : "RGD:A164938"
    }, {
      "firstName" : "J",
      "lastName" : "Dall'ava",
      "authorRank" : 4,
      "name" : "Dall'ava J",
      "referenceId" : "RGD:A143849"
    }, {
      "firstName" : "D",
      "lastName" : "Dusser",
      "authorRank" : 5,
      "name" : "Dusser D",
      "referenceId" : "RGD:A126314"
    }, {
      "firstName" : "D",
      "lastName" : "Hubert",
      "authorRank" : 6,
      "name" : "Hubert D",
      "referenceId" : "RGD:A164950"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5147865"
    } ]
  }, {
    "primaryId" : "PMID:10228155",
    "title" : "An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kitagawa M, etal., EMBO J. 1999 May 4;18(9):2401-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:31:53.000-05:00",
    "volume" : "18",
    "pages" : "2401-10",
    "abstract" : "beta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen synthase kinase-3beta (GSK-3beta)/Axin kinase complex. Here we show that FWD1 (the mouse homologue of Slimb/betaTrCP), an F-box/WD40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, Axin, GSK-3beta and APC. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with FWD1. FWD1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels. In contrast, a dominant-negative mutant  form of FWD1 inhibited the ubiquitination process and stabilized beta-catenin. These results suggest that the Skp1/Cullin/F-box protein FWD1 (SCFFWD1)-ubiquitin ligase complex is involved in beta-catenin ubiquitination and that FWD1 serves as an intracellular receptor for phosphorylated beta-catenin. FWD1 also links the phosphorylation machinery to the ubiquitin-proteasome pathway to ensure prompt and efficient proteolysis of beta-catenin in response to external signals. SCFFWD1 may be critical for tumor development and suppression through regulation  of beta-catenin protein stability.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kitagawa",
      "authorRank" : 1,
      "name" : "Kitagawa M",
      "referenceId" : "RGD:A8528"
    }, {
      "firstName" : "S",
      "lastName" : "Hatakeyama",
      "authorRank" : 2,
      "name" : "Hatakeyama S",
      "referenceId" : "RGD:A7455"
    }, {
      "firstName" : "M",
      "lastName" : "Shirane",
      "authorRank" : 3,
      "name" : "Shirane",
      "referenceId" : "RGD:A183712"
    }, {
      "firstName" : "M",
      "lastName" : "Matsumoto",
      "authorRank" : 4,
      "name" : "Matsumoto M",
      "referenceId" : "RGD:A9603"
    }, {
      "firstName" : "N",
      "lastName" : "Ishida",
      "authorRank" : 5,
      "name" : "Ishida",
      "referenceId" : "RGD:A333986"
    }, {
      "firstName" : "K",
      "lastName" : "Hattori",
      "authorRank" : 6,
      "name" : "Hattori K",
      "referenceId" : "RGD:A32564"
    }, {
      "firstName" : "I",
      "lastName" : "Nakamichi",
      "authorRank" : 7,
      "name" : "Nakamichi I",
      "referenceId" : "RGD:A130080"
    }, {
      "firstName" : "A",
      "lastName" : "Kikuchi",
      "authorRank" : 8,
      "name" : "Kikuchi A",
      "referenceId" : "RGD:A5608"
    }, {
      "firstName" : "K",
      "lastName" : "Nakayama",
      "authorRank" : 9,
      "name" : "Nakayama",
      "referenceId" : "RGD:A401086"
    }, {
      "firstName" : "K",
      "lastName" : "Nakayama",
      "authorRank" : 10,
      "name" : "Nakayama",
      "referenceId" : "RGD:A401086"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553327"
    } ]
  }, {
    "primaryId" : "PMID:10228159",
    "title" : "The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Brehm A, etal., EMBO J. 1999 May 4;18(9):2449-58.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T13:30:23.000-05:00",
    "volume" : "18",
    "pages" : "2449-58",
    "abstract" : "E7 is the main transforming protein of human papilloma virus type 16 (HPV16) which is implicated in the formation of cervical cancer. The transforming activity of E7 has been attributed to its interaction with the retinoblastoma (Rb) tumour suppressor. However, Rb binding is not sufficient for transformation  by E7. Mutations within a zinc finger domain, which is dispensable for Rb binding, also abolish E7 transformation functions. Here we show that HPV16 E7 associates with histone deacetylase in vitro and in vivo, via its zinc finger domain. Using a genetic screen, we identify Mi2beta, a component of the recently  identified NURD histone deacetylase complex, as a protein that binds directly to  the E7 zinc finger. A zinc finger point mutant which is unable to bind Mi2beta and histone deacetylase but is still able to bind Rb fails to overcome cell cycle arrest in osteosarcoma cells. Our results suggest that the binding to a histone deacetylase complex is an important parameter for the growthpromoting activity of the human papilloma virus E7 protein. This provides the first indication that viral oncoproteins control cell proliferation by targeting deacetylation pathways.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Brehm",
      "authorRank" : 1,
      "name" : "Brehm A",
      "referenceId" : "RGD:A95054"
    }, {
      "firstName" : "SJ",
      "lastName" : "Nielsen",
      "authorRank" : 2,
      "name" : "Nielsen SJ",
      "referenceId" : "RGD:A56995"
    }, {
      "firstName" : "EA",
      "lastName" : "Miska",
      "authorRank" : 3,
      "name" : "Miska EA",
      "referenceId" : "RGD:A56997"
    }, {
      "firstName" : "DJ",
      "lastName" : "McCance",
      "authorRank" : 4,
      "name" : "McCance",
      "referenceId" : "RGD:A219348"
    }, {
      "firstName" : "JL",
      "lastName" : "Reid",
      "authorRank" : 5,
      "name" : "Reid",
      "referenceId" : "RGD:A219349"
    }, {
      "firstName" : "AJ",
      "lastName" : "Bannister",
      "authorRank" : 6,
      "name" : "Bannister",
      "referenceId" : "RGD:A219350"
    }, {
      "firstName" : "T",
      "lastName" : "Kouzarides",
      "authorRank" : 7,
      "name" : "Kouzarides T",
      "referenceId" : "RGD:A38190"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11052810"
    } ]
  }, {
    "primaryId" : "PMID:10228168",
    "title" : "A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Yagi R, etal., EMBO J. 1999 May 4;18(9):2551-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:24:48.000-05:00",
    "volume" : "18",
    "pages" : "2551-62",
    "abstract" : "A protein module called the WW domain recognizes and binds to a short oligopeptide called the PY motif, PPxY, to mediate protein-protein interactions.  The PY motif is present in the transcription activation domains of a wide range of transcription factors including c-Jun, AP-2, NF-E2, C/EBPalpha and PEBP2/CBF,  suggesting that it plays an important role in transcriptional activation. We show here that mutation of the PY motif in the subregion of the activation domain of the DNA-binding subunit of PEBP2, PEBP2alpha, abolishes its transactivation function. Using yeast two-hybrid screening, we demonstrate that Yes-associated protein (YAP) binds to the PY motif of PEBP2alpha through its WW domain. The C-terminal region of YAP fused to the DNA-binding domain of GAL4 showed transactivation as strong as that of GAL4-VP16. Exogenously expressed YAP conferred transcription-stimulating activity on the PY motif fused to the GAL4 DNA-binding domain as well as to native PEBP2alpha. The osteocalcin promoter was  stimulated by exogenous PEBP2alphaA and a dominant negative form of YAP strongly  inhibited this activity, suggesting YAP involvement in this promoter activity in  vivo. These results indicate that the PY motif is a novel transcription activation domain that functions by recruiting YAP as a strong transcription activator to target genes.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Yagi",
      "authorRank" : 1,
      "name" : "Yagi R",
      "referenceId" : "RGD:A72456"
    }, {
      "firstName" : "LF",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen",
      "referenceId" : "RGD:A233920"
    }, {
      "firstName" : "K",
      "lastName" : "Shigesada",
      "authorRank" : 3,
      "name" : "Shigesada",
      "referenceId" : "RGD:A233921"
    }, {
      "firstName" : "Y",
      "lastName" : "Murakami",
      "authorRank" : 4,
      "name" : "Murakami Y",
      "referenceId" : "RGD:A20597"
    }, {
      "firstName" : "Y",
      "lastName" : "Ito",
      "authorRank" : 5,
      "name" : "Ito Y",
      "referenceId" : "RGD:A13854"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11056360"
    } ]
  }, {
    "primaryId" : "PMID:10228294",
    "title" : "Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Cunningham CK, etal., J Pediatr. 1999 May;134(5):584-8. doi: 10.1016/s0022-3476(99)70245-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:46:36.000-05:00",
    "volume" : "134",
    "pages" : "584-8",
    "abstract" : "We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4(+) T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C K",
      "lastName" : "Cunningham",
      "authorRank" : 1,
      "name" : "Cunningham CK",
      "referenceId" : "RGD:A570831"
    }, {
      "firstName" : "C A",
      "lastName" : "Bonville",
      "authorRank" : 2,
      "name" : "Bonville CA",
      "referenceId" : "RGD:A570832"
    }, {
      "firstName" : "H D",
      "lastName" : "Ochs",
      "authorRank" : 3,
      "name" : "Ochs HD",
      "referenceId" : "RGD:A570833"
    }, {
      "firstName" : "K",
      "lastName" : "Seyama",
      "authorRank" : 4,
      "name" : "Seyama K",
      "referenceId" : "RGD:A137604"
    }, {
      "firstName" : "P A",
      "lastName" : "John",
      "authorRank" : 5,
      "name" : "John PA",
      "referenceId" : "RGD:A570834"
    }, {
      "firstName" : "H A",
      "lastName" : "Rotbart",
      "authorRank" : 6,
      "name" : "Rotbart HA",
      "referenceId" : "RGD:A570835"
    }, {
      "firstName" : "L B",
      "lastName" : "Weiner",
      "authorRank" : 7,
      "name" : "Weiner LB",
      "referenceId" : "RGD:A570836"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598115183"
    } ]
  }, {
    "primaryId" : "PMID:10229101",
    "title" : "Glucocorticoids prevent NF-kappaB activation by inhibiting the early release of platelet-activating factor in response to lipopolysaccharide.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Han SJ, etal., Eur J Immunol. 1999 Apr;29(4):1334-41. doi: 10.1002/(SICI)1521-4141(199904)29:04<1334::AID-IMMU1334>3.0.CO;2-0.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-06-01T10:09:08.000-05:00",
    "volume" : "29",
    "pages" : "1334-41",
    "abstract" : "Lipopolysaccharide (LPS) is a known inducer of numerous pro-inflammatory events including the production of platelet-activating factor (PAF). PAF released in response to LPS is a major contributor to the pathological events associated with endotoxemia. The present study demonstrates that dexmethasone (DEX) inhibited the LPS-induced early plasma PAF raise in a dose- and time-dependent manner. In addition, DEX prevented the subsequent PAF-mediated pathological phenomena such as anaphylactic shock-like symptoms, symptoms of disseminated intravascular coagulation and hemorrhage in renal medullae. DEX or the PAF antagonist BN 50739 significantly inhibited LPS-induced NF-kappaB activation. The inhibition of NF-kappaB activation by DEX was overcome by the injection of exogenous PAF. Administration of PAF or LPS resulted in a rapid loss of IkappaBalpha protein. The LPS-induced degradation of IkappaBalpha was prevented by pretreatment with BN 50739, suggesting that PAF is a critical intermediate in the LPS-triggered degradation of IkappaBalpha protein. DEX prevented the LPS-induced IkappaBalpha degradation, which was also reversed by exogenous PAF. Administration of DEX or BN 50739 caused an increase in cytoplasmic IkappaBalpha level. Our results indicate that DEX inhibits IkappaBalpha degradation and subsequent NF-kappaB activation through blocking the initial release of PAF.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S J",
      "lastName" : "Han",
      "authorRank" : 1,
      "name" : "Han SJ",
      "referenceId" : "RGD:A500037"
    }, {
      "firstName" : "J H",
      "lastName" : "Choi",
      "authorRank" : 2,
      "name" : "Choi JH",
      "referenceId" : "RGD:A500038"
    }, {
      "firstName" : "H M",
      "lastName" : "Ko",
      "authorRank" : 3,
      "name" : "Ko HM",
      "referenceId" : "RGD:A500039"
    }, {
      "firstName" : "H W",
      "lastName" : "Yang",
      "authorRank" : 4,
      "name" : "Yang HW",
      "referenceId" : "RGD:A438775"
    }, {
      "firstName" : "I W",
      "lastName" : "Choi",
      "authorRank" : 5,
      "name" : "Choi IW",
      "referenceId" : "RGD:A500040"
    }, {
      "firstName" : "H K",
      "lastName" : "Lee",
      "authorRank" : 6,
      "name" : "Lee HK",
      "referenceId" : "RGD:A472487"
    }, {
      "firstName" : "O H",
      "lastName" : "Lee",
      "authorRank" : 7,
      "name" : "Lee OH",
      "referenceId" : "RGD:A500041"
    }, {
      "firstName" : "S Y",
      "lastName" : "Im",
      "authorRank" : 8,
      "name" : "Im SY",
      "referenceId" : "RGD:A500042"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:126928139"
    } ]
  }, {
    "primaryId" : "PMID:10229132",
    "title" : "Cyclooxygenases-1 and -2 are differentially localized to microglia and endothelium in rat EAE and glioma.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Deininger MH and Schluesener HJ, J Neuroimmunol. 1999 Mar 1;95(1-2):202-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-02-22T14:24:22.000-06:00",
    "volume" : "95",
    "pages" : "202-8",
    "abstract" : "Cyclooxygenases (COX) mediate a wide variety of derangements observed during diseases of the brain. Their overexpression is involved in the mediation of inflammation, immunomodulation, blood flow, apoptosis and fever. Here, we have analyzed the localization of COX-1 and COX-2 in rat experimental autoimmune encephalomyelitis (EAE), C6 glioblastoma and 9L gliosarcoma by immunohistochemistry. In healthy brain, COX-1 was expressed in single macrophages/microglial cells. Neurons and few endothelial cells expressed COX-2.  In EAE, we observed an increase in COX-1+ macrophages/microglial cells and COX-2+ endothelial cells that was closely linked to disease progression. Both COX-1+ macrophages/microglial cells and COX-2+ endothelial cells were abundant in areas  of cellular infiltration. In C6 and 9L tumors, high numbers of COX-1+ macrophages/microglial cells and COX-2+ endothelial cells were found both in the  tumor parenchyma and in areas of infiltrative tumor growth. Double labeling experiments confirmed expression of COX-2 in vWF+ (endothelial) cells and COX-1 in ED1+ (macophages), OX6+ (MHC class II) and in W3/13+ (lymphoblasts) cells. These data provide further evidence that expression of COX-1 in macrophages/microglial cells and COX-2 in endothelial cells might represent important regulatory mechanisms in inflammatory processes associated with autoimmunity and neoplasia of the rat brain.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MH",
      "lastName" : "Deininger",
      "authorRank" : 1,
      "name" : "Deininger MH",
      "referenceId" : "RGD:A112524"
    }, {
      "firstName" : "HJ",
      "lastName" : "Schluesener",
      "authorRank" : 2,
      "name" : "Schluesener HJ",
      "referenceId" : "RGD:A15356"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5688250"
    } ]
  }, {
    "primaryId" : "PMID:10229225",
    "title" : "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Carmeliet P, etal., Nat Med. 1999 May;5(5):495-502.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-14T13:00:23.000-05:00",
    "volume" : "5",
    "pages" : "495-502",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Carmeliet",
      "authorRank" : 1,
      "name" : "Carmeliet P",
      "referenceId" : "RGD:A54297"
    }, {
      "firstName" : "YS",
      "lastName" : "Ng",
      "authorRank" : 2,
      "name" : "Ng YS",
      "referenceId" : "RGD:A63053"
    }, {
      "firstName" : "D",
      "lastName" : "Nuyens",
      "authorRank" : 3,
      "name" : "Nuyens D",
      "referenceId" : "RGD:A63127"
    }, {
      "firstName" : "G",
      "lastName" : "Theilmeier",
      "authorRank" : 4,
      "name" : "Theilmeier G",
      "referenceId" : "RGD:A63128"
    }, {
      "firstName" : "K",
      "lastName" : "Brusselmans",
      "authorRank" : 5,
      "name" : "Brusselmans K",
      "referenceId" : "RGD:A63129"
    }, {
      "firstName" : "I",
      "lastName" : "Cornelissen",
      "authorRank" : 6,
      "name" : "Cornelissen I",
      "referenceId" : "RGD:A63130"
    }, {
      "firstName" : "E",
      "lastName" : "Ehler",
      "authorRank" : 7,
      "name" : "Ehler E",
      "referenceId" : "RGD:A63131"
    }, {
      "firstName" : "VV",
      "lastName" : "Kakkar",
      "authorRank" : 8,
      "name" : "Kakkar VV",
      "referenceId" : "RGD:A63132"
    }, {
      "firstName" : "I",
      "lastName" : "Stalmans",
      "authorRank" : 9,
      "name" : "Stalmans I",
      "referenceId" : "RGD:A63133"
    }, {
      "firstName" : "V",
      "lastName" : "Mattot",
      "authorRank" : 10,
      "name" : "Mattot V",
      "referenceId" : "RGD:A63134"
    }, {
      "firstName" : "JC",
      "lastName" : "Perriard",
      "authorRank" : 11,
      "name" : "Perriard JC",
      "referenceId" : "RGD:A31127"
    }, {
      "firstName" : "M",
      "lastName" : "Dewerchin",
      "authorRank" : 12,
      "name" : "Dewerchin M",
      "referenceId" : "RGD:A63135"
    }, {
      "firstName" : "W",
      "lastName" : "Flameng",
      "authorRank" : 13,
      "name" : "Flameng W",
      "referenceId" : "RGD:A61280"
    }, {
      "firstName" : "A",
      "lastName" : "Nagy",
      "authorRank" : 14,
      "name" : "Nagy A",
      "referenceId" : "RGD:A46846"
    }, {
      "firstName" : "F",
      "lastName" : "Lupu",
      "authorRank" : 15,
      "name" : "Lupu F",
      "referenceId" : "RGD:A46025"
    }, {
      "firstName" : "L",
      "lastName" : "Moons",
      "authorRank" : 16,
      "name" : "Moons L",
      "referenceId" : "RGD:A54294"
    }, {
      "firstName" : "D",
      "lastName" : "Collen",
      "authorRank" : 17,
      "name" : "Collen D",
      "referenceId" : "RGD:A54295"
    }, {
      "firstName" : "PA",
      "lastName" : "D'Amore",
      "authorRank" : 18,
      "name" : "D'Amore PA",
      "referenceId" : "RGD:A63054"
    }, {
      "firstName" : "DT",
      "lastName" : "Shima",
      "authorRank" : 19,
      "name" : "Shima DT",
      "referenceId" : "RGD:A5187"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580578"
    } ]
  }, {
    "primaryId" : "PMID:10229662",
    "title" : "Structure, alternative splicing and chromosomal localization of the cystatin-related epididymal spermatogenic gene.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Cornwall GA, etal., Biochem J 1999 May 15;340 ( Pt 1):85-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T13:38:47.000-06:00",
    "volume" : "340 ( Pt 1)",
    "pages" : "85-93",
    "abstract" : "The cystatin superfamily of cysteine protease inhibitors consists of three major families, including the stefins, cystatins and kininogens. However, the recent identification of several genes that possess sequence similarity with the cystatins but have different gene or protein structures indicates that several new cystatin families or subgroups of families might exist. We previously identified the cystatin-related epididymal spermatogenic (Cres) gene, which is related to the family 2 cystatins but exhibits highly tissue-specific expression in the reproductive tract. In the studies presented here, an analysis of gene structure as well as chromosomal mapping studies suggest that the Cres gene might represent a new subgroup within the family 2 cystatins. Although the Cres gene possesses an additional exon encoding 5' untranslated sequences, its coding exons are similar in size to the three coding exons of the cystatin family 2 genes, and the Cres exon/intron splice junctions occur in identical locations as in the cystatin C gene. Furthermore, chromosomal mapping studies show that the Cres gene co-segregates with the cystatin C gene on mouse chromosome 2. Similar to the cystatin family 2 proteins, the Cres protein possesses the type A and B disulphide loops that are necessary for cystatin folding. Interestingly, Cres protein also possesses half of a type C disulphide loop. Although probably related to the cystatin genes, the Cres gene is distinct in that its promoter contains consensus motifs typical of regulated genes. Finally, reverse transcriptase-mediated PCR studies and the identification of new Cres cDNA clones indicate that the Cres mRNA is alternatively spliced, resulting in two Cres mRNAs that might be involved in the regulation of Cres function.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GA",
      "lastName" : "Cornwall",
      "authorRank" : 1,
      "name" : "Cornwall GA",
      "referenceId" : "RGD:A7282"
    }, {
      "firstName" : "N",
      "lastName" : "Hsia",
      "authorRank" : 2,
      "name" : "Hsia N",
      "referenceId" : "RGD:A28220"
    }, {
      "firstName" : "HG",
      "lastName" : "Sutton",
      "authorRank" : 3,
      "name" : "Sutton HG",
      "referenceId" : "RGD:A28221"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727561"
    } ]
  }, {
    "primaryId" : "PMID:10229677",
    "title" : "Cloning and expression of rat pancreatic beta-cell malonyl-CoA decarboxylase.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Voilley N, etal., Biochem J 1999 May 15;340 ( Pt 1):213-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:37:35.000-05:00",
    "volume" : "340 ( Pt 1)",
    "pages" : "213-7",
    "abstract" : "To gain insight into the function and regulation of malonyl-CoA decarboxylase (MCD) we have cloned rat MCD cDNA from a differentiated insulin-secreting pancreatic beta-cell-line cDNA library. The full-length cDNA sequence shows 69% identity with the cDNA cloned previously from the goose uropygial gland, and predicts a 492 amino acid protein of 54.7 kDa. The open reading frame contains an N-terminal mitochondrial targeting sequence and the C-terminal part of the enzyme ends with a peroxisomal (Ser-Lys-Leu) targeting motif. Since the sequence does not reveal hydrophobic domains, MCD is most likely expressed in the mitochondrial matrix and inside the peroxisomes. A second methionine residue, located 3' of the mitochondrial presequence, might be the first amino acid of a putative cytosolic MCD, since the nucleotide sequence around it fits fairly well with a consensus Kozak site for translation initiation. However, primer extension detects the presence of only one transcript initiating upstream of the first ATG, indicating that the major, if not exclusive, transcript expressed in the pancreatic beta-cell encodes MCD with its mitochondrial presequence. The sequence also shows multiple possible sites of phosphorylation by casein kinase II and protein kinase C. mRNA tissue-distribution analysis indicates a transcript of 2.2 kb, and that the MCD gene is expressed over a wide range of rat tissues. The distribution of the enzyme shows a broad range of activities from very low in the brain to elevated in the liver and heart. The results provide the foundations for further studies of the role of MCD in lipid metabolism and metabolic signalling in various tissues.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Voilley",
      "authorRank" : 1,
      "name" : "Voilley N",
      "referenceId" : "RGD:A20513"
    }, {
      "firstName" : "R",
      "lastName" : "Roduit",
      "authorRank" : 2,
      "name" : "Roduit R",
      "referenceId" : "RGD:A20514"
    }, {
      "firstName" : "R",
      "lastName" : "Vicaretti",
      "authorRank" : 3,
      "name" : "Vicaretti R",
      "referenceId" : "RGD:A20515"
    }, {
      "firstName" : "C",
      "lastName" : "Bonny",
      "authorRank" : 4,
      "name" : "Bonny C",
      "referenceId" : "RGD:A20150"
    }, {
      "firstName" : "G",
      "lastName" : "Waeber",
      "authorRank" : 5,
      "name" : "Waeber G",
      "referenceId" : "RGD:A20152"
    }, {
      "firstName" : "JR",
      "lastName" : "Dyck",
      "authorRank" : 6,
      "name" : "Dyck JR",
      "referenceId" : "RGD:A9458"
    }, {
      "firstName" : "GD",
      "lastName" : "Lopaschuk",
      "authorRank" : 7,
      "name" : "Lopaschuk GD",
      "referenceId" : "RGD:A11920"
    }, {
      "firstName" : "M",
      "lastName" : "Prentki",
      "authorRank" : 8,
      "name" : "Prentki M",
      "referenceId" : "RGD:A15607"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633311"
    } ]
  }, {
    "primaryId" : "PMID:10229687",
    "title" : "Secretion of glutathione S-transferase isoforms in the seminiferous tubular fluid, tissue distribution and sex steroid binding by rat GSTM1.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Mukherjee SB, etal., Biochem J 1999 May 15;340 ( Pt 1):309-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-03-08T10:57:05.000-06:00",
    "volume" : "340 ( Pt 1)",
    "pages" : "309-20",
    "abstract" : "The seminiferous tubular fluid (STF) provides the microenvironment necessary for spermatogenesis in the adluminal compartment of the seminiferous tubule (ST), primarily through secretions of the Sertoli cell. Earlier studies from this laboratory demonstrated the presence of glutathione S-transferase (GST) in STF collected from adult rat testis and in the spent media of ST cultures. This study describes the cellular source, isoform composition and possible function of GSTs in the STF. The major GST isoforms present in STF in vivo share extensive N-terminal similarity with rat GSTM1 (rGSTM1), rGSTM2, rGSTM3 and rGST-Alpha. Molecular masses of rGSTM2, rGSTM3 and rGST-Alpha from liver and testis sources were similar, unlike STF-GSTM1, which was larger by 325 Da than its liver counterpart. Peptide digest analysis profiles on reverse-phase HPLC between liver and STF isoforms were identical, and N-terminal sequences of selected peptides obtained by digestion of the various isoforms were closely similar. The above results confirmed close structural similarity between liver and STF-GST isoforms. Active synthesis and secretion of GSTs by the STs were evident from recovery of radiolabelled GST from the spent media of ST cultures. Analysis of secreted GST isoforms showed that GST-Alpha was not secreted by the STs in vitro, whereas there was an induction of GST-Pi secretion. Detection of immunostainable GST-Mu in Sertoli cells in vitro and during different stages of the seminiferous epithelium in vivo, coupled with the recovery of radiolabelled GST from Sertoli cell-culture media, provided evidence for Sertoli cells as secretors of GST. In addition, STF of 'Sertoli cell only' animals showed no change in the profile of GST isoform secretion, thereby confirming Sertoli cells as prime GST secretors. Non-recovery of [35S]methionine-labelled GSTs from germ cell culture supernatants, but their presence in germ cell lysates, confirm the ability of the germ cells to synthesize, but not to release, GSTs. Functionally, STF-GSTM1 appeared to serve as a steroid-binding protein by its ability to bind to testosterone and oestradiol, two important hormones in the ST that are essential for spermatogenesis, with binding constants of <9.8x10(-7) M for testosterone and 9x10(-6) M for oestradiol respectively.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SB",
      "lastName" : "Mukherjee",
      "authorRank" : 1,
      "name" : "Mukherjee SB",
      "referenceId" : "RGD:A8598"
    }, {
      "firstName" : "S",
      "lastName" : "Aravinda",
      "authorRank" : 2,
      "name" : "Aravinda S",
      "referenceId" : "RGD:A8599"
    }, {
      "firstName" : "B",
      "lastName" : "Gopalakrishnan",
      "authorRank" : 3,
      "name" : "Gopalakrishnan B",
      "referenceId" : "RGD:A8600"
    }, {
      "firstName" : "S",
      "lastName" : "Nagpal",
      "authorRank" : 4,
      "name" : "Nagpal S",
      "referenceId" : "RGD:A8601"
    }, {
      "firstName" : "DM",
      "lastName" : "Salunke",
      "authorRank" : 5,
      "name" : "Salunke DM",
      "referenceId" : "RGD:A8602"
    }, {
      "firstName" : "C",
      "lastName" : "Shaha",
      "authorRank" : 6,
      "name" : "Shaha C",
      "referenceId" : "RGD:A8603"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70307"
    } ]
  }, {
    "primaryId" : "PMID:10231031",
    "title" : "cDNA cloning and sequencing, gene expression, and immunolocalization of thrombomodulin in the Sprague-Dawley rat.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wang J, etal., DNA Res 1999 Feb 26;6(1):57-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:39:41.000-05:00",
    "volume" : "6",
    "pages" : "57-62",
    "abstract" : "Thrombomodulin (TM), in addition to its significance in the protein C anticoagulant pathway and cardiovascular diseases, has recently been shown to play important roles in normal embryonic development, several inflammatory conditions, as well as in tumor biology and in the pathogenesis of chronic radiation toxicity. We cloned and sequenced the cDNA encoding the complete TM protein from the Sprague-Dawley rat. The cDNA sequence consisted of a 78-bp 5' non-coding region and a 1731-bp open reading frame encoding 577 amino acids. Comparison of the deduced amino acid sequences showed Sprague-Dawley rat TM to be 87% homologous with mouse and 70.3% with human TM. In addition to the previously described highly conserved region in the lectin-like domain, another region was found which possessed significant homology among the species and may be involved in regulating cell surface expression of TM. Primers and fluorogenic probe for 5' exonuclease-based real time RT-PCR detection (TaqMan PCR) were constructed based on the cDNA sequence information and used to determine steady-state TM mRNA levels in lung, intestine, kidney, brain, and liver. The highest TM mRNA levels were found in lung and the lowest in liver. Immunohistochemistry confirmed that TM was mainly localized on the endothelium of blood vessels and lymphatics. The alveolar capillaries of lung showed the strongest immunoreactivity, whereas the endothelium of hepatic sinusoids and cerebral cortex were virtually negative.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang J",
      "referenceId" : "RGD:A404003"
    }, {
      "firstName" : "A",
      "lastName" : "Yao",
      "authorRank" : 2,
      "name" : "Yao A",
      "referenceId" : "RGD:A24182"
    }, {
      "firstName" : "JY",
      "lastName" : "Wang",
      "authorRank" : 3,
      "name" : "Wang JY",
      "referenceId" : "RGD:A8640"
    }, {
      "firstName" : "CC",
      "lastName" : "Sung",
      "authorRank" : 4,
      "name" : "Sung CC",
      "referenceId" : "RGD:A24183"
    }, {
      "firstName" : "LM",
      "lastName" : "Fink",
      "authorRank" : 5,
      "name" : "Fink LM",
      "referenceId" : "RGD:A24184"
    }, {
      "firstName" : "JW",
      "lastName" : "Hardin",
      "authorRank" : 6,
      "name" : "Hardin JW",
      "referenceId" : "RGD:A24185"
    }, {
      "firstName" : "M",
      "lastName" : "Hauer-Jensen",
      "authorRank" : 7,
      "name" : "Hauer-Jensen M",
      "referenceId" : "RGD:A24186"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634506"
    } ]
  }, {
    "primaryId" : "PMID:10231340",
    "title" : "Polymorphisms of the endothelial nitric oxide synthase gene - no consistent association with myocardial infarction in the ECTIM study.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Poirier O, etal., Eur J Clin Invest. 1999 Apr;29(4):284-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-07-19T13:21:20.000-05:00",
    "volume" : "29",
    "pages" : "284-90",
    "abstract" : "BACKGROUND: Our aim in the present study was to determine whether endothelial NO synthase gene (ecNOS) polymorphisms are associated with myocardial infarction (MI). METHODS: Forty chromosomes from patients with MI were screened for polymorphisms of the ecNOS gene using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis and sequencing. Ten polymorphisms were detected: three in the 5' flanking sequence at positions -1474, -924 and -788, two in coding sequences 774C --> T (silent) and G894 --> T (Glu-298 --> Asp) and five in introns 2, 11, 12, 22 and 23. Five hundred and thirty-one patients with MI and 610 control subjects recruited in France and Northern Ireland in the ECTIM study were genotyped for these polymorphisms. RESULTS: Glu-298 homozygotes were more frequent among patients with MI than in control subjects in the French population [OR = 1.47 (1.03-1.97), P < 0.009], but no such difference was observed in Northern Ireland. No significant difference between cases and control subjects was detected for the other polymorphisms. Our search for a possible association of the combination of ecNOS polymorphisms with MI by logistic regression analysis was also negative. CONCLUSIONS: We have explored a set of polymorphisms of the ecNOS gene in a large case-control study of MI and found that the polymorphisms were not consistently associated with MI.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Poirier",
      "authorRank" : 1,
      "name" : "Poirier O",
      "referenceId" : "RGD:A38080"
    }, {
      "firstName" : "C",
      "lastName" : "Mao",
      "authorRank" : 2,
      "name" : "Mao C",
      "referenceId" : "RGD:A46544"
    }, {
      "firstName" : "C",
      "lastName" : "Mallet",
      "authorRank" : 3,
      "name" : "Mallet C",
      "referenceId" : "RGD:A61257"
    }, {
      "firstName" : "V",
      "lastName" : "Nicaud",
      "authorRank" : 4,
      "name" : "Nicaud V",
      "referenceId" : "RGD:A38081"
    }, {
      "firstName" : "SM",
      "lastName" : "Herrmann",
      "authorRank" : 5,
      "name" : "Herrmann SM",
      "referenceId" : "RGD:A61901"
    }, {
      "firstName" : "A",
      "lastName" : "Evans",
      "authorRank" : 6,
      "name" : "Evans A",
      "referenceId" : "RGD:A59004"
    }, {
      "firstName" : "JB",
      "lastName" : "Ruidavets",
      "authorRank" : 7,
      "name" : "Ruidavets JB",
      "referenceId" : "RGD:A61902"
    }, {
      "firstName" : "D",
      "lastName" : "Arveiler",
      "authorRank" : 8,
      "name" : "Arveiler D",
      "referenceId" : "RGD:A59002"
    }, {
      "firstName" : "G",
      "lastName" : "Luc",
      "authorRank" : 9,
      "name" : "Luc G",
      "referenceId" : "RGD:A61537"
    }, {
      "firstName" : "L",
      "lastName" : "Tiret",
      "authorRank" : 10,
      "name" : "Tiret L",
      "referenceId" : "RGD:A60968"
    }, {
      "firstName" : "F",
      "lastName" : "Soubrier",
      "authorRank" : 11,
      "name" : "Soubrier F",
      "referenceId" : "RGD:A137193"
    }, {
      "firstName" : "F",
      "lastName" : "Cambien",
      "authorRank" : 12,
      "name" : "Cambien F",
      "referenceId" : "RGD:A59005"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580285"
    } ]
  }, {
    "primaryId" : "PMID:10231362",
    "title" : "Metabolic studies using recombinant escherichia coli cells producing rat mitochondrial CYP24 CYP24 can convert 1alpha,25-dihydroxyvitamin D3 to calcitroic acid.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Sakaki T, etal., Eur J Biochem. 1999 May;262(1):43-8. doi: 10.1046/j.1432-1327.1999.00375.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-10-19T07:18:14.000-05:00",
    "volume" : "262",
    "pages" : "43-8",
    "abstract" : "Previously we expressed rat 25-hydroxyvitamin D3 24-hydroxylase (CYP24) cDNA in Escherichia coli JM109 and showed that CYP24 catalyses three-step monooxygenation towards 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 [Akiyoshi-Shibata, M., Sakaki, T., Ohyama, Y., Noshiro, M., Okuda, K. & Yabusaki, Y. (1994) Eur. J. Biochem. 224, 335-343]. In this study, we demonstrate further oxidation by CYP24 including four- and six-step monooxygenation towards 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3, respectively. When the substrate 25-hydroxyvitamin D3 was added to a culture of recombinant E. coli, four metabolites, 24, 25-dihydroxyvitamin D3, 24-oxo-25-hydroxyvitamin D3, 24-oxo-23, 25-dihydroxyvitamin D3 and 24,25,26,27-tetranor-23-hydroxyvitamin D3 were observed. These results indicate that CYP24 catalyses at least four-step monooxygenation toward 25-hydroxyvitamin D3. Furthermore, in-vivo and in-vitro metabolic studies on 1alpha,25-dihydroxyvitamin D3 clearly indicated that CYP24 catalyses six-step monooxygenation to convert 1alpha,25-dihydroxyvitamin D3 into calcitroic acid which is known as a final metabolite of 1alpha,25-dihydroxyvitamin D3 for excretion in bile. These results strongly suggest that CYP24 is largely responsible for the metabolism of both 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Sakaki",
      "authorRank" : 1,
      "name" : "Sakaki T",
      "referenceId" : "RGD:A28584"
    }, {
      "firstName" : "N",
      "lastName" : "Sawada",
      "authorRank" : 2,
      "name" : "Sawada N",
      "referenceId" : "RGD:A21224"
    }, {
      "firstName" : "Y",
      "lastName" : "Nonaka",
      "authorRank" : 3,
      "name" : "Nonaka Y",
      "referenceId" : "RGD:A6549"
    }, {
      "firstName" : "Y",
      "lastName" : "Ohyama",
      "authorRank" : 4,
      "name" : "Ohyama Y",
      "referenceId" : "RGD:A19974"
    }, {
      "firstName" : "K",
      "lastName" : "Inouye",
      "authorRank" : 5,
      "name" : "Inouye K",
      "referenceId" : "RGD:A28585"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14995316"
    } ]
  }, {
    "primaryId" : "PMID:10231370",
    "title" : "Functional characterization of rat ecto-ATPase and ecto-ATP diphosphohydrolase after heterologous expression in CHO cells.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Heine P, etal., Eur J Biochem. 1999 May;262(1):102-7. doi: 10.1046/j.1432-1327.1999.00347.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-09-06T06:07:08.000-05:00",
    "volume" : "262",
    "pages" : "102-7",
    "abstract" : "The recently cloned ecto-ATPase and ecto-apyrase (ecto-ATP diphosphohydrolase) are plasma-membrane-bound enzymes responsible for the extracellular degradation of nucleoside 5'-triphosphates and nucleoside 5'-diphosphates. We expressed the rat-derived enzymes in CHO cells to compare their molecular and functional properties. Sequence-specific polyclonal antibodies differentiate between the two proteins and reveal identical molecular masses of 70-80 kDa. Both enzymes are stimulated by either Ca2+ or Mg2+ and reveal a broad substrate specificity towards purine and pyrimidine nucleotides. Whereas ecto-apyrase hydrolyzes nucleoside 5'-diphosphates at a rate approximately 20-30% lower than nucleoside-5'-triphosphates, ecto-ATPase hydrolyzes nucleoside-5'-diphosphates only to a marginal extent. The sensitivity of the two enzymes to the inhibitors of P2 receptors suramin, PPADS and reactive blue differs. Hydrolysis of ATP by ecto-ATPase leads to the accumulation in the medium of extracellular ADP as an intermediate product, whereas ecto-apyrase dephosphorylates ATP directly to AMP. Our results suggest that previous data describing extracellular hydrolysis of ATP by a variety of intact cellular systems with unidentified ecto-nucleotidases may be explained by the coexpression of ecto-ATPase and ecto-apyrase.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Heine",
      "authorRank" : 1,
      "name" : "Heine P",
      "referenceId" : "RGD:A5720"
    }, {
      "firstName" : "N",
      "lastName" : "Braun",
      "authorRank" : 2,
      "name" : "Braun N",
      "referenceId" : "RGD:A5719"
    }, {
      "firstName" : "A",
      "lastName" : "Heilbronn",
      "authorRank" : 3,
      "name" : "Heilbronn A",
      "referenceId" : "RGD:A610431"
    }, {
      "firstName" : "H",
      "lastName" : "Zimmermann",
      "authorRank" : 4,
      "name" : "Zimmermann H",
      "referenceId" : "RGD:A5722"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:626467868"
    } ]
  }, {
    "primaryId" : "PMID:10231554",
    "title" : "Differential regulation of the expression of nucleotide pyrophosphatases/phosphodiesterases in rat liver.",
    "datePublished" : "1999-05-06T00:00:00.000-05:00",
    "citation" : "Stefan C, etal., Biochim Biophys Acta. 1999 May 6;1450(1):45-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-07-17T15:36:33.000-05:00",
    "volume" : "1450",
    "pages" : "45-52",
    "abstract" : "We propose the name nucleotide pyrophosphatases/phosphodiesterases (NPP) for the enzymes that release nucleoside-5'-monophosphates from various pyrophosphate and phosphodiester bonds. Three structurally related mammalian NPPs are known, i.e. NPPalpha (autotaxin), NPPbeta (B10/gp130RB13-6) and NPPgamma (PC-1). We report here that these isozymes have a distinct tissue distribution in the rat but that they are all three expressed in hepatocytes. In FAO rat hepatoma cells only the level of NPPgamma was stimulated by TGF-beta1. In rat liver, the concentration of the transcripts of all three isozymes was found to increase manyfold during the first weeks after birth, but the increased expression of the NPPalpha mRNA was transient. The level of the NPP transcripts transiently decreased after hepatectomy, but NPPalpha mRNA was also lost after sham operation, which suggests that it may belong to the negative acute-phase proteins. The loss of the beta- and gamma-transcripts after hepatectomy was not due to a decreased NPP gene transcription or an increased turnover of the mature transcripts. However, hepatectomy also caused a similar loss of the nuclear pool of the NPPbeta and NPPgamma mRNAs. We conclude that a deficient processing and/or an increased turnover of the NPP pre-mRNAs underlies the hepatectomy-induced decrease of the beta- and gamma-transcripts. A similar loss of nuclear NPPgamma mRNA was also noted after treatment with cycloheximide, indicating that protein(s) with a high turnover control the stability and/or processing of the immature NPPgamma transcript.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Stefan",
      "authorRank" : 1,
      "name" : "Stefan C",
      "referenceId" : "RGD:A447343"
    }, {
      "firstName" : "R",
      "lastName" : "Gijsbers",
      "authorRank" : 2,
      "name" : "Gijsbers R",
      "referenceId" : "RGD:A447344"
    }, {
      "firstName" : "W",
      "lastName" : "Stalmans",
      "authorRank" : 3,
      "name" : "Stalmans W",
      "referenceId" : "RGD:A105000"
    }, {
      "firstName" : "M",
      "lastName" : "Bollen",
      "authorRank" : 4,
      "name" : "Bollen M",
      "referenceId" : "RGD:A104634"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13204733"
    } ]
  }, {
    "primaryId" : "PMID:10231557",
    "title" : "Cloning and characterization of a 22 kDa protein from rat adipocytes: a new member of the reticulon family.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Morris NJ, etal., Biochim Biophys Acta 1999 May 6;1450(1):68-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T16:59:04.000-05:00",
    "volume" : "1450",
    "pages" : "68-76",
    "abstract" : "In the course of our examination of proteins associated with the GLUT4-containing vesicles of rat adipocytes we have identified a new 22 kDa member of the family of endoplasmic reticulum (ER) proteins known as reticulons. The protein, which we refer to as vp20, was purified from a preparation of GLUT4-containing vesicles of rat adipocytes, and tryptic peptides were micro-sequenced. From this information a cDNA encoding a single open reading frame for a protein of 22 kDa was cloned. This protein is homologous to known members of the reticulon protein family. vp20 has two hydrophobic stretches of about 35 amino acids that could be membrane spanning domains and an ER retention motif at its carboxy-terminus. vp20 was most abundant in the high density microsome fraction of adipocytes, which is the fraction most enriched in ER. Only a small fraction of vp20 was present in the GLUT4 vesicle population, and that fraction appears to be due to ER vesicles that were non-specifically bound to the adsorbent. Analysis of tissue distribution of vp20 in rats revealed that it is concentrated in muscle, fat and the brain.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NJ",
      "lastName" : "Morris",
      "authorRank" : 1,
      "name" : "Morris NJ",
      "referenceId" : "RGD:A34385"
    }, {
      "firstName" : "SA",
      "lastName" : "Ross",
      "authorRank" : 2,
      "name" : "Ross SA",
      "referenceId" : "RGD:A124064"
    }, {
      "firstName" : "JM",
      "lastName" : "Neveu",
      "authorRank" : 3,
      "name" : "Neveu JM",
      "referenceId" : "RGD:A7530"
    }, {
      "firstName" : "WS",
      "lastName" : "Lane",
      "authorRank" : 4,
      "name" : "Lane WS",
      "referenceId" : "RGD:A104579"
    }, {
      "firstName" : "GE",
      "lastName" : "Lienhard",
      "authorRank" : 5,
      "name" : "Lienhard GE",
      "referenceId" : "RGD:A105126"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633934"
    } ]
  }, {
    "primaryId" : "PMID:10231870",
    "title" : "A heterozygous frameshift mutation in the endothelin-3 (EDN-3) gene in isolated Hirschsprung's disease.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Svensson PJ, etal., Pediatr Res. 1999 May;45(5 Pt 1):714-7. doi: 10.1203/00006450-199905010-00018.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:24:28.000-05:00",
    "volume" : "45",
    "pages" : "714-7",
    "abstract" : "Hirschsprung's disease, affecting one in 5000 live newborns, is the most common cause of neonatal intestinal obstruction. The obstruction or, later in life, constipation arises from the lack of enteric ganglia in the hindgut, thus resulting in poor coordination of peristalsis. Mutations in Hirschsprung patients have so far been reported in five genes associated in two different receptor-ligand systems, RET-GDNF/NTN and EDNRB-EDN-3, and an additional gene with yet unknown precise function, SOX10. We report the results of single-stranded conformation polymorphism screening of the endothelin-3 gene in a Swedish population-based material of 66 sporadic and nine familial Hirschsprung's disease cases. We have found a novel heterozygous mutation in exon 2, c.262insG, in a patient with sporadic short segment Hirschsprung's disease without any Waardenburg features. This frameshift results in a premature stop two codons further on. Because this stop is introduced 5' of the biologically active protein, this mutation can hence be predicted to result in haplo-insufficiency.",
    "issueName" : "5 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P J",
      "lastName" : "Svensson",
      "authorRank" : 1,
      "name" : "Svensson PJ",
      "referenceId" : "RGD:A591840"
    }, {
      "firstName" : "D",
      "lastName" : "Von Tell",
      "authorRank" : 2,
      "name" : "Von Tell D",
      "referenceId" : "RGD:A591841"
    }, {
      "firstName" : "M L",
      "lastName" : "Molander",
      "authorRank" : 3,
      "name" : "Molander ML",
      "referenceId" : "RGD:A591842"
    }, {
      "firstName" : "M",
      "lastName" : "Anvret",
      "authorRank" : 4,
      "name" : "Anvret M",
      "referenceId" : "RGD:A72787"
    }, {
      "firstName" : "A",
      "lastName" : "Nordenskjöld",
      "authorRank" : 5,
      "name" : "Nordenskjöld A",
      "referenceId" : "RGD:A591843"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118041"
    } ]
  }, {
    "primaryId" : "PMID:10232613",
    "title" : "Overexpression of sialomucin complex, a rat homologue of MUC4, inhibits tumor killing by lymphokine-activated killer cells.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Komatsu M, etal., Cancer Res. 1999 May 1;59(9):2229-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-02-24T17:44:58.000-06:00",
    "volume" : "59",
    "pages" : "2229-36",
    "abstract" : "Sialomucin complex (SMC) is a large heterodimeric glycoprotein complex composed of a mucin subunit ascites sialoglycoprotein-1 and a transmembrane subunit ascites sialoglycoprotein-2. It is a rat homologue of human mucin gene MUC4 and is abundantly expressed on the cell surface of highly metastatic ascites 13762 rat mammary adenocarcinoma cells. Because of their extended and rigid structures, mucin-type glycoproteins are suggested to have suppressing effects on cell-cell and cell-matrix interactions. During the metastatic process, these effects presumably cause tumor cell detachment from the primary tumor mass and facilitate escape of the tumor cells from immunosurveillance. Analyses of human breast cancer cells in solid tumors and tumor effusions showed that the more aggressive cells in effusions are stained with polyclonal antibodies against SMC more frequently than cells in solid tumors, suggesting a role for MUC4/SMC in tumor progression and metastasis. Previously, we generated recombinant cDNAs for SMC that vary in the number of mucin repeats to study the putative functions of SMC in tumor metastasis. These cDNAs were transfected into human cancer cell lines and tested for the effect of the expression of this gene. Here, using a tetracycline-responsive inducible expression system, we demonstrate that overexpression of SMC masks the surface antigens on target tumor cells and effectively suppresses tumor cell killing by cytotoxic lymphocytes. This effect results from the ability of SMC to block killer cell binding to the tumor cells and is dependent on both overexpression of the mucin and the number of mucin repeats in the expressed SMC. These results provide an explanation for the proposed role of SMC/MUC4 in tumor progression.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Komatsu",
      "authorRank" : 1,
      "name" : "Komatsu M",
      "referenceId" : "RGD:A10325"
    }, {
      "firstName" : "L",
      "lastName" : "Yee",
      "authorRank" : 2,
      "name" : "Yee L",
      "referenceId" : "RGD:A103980"
    }, {
      "firstName" : "KL",
      "lastName" : "Carraway",
      "authorRank" : 3,
      "name" : "Carraway KL",
      "referenceId" : "RGD:A20872"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303754"
    } ]
  }, {
    "primaryId" : "PMID:10233031",
    "title" : "Phenotypic variation in sensorimotor performance among eleven inbred rat strains.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Biesiadecki BJ, etal., Am J Physiol 1999 May;276(5 Pt 2):R1383-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-07-30T15:47:07.000-05:00",
    "volume" : "276",
    "pages" : "R1383-9",
    "abstract" : "As a first step toward identifying the genes that determine sensorimotor ability (motor coordination) we subjected 11 inbred strains of rats to three different tests for this trait. Rats were tested at 13 wk of age to determine how long they could remain on 1) a rotating cylinder as the velocity of rotation increased every 5 s (1-direction rotation test), 2) a rotating cylinder that reversed direction every 5 s and increased velocity every 10 s (2-direction rotation test), and 3) a platform that was tilted 2 degrees every 5 s from 22 to 47 degrees (tilt test). On all three tests, rats of the PVG strain demonstrated the greatest sensorimotor ability. In contrast, rats of the MNS strain were most often represented among the group of strains that demonstrated the lowest performance on all tests. Considering all three tests, there was a 3- to 13-fold range in sensorimotor performance between the highest and lowest strains. This large divergence between the highest and lowest strains provides a genetic model that can be used to identify intermediate phenotypes and quantitative trait loci that contribute to sensorimotor ability.",
    "issueName" : "5 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BJ",
      "lastName" : "Biesiadecki",
      "authorRank" : 1,
      "name" : "Biesiadecki BJ",
      "referenceId" : "RGD:A10739"
    }, {
      "firstName" : "PH",
      "lastName" : "Brand",
      "authorRank" : 2,
      "name" : "Brand PH",
      "referenceId" : "RGD:A10740"
    }, {
      "firstName" : "LG",
      "lastName" : "Koch",
      "authorRank" : 3,
      "name" : "Koch LG",
      "referenceId" : "RGD:A10571"
    }, {
      "firstName" : "PJ",
      "lastName" : "Metting",
      "authorRank" : 4,
      "name" : "Metting PJ",
      "referenceId" : "RGD:A10741"
    }, {
      "firstName" : "SL",
      "lastName" : "Britton",
      "authorRank" : 5,
      "name" : "Britton SL",
      "referenceId" : "RGD:A10742"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619608"
    } ]
  }, {
    "primaryId" : "PMID:10233227",
    "title" : "Skin fragility and hypohidrotic ectodermal dysplasia resulting from ablation of plakophilin 1.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "McGrath JA, etal., Br J Dermatol. 1999 Feb;140(2):297-307. doi: 10.1046/j.1365-2133.1999.02667.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:53:31.000-05:00",
    "volume" : "140",
    "pages" : "297-307",
    "abstract" : "We report a 2-year-old boy with an unusual autosomal recessively inherited skin disease comprising trauma-induced skin fragility and congenital ectodermal dysplasia affecting hair, nails and sweat glands. Skin biopsy showed widening of intercellular spaces between keratinocytes and ultrastructural findings of small, poorly formed desmosomes with reduced connections to the keratin filament cytoskeleton. Immunohistochemical analysis revealed a complete absence of staining for the accessory desmosomal plaque protein plakophilin 1 (PKP1; band 6 protein). The affected individual was a compound heterozygote for null mutations on both alleles of the PKP1 gene. Both mutations occurred within the amino terminus of PKP1, the domain which normally binds the cytoskeletal keratin filament network to the cell membrane. Apart from its localization within desmosomal plaques, PKP1 may also be present within the cytoplasm and nucleus and has putative roles in signal transduction and regulation of gene activity. The clinicopathological observations in this patient demonstrate the relevance of PKP1 to desmosome formation, cutaneous cell-cell adhesion and epidermal development and demonstrate the specific manifestations of human functional knockout mutations in this gene.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J A",
      "lastName" : "McGrath",
      "authorRank" : 1,
      "name" : "McGrath JA",
      "referenceId" : "RGD:A577748"
    }, {
      "firstName" : "P H",
      "lastName" : "Hoeger",
      "authorRank" : 2,
      "name" : "Hoeger PH",
      "referenceId" : "RGD:A585623"
    }, {
      "firstName" : "A M",
      "lastName" : "Christiano",
      "authorRank" : 3,
      "name" : "Christiano AM",
      "referenceId" : "RGD:A441980"
    }, {
      "firstName" : "J R",
      "lastName" : "McMillan",
      "authorRank" : 4,
      "name" : "McMillan JR",
      "referenceId" : "RGD:A581450"
    }, {
      "firstName" : "J E",
      "lastName" : "Mellerio",
      "authorRank" : 5,
      "name" : "Mellerio JE",
      "referenceId" : "RGD:A585624"
    }, {
      "firstName" : "G H",
      "lastName" : "Ashton",
      "authorRank" : 6,
      "name" : "Ashton GH",
      "referenceId" : "RGD:A585625"
    }, {
      "firstName" : "P J",
      "lastName" : "Dopping-Hepenstal",
      "authorRank" : 7,
      "name" : "Dopping-Hepenstal PJ",
      "referenceId" : "RGD:A585626"
    }, {
      "firstName" : "B D",
      "lastName" : "Lake",
      "authorRank" : 8,
      "name" : "Lake BD",
      "referenceId" : "RGD:A585627"
    }, {
      "firstName" : "I M",
      "lastName" : "Leigh",
      "authorRank" : 9,
      "name" : "Leigh IM",
      "referenceId" : "RGD:A438069"
    }, {
      "firstName" : "J I",
      "lastName" : "Harper",
      "authorRank" : 10,
      "name" : "Harper JI",
      "referenceId" : "RGD:A585628"
    }, {
      "firstName" : "R A",
      "lastName" : "Eady",
      "authorRank" : 11,
      "name" : "Eady RA",
      "referenceId" : "RGD:A438072"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598117138"
    } ]
  }, {
    "primaryId" : "PMID:10233365",
    "title" : "A case of complete adenylate kinase deficiency due to a nonsense mutation in AK-1 gene (Arg 107 --> Stop, CGA --> TGA) associated with chronic haemolytic anaemia.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Bianchi P, etal., Br J Haematol 1999 Apr;105(1):75-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T12:09:38.000-05:00",
    "volume" : "105",
    "pages" : "75-9",
    "abstract" : "Two siblings of Italian origin with mild chronic haemolytic anaemia, psychomotor impairment and undetectable adenylate kinase (AK) activity are reported. The other red cell enzyme activities were normal except for a slight decrease of PFK. 2,3-DPG levels were increased in both siblings, and AMP decreased in one only. The parents were not consanguineous and displayed intermediate AK activity. The sequence of complete erythrocyte AK-1 cDNA showed the presence of a nonsense homozygous mutation at codon 107 (CGA --> TGA, Arg --> Stop) in the siblings. The mutation results in a truncated protein of 107 amino acids in comparison with the 194 of the normal one. Moreover a 37 bp deletion in the first part of exon 6 (from nt 326 to nt 362 of the cDNA sequence) was detected in one allele; this deletion is not likely to further affect the enzyme structure, being localized after the stop codon. The new variant was named AK Fidenza, from the origin of the patients.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Bianchi",
      "authorRank" : 1,
      "name" : "Bianchi P",
      "referenceId" : "RGD:A44406"
    }, {
      "firstName" : "M",
      "lastName" : "Zappa",
      "authorRank" : 2,
      "name" : "Zappa M",
      "referenceId" : "RGD:A44407"
    }, {
      "firstName" : "E",
      "lastName" : "Bredi",
      "authorRank" : 3,
      "name" : "Bredi E",
      "referenceId" : "RGD:A44408"
    }, {
      "firstName" : "C",
      "lastName" : "Vercellati",
      "authorRank" : 4,
      "name" : "Vercellati C",
      "referenceId" : "RGD:A44409"
    }, {
      "firstName" : "G",
      "lastName" : "Pelissero",
      "authorRank" : 5,
      "name" : "Pelissero G",
      "referenceId" : "RGD:A44410"
    }, {
      "firstName" : "F",
      "lastName" : "Barraco",
      "authorRank" : 6,
      "name" : "Barraco F",
      "referenceId" : "RGD:A44411"
    }, {
      "firstName" : "A",
      "lastName" : "Zanella",
      "authorRank" : 7,
      "name" : "Zanella A",
      "referenceId" : "RGD:A44412"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300279"
    } ]
  }, {
    "primaryId" : "PMID:10233424",
    "title" : "The physiological response of thrombopoietin (c-Mpl ligand) to thrombocytopenia in the rat.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Yang C, etal., Br J Haematol. 1999 May;105(2):478-85.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-06-22T10:33:32.000-05:00",
    "volume" : "105",
    "pages" : "478-85",
    "abstract" : "It has been suggested that circulating levels of thrombopoietin (TPO) are determined primarily by platelet and megakaryocyte clearance of TPO and not by changes in hepatic TPO production. The experimental evidence accumulated so far to support this hypothesis is incomplete. We have therefore developed a new model of non-immune thrombocytopenia in the rat and used it to assess the relationship of TPO (c-mpl ligand) to the platelet mass. 14 d following the administration of busulphan, the platelet count reached a nadir of <2% of its initial value and remained at this level for up to 6 d. Circulating TPO was measured by two different bioassays which were sensitive enough to measure normal levels of TPO and levels rose from 106 +/- 29 pg/ml in animals with a normal platelet count to 2015 +/- 544 pg/ml in those with thrombocytopenia. These elevated levels of TPO were solely a response to the low platelet count since transfusion of a normal mass of platelets into the thrombocytopenic animals returned the TPO levels exactly to normal. The increase in TPO levels in thrombocytopenic animals was not due to increased TPO production since the thrombocytopenic animals did not show any increase in TPO mRNA in total or polysome-associated hepatic RNA. Rather, rat platelets were able to bind and stoichiometrically remove TPO from thrombocytopenic plasma via high-affinity receptors (Kd = 38 +/- 10 pm; 233 +/- 32 receptors/platelet). These results serve as a proof that the circulating level of TPO is determined not by alterations in TPO transcription or translation but by the ability of the platelet mass to bind and remove TPO from the circulation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang C",
      "referenceId" : "RGD:A39718"
    }, {
      "firstName" : "YC",
      "lastName" : "Li",
      "authorRank" : 2,
      "name" : "Li YC",
      "referenceId" : "RGD:A9112"
    }, {
      "firstName" : "DJ",
      "lastName" : "Kuter",
      "authorRank" : 3,
      "name" : "Kuter DJ",
      "referenceId" : "RGD:A21820"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580081"
    } ]
  }, {
    "primaryId" : "PMID:10233680",
    "title" : "An antiserum raised against the recombinant cytoplasmic tail of the human CD43 glycoprotein identifies CD43 in many mammalian species.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Szlanka T, etal., Immunology. 1999 Jan;96(1):74-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-03-25T13:03:53.000-05:00",
    "volume" : "96",
    "pages" : "74-82",
    "abstract" : "Leukosialin or CD43 is a heavily O-glycosylated transmembrane protein expressed on all cells of the haematopoietic cell lineage with the exception of red blood cells and mature B cells. This antigen has been identified in human, mouse and rat with monoclonal antibodies. Although orthologues of many human and rodent leucocyte cell surface antigens have been described in recent years, CD43, despite its abundance on human and rodent cells, remained uncharacterized in other vertebrate species. The comparison of CD43 amino acid sequences from human, mouse and rat indicated a high level of homology in the cytoplasmic domain. A serum, (p.aCD43cp) raised against the recombinant cytoplasmic tail of the human CD43, was shown not only to recognize human CD43, but it bound to putative CD43 orthologues in many mammalian species. CD43 was found to be expressed in the same leucocyte subpopulations and circumstantial evidence suggested that CD43 is also regulated similarly during leucocyte ontogeny in all species investigated. As CD43+ cells were readily observed in fixed tissues, the p.aCD43cp serum may be used as a reliable reagent for the verification of the haematopoietic origin of infiltrations and, used together with other reagents, for the serological characterization of normal and pathological lymphoid tissues and lymphoid infiltrations in experimental work and in animal disease.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Szlanka",
      "authorRank" : 1,
      "name" : "Szlanka T",
      "referenceId" : "RGD:A105102"
    }, {
      "firstName" : "GK",
      "lastName" : "Toth",
      "authorRank" : 2,
      "name" : "Toth GK",
      "referenceId" : "RGD:A105103"
    }, {
      "firstName" : "I",
      "lastName" : "Ocsovszki",
      "authorRank" : 3,
      "name" : "Ocsovszki I",
      "referenceId" : "RGD:A105104"
    }, {
      "firstName" : "G",
      "lastName" : "Keresztes",
      "authorRank" : 4,
      "name" : "Keresztes G",
      "referenceId" : "RGD:A105105"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306197"
    } ]
  }, {
    "primaryId" : "PMID:10234022",
    "title" : "Change in the shape of dendritic spines caused by overexpression of drebrin in cultured cortical neurons.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Hayashi K and Shirao T, J Neurosci. 1999 May 15;19(10):3918-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-28T13:37:12.000-05:00",
    "volume" : "19",
    "pages" : "3918-25",
    "abstract" : "Dendritic spines are known to be extremely motile, providing a structural mechanism for synaptic plasticity. Actin filaments are thought to be responsible  for the changes in the shape of spines. We tested our hypothesis that drebrin, an actin-binding protein, is a regulator of spine shape. In high-density long-term primary cultures of rat cerebral cortex neurons, drebrin was colocalized with actin filaments at spines. We introduced drebrin tagged with green fluorescent protein (GFP) into these neurons to test the ability of exogenous drebrin to localize at spines and the effect of overexpression of drebrin on spine shape. We observed that exogenous drebrin indeed accumulated in spines. But when the actin-binding domain of drebrin was deleted, the protein was distributed in both  spines and dendritic shafts, indicating that accumulation of drebrin in the spines required its actin-binding activity. Statistical analysis of the lengths of spines as determined from confocal laser microscopic images revealed that the  spines were significantly longer in GFP-drebrin-expressing neurons than in GFP-expressing neurons. The longer spines labeled with GFP-drebrin were demonstrated to be postsynaptic by double labeling of the presynaptic terminals with antibody against synaptophysin. These results directly indicate that drebrin binds to actin filaments at dendritic spines and alters spine shape.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Hayashi",
      "authorRank" : 1,
      "name" : "Hayashi",
      "referenceId" : "RGD:A403057"
    }, {
      "firstName" : "T",
      "lastName" : "Shirao",
      "authorRank" : 2,
      "name" : "Shirao T",
      "referenceId" : "RGD:A9874"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10395287"
    } ]
  }, {
    "primaryId" : "PMID:10234023",
    "title" : "Postsynaptic density-93 interacts with the delta2 glutamate receptor subunit at parallel fiber synapses.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Roche KW, etal., J Neurosci. 1999 May 15;19(10):3926-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:17:57.000-05:00",
    "volume" : "19",
    "pages" : "3926-34",
    "abstract" : "The glutamate receptor subunit delta2 has a unique distribution at the parallel fiber-Purkinje cell synapse of the cerebellum, which is developmentally regulated such that delta2 occurs at both parallel fiber synapses and climbing fiber synapses early in development but is restricted to parallel fiber synapses in adult animals. To identify proteins that might be involved in the trafficking or  docking of delta2 receptors, we screened a yeast two-hybrid library with the cytosolic C terminus of delta2 and isolated a member of the postsynaptic density  (PSD)-95 family of proteins, which are known to interact with the extreme C termini of NMDA receptors. We find that delta2 binds specifically to PSD-93, which is enriched in Purkinje cells. In addition, PSD-93 clusters delta2 when they are coexpressed in heterologous cells, and clustering is disrupted by point  mutations of delta2 that disrupt the delta2-PSD-93 interaction. Ultrastructural localization of PSD-93 and delta2 shows they are colocalized at parallel fiber synapses; however, PSD-93 also is present at climbing fiber synapses of the adult rat, where delta2 is not found, indicating that the presence of PSD-93 alone is not sufficient for determining the synaptic expression of delta2.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KW",
      "lastName" : "Roche",
      "authorRank" : 1,
      "name" : "Roche KW",
      "referenceId" : "RGD:A8668"
    }, {
      "firstName" : "CD",
      "lastName" : "Ly",
      "authorRank" : 2,
      "name" : "Ly CD",
      "referenceId" : "RGD:A8667"
    }, {
      "firstName" : "RS",
      "lastName" : "Petralia",
      "authorRank" : 3,
      "name" : "Petralia RS",
      "referenceId" : "RGD:A11936"
    }, {
      "firstName" : "YX",
      "lastName" : "Wang",
      "authorRank" : 4,
      "name" : "Wang YX",
      "referenceId" : "RGD:A40710"
    }, {
      "firstName" : "AW",
      "lastName" : "McGee",
      "authorRank" : 5,
      "name" : "McGee",
      "referenceId" : "RGD:A183576"
    }, {
      "firstName" : "DS",
      "lastName" : "Bredt",
      "authorRank" : 6,
      "name" : "Bredt",
      "referenceId" : "RGD:A405890"
    }, {
      "firstName" : "RJ",
      "lastName" : "Wenthold",
      "authorRank" : 7,
      "name" : "Wenthold RJ",
      "referenceId" : "RGD:A4782"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041018"
    } ]
  }, {
    "primaryId" : "PMID:10234505",
    "title" : "Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Rugg EL, etal., Eur J Hum Genet. 1999 Apr;7(3):293-300. doi: 10.1038/sj.ejhg.5200292.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:18:33.000-05:00",
    "volume" : "7",
    "pages" : "293-300",
    "abstract" : "Epidermolysis bullosa simplex (EBS) arises from mutations within the keratin 5 and 14 (K5 and K14) genes which alter the integrity of basal keratinocytes cytoskeleton. The majority of these defects are missense mutations in the rod domain, whose locations influence the disease severity. We investigated a large family dominantly affected with the Dowling-Meara form of EBS (EBS-DM). Sequencing of amplified and cloned K5 cDNA from cultured keratinocytes revealed a 66 nucleotide deletion in one allele corresponding to the last 22 amino acid residues encoded by exon 1 (Val164 to Lys185). Sequencing of amplified genomic DNA spanning the mutant region revealed a heterozygous G-to-A transition at +1 position of the consensus GT donor splice site of intron 1 of K5. This mutation leads to the use of an exonic GT cryptic donor splice site, located 66 nucleotides upstream from the normal donor splice site of intron 1. The corresponding peptide deletion includes the last five amino acids of the H1 head domain and the first 17 amino acids of the conserved amino terminal end of the 1A rod domain, including the first two heptad repeats and the helix initiation peptide. The shortened polypeptide is expressed in cultured keratinocytes at levels which are comparable to the normal K5 protein. This is the first splice site mutation to be reported as a cause of EBS-DM. Owing to the functional importance of the removed region, our data strongly suggest that shortened keratin polypeptide can impair keratin filament assembly in a dominant manner and causes EBS-DM.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E L",
      "lastName" : "Rugg",
      "authorRank" : 1,
      "name" : "Rugg EL",
      "referenceId" : "RGD:A563196"
    }, {
      "firstName" : "M O",
      "lastName" : "Rachet-Préhu",
      "authorRank" : 2,
      "name" : "Rachet-Préhu MO",
      "referenceId" : "RGD:A563197"
    }, {
      "firstName" : "A",
      "lastName" : "Rochat",
      "authorRank" : 3,
      "name" : "Rochat A",
      "referenceId" : "RGD:A72488"
    }, {
      "firstName" : "Y",
      "lastName" : "Barrandon",
      "authorRank" : 4,
      "name" : "Barrandon Y",
      "referenceId" : "RGD:A24788"
    }, {
      "firstName" : "M",
      "lastName" : "Goossens",
      "authorRank" : 5,
      "name" : "Goossens M",
      "referenceId" : "RGD:A164969"
    }, {
      "firstName" : "E B",
      "lastName" : "Lane",
      "authorRank" : 6,
      "name" : "Lane EB",
      "referenceId" : "RGD:A563198"
    }, {
      "firstName" : "A",
      "lastName" : "Hovnanian",
      "authorRank" : 7,
      "name" : "Hovnanian A",
      "referenceId" : "RGD:A36214"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598114356"
    } ]
  }, {
    "primaryId" : "PMID:10234611",
    "title" : "Molecular heterogeneity of Krabbe disease.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Fu L, etal., J Inherit Metab Dis. 1999 Apr;22(2):155-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:19:04.000-05:00",
    "volume" : "22",
    "pages" : "155-62",
    "abstract" : "Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder that affects both the central and peripheral nervous system due to an enzymatic defect of galactocerebrosidase (GALC). Following its cloning, many mutations in the galactocerebrosidase gene have been reported, but  the correlation between phenotype and genotype was not clear in many cases. In this study we further investigated the molecular defects in another 10 patients (6 Japanese and 4 non-Japanese), using cultured skin fibroblasts, and found 10 mutations, of which 8 were novel, including a nonsense mutation (W647X) and 7 missense mutations (G43R, S52F, T262I, Y319C. W410G, R515H, T652R) in the coding  region. Some phenotype-specific mutations were found but the other mutations were private. Mutations reported so far have been distributed over the whole GALC gene and it is difficult to speculate on functional domains of the GALC protein and phenotypically specific regions.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Fu",
      "authorRank" : 1,
      "name" : "Fu L",
      "referenceId" : "RGD:A23013"
    }, {
      "firstName" : "K",
      "lastName" : "Inui",
      "authorRank" : 2,
      "name" : "Inui",
      "referenceId" : "RGD:A387003"
    }, {
      "firstName" : "T",
      "lastName" : "Nishigaki",
      "authorRank" : 3,
      "name" : "Nishigaki T",
      "referenceId" : "RGD:A55877"
    }, {
      "firstName" : "N",
      "lastName" : "Tatsumi",
      "authorRank" : 4,
      "name" : "Tatsumi N",
      "referenceId" : "RGD:A55876"
    }, {
      "firstName" : "H",
      "lastName" : "Tsukamoto",
      "authorRank" : 5,
      "name" : "Tsukamoto H",
      "referenceId" : "RGD:A12791"
    }, {
      "firstName" : "C",
      "lastName" : "Kokubu",
      "authorRank" : 6,
      "name" : "Kokubu",
      "referenceId" : "RGD:A267337"
    }, {
      "firstName" : "T",
      "lastName" : "Muramatsu",
      "authorRank" : 7,
      "name" : "Muramatsu T",
      "referenceId" : "RGD:A22404"
    }, {
      "firstName" : "S",
      "lastName" : "Okada",
      "authorRank" : 8,
      "name" : "Okada",
      "referenceId" : "RGD:A413891"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067194"
    } ]
  }, {
    "primaryId" : "PMID:10235258",
    "title" : "Co-carcinogenic effect of beta-carotene.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Paolini M, etal., Nature 1999 Apr 29;398(6730):760-1.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-04T13:16:12.000-06:00",
    "volume" : "398",
    "pages" : "760-1",
    "issueName" : "6730",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Paolini",
      "authorRank" : 1,
      "name" : "Paolini M",
      "referenceId" : "RGD:A38534"
    }, {
      "firstName" : "G",
      "lastName" : "Cantelli-Forti",
      "authorRank" : 2,
      "name" : "Cantelli-Forti G",
      "referenceId" : "RGD:A38535"
    }, {
      "firstName" : "P",
      "lastName" : "Perocco",
      "authorRank" : 3,
      "name" : "Perocco P",
      "referenceId" : "RGD:A38536"
    }, {
      "firstName" : "GF",
      "lastName" : "Pedulli",
      "authorRank" : 4,
      "name" : "Pedulli GF",
      "referenceId" : "RGD:A38537"
    }, {
      "firstName" : "SZ",
      "lastName" : "Abdel-Rahman",
      "authorRank" : 5,
      "name" : "Abdel-Rahman SZ",
      "referenceId" : "RGD:A38538"
    }, {
      "firstName" : "MS",
      "lastName" : "Legator",
      "authorRank" : 6,
      "name" : "Legator MS",
      "referenceId" : "RGD:A38539"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734994"
    } ]
  }, {
    "primaryId" : "PMID:10235270",
    "title" : "Genetic association between alcohol withdrawal symptoms and polymorphism of CCK gene promoter.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Okubo T, etal., Alcohol Clin Exp Res. 1999 Apr;23(4 Suppl):11S-12S. doi: 10.1111/j.1530-0277.1999.tb04525.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-07-17T09:06:18.000-05:00",
    "volume" : "23",
    "pages" : "11S-12S",
    "abstract" : "In the central nervous system, cholecystokinin (CCK) is an important neurotransmitter that gives the influences on firings, anxiety, notiception, and dopamine-related behavior. CCK co-exists in the dopaminergic neurons, interacting with dopamine. In this study, we examined the genetic variant -45 C to T substitution of the CCK gene promoter region among 195 healthy Japanese and 174 patients with alcohol withdrawal syndrome (52 delirium tremens, 39 hallucinosis, 20 seizures, and 92 lack of these symptoms) by using polymerase chain reaction-based single-strand conformational polymorphism analysis. Patients with delirium tremens showed a significantly higher frequency of the variant, compared with the controls (chi2 = 4.91, p < 0.03), but patients with other symptoms showed no difference. These data suggested that the individuals possessing allelic mutation (-45T) in the promoter region of the CCK gene might be susceptible to delirium tremens caused by alcohol abuse.",
    "issueName" : "4 Suppl",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Okubo",
      "authorRank" : 1,
      "name" : "Okubo T",
      "referenceId" : "RGD:A542716"
    }, {
      "firstName" : "S",
      "lastName" : "Harada",
      "authorRank" : 2,
      "name" : "Harada S",
      "referenceId" : "RGD:A49339"
    }, {
      "firstName" : "S",
      "lastName" : "Higuchi",
      "authorRank" : 3,
      "name" : "Higuchi S",
      "referenceId" : "RGD:A161713"
    }, {
      "firstName" : "S",
      "lastName" : "Matsushita",
      "authorRank" : 4,
      "name" : "Matsushita S",
      "referenceId" : "RGD:A48404"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:406351024"
    } ]
  }, {
    "primaryId" : "PMID:10235295",
    "title" : "Allele dose analysis in recombinant inbred strains: a tool for multiple phenotype analysis with implications for quantitative trait loci mapping.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Markel PD and Erwin VG, Alcohol Clin Exp Res 1999 Apr;23(4):605-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-07-02T15:38:34.000-05:00",
    "volume" : "23",
    "pages" : "605-10",
    "abstract" : "A considerable investment in genetic mapping is necessary to confirm linkages of quantitative trait loci for complex traits such as ethanol sensitivity, a significant predictor of alcoholism. Before embarking on such intensive mapping efforts in large intercrosses, we suggest an approach based on genetic marker data in recombinant strains that yield a rationale for selecting a battery of related phenotypes for confirmation studies of quantitative trait loci action. Using this approach with selected strains of mice, we retrospectively consider the relationship between ethanol sensitivity and neurotensin levels in several mammalian brain regions.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PD",
      "lastName" : "Markel",
      "authorRank" : 1,
      "name" : "Markel PD",
      "referenceId" : "RGD:A10511"
    }, {
      "firstName" : "VG",
      "lastName" : "Erwin",
      "authorRank" : 2,
      "name" : "Erwin VG",
      "referenceId" : "RGD:A10512"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70869"
    } ]
  }, {
    "primaryId" : "PMID:10235303",
    "title" : "Effect of acute alcohol treatment on the release of ACTH, corticosterone, and pro-inflammatory cytokines in response to endotoxin.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Rivier C, Alcohol Clin Exp Res. 1999 Apr;23(4):673-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-28T09:56:21.000-05:00",
    "volume" : "23",
    "pages" : "673-82",
    "abstract" : "This study investigated the effects of acute alcohol pretreatment on endotoxin lipopolysaccharide (LPS)-induced release of ACTH, corticosterone, and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in plasma and at various tissues sites. Specifically, we wanted to determine whether alcohol pretreatment would alter the ACTH, corticosterone, and cytokine responses to LPS, and whether the alcohol-induced changes in ACTH/corticosterone secretory rates of endotoxemic rats were accompanied by similar changes in cytokine production. Alcohol, 3.0 g/kg, intragastric (i.g.), was administered 3 hr before LPS treatment [1.0 or 5.0 microg/kg, intravenous (i.v.)], and ACTH, corticosterone, and cytokines levels were measured over a 4 hr post LPS treatment. In intact rats, the alcohol-induced plasma ACTH and corticosterone responses had returned to basal levels by the time of LPS injection, and alcohol pretreatment increased the corticosterone but not the ACTH response after LPS treatment. In contrast, in adrenalectomized corticosterone-replaced animals, the alcohol-induced ACTH response was still elevated at the time of LPS injection. However, the overall ACTH response of rats pretreated with the vehicle or alcohol was statistically similar. As expected, LPS also significantly stimulated both TNF-alpha and IL-6 release into the general circulation. The IL-6, but not the TNF-alpha, response was inhibited by alcohol pretreatment in intact rats, a phenomenon that was not present in adrenalectomized animals. Finally, we showed that LPS also augmented the TNF-alpha and/or IL-6 content of the pituitary, adrenal glands, and spleen, and that these responses were not altered by alcohol pretreatment. On the basis of these results, we concluded that acute alcohol treatment increased LPS-induced corticosterone response, while it blunted the IL-6 response. LPS also significantly elevated pituitary, adrenal, and splenic contents of TNF-alpha and IL-6, and alcohol did not influence these changes.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Rivier",
      "authorRank" : 1,
      "name" : "Rivier C",
      "referenceId" : "RGD:A8164"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598148179"
    } ]
  }, {
    "primaryId" : "PMID:10235436",
    "title" : "Haemostatic abnormalities, cardiac involvement and serum tumor necrosis factor levels in X-linked dystrophic patients.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Porreca E, etal., Thromb Haemost. 1999 Apr;81(4):543-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-05T18:32:02.000-06:00",
    "volume" : "81",
    "pages" : "543-6",
    "abstract" : "Left ventricular thrombosis and systemic emboli have been demonstrated to complicate cardiomyopathy in Duchenne and Becker muscular dystrophy (DMD, BMD). We investigated plasma levels of prothrombin fragment 1+2 (F1+2). thrombin-antithrombin III complex (TAT) and circulating levels of tumor necrosis  factor-alpha (TNF-alpha), a procoagulant cytokine that has been shown to be elevated in patients with depressed cardiac function, in 20 patients with DMD and 12 patients with BMD as compared with 30 age-matched control subjects. Significantly elevated levels of F1+2 (DMD: 1.4+/-0.8 nmol/l; BMD: 1.8+/-0.8 nmol/l vs. controls: 0.7+/-0.2 nmol/l, p <0.01 and p <0.001, respectively), TAT complexes (DMD: 4.7+/-2.7 microg/l, BMD: 5+/-2.3 microg/l vs. controls: 1.6+/-0.5 microg/l, p <0.001) and TNF-alpha (54+/-9 vs. 25+/-7 pg/ml, p <0.001) were observed in patients with the dystrophic disease compared to control subjects. A  significantly negative correlation was also found between F1+2 and TAT complexes  and left ventricular ejection fraction (r = -0.65, p <0.0001; r = -0.80, p < 0.0001, respectively) and a positive correlation between F1+2 and TAT complexes and serum TNF-alpha levels (r = 0.67, p <0.0001; r = 0.70, p <0.0001, respectively). Our results indicate a hypercoagulable state in X-linked dystrophic patients. A possible relationship between haemostatic activation, left ventricular dysfunction and TNF-alpha system upregulation may be suggested.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Porreca",
      "authorRank" : 1,
      "name" : "Porreca",
      "referenceId" : "RGD:A209846"
    }, {
      "firstName" : "MD",
      "lastName" : "Guglielmi",
      "authorRank" : 2,
      "name" : "Guglielmi",
      "referenceId" : "RGD:A209847"
    }, {
      "firstName" : "A",
      "lastName" : "Uncini",
      "authorRank" : 3,
      "name" : "Uncini",
      "referenceId" : "RGD:A209848"
    }, {
      "firstName" : "P",
      "lastName" : "Di Gregorio",
      "authorRank" : 4,
      "name" : "Di Gregorio",
      "referenceId" : "RGD:A209849"
    }, {
      "firstName" : "A",
      "lastName" : "Angelini",
      "authorRank" : 5,
      "name" : "Angelini",
      "referenceId" : "RGD:A209850"
    }, {
      "firstName" : "C",
      "lastName" : "Di Febbo",
      "authorRank" : 6,
      "name" : "Di Febbo",
      "referenceId" : "RGD:A209851"
    }, {
      "firstName" : "SD",
      "lastName" : "Pierdomenico",
      "authorRank" : 7,
      "name" : "Pierdomenico",
      "referenceId" : "RGD:A209852"
    }, {
      "firstName" : "G",
      "lastName" : "Baccante",
      "authorRank" : 8,
      "name" : "Baccante",
      "referenceId" : "RGD:A209853"
    }, {
      "firstName" : "F",
      "lastName" : "Cuccurullo",
      "authorRank" : 9,
      "name" : "Cuccurullo F",
      "referenceId" : "RGD:A66162"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10449464"
    } ]
  }, {
    "primaryId" : "PMID:10235552",
    "title" : "Retinal ischemia-reperfusion injury attenuated by blocking of adhesion molecules  of vascular endothelium.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Tsujikawa A, etal., Invest Ophthalmol Vis Sci. 1999 May;40(6):1183-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-19T18:22:20.000-06:00",
    "volume" : "40",
    "pages" : "1183-90",
    "abstract" : "PURPOSE: To evaluate quantitatively the effects of blocking of adhesion molecules (P-selectin or intercellular adhesion molecule-1 [ICAM-1]) on leukocyte dynamics  in the retinal microcirculation in vivo during ischemia-reperfusion injury and the therapeutic efficacy of the blocking of adhesion molecules on retinal ischemia-reperfusion injury. METHODS: Retinal ischemia was induced for 60 minutes in anesthetized pigmented rats by temporary ligation of the optic nerve. P-selectin or ICAM-1 monoclonal antibody (mAb) was administered at 5 minutes before reperfusion. At 4, 12, and 24 hours after onset of reperfusion, leukocyte  behavior in the retinal microcirculation was evaluated in vivo with acridine orange digital fluorography. After 7 or 14 days of reperfusion, retinal damage was evaluated histologically. RESULTS: P-selectin mAb significantly inhibited leukocyte rolling along the major retinal veins after reperfusion. Subsequently,  the number of accumulated leukocytes decreased in the P-selectin-inhibited rats.  ICAM-1 mAb also inhibited leukocyte accumulation during the reperfusion period in a more substantial manner than P-selectin mAb. Histologic examination demonstrated the protective effect of the blocking of P-selectin or ICAM-1. In accordance with a reduction in leukocyte accumulation, the protective effect of mAb on retinal ischemia-reperfusion injury was more substantial in ICAM-1-inhibited rats. CONCLUSIONS: The present study demonstrates the inhibitory effect of P-selectin and ICAM-1 mAb on leukocyte accumulation and subsequent tissue injury during retinal ischemia-reperfusion injury.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Tsujikawa",
      "authorRank" : 1,
      "name" : "Tsujikawa A",
      "referenceId" : "RGD:A113520"
    }, {
      "firstName" : "Y",
      "lastName" : "Ogura",
      "authorRank" : 2,
      "name" : "Ogura Y",
      "referenceId" : "RGD:A43496"
    }, {
      "firstName" : "N",
      "lastName" : "Hiroshiba",
      "authorRank" : 3,
      "name" : "Hiroshiba",
      "referenceId" : "RGD:A179723"
    }, {
      "firstName" : "K",
      "lastName" : "Miyamoto",
      "authorRank" : 4,
      "name" : "Miyamoto K",
      "referenceId" : "RGD:A11191"
    }, {
      "firstName" : "J",
      "lastName" : "Kiryu",
      "authorRank" : 5,
      "name" : "Kiryu J",
      "referenceId" : "RGD:A14460"
    }, {
      "firstName" : "SJ",
      "lastName" : "Tojo",
      "authorRank" : 6,
      "name" : "Tojo",
      "referenceId" : "RGD:A179724"
    }, {
      "firstName" : "M",
      "lastName" : "Miyasaka",
      "authorRank" : 7,
      "name" : "Miyasaka",
      "referenceId" : "RGD:A364180"
    }, {
      "firstName" : "Y",
      "lastName" : "Honda",
      "authorRank" : 8,
      "name" : "Honda Y",
      "referenceId" : "RGD:A14462"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547704"
    } ]
  }, {
    "primaryId" : "PMID:102365",
    "title" : "Amino acid sequence of the human myeloma lambda chain Win.",
    "datePublished" : "1978-11-01T00:00:00.000-06:00",
    "citation" : "Chen BL, etal., Biochim Biophys Acta. 1978 Nov 20;537(1):9-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-11-09T20:24:28.000-06:00",
    "volume" : "537",
    "pages" : "9-21",
    "abstract" : "The complete amino acid sequence of the variable region of a human myeloma immunoglobulin light chain (Win) has been determined. The sequence of the constant region has been verified by compositional analysis of its tryptic peptides. The amino acid sequence of the light chain Win corresponds to sub group II and shows no unusual amino acid replacements in its constant or variable regions when compared to other human gamma chains.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BL",
      "lastName" : "Chen",
      "authorRank" : 1,
      "name" : "Chen BL",
      "referenceId" : "RGD:A117645"
    }, {
      "firstName" : "YY",
      "lastName" : "Chiu",
      "authorRank" : 2,
      "name" : "Chiu",
      "referenceId" : "RGD:A396733"
    }, {
      "firstName" : "RL",
      "lastName" : "Humphrey",
      "authorRank" : 3,
      "name" : "Humphrey",
      "referenceId" : "RGD:A409684"
    }, {
      "firstName" : "RJ",
      "lastName" : "Poljak",
      "authorRank" : 4,
      "name" : "Poljak",
      "referenceId" : "RGD:A225131"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11561628"
    } ]
  }, {
    "primaryId" : "PMID:102414",
    "title" : "Demonstration of a specific localization of carbonic anhydrase C in the glial cells of rat CNS by an immunohistochemical method.",
    "datePublished" : "1979-05-01T00:00:00.000-05:00",
    "citation" : "Roussel G, etal., Brain Res. 1979 Jan 5;160(1):47-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:36:15.000-05:00",
    "volume" : "160",
    "pages" : "47-55",
    "abstract" : "The localization of carbonic anhydrase C isoenzyme in the central nervous system  (CNS) of the rat has been investigated using the indirect immunoperoxidase technique, at both optic and electron microscopic levels. Evidence is presented for a specific localization of the enzyme in the cytoplasm of the oligodendrocytes and astrocytes. Myelinated fibers show a weak staining. The positive reaction is restricted to the cytoplasmic areas of the myelin sheath and does not appear in the compact myelin. Neuronal cell bodies do not stain at all.  A strong positive reaction to the antiserum was also observed in the choroid plexus.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Roussel",
      "authorRank" : 1,
      "name" : "Roussel G",
      "referenceId" : "RGD:A32436"
    }, {
      "firstName" : "JP",
      "lastName" : "Delaunoy",
      "authorRank" : 2,
      "name" : "Delaunoy",
      "referenceId" : "RGD:A184767"
    }, {
      "firstName" : "JL",
      "lastName" : "Nussbaum",
      "authorRank" : 3,
      "name" : "Nussbaum JL",
      "referenceId" : "RGD:A31700"
    }, {
      "firstName" : "P",
      "lastName" : "Mandel",
      "authorRank" : 4,
      "name" : "Mandel P",
      "referenceId" : "RGD:A103078"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553734"
    } ]
  }, {
    "primaryId" : "PMID:102501",
    "title" : "Immunocytoma effect upon circadian variation in murine urinary excretion of beta-aminoisobutyric acid, beta-alanine, phenylalanine and tyrosine.",
    "datePublished" : "1978-09-01T00:00:00.000-05:00",
    "citation" : "Halberg F, etal., Chronobiologia 1978 Jul-Sep;5(3):263-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-26T11:04:45.000-05:00",
    "volume" : "5",
    "pages" : "263-76",
    "abstract" : "Under the conditions of disynchronization by the manipulation of both the alternation of light and darkness and the availability and unavailability of food, circadian rhythms characterize the excretion of several amino acids by inbred LOU rats bearing an immunocytoma. Large amplitude rhythms can be demonstrated for urinary beta-aminoisobutyric acid, beta-alanine, phenylalanine and tyrosine. Under the same conditions of disynchronization, control animals excrete the same compounds also with a marked circadian variation but at an invariably lower average rate. These excretory rhythms, along with those demonstrated earlier for polyamines and light-chains, are of interest as potential markers for the chronotherapy of cancer.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Halberg",
      "authorRank" : 1,
      "name" : "Halberg F",
      "referenceId" : "RGD:A25078"
    }, {
      "firstName" : "CW",
      "lastName" : "Gehrke",
      "authorRank" : 2,
      "name" : "Gehrke CW",
      "referenceId" : "RGD:A25079"
    }, {
      "firstName" : "K",
      "lastName" : "Kuo",
      "authorRank" : 3,
      "name" : "Kuo K",
      "referenceId" : "RGD:A25080"
    }, {
      "firstName" : "WL",
      "lastName" : "Nelson",
      "authorRank" : 4,
      "name" : "Nelson WL",
      "referenceId" : "RGD:A25081"
    }, {
      "firstName" : "RB",
      "lastName" : "Sothern",
      "authorRank" : 5,
      "name" : "Sothern RB",
      "referenceId" : "RGD:A25082"
    }, {
      "firstName" : "LM",
      "lastName" : "Cadotte",
      "authorRank" : 6,
      "name" : "Cadotte LM",
      "referenceId" : "RGD:A25083"
    }, {
      "firstName" : "E",
      "lastName" : "Haus",
      "authorRank" : 7,
      "name" : "Haus E",
      "referenceId" : "RGD:A25084"
    }, {
      "firstName" : "LE",
      "lastName" : "Scheving",
      "authorRank" : 8,
      "name" : "Scheving LE",
      "referenceId" : "RGD:A25085"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634785"
    } ]
  }, {
    "primaryId" : "PMID:103003",
    "title" : "Rearrangement of genetic information may produce immunoglobulin diversity.",
    "datePublished" : "1978-06-01T00:00:00.000-05:00",
    "citation" : "Weigert M, etal., Nature. 1978 Dec 21-28;276(5690):785-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:32:43.000-05:00",
    "volume" : "276",
    "pages" : "785-90",
    "abstract" : "The nearly complete amino-acid sequences of 22 closely related immunoglobulin kappa variable (Vkappa) regions from the inbred NZB mouse are presented. This group of Vkappa regions is encoded by at least six germline Vkappa genes. These data also suggest that the mouse kappa gene is divided into three segments termed V or variable (residues 1 to 98 or 99), J or joining (residues 99 or 100 to 112)  and C or constant (residues 113--219). Tonegawa et la. have recently described a  similar J segment for mouse lambda chains. Inbred mice contain multiple Vkappa and Jkappa gene segments. Therefore, different combinations of V and J gene segments may be joined at the DNA level during the differentiation of individual  lymphocytes to contribute to antibody diversity.",
    "issueName" : "5690",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Weigert",
      "authorRank" : 1,
      "name" : "Weigert",
      "referenceId" : "RGD:A235404"
    }, {
      "firstName" : "L",
      "lastName" : "Gatmaitan",
      "authorRank" : 2,
      "name" : "Gatmaitan",
      "referenceId" : "RGD:A330895"
    }, {
      "firstName" : "E",
      "lastName" : "Loh",
      "authorRank" : 3,
      "name" : "Loh",
      "referenceId" : "RGD:A372218"
    }, {
      "firstName" : "J",
      "lastName" : "Schilling",
      "authorRank" : 4,
      "name" : "Schilling J",
      "referenceId" : "RGD:A9802"
    }, {
      "firstName" : "L",
      "lastName" : "Hood",
      "authorRank" : 5,
      "name" : "Hood L",
      "referenceId" : "RGD:A55620"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340444"
    } ]
  }, {
    "primaryId" : "PMID:103004",
    "title" : "The arrangement and rearrangement of antibody genes.",
    "datePublished" : "1978-04-01T00:00:00.000-06:00",
    "citation" : "Seidman JG and Leder P, Nature. 1978 Dec 21-28;276(5690):790-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T13:37:10.000-05:00",
    "volume" : "276",
    "pages" : "790-5",
    "abstract" : "Cloned segments of mouse chromosomal DNA provide direct evidence for the somatic  rearrangement of kappa variable and constant region genes in antibody producing cells. This rearrangement apparently affects only one member of an allelic pair of light chain genes.",
    "issueName" : "5690",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JG",
      "lastName" : "Seidman",
      "authorRank" : 1,
      "name" : "Seidman JG",
      "referenceId" : "RGD:A32536"
    }, {
      "firstName" : "P",
      "lastName" : "Leder",
      "authorRank" : 2,
      "name" : "Leder P",
      "referenceId" : "RGD:A20577"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11053223"
    } ]
  }, {
    "primaryId" : "PMID:10318818",
    "title" : "Calpastatin is up-regulated in response to hypoxia and is a suicide substrate to calpain after neonatal cerebral hypoxia-ischemia.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Blomgren K, etal., J Biol Chem. 1999 May 14;274(20):14046-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-11-28T17:24:45.000-06:00",
    "volume" : "274",
    "pages" : "14046-52",
    "abstract" : "In a model of cerebral hypoxia-ischemia in the immature rat, widespread brain injury is produced in the ipsilateral hemisphere, whereas the contralateral hemisphere is left undamaged. Previously, we found that calpains were equally translocated to cellular membranes (a prerequisite for protease activation) in the ipsilateral and contralateral hemispheres. However, activation, as judged by degradation of fodrin, occurred only in the ipsilateral hemisphere. In this study we demonstrate that calpastatin, the specific, endogenous inhibitor protein to calpain, is up-regulated in response to hypoxia and may be responsible for the halted calpain activation in the contralateral hemisphere. Concomitantly, extensive degradation of calpastatin occurred in the ipsilateral hemisphere, as demonstrated by the appearance of a membrane-bound 50-kDa calpastatin breakdown product. The calpastatin breakdown product accumulated in the synaptosomal fraction, displaying a peak 24 h post-insult, but was not detectable in the cytosolic fraction. The degradation of calpastatin was blocked by administration of CX295, a calpain inhibitor, indicating that calpastatin acts as a suicide substrate to calpain during hypoxia-ischemia. In summary, calpastatin was up-regulated in areas that remain undamaged and degraded in areas where excessive activation of calpains and infarction occurs.",
    "issueName" : "20",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Blomgren",
      "authorRank" : 1,
      "name" : "Blomgren K",
      "referenceId" : "RGD:A13326"
    }, {
      "firstName" : "U",
      "lastName" : "Hallin",
      "authorRank" : 2,
      "name" : "Hallin U",
      "referenceId" : "RGD:A147956"
    }, {
      "firstName" : "AL",
      "lastName" : "Andersson",
      "authorRank" : 3,
      "name" : "Andersson AL",
      "referenceId" : "RGD:A147957"
    }, {
      "firstName" : "M",
      "lastName" : "Puka-Sundvall",
      "authorRank" : 4,
      "name" : "Puka-Sundvall M",
      "referenceId" : "RGD:A147958"
    }, {
      "firstName" : "BA",
      "lastName" : "Bahr",
      "authorRank" : 5,
      "name" : "Bahr BA",
      "referenceId" : "RGD:A84868"
    }, {
      "firstName" : "A",
      "lastName" : "McRae",
      "authorRank" : 6,
      "name" : "McRae A",
      "referenceId" : "RGD:A147959"
    }, {
      "firstName" : "TC",
      "lastName" : "Saido",
      "authorRank" : 7,
      "name" : "Saido TC",
      "referenceId" : "RGD:A7613"
    }, {
      "firstName" : "S",
      "lastName" : "Kawashima",
      "authorRank" : 8,
      "name" : "Kawashima S",
      "referenceId" : "RGD:A28476"
    }, {
      "firstName" : "H",
      "lastName" : "Hagberg",
      "authorRank" : 9,
      "name" : "Hagberg H",
      "referenceId" : "RGD:A13328"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5683321"
    } ]
  }, {
    "primaryId" : "PMID:10318820",
    "title" : "Glucose transporter Glut3 is targeted to secretory vesicles in neurons and PC12 cells.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Thoidis G, etal., J Biol Chem. 1999 May 14;274(20):14062-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-10-17T17:40:09.000-05:00",
    "volume" : "274",
    "pages" : "14062-6",
    "abstract" : "In rat brain and cultured neuroendocrine PC12 cells, Glut3 is localized at the cell surface and, also, in a distinct population of homogenous synaptic-like vesicles. Glut3-containing vesicles co-purify with \"classical\" synaptic vesicles, but can be separated from the latter by sucrose gradient centrifugation. Unlike classical synaptic vesicles, Glut3-containing vesicles possess a high level of aminopeptidase activity, which has been identified as aminopeptidase B. This enzyme has recently been shown to be a marker of the secretory pathway in PC12 cells (Balogh, A., Cadel, S., Foulon, T., Picart, R., Der Garabedian, A., Rousselet, A., Tougard, C., and Cohen, P. (1998) J. Cell Sci. 111, 161-169). We, therefore, conclude that Glut3 is targeted to secretory vesicles in both neurons and PC12 cells.",
    "issueName" : "20",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Thoidis",
      "authorRank" : 1,
      "name" : "Thoidis G",
      "referenceId" : "RGD:A67975"
    }, {
      "firstName" : "T",
      "lastName" : "Kupriyanova",
      "authorRank" : 2,
      "name" : "Kupriyanova T",
      "referenceId" : "RGD:A89088"
    }, {
      "firstName" : "JM",
      "lastName" : "Cunningham",
      "authorRank" : 3,
      "name" : "Cunningham JM",
      "referenceId" : "RGD:A8971"
    }, {
      "firstName" : "P",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen P",
      "referenceId" : "RGD:A9974"
    }, {
      "firstName" : "S",
      "lastName" : "Cadel",
      "authorRank" : 5,
      "name" : "Cadel S",
      "referenceId" : "RGD:A33549"
    }, {
      "firstName" : "T",
      "lastName" : "Foulon",
      "authorRank" : 6,
      "name" : "Foulon T",
      "referenceId" : "RGD:A31791"
    }, {
      "firstName" : "P",
      "lastName" : "Cohen",
      "authorRank" : 7,
      "name" : "Cohen P",
      "referenceId" : "RGD:A20611"
    }, {
      "firstName" : "RE",
      "lastName" : "Fine",
      "authorRank" : 8,
      "name" : "Fine RE",
      "referenceId" : "RGD:A89089"
    }, {
      "firstName" : "KV",
      "lastName" : "Kandror",
      "authorRank" : 9,
      "name" : "Kandror KV",
      "referenceId" : "RGD:A67976"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642814"
    } ]
  }, {
    "primaryId" : "PMID:10318917",
    "title" : "Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Shen WJ, etal., Proc Natl Acad Sci U S A 1999 May 11;96(10):5528-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:55.000-05:00",
    "volume" : "96",
    "pages" : "5528-32",
    "abstract" : "Hormone-sensitive lipase (HSL) is a cytosolic neutral lipase that functions as the rate-limiting enzyme for the mobilization of free fatty acids in adipose tissue. By using the yeast two-hybrid system to examine the potential interaction of HSL with other cellular proteins, evidence is provided to demonstrate a direct interaction of HSL with adipocyte lipid-binding protein (ALBP), a member of the family of intracellular lipid-binding proteins that binds fatty acids, retinoids, and other hydrophobic ligands. The interaction was demonstrated in vitro by the binding of ALBP to HSL translated in vitro, to HSL in extracts of HSL overexpressing Chinese hamster ovary (CHO) cells, and to HSL in extracts of rat adipose tissue. Finally, the presence of ALBP was documented in immune complexes from rat adipose tissue immunoprecipitated with anti-HSL antibodies. The HSL-ALBP interaction was mapped to an N-terminal 300-aa region of HSL that is distinct from the C-terminal catalytic domain. These results suggest that HSL-derived fatty acids are bound by ALBP to facilitate intracellular trafficking of hydrophobic lipids.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WJ",
      "lastName" : "Shen",
      "authorRank" : 1,
      "name" : "Shen WJ",
      "referenceId" : "RGD:A5801"
    }, {
      "firstName" : "K",
      "lastName" : "Sridhar",
      "authorRank" : 2,
      "name" : "Sridhar K",
      "referenceId" : "RGD:A5802"
    }, {
      "firstName" : "DA",
      "lastName" : "Bernlohr",
      "authorRank" : 3,
      "name" : "Bernlohr DA",
      "referenceId" : "RGD:A5803"
    }, {
      "firstName" : "FB",
      "lastName" : "Kraemer",
      "authorRank" : 4,
      "name" : "Kraemer FB",
      "referenceId" : "RGD:A5804"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68775"
    } ]
  }, {
    "primaryId" : "PMID:10318933",
    "title" : "An imprinted, mammalian bicistronic transcript encodes two independent proteins.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Gray TA, etal., Proc Natl Acad Sci U S A 1999 May 11;96(10):5616-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:55.000-05:00",
    "volume" : "96",
    "pages" : "5616-21",
    "abstract" : "Polycistronic transcripts are common in prokaryotes but rare in eukaryotes. Phylogenetic analysis of the SNRPN (SmN) mRNA in five eutherian mammals reveals a second highly conserved coding sequence, termed SNURF (SNRPN upstream reading frame). The vast majority of nucleotide substitutions in SNURF occur in the wobble codon position, providing strong evolutionary evidence for selection for protein-coding function. Because SNURF-SNRPN maps to human chromosome 15q11-q13 and is paternally expressed, each cistron is a candidate for a role in the imprinted Prader-Willi syndrome (PWS) and PWS mouse models. SNURF encodes a highly basic 71-aa protein that is nuclear-localized (as is SmN). Because SNURF is the only protein-coding sequence within the imprinting regulatory region in 15q11-q13, it may have provided the original selection for imprinting in this domain. Whereas some human tissues express a minor SNURF-only transcript, mouse tissues express only the bicistronic Snurf-Snrpn transcript. We show that both SNURF and SNRPN are translated in normal, but not PWS, human, and mouse tissues and cell lines. These findings identify SNURF as a protein that is produced along with SmN from a bicistronic transcript; polycistronic mRNAs therefore are encoded in mammalian genomes where they may form functional operons.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TA",
      "lastName" : "Gray",
      "authorRank" : 1,
      "name" : "Gray TA",
      "referenceId" : "RGD:A23364"
    }, {
      "firstName" : "S",
      "lastName" : "Saitoh",
      "authorRank" : 2,
      "name" : "Saitoh S",
      "referenceId" : "RGD:A23365"
    }, {
      "firstName" : "RD",
      "lastName" : "Nicholls",
      "authorRank" : 3,
      "name" : "Nicholls RD",
      "referenceId" : "RGD:A23366"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634164"
    } ]
  }, {
    "primaryId" : "PMID:10318940",
    "title" : "Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Tsenova L, etal., Proc Natl Acad Sci U S A. 1999 May 11;96(10):5657-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-05T16:31:07.000-06:00",
    "volume" : "96",
    "pages" : "5657-62",
    "abstract" : "The pathogenesis of tuberculous meningitis, a devastating complication of tuberculosis in man, is poorly understood. We previously reported that rabbits with experimental tuberculous meningitis were protected from death by a combination of antibiotics and thalidomide therapy. Survival was associated with  inhibition of tumor necrosis factor alpha (TNF-alpha) production by thalidomide.  To test whether cerebrospinal fluid (CSF) levels of TNF-alpha correlated with pathogenesis, the response of rabbits infected in the central nervous system (CNS) with various mycobacterial strains was studied. CNS infection with Mycobacterium bovis Ravenel, M. bovis bacillus Calmette-Guerin (BCG) Pasteur, and M. bovis BCG Montreal were compared. M. bovis Ravenel induced the highest levels  of TNF-alpha in the CSF in association with high leukocytosis, protein accumulation, and severe meningeal inflammation. BCG Pasteur had intermediate effects, and BCG Montreal was the least virulent. In addition, M. bovis Ravenel numbers were highest in the brain and CSF and the bacilli also disseminated more  efficiently to distant organs, compared with BCG Pasteur and BCG Montreal. In subsequent experiments, rabbits were infected with either recombinant M. bovis BCG Montreal (vector), or BCG Montreal expressing the murine gene for TNF-alpha (BCG mTNF-alpha). BCG Montreal was rendered virulent by the expression of murine  TNF-alpha, as demonstrated by high CSF leukocytosis, high protein accumulation, severe meningeal inflammation, persistent bacillary load, and progressive clinical deterioration. Taken together, these results demonstrate that the level  of TNF-alpha produced during mycobacterial CNS infection determines, at least in  part, the extent of pathogenesis.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Tsenova",
      "authorRank" : 1,
      "name" : "Tsenova",
      "referenceId" : "RGD:A209817"
    }, {
      "firstName" : "A",
      "lastName" : "Bergtold",
      "authorRank" : 2,
      "name" : "Bergtold",
      "referenceId" : "RGD:A175512"
    }, {
      "firstName" : "VH",
      "lastName" : "Freedman",
      "authorRank" : 3,
      "name" : "Freedman",
      "referenceId" : "RGD:A209818"
    }, {
      "firstName" : "RA",
      "lastName" : "Young",
      "authorRank" : 4,
      "name" : "Young RA",
      "referenceId" : "RGD:A112746"
    }, {
      "firstName" : "G",
      "lastName" : "Kaplan",
      "authorRank" : 5,
      "name" : "Kaplan G",
      "referenceId" : "RGD:A146257"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10449456"
    } ]
  }, {
    "primaryId" : "PMID:10318963",
    "title" : "TRP2: a candidate transduction channel for mammalian pheromone sensory signaling.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Liman ER, etal., Proc Natl Acad Sci U S A 1999 May 11;96(10):5791-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:31:11.000-05:00",
    "volume" : "96",
    "pages" : "5791-6",
    "abstract" : "The vomeronasal organ (VNO) of terrestrial vertebrates plays a key role in the detection of pheromones, chemicals released by animals that elicit stereotyped sexual and aggressive behaviors among conspecifics. Sensory transduction in the VNO appears unrelated to that in the vertebrate olfactory and visual systems: the putative pheromone receptors of the VNO are evolutionarily independent from the odorant receptors and, in contrast to vertebrate visual and olfactory transduction, vomeronasal transduction is unlikely to be mediated by cyclic-nucleotide-gated channels. We hypothesized that sensory transduction in the VNO might instead involve an ion channel of the transient receptor potential (TRP) family, members of which mediate cyclic-nucleotide-independent sensory responses in Drosophila melanogaster and Caenorhabditis elegans and play unknown functions in mammals. We have isolated a cDNA (rTRP2) from rat VNO encoding a protein of 885 amino acids that is equally distant from vertebrate and invertebrate TRP channels (10-30% amino acid identity). rTRP2 mRNA is exclusively expressed in VNO neurons, and the protein is highly localized to VNO sensory microvilli, the proposed site of pheromone sensory transduction. The absence of Ca2+ stores in sensory microvilli suggests that, in contrast to a proposed mechanism of activation of mammalian TRP channels, but in accord with analysis of TRP function in Drosophila phototransduction, the gating of TRP2 is independent from the depletion of internal Ca2+ stores. Thus, TRP2 is likely to participate in vomeronasal sensory transduction, which may share additional similarities with light-induced signaling in the Drosophila eye.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ER",
      "lastName" : "Liman",
      "authorRank" : 1,
      "name" : "Liman ER",
      "referenceId" : "RGD:A17192"
    }, {
      "firstName" : "DP",
      "lastName" : "Corey",
      "authorRank" : 2,
      "name" : "Corey DP",
      "referenceId" : "RGD:A23617"
    }, {
      "firstName" : "C",
      "lastName" : "Dulac",
      "authorRank" : 3,
      "name" : "Dulac C",
      "referenceId" : "RGD:A23618"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634237"
    } ]
  }, {
    "primaryId" : "PMID:10318966",
    "title" : "Aquaporin-6: An intracellular vesicle water channel protein in renal epithelia.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Yasui M, etal., Proc Natl Acad Sci U S A 1999 May 11;96(10):5808-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:19:59.000-05:00",
    "volume" : "96",
    "pages" : "5808-13",
    "abstract" : "All characterized mammalian aquaporins (AQPs) are localized to plasma membranes where they function chiefly to mediate water transport across cells. Here we show that AQP6 is localized exclusively in intracellular membranes in renal epithelia. By using a polyclonal antibody to the C terminus of AQP6, immunoblots revealed a major 30-kDa band in membranes from rat renal cortex and medulla. Endoglycosidase treatment demonstrated presence of an intracellular high mannose glycan on each subunit. Sequential ultracentrifugation of rat kidney homogenates confirmed that AQP6 resides predominantly in vesicular fractions, and immunohistochemical and immunoelectron microscopic studies confirmed that >98% of AQP6 is located in intracellular membrane vesicles. In glomeruli, AQP6 is present in membrane vesicles within podocyte cell bodies and foot processes. In proximal tubules, AQP6 is also abundant in membrane vesicles within the subapical compartment of segment 2 and segment 3 cells, but was not detected in the brush border or basolateral membranes. In collecting duct, AQP6 resides in intracellular membrane vesicles in apical, mid, and basolateral cytoplasm of type A intercalated cells, but was not observed in the plasma membrane. Unlike other members of the AQP family, the unique distribution in intracellular membrane vesicles in multiple types of renal epithelia indicates that AQP6 is not simply involved in transcellular fluid absorption. Moreover, our studies predict that AQP6 participates in distinct physiological functions such as glomerular filtration, tubular endocytosis, and acid-base metabolism.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Yasui",
      "authorRank" : 1,
      "name" : "Yasui M",
      "referenceId" : "RGD:A9677"
    }, {
      "firstName" : "TH",
      "lastName" : "Kwon",
      "authorRank" : 2,
      "name" : "Kwon TH",
      "referenceId" : "RGD:A4464"
    }, {
      "firstName" : "MA",
      "lastName" : "Knepper",
      "authorRank" : 3,
      "name" : "Knepper MA",
      "referenceId" : "RGD:A4467"
    }, {
      "firstName" : "S",
      "lastName" : "Nielsen",
      "authorRank" : 4,
      "name" : "Nielsen S",
      "referenceId" : "RGD:A4469"
    }, {
      "firstName" : "P",
      "lastName" : "Agre",
      "authorRank" : 5,
      "name" : "Agre P",
      "referenceId" : "RGD:A9678"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70663"
    } ]
  }, {
    "primaryId" : "PMID:10319206",
    "title" : "Robinow syndrome in monozygotic twins with normal stature.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Saraiva JM, etal., Clin Dysmorphol. 1999 Apr;8(2):147-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-05-11T17:34:16.000-05:00",
    "volume" : "8",
    "pages" : "147-50",
    "abstract" : "Robinow syndrome was found in two monozygotic twins. We describe the clinical and radiographic manifestations in these patients, both with normal stature and one with omphalocele, with a follow-up of 13 years. Families with Robinow syndrome of both autosomal dominant and recessive inheritance have been reported. We apply the criteria suggested to assign isolated cases to one of the two forms and conclude that autosomal dominant inheritance is more likely.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Saraiva",
      "authorRank" : 1,
      "name" : "Saraiva JM",
      "referenceId" : "RGD:A59900"
    }, {
      "firstName" : "I",
      "lastName" : "Cordeiro",
      "authorRank" : 2,
      "name" : "Cordeiro I",
      "referenceId" : "RGD:A72298"
    }, {
      "firstName" : "HG",
      "lastName" : "Santos",
      "authorRank" : 3,
      "name" : "Santos",
      "referenceId" : "RGD:A291048"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11075834"
    } ]
  }, {
    "primaryId" : "PMID:10319321",
    "title" : "Isolation and molecular characterization of AKAP110, a novel, sperm-specific protein kinase A-anchoring protein.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Vijayaraghavan S, etal., Mol Endocrinol 1999 May;13(5):705-17.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-31T15:18:48.000-05:00",
    "volume" : "13",
    "pages" : "705-17",
    "abstract" : "Agents that increase intracellular cAMP are potent stimulators of sperm motility. Anchoring inhibitor peptides, designed to disrupt the interaction of the cAMP-dependent protein kinase A (PKA) with A kinase-anchoring proteins (AKAPs), are potent inhibitors of sperm motility. These data suggest that PKA anchoring is a key biochemical mechanism controlling motility. We now report the isolation, identification, cloning, and characterization of AKAP110, the predominant AKAP detected in sperm lysates. AKAP110 cDNA was isolated and sequenced from mouse, bovine, and human testis libraries. Using truncated mutants, the RII-binding domain was identified. Alignment of the RII-binding domain on AKAP110 to those from other AKAPs reveals that AKAPs contain eight functionally conserved positions within an amphipathic helix structure that are responsible for RII interaction. Northern analysis of eight different tissues detected AKAP110 only in the testis, and in situ hybridization analysis detected AKAP110 only in round spermatids, suggesting that AKAP110 is a protein found only in male germ cells. Sperm cells contain both RI, located primarily in the acrosomal region of the head, and RII, located exclusively in the tail, regulatory subunits of PKA. Immunocytochemical analysis detected AKAP110 in the acrosomal region of the sperm head and along the entire length of the principal piece. These data suggest that AKAP110 shares compartments with both RI and RII isoforms of PKA and may function as a regulator of both motility- and head-associated functions such as capacitation and the acrosome reaction.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Vijayaraghavan",
      "authorRank" : 1,
      "name" : "Vijayaraghavan S",
      "referenceId" : "RGD:A55125"
    }, {
      "firstName" : "GA",
      "lastName" : "Liberty",
      "authorRank" : 2,
      "name" : "Liberty GA",
      "referenceId" : "RGD:A55126"
    }, {
      "firstName" : "J",
      "lastName" : "Mohan",
      "authorRank" : 3,
      "name" : "Mohan J",
      "referenceId" : "RGD:A55127"
    }, {
      "firstName" : "VP",
      "lastName" : "Winfrey",
      "authorRank" : 4,
      "name" : "Winfrey VP",
      "referenceId" : "RGD:A55128"
    }, {
      "firstName" : "GE",
      "lastName" : "Olson",
      "authorRank" : 5,
      "name" : "Olson GE",
      "referenceId" : "RGD:A55129"
    }, {
      "firstName" : "DW",
      "lastName" : "Carr",
      "authorRank" : 6,
      "name" : "Carr DW",
      "referenceId" : "RGD:A21902"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549472"
    } ]
  }, {
    "primaryId" : "PMID:10319528",
    "title" : "DNA topoisomerase I activity in regenerating liver of hypothyroid rats.",
    "datePublished" : "1998-03-01T00:00:00.000-06:00",
    "citation" : "Merlo M, etal., Boll Soc Ital Biol Sper. 1998 Jan-Feb;74(1-2):9-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-11T13:54:55.000-06:00",
    "volume" : "74",
    "pages" : "9-14",
    "abstract" : "DNA topoisomerase I activity is known to be inhibited by poly(ADP-ribosyl)ation. Both poly(ADP-ribose)polymerase and DNA topoisomerase I participate to major biological events, such as DNA transcription, repair and synthesis. Previously, a 2-fold increase in PARP activity has been shown in hypothyroid animals. Using the regenerating rat liver model, we have studied the behaviour of DNA topoisomerase I activity in hypothyroid rats. PARP activity, was also studied in another set of experiments. DNA topoisomerase I relaxing activity was determined on supercoiled plasmid DNA, and topoisomers separated by agarose gel electrophoresis. An increase in the relaxing activity of Topo I was observed early after hepatectomy. This enhancement well correlates with the reported inhibition of PARP activity at the scheduled times. The data from hypothyroid animals support an inverse relationship between PARP and Topo I. These results are completely reversed with respect to those obtained during liver regeneration in euthyroids.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Merlo",
      "authorRank" : 1,
      "name" : "Merlo M",
      "referenceId" : "RGD:A120253"
    }, {
      "firstName" : "L",
      "lastName" : "Scarabelli",
      "authorRank" : 2,
      "name" : "Scarabelli L",
      "referenceId" : "RGD:A120254"
    }, {
      "firstName" : "C",
      "lastName" : "Bottazzi",
      "authorRank" : 3,
      "name" : "Bottazzi C",
      "referenceId" : "RGD:A120255"
    }, {
      "firstName" : "I",
      "lastName" : "Demori",
      "authorRank" : 4,
      "name" : "Demori I",
      "referenceId" : "RGD:A59418"
    }, {
      "firstName" : "CF",
      "lastName" : "Cesarone",
      "authorRank" : 5,
      "name" : "Cesarone CF",
      "referenceId" : "RGD:A120256"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317064"
    } ]
  }, {
    "primaryId" : "PMID:10319819",
    "title" : "Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Gervais FG, etal., Cell 1999 Apr 30;97(3):395-406.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T12:03:08.000-06:00",
    "volume" : "97",
    "pages" : "395-406",
    "abstract" : "The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-beta (A beta) peptide formation. The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or ischemic brain injury. Caspase-3 is the predominant caspase involved in APP cleavage, consistent with its marked elevation in dying neurons of Alzheimer's disease brains and colocalization of its APP cleavage product with A beta in senile plaques. Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for A beta peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer's disease.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FG",
      "lastName" : "Gervais",
      "authorRank" : 1,
      "name" : "Gervais FG",
      "referenceId" : "RGD:A36704"
    }, {
      "firstName" : "D",
      "lastName" : "Xu",
      "authorRank" : 2,
      "name" : "Xu D",
      "referenceId" : "RGD:A10982"
    }, {
      "firstName" : "GS",
      "lastName" : "Robertson",
      "authorRank" : 3,
      "name" : "Robertson GS",
      "referenceId" : "RGD:A12233"
    }, {
      "firstName" : "JP",
      "lastName" : "Vaillancourt",
      "authorRank" : 4,
      "name" : "Vaillancourt JP",
      "referenceId" : "RGD:A36705"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhu",
      "authorRank" : 5,
      "name" : "Zhu Y",
      "referenceId" : "RGD:A162476"
    }, {
      "firstName" : "J",
      "lastName" : "Huang",
      "authorRank" : 6,
      "name" : "Huang J",
      "referenceId" : "RGD:A20796"
    }, {
      "firstName" : "A",
      "lastName" : "LeBlanc",
      "authorRank" : 7,
      "name" : "LeBlanc A",
      "referenceId" : "RGD:A36706"
    }, {
      "firstName" : "D",
      "lastName" : "Smith",
      "authorRank" : 8,
      "name" : "Smith D",
      "referenceId" : "RGD:A36707"
    }, {
      "firstName" : "M",
      "lastName" : "Rigby",
      "authorRank" : 9,
      "name" : "Rigby M",
      "referenceId" : "RGD:A36708"
    }, {
      "firstName" : "MS",
      "lastName" : "Shearman",
      "authorRank" : 10,
      "name" : "Shearman MS",
      "referenceId" : "RGD:A36709"
    }, {
      "firstName" : "EE",
      "lastName" : "Clarke",
      "authorRank" : 11,
      "name" : "Clarke EE",
      "referenceId" : "RGD:A36710"
    }, {
      "firstName" : "H",
      "lastName" : "Zheng",
      "authorRank" : 12,
      "name" : "Zheng H",
      "referenceId" : "RGD:A11217"
    }, {
      "firstName" : "LH",
      "lastName" : "Van der Ploeg",
      "authorRank" : 13,
      "name" : "Van der Ploeg LH",
      "referenceId" : "RGD:A16222"
    }, {
      "firstName" : "SC",
      "lastName" : "Ruffolo",
      "authorRank" : 14,
      "name" : "Ruffolo SC",
      "referenceId" : "RGD:A36711"
    }, {
      "firstName" : "NA",
      "lastName" : "Thornberry",
      "authorRank" : 15,
      "name" : "Thornberry NA",
      "referenceId" : "RGD:A36712"
    }, {
      "firstName" : "S",
      "lastName" : "Xanthoudakis",
      "authorRank" : 16,
      "name" : "Xanthoudakis S",
      "referenceId" : "RGD:A12226"
    }, {
      "firstName" : "RJ",
      "lastName" : "Zamboni",
      "authorRank" : 17,
      "name" : "Zamboni RJ",
      "referenceId" : "RGD:A36713"
    }, {
      "firstName" : "S",
      "lastName" : "Roy",
      "authorRank" : 18,
      "name" : "Roy S",
      "referenceId" : "RGD:A12227"
    }, {
      "firstName" : "DW",
      "lastName" : "Nicholson",
      "authorRank" : 19,
      "name" : "Nicholson DW",
      "referenceId" : "RGD:A12235"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734692"
    } ]
  }, {
    "primaryId" : "PMID:10319851",
    "title" : "A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Merienne K, etal., Nat Genet. 1999 May;22(1):13-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-26T15:33:31.000-05:00",
    "volume" : "22",
    "pages" : "13-4",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Merienne",
      "authorRank" : 1,
      "name" : "Merienne K",
      "referenceId" : "RGD:A81704"
    }, {
      "firstName" : "S",
      "lastName" : "Jacquot",
      "authorRank" : 2,
      "name" : "Jacquot S",
      "referenceId" : "RGD:A81701"
    }, {
      "firstName" : "S",
      "lastName" : "Pannetier",
      "authorRank" : 3,
      "name" : "Pannetier S",
      "referenceId" : "RGD:A81702"
    }, {
      "firstName" : "M",
      "lastName" : "Zeniou",
      "authorRank" : 4,
      "name" : "Zeniou M",
      "referenceId" : "RGD:A81705"
    }, {
      "firstName" : "A",
      "lastName" : "Bankier",
      "authorRank" : 5,
      "name" : "Bankier A",
      "referenceId" : "RGD:A81706"
    }, {
      "firstName" : "J",
      "lastName" : "Gecz",
      "authorRank" : 6,
      "name" : "Gecz J",
      "referenceId" : "RGD:A45030"
    }, {
      "firstName" : "JL",
      "lastName" : "Mandel",
      "authorRank" : 7,
      "name" : "Mandel JL",
      "referenceId" : "RGD:A44693"
    }, {
      "firstName" : "J",
      "lastName" : "Mulley",
      "authorRank" : 8,
      "name" : "Mulley J",
      "referenceId" : "RGD:A45022"
    }, {
      "firstName" : "P",
      "lastName" : "Sassone-Corsi",
      "authorRank" : 9,
      "name" : "Sassone-Corsi P",
      "referenceId" : "RGD:A41182"
    }, {
      "firstName" : "A",
      "lastName" : "Hanauer",
      "authorRank" : 10,
      "name" : "Hanauer A",
      "referenceId" : "RGD:A81703"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601644"
    } ]
  }, {
    "primaryId" : "PMID:10319853",
    "title" : "Alpha-2 macroglobulin polymorphism and Alzheimer disease risk in the UK.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Dow DJ, etal., Nat Genet 1999 May;22(1):16-7; author reply 21-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T13:36:14.000-05:00",
    "volume" : "22",
    "pages" : "16-7; author reply 21-2",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Dow",
      "authorRank" : 1,
      "name" : "Dow DJ",
      "referenceId" : "RGD:A44639"
    }, {
      "firstName" : "N",
      "lastName" : "Lindsey",
      "authorRank" : 2,
      "name" : "Lindsey N",
      "referenceId" : "RGD:A44640"
    }, {
      "firstName" : "NJ",
      "lastName" : "Cairns",
      "authorRank" : 3,
      "name" : "Cairns NJ",
      "referenceId" : "RGD:A44641"
    }, {
      "firstName" : "C",
      "lastName" : "Brayne",
      "authorRank" : 4,
      "name" : "Brayne C",
      "referenceId" : "RGD:A44642"
    }, {
      "firstName" : "D",
      "lastName" : "Robinson",
      "authorRank" : 5,
      "name" : "Robinson D",
      "referenceId" : "RGD:A44643"
    }, {
      "firstName" : "FA",
      "lastName" : "Huppert",
      "authorRank" : 6,
      "name" : "Huppert FA",
      "referenceId" : "RGD:A44644"
    }, {
      "firstName" : "ES",
      "lastName" : "Paykel",
      "authorRank" : 7,
      "name" : "Paykel ES",
      "referenceId" : "RGD:A44645"
    }, {
      "firstName" : "J",
      "lastName" : "Xuereb",
      "authorRank" : 8,
      "name" : "Xuereb J",
      "referenceId" : "RGD:A44646"
    }, {
      "firstName" : "G",
      "lastName" : "Wilcock",
      "authorRank" : 9,
      "name" : "Wilcock G",
      "referenceId" : "RGD:A44647"
    }, {
      "firstName" : "JL",
      "lastName" : "Whittaker",
      "authorRank" : 10,
      "name" : "Whittaker JL",
      "referenceId" : "RGD:A44648"
    }, {
      "firstName" : "DC",
      "lastName" : "Rubinsztein",
      "authorRank" : 11,
      "name" : "Rubinsztein DC",
      "referenceId" : "RGD:A44649"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300322"
    } ]
  }, {
    "primaryId" : "PMID:10319858",
    "title" : "A radiation hybrid map of the rat genome containing 5,255 markers.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Watanabe TK, etal., Nat Genet 1999 May;22(1):27-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-10-22T12:23:02.000-05:00",
    "volume" : "22",
    "pages" : "27-36",
    "abstract" : "A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TK",
      "lastName" : "Watanabe",
      "authorRank" : 1,
      "name" : "Watanabe TK",
      "referenceId" : "RGD:A88768"
    }, {
      "firstName" : "MT",
      "lastName" : "Bihoreau",
      "authorRank" : 2,
      "name" : "Bihoreau MT",
      "referenceId" : "RGD:A156487"
    }, {
      "firstName" : "LC",
      "lastName" : "McCarthy",
      "authorRank" : 3,
      "name" : "McCarthy LC",
      "referenceId" : "RGD:A47336"
    }, {
      "firstName" : "SL",
      "lastName" : "Kiguwa",
      "authorRank" : 4,
      "name" : "Kiguwa SL",
      "referenceId" : "RGD:A47337"
    }, {
      "firstName" : "H",
      "lastName" : "Hishigaki",
      "authorRank" : 5,
      "name" : "Hishigaki H",
      "referenceId" : "RGD:A162342"
    }, {
      "firstName" : "A",
      "lastName" : "Tsuji",
      "authorRank" : 6,
      "name" : "Tsuji A",
      "referenceId" : "RGD:A162343"
    }, {
      "firstName" : "J",
      "lastName" : "Browne",
      "authorRank" : 7,
      "name" : "Browne J",
      "referenceId" : "RGD:A162344"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamasaki",
      "authorRank" : 8,
      "name" : "Yamasaki Y",
      "referenceId" : "RGD:A162345"
    }, {
      "firstName" : "A",
      "lastName" : "Mizoguchi-Miyakita",
      "authorRank" : 9,
      "name" : "Mizoguchi-Miyakita A",
      "referenceId" : "RGD:A162346"
    }, {
      "firstName" : "K",
      "lastName" : "Oga",
      "authorRank" : 10,
      "name" : "Oga K",
      "referenceId" : "RGD:A162347"
    }, {
      "firstName" : "T",
      "lastName" : "Ono",
      "authorRank" : 11,
      "name" : "Ono T",
      "referenceId" : "RGD:A162348"
    }, {
      "firstName" : "S",
      "lastName" : "Okuno",
      "authorRank" : 12,
      "name" : "Okuno S",
      "referenceId" : "RGD:A162349"
    }, {
      "firstName" : "N",
      "lastName" : "Kanemoto",
      "authorRank" : 13,
      "name" : "Kanemoto N",
      "referenceId" : "RGD:A162350"
    }, {
      "firstName" : "E",
      "lastName" : "Takahashi",
      "authorRank" : 14,
      "name" : "Takahashi E",
      "referenceId" : "RGD:A162351"
    }, {
      "firstName" : "K",
      "lastName" : "Tomita",
      "authorRank" : 15,
      "name" : "Tomita K",
      "referenceId" : "RGD:A162352"
    }, {
      "firstName" : "H",
      "lastName" : "Hayashi",
      "authorRank" : 16,
      "name" : "Hayashi H",
      "referenceId" : "RGD:A162353"
    }, {
      "firstName" : "M",
      "lastName" : "Adachi",
      "authorRank" : 17,
      "name" : "Adachi M",
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    }, {
      "firstName" : "C",
      "lastName" : "Webber",
      "authorRank" : 18,
      "name" : "Webber C",
      "referenceId" : "RGD:A162355"
    }, {
      "firstName" : "M",
      "lastName" : "Davis",
      "authorRank" : 19,
      "name" : "Davis M",
      "referenceId" : "RGD:A162356"
    }, {
      "firstName" : "S",
      "lastName" : "Kiel",
      "authorRank" : 20,
      "name" : "Kiel S",
      "referenceId" : "RGD:A162357"
    }, {
      "firstName" : "C",
      "lastName" : "Knights",
      "authorRank" : 21,
      "name" : "Knights C",
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    }, {
      "firstName" : "A",
      "lastName" : "Smith",
      "authorRank" : 22,
      "name" : "Smith A",
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    }, {
      "firstName" : "R",
      "lastName" : "Critcher",
      "authorRank" : 23,
      "name" : "Critcher R",
      "referenceId" : "RGD:A162360"
    }, {
      "firstName" : "J",
      "lastName" : "Miller",
      "authorRank" : 24,
      "name" : "Miller J",
      "referenceId" : "RGD:A162361"
    }, {
      "firstName" : "MR",
      "lastName" : "James",
      "authorRank" : 25,
      "name" : "James MR",
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    }, {
      "firstName" : "P J",
      "lastName" : "Day",
      "authorRank" : 26,
      "name" : "Day P J",
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    }, {
      "firstName" : "J R",
      "lastName" : "Hudson",
      "authorRank" : 27,
      "name" : "Hudson J R",
      "referenceId" : "RGD:A162364"
    }, {
      "firstName" : "Y",
      "lastName" : "Irie",
      "authorRank" : 28,
      "name" : "Irie Y",
      "referenceId" : "RGD:A162365"
    }, {
      "firstName" : "T",
      "lastName" : "Takagi",
      "authorRank" : 29,
      "name" : "Takagi T",
      "referenceId" : "RGD:A162366"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakamura",
      "authorRank" : 30,
      "name" : "Nakamura Y",
      "referenceId" : "RGD:A162367"
    }, {
      "firstName" : "P N",
      "lastName" : "Goodfellow",
      "authorRank" : 31,
      "name" : "Goodfellow P N",
      "referenceId" : "RGD:A162368"
    }, {
      "firstName" : "G M",
      "lastName" : "Lathrop",
      "authorRank" : 32,
      "name" : "Lathrop G M",
      "referenceId" : "RGD:A162369"
    }, {
      "firstName" : "A",
      "lastName" : "Tanigami",
      "authorRank" : 33,
      "name" : "Tanigami A",
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    }, {
      "firstName" : "M R",
      "lastName" : "James",
      "authorRank" : 34,
      "name" : "James M R",
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    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302807"
    } ]
  }, {
    "primaryId" : "PMID:10319860",
    "title" : "Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Rane SG, etal., Nat Genet. 1999 May;22(1):44-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-11-20T13:26:15.000-06:00",
    "volume" : "22",
    "pages" : "44-52",
    "abstract" : "To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule with an activating mutation. Embryonic fibroblasts proliferate normally in the absence of Cdk4 but have a delayed S phase on re-entry into the cell cycle. Moreover, mice devoid of Cdk4 are viable, but small in size and infertile. These mice also develop insulin-deficient diabetes due to a reduction in beta-islet pancreatic cells. In contrast, mice expressing a mutant Cdk4 that cannot bind the cell-cycle inhibitor P16INK4a display pancreatic hyperplasia due to abnormal proliferation of beta-islet cells. These results establish Cdk4 as an essential regulator of specific cell types.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SG",
      "lastName" : "Rane",
      "authorRank" : 1,
      "name" : "Rane SG",
      "referenceId" : "RGD:A51598"
    }, {
      "firstName" : "P",
      "lastName" : "Dubus",
      "authorRank" : 2,
      "name" : "Dubus P",
      "referenceId" : "RGD:A115488"
    }, {
      "firstName" : "RV",
      "lastName" : "Mettus",
      "authorRank" : 3,
      "name" : "Mettus RV",
      "referenceId" : "RGD:A115489"
    }, {
      "firstName" : "EJ",
      "lastName" : "Galbreath",
      "authorRank" : 4,
      "name" : "Galbreath EJ",
      "referenceId" : "RGD:A41395"
    }, {
      "firstName" : "G",
      "lastName" : "Boden",
      "authorRank" : 5,
      "name" : "Boden G",
      "referenceId" : "RGD:A82762"
    }, {
      "firstName" : "EP",
      "lastName" : "Reddy",
      "authorRank" : 6,
      "name" : "Reddy EP",
      "referenceId" : "RGD:A51599"
    }, {
      "firstName" : "M",
      "lastName" : "Barbacid",
      "authorRank" : 7,
      "name" : "Barbacid M",
      "referenceId" : "RGD:A24831"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2314613"
    } ]
  }, {
    "primaryId" : "PMID:10319867",
    "title" : "Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kitao S, etal., Nat Genet. 1999 May;22(1):82-4. doi: 10.1038/8788.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:46:13.000-05:00",
    "volume" : "22",
    "pages" : "82-4",
    "abstract" : "Rothmund-Thomson syndrome (RTS; also known as poikiloderma congenitale) is a rare, autosomal recessive genetic disorder characterized by abnormalities in skin and skeleton, juvenile cataracts, premature ageing and a predisposition to neoplasia. Cytogenetic studies indicate that cells from affected patients show genomic instability often associated with chromosomal rearrangements causing an acquired somatic mosaicism. The gene(s) responsible for RTS remains unknown. The genes responsible for Werner and Bloom syndromes (WRN and BLM, respectively) have been identified as homologues of Escherichia coli RecQ, which encodes a DNA helicase that unwinds double-stranded DNA into single-stranded DNAs. Other eukaryotic homologues thus far identified are human RECQL, Saccharomyces cerevisiae SGS1 and Schizosaccharomyces pombe rqh1. We recently cloned two new human helicase genes, RECQL4 at 8q24.3 and RECQL5 at 17q25, which encode members of the RecQ helicase family. Here, we report that three RTS patients carried two types of compound heterozygous mutations in RECQL4. The fact that the mutated alleles were inherited from the parents in one affected family and were not found in ethnically matched controls suggests that mutation of RECQL4 at human chromosome 8q24.3 is responsible for at least some cases of RTS.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kitao",
      "authorRank" : 1,
      "name" : "Kitao S",
      "referenceId" : "RGD:A73772"
    }, {
      "firstName" : "A",
      "lastName" : "Shimamoto",
      "authorRank" : 2,
      "name" : "Shimamoto A",
      "referenceId" : "RGD:A28938"
    }, {
      "firstName" : "M",
      "lastName" : "Goto",
      "authorRank" : 3,
      "name" : "Goto M",
      "referenceId" : "RGD:A21691"
    }, {
      "firstName" : "R W",
      "lastName" : "Miller",
      "authorRank" : 4,
      "name" : "Miller RW",
      "referenceId" : "RGD:A589773"
    }, {
      "firstName" : "W A",
      "lastName" : "Smithson",
      "authorRank" : 5,
      "name" : "Smithson WA",
      "referenceId" : "RGD:A595765"
    }, {
      "firstName" : "N M",
      "lastName" : "Lindor",
      "authorRank" : 6,
      "name" : "Lindor NM",
      "referenceId" : "RGD:A577076"
    }, {
      "firstName" : "Y",
      "lastName" : "Furuichi",
      "authorRank" : 7,
      "name" : "Furuichi Y",
      "referenceId" : "RGD:A28939"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118690"
    } ]
  }, {
    "primaryId" : "PMID:10319869",
    "title" : "Position of a 'green-red' hybrid gene in the visual pigment array determines colour-vision phenotype.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Hayashi T, etal., Nat Genet. 1999 May;22(1):90-3. doi: 10.1038/8798.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:47:32.000-05:00",
    "volume" : "22",
    "pages" : "90-3",
    "abstract" : "The X-linked red- and green-pigment genes are arranged in a head-to-tail tandem array. The colour-vision defect of deuteranomaly (in 5% of males of European descent) is associated with a 5'-green-red-3' visual-pigment hybrid gene, which may also exist in males with normal colour vision. To explain why males with a normal red, a normal green and a green-red hybrid gene may have either normal or deutan colour vision, we hypothesized that only the first two genes are expressed and deuteranomaly results only if the green-red hybrid gene occupies the second position and is expressed preferentially over normal green-pigment genes occupying more distal positions. We used long-range PCR amplification and studied 10 deutan males (8 deuteranomalous and 2 deuteranopic) with 3 visual pigment genes (red, green and green-red hybrid) to investigate whether position of the hybrid gene in the array determined gene expression. The green-red hybrid gene was always at the second position (and the first position was always occupied by the red gene). Conversely, in two men with red, green and green-red hybrid genes and normal colour vision, the hybrid gene occupied the third position. When pigment gene mRNA expression was assessed in post-mortem retinae of three men with the red, green and green-red genotype, the green-red hybrid gene was expressed only when located in the second position. We conclude that the green-red hybrid gene will only cause deutan defects when it occupies the second position of the pigment gene array.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Hayashi",
      "authorRank" : 1,
      "name" : "Hayashi T",
      "referenceId" : "RGD:A20275"
    }, {
      "firstName" : "A G",
      "lastName" : "Motulsky",
      "authorRank" : 2,
      "name" : "Motulsky AG",
      "referenceId" : "RGD:A571121"
    }, {
      "firstName" : "S S",
      "lastName" : "Deeb",
      "authorRank" : 3,
      "name" : "Deeb SS",
      "referenceId" : "RGD:A571122"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598115211"
    } ]
  }, {
    "primaryId" : "PMID:10319895",
    "title" : "Congenital hypomyelination due to myelin protein zero Q215X mutation.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Mandich P, etal., Ann Neurol. 1999 May;45(5):676-8. doi: 10.1002/1531-8249(199905)45:5<676::aid-ana21>3.0.co;2-k.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:42:32.000-05:00",
    "volume" : "45",
    "pages" : "676-8",
    "abstract" : "Congenital hypomyelination (CH) is a hereditary demyelinating peripheral neuropathy characterized by early infancy onset, distal muscle weakness, hypotonia, areflexia, and severe slowing of nerve conduction velocities. In the present report, the clinical, morphological, and immunohistochemical features of a CH case and the identification of a mutation in the gene (MPZ) for protein zero (P0) associated with this phenotype are described. This \"de novo\" mutation in a patient presenting with clinical features quite distinct from those of the more frequent Charcot-Marie-Tooth type 1B disease (CMT1B) or Dejerine-Sottas syndrome (DSS) confirms that CH is allelic with other disorders characterized by a less severe phenotype and a different clinical and neuropathological profile.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Mandich",
      "authorRank" : 1,
      "name" : "Mandich P",
      "referenceId" : "RGD:A53360"
    }, {
      "firstName" : "G L",
      "lastName" : "Mancardi",
      "authorRank" : 2,
      "name" : "Mancardi GL",
      "referenceId" : "RGD:A595063"
    }, {
      "firstName" : "A",
      "lastName" : "Varese",
      "authorRank" : 3,
      "name" : "Varese A",
      "referenceId" : "RGD:A53357"
    }, {
      "firstName" : "S",
      "lastName" : "Soriani",
      "authorRank" : 4,
      "name" : "Soriani S",
      "referenceId" : "RGD:A53356"
    }, {
      "firstName" : "E",
      "lastName" : "Di Maria",
      "authorRank" : 5,
      "name" : "Di Maria E",
      "referenceId" : "RGD:A43581"
    }, {
      "firstName" : "E",
      "lastName" : "Bellone",
      "authorRank" : 6,
      "name" : "Bellone E",
      "referenceId" : "RGD:A53355"
    }, {
      "firstName" : "M",
      "lastName" : "Bado",
      "authorRank" : 7,
      "name" : "Bado M",
      "referenceId" : "RGD:A74206"
    }, {
      "firstName" : "L",
      "lastName" : "Gross",
      "authorRank" : 8,
      "name" : "Gross L",
      "referenceId" : "RGD:A595064"
    }, {
      "firstName" : "A J",
      "lastName" : "Windebank",
      "authorRank" : 9,
      "name" : "Windebank AJ",
      "referenceId" : "RGD:A595065"
    }, {
      "firstName" : "F",
      "lastName" : "Ajmar",
      "authorRank" : 10,
      "name" : "Ajmar F",
      "referenceId" : "RGD:A53359"
    }, {
      "firstName" : "A",
      "lastName" : "Schenone",
      "authorRank" : 11,
      "name" : "Schenone A",
      "referenceId" : "RGD:A33164"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118581"
    } ]
  }, {
    "primaryId" : "PMID:10320102",
    "title" : "Immunolocalization of tenascin in the chinchilla inner ear.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Swartz DJ and Santi PA, Hear Res. 1999 Apr;130(1-2):108-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-13T17:57:28.000-05:00",
    "volume" : "130",
    "pages" : "108-14",
    "abstract" : "Tenascin was immunolocalized in the chinchilla cochlea and vestibular system to better understand the functional morphology of the inner ear. Inner ear tissues were fixed with acetone, decalcified and cryosectioned. Indirect immunofluorescence, using antibodies directed against human tenascin epitopes, were used to detect tenascin. As a positive control, tenascin immunoreactivity was found in kidney, cortical mesangial cells and the extracellular matrix of glomeruli and medullary tubule interstitial spaces, concurring with previously reported results. In the cochlea, tenascin immunoreactivity was present in osteocytes, the mesothelial cells underlying the basilar membrane (BM) and within the fibrous matrix of the BM. Greater reactivity was observed in the mesothelial  cells than in the fibrous matrix of the BM. In the vestibular system, tenascin immunoreactivity formed a diffuse band directly beneath the basal lamina of the ampullary and otoconial organs. Tenascin immunoreactivity was also observed in cup-shaped regions between the type I vestibular hair cells and their surrounding VIII nerve calyces in the ampullary and otoconial organs. This is the first report of the anatomical distribution of tenascin in the adult, mammalian inner ear, other than our previously published abstract P.A. Santi and D. Swartz, Soc.  Neurosci. Abstr. 23 (1997) 731.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Swartz",
      "authorRank" : 1,
      "name" : "Swartz",
      "referenceId" : "RGD:A397761"
    }, {
      "firstName" : "PA",
      "lastName" : "Santi",
      "authorRank" : 2,
      "name" : "Santi",
      "referenceId" : "RGD:A397762"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11553836"
    } ]
  }, {
    "primaryId" : "PMID:10320620",
    "title" : "Susceptibility of B-cell deficient C57BL/6 (microMT) mice to Neospora caninum infection.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Eperon S, etal., Parasite Immunol. 1999 May;21(5):225-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:40:22.000-05:00",
    "volume" : "21",
    "pages" : "225-36",
    "abstract" : "Neospora caninum is a coccidian parasite of veterinary importance by causing abortion or stillbirth in cattle among other problems in diverse animal species.  We assessed an experimental murine model for its suitability to study the immune  response to N. caninum infection. Thus, wild-type (wt) C57BL/6 mice and B-cell (and consequently antibody)-deficient microMT mice were infected with N. caninum  tachyzoites and sacrificed at days 10, 24 and 29-44 post infection (dpi). Various organs were collected for parasitological and pathological analysis, spleen and serum for immunological investigations. Splenocytes were in vitro-stimulated with N. caninum (NC)- and T. gondii-antigens for assessing T cell proliferation and cytokine production. While wt mice were resistant to disease, microMT mice died starting from 29 dpi onwards. Histological examination of brain tissue from microMT mice exhibited a high infection intensity with multifocal necrotic cerebral lesions, which were absent in the brains of wt mice. NC antigen-stimulated spleen cells of both wt and microMT mice infected with N. caninum showed a marked proliferative depression at 10 dpi. At 24 dpi, this immunosuppression was still maintained in microMT mice whereas it was restored in wt mice. Stimulated splenocytes of infected microMT mice secreted significantly less IFN-gamma and less IL-10 than corresponding wt splenocytes. For IL-10, this  difference increased with time. The susceptibility of microMT mice appeared associated to B-cell deficiency, allowing the persistent spread of the parasite causing immunosuppression and finally resulting in a lethal outcome of infection.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Eperon",
      "authorRank" : 1,
      "name" : "Eperon",
      "referenceId" : "RGD:A332017"
    }, {
      "firstName" : "K",
      "lastName" : "Bronnimann",
      "authorRank" : 2,
      "name" : "Bronnimann",
      "referenceId" : "RGD:A332018"
    }, {
      "firstName" : "A",
      "lastName" : "Hemphill",
      "authorRank" : 3,
      "name" : "Hemphill A",
      "referenceId" : "RGD:A54763"
    }, {
      "firstName" : "B",
      "lastName" : "Gottstein",
      "authorRank" : 4,
      "name" : "Gottstein",
      "referenceId" : "RGD:A332019"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340880"
    } ]
  }, {
    "primaryId" : "PMID:10320723",
    "title" : "An immunohistochemical marker for Wallerian degeneration of fibers in the central and peripheral nervous system.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Pesini P, etal., Brain Res. 1999 May 15;828(1-2):41-59.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-09-12T10:34:04.000-05:00",
    "volume" : "828",
    "pages" : "41-59",
    "abstract" : "This work was prompted by the accidental observation that a newly developed, affinity purified polyclonal antibody against the C-terminus of the neuropeptide tyrosine (NPY) Y1-receptor protein decorates degenerating fibers in the central nervous system (CNS). This staining did not appear in control animals in which the antibody marked perikarya and dendrites at previously described locations [X. Zhang, L. Bao, Z.-Q. Xu, J. Kopp, U. Arvidsson, R. Elde, T. Hokfelt, Localization of neuropeptide Y Y1-receptors in the rat nervous system with special reference to somatic receptors on small dorsal root ganglion neurons, Proc. Natl. Acad. Sci. USA 91 (1994) 11738-11742]. Three models of experimental lesions were studied: sciatic nerve transection, spinal cord transection and parietal cortex thermocoagulation. In each model, animals were divided in groups (n=2) and processed for indirect immunofluorescence at different time intervals up to 28 days post-lesion (PL) (see below). All three experimental lesions produced a very intense immunolabeling of fibers in the projection pathways of the lesioned structures, strongly reminding of Wallerian degeneration (WD). In the sciatic nerve, the staining first appeared on day 1 PL, was strongly increased on day 3 PL, then declined after 7 days and had almost completely disappeared after 14 days. In the CNS, the staining appeared later and was first observed on day 3 PL and remained for a longer period, thus showing different time courses in the brain and spinal cord as compared to the sciatic nerve. The labeling was completely abolished, both in the CNS and in the sciatic nerve, by pre-incubation of the Y1-R antibody with the immunogenic peptide at a dilution of 10-6 M. The appearance of the staining and its time course strongly suggest that the process was related to degenerating axons. Although the protein actually detected remains to be determined, it is suggested that the staining ability of this antibody could be used as a positive marker of axonal degeneration following experimental or naturally occurring lesions of the nervous system.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Pesini",
      "authorRank" : 1,
      "name" : "Pesini P",
      "referenceId" : "RGD:A87770"
    }, {
      "firstName" : "J",
      "lastName" : "Kopp",
      "authorRank" : 2,
      "name" : "Kopp J",
      "referenceId" : "RGD:A87767"
    }, {
      "firstName" : "H",
      "lastName" : "Wong",
      "authorRank" : 3,
      "name" : "Wong H",
      "referenceId" : "RGD:A24772"
    }, {
      "firstName" : "JH",
      "lastName" : "Walsh",
      "authorRank" : 4,
      "name" : "Walsh JH",
      "referenceId" : "RGD:A87771"
    }, {
      "firstName" : "G",
      "lastName" : "Grant",
      "authorRank" : 5,
      "name" : "Grant G",
      "referenceId" : "RGD:A82279"
    }, {
      "firstName" : "T",
      "lastName" : "Hokfelt",
      "authorRank" : 6,
      "name" : "Hokfelt T",
      "referenceId" : "RGD:A11608"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642322"
    } ]
  }, {
    "primaryId" : "PMID:10320758",
    "title" : "Suppression of an actin-binding protein, drebrin, by antisense transfection attenuates neurite outgrowth in neuroblastoma B104 cells.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Toda M, etal., Brain Res Dev Brain Res. 1999 May 14;114(2):193-200.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-28T12:55:31.000-05:00",
    "volume" : "114",
    "pages" : "193-200",
    "abstract" : "Drebrins, actin-binding proteins, are dominantly expressed during embryogenesis and accumulated in neurite processes of postmigratory neurons. While the cytoskeletal proteins are the important factors for regulating neurite outgrowth, the cellular mechanism in neurons is still unclear. To address the role of drebrins in the neurite outgrowth, we have studied the effect of suppression of drebrin on a rat neuroblastoma B104 cell line, which constitutively expresses drebrin. Deprivation of serum or addition of gangliosides in the culture medium induced remarkable neurite outgrowth of B104 cells. We transfected B104 cells with an antisense construct of human drebrin E cDNA and found that the drebrin expression was significantly reduced in the stable antisense cell lines. In response to serum deprivation and gangliosides treatment, their ability to extend neurite processes was significantly attenuated. In contrast, the cell proliferation of the antisense transfectants was arrested by serum deprivation similar to control B104 cells. These data suggest that the drebrins are required  for neurite outgrowth in neuronal cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Toda",
      "authorRank" : 1,
      "name" : "Toda M",
      "referenceId" : "RGD:A60667"
    }, {
      "firstName" : "T",
      "lastName" : "Shirao",
      "authorRank" : 2,
      "name" : "Shirao T",
      "referenceId" : "RGD:A9874"
    }, {
      "firstName" : "K",
      "lastName" : "Uyemura",
      "authorRank" : 3,
      "name" : "Uyemura K",
      "referenceId" : "RGD:A20901"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10395285"
    } ]
  }, {
    "primaryId" : "PMID:10320792",
    "title" : "Molecular cloning and characterization of a novel developmentally regulated gene, Bdm1, showing predominant expression in postnatal rat brain.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Yamauchi Y, etal., Brain Res Mol Brain Res 1999 May 7;68(1-2):149-58.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-12-22T09:53:44.000-06:00",
    "volume" : "68",
    "pages" : "149-58",
    "abstract" : "Postnatal development, such as synapse refinement, is necessary for the establishment of a mature and functional central nervous system (CNS). Using differential display analysis, we identified a novel gene, termed Bdm1, that is more abundantly expressed in the adult brain than in the embryonic brain. The full-length Bdm1 cDNA is 2718 base pairs long and contains an open reading frame of 1059 base pairs encoding a 38-kDa protein. Northern blot analysis revealed that expression of Bdm1 mRNA in the brain was weak on embryonic days and increased in the early postnatal period. Bdm1 mRNA was significantly expressed in the brain and heart, but there was no or little expression in other tissues. During the differentiation of mouse carcinoma cells P19 to neuron-like cells by retinoic acid, Bdm1 mRNA was up-regulated almost parallel to neurofilament mRNA. Expression of Bdm1 mRNA was observed appreciably in PC12 cells after neuronal differentiation but not in the nonneural cell lines examined. In situ hybridization demonstrated that Bdm1 was expressed widely in the olfactory bulb, cerebral cortex, hippocampus, cerebellum, thalamus, and medulla oblongata. Taken together, these data suggest that Bdm1 gene plays a role in the early postnatal development and function of neuronal cells.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Yamauchi",
      "authorRank" : 1,
      "name" : "Yamauchi Y",
      "referenceId" : "RGD:A19238"
    }, {
      "firstName" : "S",
      "lastName" : "Hongo",
      "authorRank" : 2,
      "name" : "Hongo S",
      "referenceId" : "RGD:A19237"
    }, {
      "firstName" : "T",
      "lastName" : "Ohashi",
      "authorRank" : 3,
      "name" : "Ohashi T",
      "referenceId" : "RGD:A19239"
    }, {
      "firstName" : "S",
      "lastName" : "Shioda",
      "authorRank" : 4,
      "name" : "Shioda S",
      "referenceId" : "RGD:A16066"
    }, {
      "firstName" : "C",
      "lastName" : "Zhou",
      "authorRank" : 5,
      "name" : "Zhou C",
      "referenceId" : "RGD:A48959"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakai",
      "authorRank" : 6,
      "name" : "Nakai Y",
      "referenceId" : "RGD:A48960"
    }, {
      "firstName" : "N",
      "lastName" : "Nishinaka",
      "authorRank" : 7,
      "name" : "Nishinaka N",
      "referenceId" : "RGD:A19236"
    }, {
      "firstName" : "R",
      "lastName" : "Takahashi",
      "authorRank" : 8,
      "name" : "Takahashi R",
      "referenceId" : "RGD:A13527"
    }, {
      "firstName" : "F",
      "lastName" : "Takeda",
      "authorRank" : 9,
      "name" : "Takeda F",
      "referenceId" : "RGD:A19242"
    }, {
      "firstName" : "M",
      "lastName" : "Takeda",
      "authorRank" : 10,
      "name" : "Takeda M",
      "referenceId" : "RGD:A8225"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1304220"
    } ]
  }, {
    "primaryId" : "PMID:10320809",
    "title" : "Characterization of the transacylase activity of rat liver 60-kDa lysophospholipase-transacylase. Acyl transfer from the sn-2 to the sn-1 position.",
    "datePublished" : "1999-05-18T00:00:00.000-05:00",
    "citation" : "Sugimoto H and Yamashita S, Biochim Biophys Acta. 1999 May 18;1438(2):264-72. doi: 10.1016/s1388-1981(99)00059-1.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-07-03T03:16:56.000-05:00",
    "volume" : "1438",
    "pages" : "264-72",
    "abstract" : "Rat liver 60-kDa lysophospholipase-transacylase catalyzes not only the hydrolysis of 1-acyl-sn-glycero-3-phosphocholine, but also the transfer of its acyl chain to a second molecule of 1-acyl-sn-glycero-3-phosphocholine to form phosphatidylcholine (H. Sugimoto, S. Yamashita, J. Biol. Chem. 269 (1994) 6252-6258). Here we report the detailed characterization of the transacylase activity of the enzyme. The enzyme mediated three types of acyl transfer between donor and acceptor lipids, transferring acyl residues from: (1) the sn-1 to -1(3); (2) sn-1 to -2; and (3) sn-2 to -1 positions. In the sn-1 to -1(3) transfer, the sn-1 acyl residue of 1-acyl-sn-glycero-3-phosphocholine was transferred to the sn-1(3) positions of glycerol and 2-acyl-sn-glycerol, producing 1(3)-acyl-sn-glycerol and 1,2-diacyl-sn-glycerol, respectively. In the sn-1 to -2 transfer, the sn-1 acyl residue of 1-acyl-sn-glycero-3-phosphocholine was transferred to not only the sn-2 positions of 1-acyl-sn-glycero-3-phosphocholine, but also 1-acyl-sn-glycero-3-phosphoethanolamine, producing phosphatidylcholine and phosphatidylethanolamine, respectively. 1-Acyl-sn-glycero-3-phospho-myo-inositol and 1-acyl-sn-glycero-3-phosphoserine were much less effectively transacylated by the enzyme. In the sn-2 to -1 transfer, the sn-2 acyl residue of 2-acyl-sn-glycero-3-phosphocholine was transferred to the sn-1 position of 2-acyl-sn-glycero-3-phosphocholine and 2-acyl-sn-glycero-3-phosphoethanolamine, producing phosphatidylcholine and phosphatidylethanolamine, respectively. Consistently, the enzyme hydrolyzed the sn-2 acyl residue from 2-acyl-sn-glycero-3-phosphocholine. By the sn-2 to -1 transfer activity, arachidonic acid was transferred from the sn-2 position of donor lipids to the sn-1 position of acceptor lipids, thus producing 1-arachidonoyl phosphatidylcholine. When 2-arachidonoyl-sn-glycero-3-phosphocholine was used as the sole substrate, diarachidonoyl phosphatidylcholine was synthesized at a rate of 0.23 micromol/min/mg protein. Thus, 60-kDa lysophospholipase-transacylase may play a role in the synthesis of 1-arachidonoyl phosphatidylcholine needed for important cell functions, such as anandamide synthesis.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Sugimoto",
      "authorRank" : 1,
      "name" : "Sugimoto H",
      "referenceId" : "RGD:A8616"
    }, {
      "firstName" : "S",
      "lastName" : "Yamashita",
      "authorRank" : 2,
      "name" : "Yamashita S",
      "referenceId" : "RGD:A125020"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14695081"
    } ]
  }, {
    "primaryId" : "PMID:10320864",
    "title" : "Characterization of two nonsense mutations in the human dystrophin gene.",
    "datePublished" : "1998-04-01T00:00:00.000-06:00",
    "citation" : "Fajkusova L, etal., J Neurogenet. 1998 Sep;12(3):183-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:53:38.000-05:00",
    "volume" : "12",
    "pages" : "183-9",
    "abstract" : "Forty Duchenne muscular dystrophy patients from the province of Moravia in the Czech Republic, who were previously found negative for large deletions in the dystrophin gene, were tested for the presence of point mutations in selected exons. Besides several intron and exon polymorphisms, two cases of nonsense mutations were detected in exon 70, thus causing the loss of the C-terminal domain of dystrophin. One of these, the mutation, S3365X, is newly reported here  while the other, R3381X, has been described previously. These mutations, only 16  bp distant from each other, have a very different impact on the mental abilities  of the corresponding patients.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Fajkusova",
      "authorRank" : 1,
      "name" : "Fajkusova",
      "referenceId" : "RGD:A251382"
    }, {
      "firstName" : "V",
      "lastName" : "Pekarik",
      "authorRank" : 2,
      "name" : "Pekarik",
      "referenceId" : "RGD:A265209"
    }, {
      "firstName" : "J",
      "lastName" : "Hajek",
      "authorRank" : 3,
      "name" : "Hajek",
      "referenceId" : "RGD:A265210"
    }, {
      "firstName" : "V",
      "lastName" : "Kuhrova",
      "authorRank" : 4,
      "name" : "Kuhrova",
      "referenceId" : "RGD:A192563"
    }, {
      "firstName" : "M",
      "lastName" : "Blazkova",
      "authorRank" : 5,
      "name" : "Blazkova",
      "referenceId" : "RGD:A192564"
    }, {
      "firstName" : "J",
      "lastName" : "Fajkus",
      "authorRank" : 6,
      "name" : "Fajkus",
      "referenceId" : "RGD:A259505"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066532"
    } ]
  }, {
    "primaryId" : "PMID:10321247",
    "title" : "The septin CDCrel-1 binds syntaxin and inhibits exocytosis.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Beites CL, etal., Nat Neurosci 1999 May;2(5):434-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-11-05T13:13:28.000-06:00",
    "volume" : "2",
    "pages" : "434-9",
    "abstract" : "Septins are GTPases required for the completion of cytokinesis in diverse organisms, yet their roles in cytokinesis or other cellular processes remain unknown. Here we describe studies of a newly identified septin, CDCrel-1, which is predominantly expressed in the nervous system. This protein was associated with membrane fractions, and a significant fraction of the protein copurified and coprecipitated with synaptic vesicles. In detergent extracts, CDCrel-1 and another septin, Nedd5, immunoprecipitated with the SNARE protein syntaxin by directly binding to syntaxin via the SNARE interaction domain. Transfection of HIT-T15 cells with wild-type CDCrel-1 inhibited secretion, whereas GTPase dominant-negative mutants enhanced secretion. These data suggest that septins may regulate vesicle dynamics through interactions with syntaxin.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CL",
      "lastName" : "Beites",
      "authorRank" : 1,
      "name" : "Beites CL",
      "referenceId" : "RGD:A47579"
    }, {
      "firstName" : "H",
      "lastName" : "Xie",
      "authorRank" : 2,
      "name" : "Xie H",
      "referenceId" : "RGD:A47580"
    }, {
      "firstName" : "R",
      "lastName" : "Bowser",
      "authorRank" : 3,
      "name" : "Bowser R",
      "referenceId" : "RGD:A47581"
    }, {
      "firstName" : "WS",
      "lastName" : "Trimble",
      "authorRank" : 4,
      "name" : "Trimble WS",
      "referenceId" : "RGD:A34189"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302866"
    } ]
  }, {
    "primaryId" : "PMID:10321446",
    "title" : "Identification of upregulated genes in the thymus of spontaneously hypertensive rats by cDNA representational difference analysis.",
    "datePublished" : "1998-02-01T00:00:00.000-06:00",
    "citation" : "Zhao XS, etal., Blood Press. 1998 Nov;7(5-6):316-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-02-01T12:59:29.000-06:00",
    "volume" : "7",
    "pages" : "316-23",
    "abstract" : "OBJECTIVE: To investigate molecular events associated with thymus dysfunction in the spontaneously hypertensive rat (SHR), we analysed the difference in gene expression of the thymus between SHR and Wistar-Kyoto (WKY) rats. METHODS: cDNA representational difference analysis (cDNA-RDA) was applied to compare the gene expression in the thymus between SHR and WKY. The difference products of cDNA-RDA were cloned into pBluescript SK (+) for differential screening. The positive clones were sequenced, and the sequences were analysed using the BLAST program for the homology search. Northern blot analysis was used to confirm the results of differential screening. RESULTS: The results of differential screening showed that eight genes were over-expressed in the thymus of SHR. Comparison of eight sequences against the databases identified four known and four novel genes. The known genes included cathepsin B, AT1-46, cytochrome C oxidase subunit I and metastasis suppressor homolog (KAI1). Two of the novel genes are members of immunoglobulin superfamily genes, and the rest of the novel genes have no significant homology to non-redundant GenBank + EMBL + DDBJ + PDB. By Northern blot hybridization, cathepsin B and clone #7 (GenBank accession #AF106623) genes were confirmed to be overexpressed in the SHR thymus. CONCLUSION: cDNA-RDA combined with differential screening can be used to detect easily the differentially regulated genes in two comparable tissues. The eight isolated genes are good clues toward understanding the development and function of SHR thymus.",
    "issueName" : "5-6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "XS",
      "lastName" : "Zhao",
      "authorRank" : 1,
      "name" : "Zhao XS",
      "referenceId" : "RGD:A91182"
    }, {
      "firstName" : "XB",
      "lastName" : "Li",
      "authorRank" : 2,
      "name" : "Li XB",
      "referenceId" : "RGD:A23805"
    }, {
      "firstName" : "YC",
      "lastName" : "Zhu",
      "authorRank" : 3,
      "name" : "Zhu YC",
      "referenceId" : "RGD:A84533"
    }, {
      "firstName" : "DF",
      "lastName" : "Wan",
      "authorRank" : 4,
      "name" : "Wan DF",
      "referenceId" : "RGD:A91183"
    }, {
      "firstName" : "T",
      "lastName" : "Yao",
      "authorRank" : 5,
      "name" : "Yao T",
      "referenceId" : "RGD:A35959"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289422"
    } ]
  }, {
    "primaryId" : "PMID:10321732",
    "title" : "JTB: a novel membrane protein gene at 1q21 rearranged in a jumping translocation.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Hatakeyama S, etal., Oncogene 1999 Mar 25;18(12):2085-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:05.000-06:00",
    "volume" : "18",
    "pages" : "2085-90",
    "abstract" : "1q21 is frequently involved in different types of translocation in many types of cancers. Jumping translocation (JT) is an unbalanced translocation that comprises amplified chromosomal segments jumping to various telomeres. In this study, we identified a novel gene human JTB (Jumping Translocation Breakpoint) at 1q21, which fused with the telomeric repeats of acceptor telomeres in a case of JT. hJTB (human JTB) encodes a trans-membrane protein that is highly conserved among divergent eukaryotic species. JT results in a hJTB truncation, which potentially produces an hJTB product devoid of the trans-membrane domain. hJTB is located in a gene-rich region at 1q21, called EDC (Epidermal Differentiation Complex). This is the first report identifying the gene involved in unbalanced translocations at 1q21.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Hatakeyama",
      "authorRank" : 1,
      "name" : "Hatakeyama S",
      "referenceId" : "RGD:A7455"
    }, {
      "firstName" : "M",
      "lastName" : "Osawa",
      "authorRank" : 2,
      "name" : "Osawa M",
      "referenceId" : "RGD:A7456"
    }, {
      "firstName" : "M",
      "lastName" : "Omine",
      "authorRank" : 3,
      "name" : "Omine M",
      "referenceId" : "RGD:A7457"
    }, {
      "firstName" : "F",
      "lastName" : "Ishikawa",
      "authorRank" : 4,
      "name" : "Ishikawa F",
      "referenceId" : "RGD:A7458"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69865"
    } ]
  }, {
    "primaryId" : "PMID:10322635",
    "title" : "Screen for genes regulated during early kidney morphogenesis.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Leimeister C, etal., Dev Genet 1999;24(3-4):273-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-07T12:39:14.000-06:00",
    "volume" : "24",
    "pages" : "273-83",
    "abstract" : "Kidney development starts with the reciprocal induction of mesenchymal and ureteric bud cells which leads to condensation, epithelialization, and nephron formation in the mesenchyme. To identify changes in gene expression during these processes, we compared differential display polymerase chain reaction (PCR) profiles of uninduced and induced mesenchymal cells. In vitro kidney development in the form of the transfilter organ culture system was used to generate homogeneous cell populations for this type of comparison. Here we describe the isolation of known and novel genetags from this screening. Among the known genes the ufo receptor tyrosine kinase, sFRP2, and the groucho related gene (grg) were verified as being upregulated upon induction. With four of eight novel genes tested, Northern blot analysis proved to be sensitive enough to confirm differential expression. To improve sensitivity and gain additional spatial information, in situ hybridization was performed. Expression analysis of two differential display PCR products, designated C0-5 and M2-4, demonstrated the cell-specific and dynamic expression of these novel genetags in the developing kidney and other tissues. C0-5 transcripts were expressed in the ureteric bud, S-shaped bodies, and in the collecting system. Signals for M2-4, a gene not detectable by Northern blot analysis, were only found in condensing mesenchymal cells and early differentiation stages, but not in the collecting ducts. The large fraction of novel genetags from the present screening that have not yet been analyzed provides a rich resource to clone genetic networks regulating early nephrogenesis.",
    "issueName" : "3-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Leimeister",
      "authorRank" : 1,
      "name" : "Leimeister C",
      "referenceId" : "RGD:A56810"
    }, {
      "firstName" : "A",
      "lastName" : "Bach",
      "authorRank" : 2,
      "name" : "Bach A",
      "referenceId" : "RGD:A30809"
    }, {
      "firstName" : "AS",
      "lastName" : "Woolf",
      "authorRank" : 3,
      "name" : "Woolf AS",
      "referenceId" : "RGD:A56811"
    }, {
      "firstName" : "M",
      "lastName" : "Gessler",
      "authorRank" : 4,
      "name" : "Gessler M",
      "referenceId" : "RGD:A47363"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556607"
    } ]
  }, {
    "primaryId" : "PMID:10322855",
    "title" : "[Treatment of integrated traditional and Western medicine in recurrent spontaneous abortion of immune abnormality type].",
    "datePublished" : "1997-07-01T00:00:00.000-05:00",
    "citation" : "Li DJ, etal., Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997 Jul;17(7):390-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-10-13T22:30:04.000-05:00",
    "volume" : "17",
    "pages" : "390-2",
    "abstract" : "<br><b>UNLABELLED: </b>Immune abnormality type of recurrent spontaneous abortion (RSA) is an important etiological type, major findings of that are the abnormal increases in auto and/or allo-antibodies of anti-zona pellucida, antiphospholipid and anti-ABO blood group. In the present study, to assess the clinical values of integrated traditional and Western medicine and its therapeutic mechanisms in treating immune abnormality type of RSA.<br><b>METHODS: </b>Aborters were treated by Zhibai Dihuang Pills for anti-zona pellucida antibodies, and clear evil Heat, remove Dampness, replenish blood and activate circulation by Chinese medicinal herbs recipe for anti-phospholipid and anti-ABO group antibodies.<br><b>RESULTS: </b>After they had been treated by these recipe, 92.3% of them became pregnant with normal delivery. It was found in dynamic investigation that level of the antibodies turned to decrease gradually during the treatment, and that of anti-phospholipid and anti-ABO group antibodies increased again at beginning of pregnancy and then decreased gradually with continuing pregnancy.<br><b>CONCLUSION: </b>Chinese herbs recipe could be used to treat RSA of the immune abnormality type by way of decreasing the elevated levels of auto and/or allo-antibodies.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D J",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li DJ",
      "referenceId" : "RGD:A489269"
    }, {
      "firstName" : "C J",
      "lastName" : "Li",
      "authorRank" : 2,
      "name" : "Li CJ",
      "referenceId" : "RGD:A474510"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhu",
      "authorRank" : 3,
      "name" : "Zhu Y",
      "referenceId" : "RGD:A162476"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:39938842"
    } ]
  }, {
    "primaryId" : "PMID:10323205",
    "title" : "Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Sun SH, etal., Int Immunol 1999 Apr;11(4):529-34",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:46.000-05:00",
    "volume" : "11",
    "pages" : "529-34",
    "abstract" : "The present study attempts to identify specific genetic loci contributing to experimental autoimmune uveoretinitis (EAU) susceptibility in F2 progeny of resistant Fischer (F344/N) and susceptible Lewis (LEW/N) inbred rats. F2 progeny of F344/N x LEW/N inbred rats were immunized with the R16 peptide of interphotoreceptor retinoid-binding protein (IRBP). A genome-wide scan was conducted using 125 simple sequence length polymorphism markers in selected F2 animals that developed severe eye disease or remained unaffected to identify phenotype:genotype co-segregation. The F2 population (n = 1287) demonstrated a wide range of histologically assessed EAU scores (assessed on a scale of 0-4). The disease incidence and severity were not consistent with a simple Mendelian inheritance model. Of the F2 hybrid rats, 60% developed EAU, implying the existence of a potent susceptibility locus with incomplete penetrance associated with the LEW genome or a more complex polygenic model of inheritance. Two genomic regions, on chromosomes 4 and 12, showed strong genetic linkage to the EAU phenotype (P < 0.0016), suggesting the presence of susceptibility loci in these chromosomal regions. In conclusion, we have identified two genomic candidate intervals from D4Arb8 to D4Mit17 on chromosome 4 and from the chromosome end to D12Arb8 on chromosome 12, that appear to influence EAU susceptibility in LEW/F344 rats. Further analysis of these genomic regions may lead to identification of the susceptibility genes and to characterization of their function.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SH",
      "lastName" : "Sun",
      "authorRank" : 1,
      "name" : "Sun SH",
      "referenceId" : "RGD:A97641"
    }, {
      "firstName" : "PB",
      "lastName" : "Silver",
      "authorRank" : 2,
      "name" : "Silver PB",
      "referenceId" : "RGD:A97640"
    }, {
      "firstName" : "RR",
      "lastName" : "Caspi",
      "authorRank" : 3,
      "name" : "Caspi RR",
      "referenceId" : "RGD:A131841"
    }, {
      "firstName" : "Y",
      "lastName" : "Du",
      "authorRank" : 4,
      "name" : "Du Y",
      "referenceId" : "RGD:A155809"
    }, {
      "firstName" : "CC",
      "lastName" : "Chan",
      "authorRank" : 5,
      "name" : "Chan CC",
      "referenceId" : "RGD:A144290"
    }, {
      "firstName" : "RL",
      "lastName" : "Wilder",
      "authorRank" : 6,
      "name" : "Wilder RL",
      "referenceId" : "RGD:A153568"
    }, {
      "firstName" : "EF",
      "lastName" : "Remmers",
      "authorRank" : 7,
      "name" : "Remmers EF",
      "referenceId" : "RGD:A153565"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61073"
    } ]
  }, {
    "primaryId" : "PMID:10323242",
    "title" : "Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Li SS, etal., Hum Genet. 1999 Mar;104(3):201-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:34:35.000-05:00",
    "volume" : "104",
    "pages" : "201-4",
    "abstract" : "A total of 18 families with multiple cases of breast cancer were identified from  southern Taiwan, and 5 of these families were found to carry cancer-associated germline mutations in the BRCA1 and BRCA2 genes. One novel cryptic splicing mutation of the BRCA1 gene, found in two unrelated families, was shown to be a deletion of 10 bp near the branch site in intron 7. This mutation causes an insertion of 59 nucleotides derived from intron 7 and results in a frameshift, leading to premature translational termination of BRCA1 mRNA in exon 8. Deletions of 2670delC, 3073delT and 6696-7delTC in the BRCA2 gene were found in three other breast cancer families. All three deletions are predicted to generate frameshifts and to result in the premature termination of BRCA2 protein translation. Several  genetic polymorphisms in both BRCA1 and BRCA2 genes were also detected in this investigation.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SS",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li SS",
      "referenceId" : "RGD:A5947"
    }, {
      "firstName" : "HM",
      "lastName" : "Tseng",
      "authorRank" : 2,
      "name" : "Tseng",
      "referenceId" : "RGD:A284775"
    }, {
      "firstName" : "TP",
      "lastName" : "Yang",
      "authorRank" : 3,
      "name" : "Yang",
      "referenceId" : "RGD:A254541"
    }, {
      "firstName" : "CH",
      "lastName" : "Liu",
      "authorRank" : 4,
      "name" : "Liu CH",
      "referenceId" : "RGD:A81548"
    }, {
      "firstName" : "SJ",
      "lastName" : "Teng",
      "authorRank" : 5,
      "name" : "Teng",
      "referenceId" : "RGD:A284776"
    }, {
      "firstName" : "HW",
      "lastName" : "Huang",
      "authorRank" : 6,
      "name" : "Huang HW",
      "referenceId" : "RGD:A147499"
    }, {
      "firstName" : "LM",
      "lastName" : "Chen",
      "authorRank" : 7,
      "name" : "Chen LM",
      "referenceId" : "RGD:A12823"
    }, {
      "firstName" : "HW",
      "lastName" : "Kao",
      "authorRank" : 8,
      "name" : "Kao",
      "referenceId" : "RGD:A212806"
    }, {
      "firstName" : "JH",
      "lastName" : "Chen",
      "authorRank" : 9,
      "name" : "Chen JH",
      "referenceId" : "RGD:A43606"
    }, {
      "firstName" : "JN",
      "lastName" : "Tseng",
      "authorRank" : 10,
      "name" : "Tseng",
      "referenceId" : "RGD:A284777"
    }, {
      "firstName" : "A",
      "lastName" : "Chen",
      "authorRank" : 11,
      "name" : "Chen A",
      "referenceId" : "RGD:A10458"
    }, {
      "firstName" : "MF",
      "lastName" : "Hou",
      "authorRank" : 12,
      "name" : "Hou MF",
      "referenceId" : "RGD:A66792"
    }, {
      "firstName" : "TJ",
      "lastName" : "Huang",
      "authorRank" : 13,
      "name" : "Huang TJ",
      "referenceId" : "RGD:A59717"
    }, {
      "firstName" : "HT",
      "lastName" : "Chang",
      "authorRank" : 14,
      "name" : "Chang HT",
      "referenceId" : "RGD:A154661"
    }, {
      "firstName" : "KT",
      "lastName" : "Mok",
      "authorRank" : 15,
      "name" : "Mok",
      "referenceId" : "RGD:A284778"
    }, {
      "firstName" : "JH",
      "lastName" : "Tsai",
      "authorRank" : 16,
      "name" : "Tsai",
      "referenceId" : "RGD:A170120"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073514"
    } ]
  }, {
    "primaryId" : "PMID:10323327",
    "title" : "Anti-inflammatory agents and inducibility of hepatic drug metabolism.",
    "datePublished" : "1998-09-01T00:00:00.000-05:00",
    "citation" : "Pappas P, etal., Eur J Drug Metab Pharmacokinet. 1998 Oct-Dec;23(4):457-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-09-11T16:00:17.000-05:00",
    "volume" : "23",
    "pages" : "457-60",
    "abstract" : "Two rat liver cytosolic aldehyde dehydrogenases, ALDH1 and ALDH3c, are of particular interest because they are inducible by different classes of xenobiotics. ALDHI is mainly increased by phenobarbital-type inducers; polycyclic aromatic hydrocarbons (PAHs), such as 3- methylcholanthrene (3MC), increase ALDH3c enzyme activity in all rat species currently tested. In addition, ALDH3c has been found to reflect the subfamily CYPIA of cytochrome P-450, as well as other enzymes functionally related to the aryl hydrocarbon receptor (the \"Ah-receptor enzyme battery\"), which is activated by the same type of inducers. In the present study we investigated whether the induction of ALDH3c might be connected with a chemically produced aseptic inflammation of the hepatocyte. To answer this question, we examined the relationship between the induction of ALDH3c by 3MC and the arachidonic acid cascade. Different non-steroid anti-inflammatory drugs (NSAIDs) were tested in combination with 3MC and in post-treatment. The 3MC-induced ALDH3c activity was significantly diminished by the co-administered anti-inflammatory agents. Two microsomal enzyme activities (ethoxyresorufin-O-deethylase, EROD; aryl-hydrocarbon-hydroxylase, AHH) were also decreased. Similar results were obtained with NSAIDs administered to animals pre- treated with 3MC, as far as the ALDH3c activity was concerned, but not for the microsomal enzyme activity (EROD and AHH). In conclusion, the induction of ALDH3c, after PAH treatment, may be related to an aseptic inflammation of the hepatocytes. This effect is reduced by commonly used steroid and non-steroid anti- inflammatory drugs, and although the mechanism of inhibition has not yet been elucidated, it appears likely that ALDH3c and CYP1A activities are associated with the \"acute phase\" response.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Pappas",
      "authorRank" : 1,
      "name" : "Pappas P",
      "referenceId" : "RGD:A24274"
    }, {
      "firstName" : "P",
      "lastName" : "Stephanou",
      "authorRank" : 2,
      "name" : "Stephanou P",
      "referenceId" : "RGD:A24275"
    }, {
      "firstName" : "V",
      "lastName" : "Vasiliou",
      "authorRank" : 3,
      "name" : "Vasiliou V",
      "referenceId" : "RGD:A24277"
    }, {
      "firstName" : "M",
      "lastName" : "Marselos",
      "authorRank" : 4,
      "name" : "Marselos M",
      "referenceId" : "RGD:A24278"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2300315"
    } ]
  }, {
    "primaryId" : "PMID:10323328",
    "title" : "Zoxazolamine-induced paralysis in two rat substrains: differences in hepatic drug metabolism.",
    "datePublished" : "1998-04-01T00:00:00.000-06:00",
    "citation" : "Pappas P, etal., Eur J Drug Metab Pharmacokinet. 1998 Oct-Dec;23(4):461-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-04-09T10:23:35.000-05:00",
    "volume" : "23",
    "pages" : "461-7",
    "abstract" : "Aldehyde dehydrogenase (ALDH) is involved in the metabolism of endogenous and exogenous aldehydes originating from biogenic amines, lipids, food and drugs. Rat liver contains at least two cytosolic ALDHs that can be stimulated by inducers of drug metabolism. Phenobarbital- type inducers increase ALDH1 activity while polycyclic aromatic hydrocarbons (such as benzo[alpha]pyrene) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increase ALDH3c isoenzyme activity. Two rat substrains were isolated according to a different induction of hepatic ALDH after treatment with phenobarbital (PB). Animals that responded to treatment (RR) and those that did not respond (rr) were inbred and divided into two homogenous groups. These animals constituted an ideal experimental model due to their common origin. Apart from the dramatic induction of cytosolic ALDH1 and ALDH3c, the effects of PB on pentoxy-, ethoxy- and methoxy-resorufin-O-dealkylase (P-, E-, and MROD) between the two substrains were also studied. 3-Methylcholanthrene (3MC) greatly increased ALDH3c levels in both substrains, although it was slightly more pronounced in the rr rats, in which it was assessed either as ALDH3c or as total cytosolic ALDH. A similar trend was also noted in EROD, PROD and MROD activities. Dealkylation of the methoxy group was found to be statistically different between the two substrains (rr > RR). The relevance of the biochemical findings with the in vivo hepatic capacity for drug metabolism was investigated by measuring the duration of zoxazolamine paralysis. Both animal substrains were tested with zoxazolamine either without pretreatment or after administration of PB or 3MC: the paralysis produced by zoxazolamine lasted for a longer period in rr than in RR rats. After pretreatment with PB, the duration of paralysis was greatly reduced, but the differences between the two substrains remained. Pretreatment with various doses of 3MC produced differences in the duration of paralysis in RR and rr rats, although the time period was much shorter than that observed in control animals.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Pappas",
      "authorRank" : 1,
      "name" : "Pappas P",
      "referenceId" : "RGD:A24274"
    }, {
      "firstName" : "P",
      "lastName" : "Stephanou",
      "authorRank" : 2,
      "name" : "Stephanou P",
      "referenceId" : "RGD:A24275"
    }, {
      "firstName" : "V",
      "lastName" : "Vasiliou",
      "authorRank" : 3,
      "name" : "Vasiliou V",
      "referenceId" : "RGD:A24277"
    }, {
      "firstName" : "M",
      "lastName" : "Marselos",
      "authorRank" : 4,
      "name" : "Marselos M",
      "referenceId" : "RGD:A24278"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306338"
    } ]
  }, {
    "primaryId" : "PMID:10323341",
    "title" : "Contribution of TAP genes to genetic predisposition for diffuse panbronchiolitis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Keicho N, etal., Tissue Antigens. 1999 Apr;53(4 Pt 1):366-73.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-08-25T11:53:12.000-05:00",
    "volume" : "53",
    "pages" : "366-73",
    "abstract" : "Diffuse panbronchiolitis is a chronic obstructive pulmonary disease found in Asian populations. Although diffuse panbronchiolitis is considered to be a multifactorial disease of unknown etiology, the disease susceptibility appears to be determined by a genetic predisposition unique to Asians. An earlier study showed that human leukocyte antigen (HLA)-B54 predominantly found in East Asians was strongly associated with the disease. A possible interpretation of this association is that the class I molecule or class I antigen presenting system is directly involved in its pathogenesis. Recent observations in which impaired expression of class I molecules causes a syndrome resembling diffuse panbronchiolitis further prompted us to test this possibility. Genes of the molecules implicated in the class I pathway, TAP1, TAP2 and LMP2, which are located in the HLA region of the sixth chromosome were analyzed in 76 patients with diffuse panbronchiolitis and 120 normal controls. The combination of Ala-665 and Gln-687 in exon 11 of the TAP2 gene was associated with the disease (P=0.0028, Pc<0.05). Although this positive association might be partly explained by linkage disequilibrium with HLA-B*5401, this TAP2 variation was associated with the disease even in the B*5401-negative subgroup. On the other hand, the His-60 substitution within the LMP2 gene exhibited a negative association with the disease. This negative association, however, could be explained by a strong linkage disequilibrium with HLA-B44 which showed a negative association with the disease in the previous study. These results support the notion that diffuse panbronchiolitis is influenced by genetic factors in the HLA region. Besides the class I gene itself, genes relevant to the class I antigen presenting system might contribute to its genetic predisposition.",
    "issueName" : "4 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Keicho",
      "authorRank" : 1,
      "name" : "Keicho N",
      "referenceId" : "RGD:A50391"
    }, {
      "firstName" : "K",
      "lastName" : "Tokunaga",
      "authorRank" : 2,
      "name" : "Tokunaga K",
      "referenceId" : "RGD:A38664"
    }, {
      "firstName" : "K",
      "lastName" : "Nakata",
      "authorRank" : 3,
      "name" : "Nakata K",
      "referenceId" : "RGD:A44340"
    }, {
      "firstName" : "Y",
      "lastName" : "Taguchi",
      "authorRank" : 4,
      "name" : "Taguchi Y",
      "referenceId" : "RGD:A10102"
    }, {
      "firstName" : "A",
      "lastName" : "Azuma",
      "authorRank" : 5,
      "name" : "Azuma A",
      "referenceId" : "RGD:A50392"
    }, {
      "firstName" : "K",
      "lastName" : "Tanabe",
      "authorRank" : 6,
      "name" : "Tanabe K",
      "referenceId" : "RGD:A6071"
    }, {
      "firstName" : "M",
      "lastName" : "Matsushita",
      "authorRank" : 7,
      "name" : "Matsushita M",
      "referenceId" : "RGD:A5979"
    }, {
      "firstName" : "M",
      "lastName" : "Emi",
      "authorRank" : 8,
      "name" : "Emi M",
      "referenceId" : "RGD:A143772"
    }, {
      "firstName" : "N",
      "lastName" : "Ohishi",
      "authorRank" : 9,
      "name" : "Ohishi N",
      "referenceId" : "RGD:A19727"
    }, {
      "firstName" : "S",
      "lastName" : "Kudoh",
      "authorRank" : 10,
      "name" : "Kudoh S",
      "referenceId" : "RGD:A50396"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5147847"
    } ]
  }, {
    "primaryId" : "PMID:10323394",
    "title" : "\"Hot spot\" in the PROP1 gene responsible for combined pituitary hormone deficiency.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Deladoey J, etal., J Clin Endocrinol Metab. 1999 May;84(5):1645-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:38:00.000-05:00",
    "volume" : "84",
    "pages" : "1645-50",
    "abstract" : "As pituitary function depends on the integrity of the hypothalamic-pituitary axis, any defect in the development and organogenesis of this gland may account for a form of combined pituitary hormone deficiency (CPHD). Although pit-1 was 1  of the first factors identified as a cause of CPHD in mice, many other homeodomain and transcription factors have been characterized as being involved in different developmental stages of pituitary gland development, such as prophet of pit-1 (prop-1), P-Lim, ETS-1, and Brn 4. The aims of the present study were first to screen families and patients suffering from different forms of CPHD for  PROP1 gene alterations, and second to define possible hot spots and the frequency of the different gene alterations found. Of 73 subjects (36 families) analyzed, we found 35 patients, belonging to 18 unrelated families, with CPHD caused by a PROP1 gene defect. The PROP1 gene alterations included 3 missense mutations, 2 frameshift mutations, and 1 splice site mutation. The 2 reported frameshift mutations could be caused by any 2-bp GA or AG deletion at either the 148-GGA-GGG-153 or 295-CGA-GAG-AGT-303 position. As any combination of a GA or AG deletion yields the same sequencing data, the frameshift mutations were called 149delGA and 296delGA, respectively. All but 1 mutation were located in the PROP1 gene encoding the homeodomain. Importantly, 3 tandem repeats of the dinucleotides GA at location 296-302 in the PROP1 gene represent a hot spot for CPHD. In conclusion, the PROP1 gene seems to be a major candidate gene for CPHD; however,  further studies are needed to evaluate other genetic defects involved in pituitary development.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Deladoey",
      "authorRank" : 1,
      "name" : "Deladoey J",
      "referenceId" : "RGD:A80479"
    }, {
      "firstName" : "C",
      "lastName" : "Fluck",
      "authorRank" : 2,
      "name" : "Fluck C",
      "referenceId" : "RGD:A80485"
    }, {
      "firstName" : "A",
      "lastName" : "Buyukgebiz",
      "authorRank" : 3,
      "name" : "Buyukgebiz",
      "referenceId" : "RGD:A223182"
    }, {
      "firstName" : "BV",
      "lastName" : "Kuhlmann",
      "authorRank" : 4,
      "name" : "Kuhlmann",
      "referenceId" : "RGD:A259047"
    }, {
      "firstName" : "A",
      "lastName" : "Eble",
      "authorRank" : 5,
      "name" : "Eble A",
      "referenceId" : "RGD:A80481"
    }, {
      "firstName" : "PC",
      "lastName" : "Hindmarsh",
      "authorRank" : 6,
      "name" : "Hindmarsh PC",
      "referenceId" : "RGD:A80920"
    }, {
      "firstName" : "W",
      "lastName" : "Wu",
      "authorRank" : 7,
      "name" : "Wu W",
      "referenceId" : "RGD:A25336"
    }, {
      "firstName" : "PE",
      "lastName" : "Mullis",
      "authorRank" : 8,
      "name" : "Mullis PE",
      "referenceId" : "RGD:A25344"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064564"
    } ]
  }, {
    "primaryId" : "PMID:10323403",
    "title" : "A novel 9-base pair duplication in RET exon 8 in familial medullary thyroid carcinoma.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Pigny P, etal., J Clin Endocrinol Metab. 1999 May;84(5):1700-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:14:19.000-05:00",
    "volume" : "84",
    "pages" : "1700-4",
    "abstract" : "Familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia type 2A syndromes are dominantly inherited diseases caused by activating germline mutations of the RET protooncogene. The majority of these patients carry a germline point mutation affecting one of five cysteine residues encoded by exon 10 (codon 609, 611, 618, or 620) or 11 (codon 634). In a few FMTC families, point mutations involving noncysteine codons in exon 13 (codons 768, 790, and 791), 14  (codon 804), or 15 (codon 891) have been reported. Hirschsprung's disease is a nonneoplastic disorder associated with RET mutations leading to a loss of function effect. Mutations are identified in 50% of the familial cases and are scattered along the gene. We now report the study of a FMTC family with four affected members and a history of fatal neonatal intestinal obstruction in the sister of the proband. Genetic analysis demonstrated the absence of an usual FMTC mutation and the presence of a germline 9-bp duplication in RET exon 8 in the heterozygous state in all patients with MTC. This new mutation creates an additional cysteine residue in the extracellular cysteine-rich domain of RET. Further studies are warranted to confirm whether this new mutation is causing MTC only or could be associated with Hirschsprung's disease.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Pigny",
      "authorRank" : 1,
      "name" : "Pigny",
      "referenceId" : "RGD:A259944"
    }, {
      "firstName" : "C",
      "lastName" : "Bauters",
      "authorRank" : 2,
      "name" : "Bauters C",
      "referenceId" : "RGD:A68693"
    }, {
      "firstName" : "JL",
      "lastName" : "Wemeau",
      "authorRank" : 3,
      "name" : "Wemeau",
      "referenceId" : "RGD:A227523"
    }, {
      "firstName" : "ML",
      "lastName" : "Houcke",
      "authorRank" : 4,
      "name" : "Houcke",
      "referenceId" : "RGD:A283807"
    }, {
      "firstName" : "M",
      "lastName" : "Crepin",
      "authorRank" : 5,
      "name" : "Crepin",
      "referenceId" : "RGD:A279980"
    }, {
      "firstName" : "P",
      "lastName" : "Caron",
      "authorRank" : 6,
      "name" : "Caron",
      "referenceId" : "RGD:A219499"
    }, {
      "firstName" : "S",
      "lastName" : "Giraud",
      "authorRank" : 7,
      "name" : "Giraud S",
      "referenceId" : "RGD:A44758"
    }, {
      "firstName" : "A",
      "lastName" : "Calender",
      "authorRank" : 8,
      "name" : "Calender A",
      "referenceId" : "RGD:A44757"
    }, {
      "firstName" : "MP",
      "lastName" : "Buisine",
      "authorRank" : 9,
      "name" : "Buisine MP",
      "referenceId" : "RGD:A123662"
    }, {
      "firstName" : "JP",
      "lastName" : "Kerckaert",
      "authorRank" : 10,
      "name" : "Kerckaert JP",
      "referenceId" : "RGD:A42200"
    }, {
      "firstName" : "N",
      "lastName" : "Porchet",
      "authorRank" : 11,
      "name" : "Porchet N",
      "referenceId" : "RGD:A123183"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073162"
    } ]
  }, {
    "primaryId" : "PMID:10323602",
    "title" : "JTT-608 restores impaired early insulin secretion in diabetic Goto-Kakizaki rats.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ohta T, etal., Br J Pharmacol. 1999 Apr;126(7):1674-80. doi: 10.1038/sj.bjp.0702481.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-07-07T14:13:48.000-05:00",
    "volume" : "126",
    "pages" : "1674-80",
    "abstract" : "1. We investigated the pharmacological effects of a new antidiabetic agent, JTT-608, in comparison with the sulphonylurea tolbutamide, in Goto-Kakizaki (GK) rats, a genetic model of non-obese insulin-dependent diabetes mellitus (NIDDM). 2. In isolated perfused pancreas from GK rats, JTT-608 (200 microM) enhanced 11.1 mM glucose-stimulated insulin secretion in the first and second phases, but had little effect on insulin secretion at 2.8 mM glucose. In contrast, tolbutamide (100 microM) markedly stimulated insulin secretion at 2.8 mM glucose and enhanced the second phase of insulin secretion but not the first phase at 11.1 mM glucose. 3. In vivo JTT-608 also enhanced early insulin secretion only with glucose-loading. In contrast, tolbutamide enhanced insulin secretion both with and without glucose-loading. 4. JTT-608 (10-100 mg kg(-1)) improved oral glucose tolerance with enhanced insulin secretion in a meal tolerance test (MTT). In comparison with tolbutamide, JTT-608 improved glucose tolerance more efficiently in GK rats than in Wistar rats. 5. We conclude that in diabetic GK rats JTT-608 suppressed postprandial glucose excursions with enhanced glucose-stimulated insulin secretion, especially the first phase of insulin secretion.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Ohta",
      "authorRank" : 1,
      "name" : "Ohta T",
      "referenceId" : "RGD:A21314"
    }, {
      "firstName" : "N",
      "lastName" : "Furukawa",
      "authorRank" : 2,
      "name" : "Furukawa N",
      "referenceId" : "RGD:A72245"
    }, {
      "firstName" : "G",
      "lastName" : "Komuro",
      "authorRank" : 3,
      "name" : "Komuro G",
      "referenceId" : "RGD:A501982"
    }, {
      "firstName" : "F",
      "lastName" : "Yonemori",
      "authorRank" : 4,
      "name" : "Yonemori F",
      "referenceId" : "RGD:A501983"
    }, {
      "firstName" : "K",
      "lastName" : "Wakitani",
      "authorRank" : 5,
      "name" : "Wakitani K",
      "referenceId" : "RGD:A492926"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:127338471"
    } ]
  }, {
    "primaryId" : "PMID:10323886",
    "title" : "Expression and activity of mitogen activated protein kinases in human colorectal carcinoma.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Eggstein S, etal., Gut. 1999 Jun;44(6):834-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-09-11T15:42:21.000-05:00",
    "volume" : "44",
    "pages" : "834-8",
    "abstract" : "<br><b>BACKGROUND: </b>Mitogen activated protein kinases (MAPKs) play a central role in the regulation of both cell growth and differentiation. They are involved in signal transduction of oncogenes and growth factors. The role of MAPK in colonic carcinoma is unknown.<br><b>AIMS: </b>To establish whether the expression and activity of p42/44 MAPKs are altered in colorectal tumours as compared with normal mucosa.<br><b>METHODS: </b>The expression and activity of p42/p44 MAPK were investigated in 22 colorectal carcinomas, four adenomas, and the corresponding normal colorectal mucosa by the use of western blotting, immunoprecipitation, and in vitro kinase assays.<br><b>RESULTS: </b>After immunoprecipitation with an antibody specific for p42 MAPK, we found significant inactivation of p42 MAPK in colonic carcinomas as well as in adenomas, whereas most sample pairs showed only minor differences in p42 MAPK expression. Investigation of MAPK with an antibody capable of detecting both p42 and p44 MAPK showed a slight but significant decrease in p44 MAPK content in malignant tissues. With this antibody, only minor alterations in MAPK activity and no correlation with p42 MAPK activity were found.<br><b>CONCLUSIONS: </b>Inactivation of p42 MAPK could be associated with colonic carcinogenesis.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Eggstein",
      "authorRank" : 1,
      "name" : "Eggstein S",
      "referenceId" : "RGD:A450405"
    }, {
      "firstName" : "M",
      "lastName" : "Franke",
      "authorRank" : 2,
      "name" : "Franke M",
      "referenceId" : "RGD:A450406"
    }, {
      "firstName" : "I",
      "lastName" : "Kutschka",
      "authorRank" : 3,
      "name" : "Kutschka I",
      "referenceId" : "RGD:A450407"
    }, {
      "firstName" : "G",
      "lastName" : "Manthey",
      "authorRank" : 4,
      "name" : "Manthey G",
      "referenceId" : "RGD:A450408"
    }, {
      "firstName" : "B U",
      "lastName" : "von Specht",
      "authorRank" : 5,
      "name" : "von Specht BU",
      "referenceId" : "RGD:A450409"
    }, {
      "firstName" : "G",
      "lastName" : "Ruf",
      "authorRank" : 6,
      "name" : "Ruf G",
      "referenceId" : "RGD:A450410"
    }, {
      "firstName" : "E H",
      "lastName" : "Farthmann",
      "authorRank" : 7,
      "name" : "Farthmann EH",
      "referenceId" : "RGD:A450411"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13210794"
    } ]
  }, {
    "primaryId" : "PMID:10323887",
    "title" : "Microsatellite instability-a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups  of patients with colorectal cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Lamberti C, etal., Gut. 1999 Jun;44(6):839-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:45:30.000-05:00",
    "volume" : "44",
    "pages" : "839-43",
    "abstract" : "BACKGROUND: Clinical diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is based on a typical family history. As molecular genetic testing is predominantly restricted to these families, gene carriers not meeting the clinical criteria may be missed. AIMS: To examine the value of microsatellite instability (MSI) as a tool to increase the likelihood for uncovering a mismatch  repair germline mutation in patients with colorectal cancer and to identify a genotype-phenotype relation in families with verified mutations. METHODS: Systematic search for germline mutations (hMSH2 and hMLH1 genes) was performed in 96 patients: 57 fulfilled the Amsterdam criteria (group 1) and 12 the looser HNPCC criteria (group 2). Seventeen patients showed familial clustering of cancers (group 3) and 10 patients under 50 years had sporadic cancer (group 4), the latter of whom all exhibited MSI+ tumours. RESULTS: A similar proportion of germline mutations was found in patients who fulfilled the clinical criteria of HNPCC and had MSI+ tumours (groups 1 and 2; 15/39) compared with patients who did not meet these clinical criteria but who had MSI+ tumours (groups 3 and 4; 8/27 patients). Affected relatives of patients with hMLH1 mutations showed a significantly higher frequency of colorectal cancer but a lower frequency of endometrium cancer than those with hMSH2 mutations. CONCLUSIONS: MSI in tumour tissue is a useful criterion for selecting patients who should be tested for germline mutations in the mismatch repair genes hMSH2 and hMLH1 irrespective of their family history. Among carriers of hMSH2 mutations the tumour spectrum was broader than among carriers of hMLH1 mutations.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Lamberti",
      "authorRank" : 1,
      "name" : "Lamberti",
      "referenceId" : "RGD:A251600"
    }, {
      "firstName" : "R",
      "lastName" : "Kruse",
      "authorRank" : 2,
      "name" : "Kruse R",
      "referenceId" : "RGD:A74370"
    }, {
      "firstName" : "C",
      "lastName" : "Ruelfs",
      "authorRank" : 3,
      "name" : "Ruelfs",
      "referenceId" : "RGD:A279703"
    }, {
      "firstName" : "R",
      "lastName" : "Caspari",
      "authorRank" : 4,
      "name" : "Caspari",
      "referenceId" : "RGD:A251597"
    }, {
      "firstName" : "Y",
      "lastName" : "Wang",
      "authorRank" : 5,
      "name" : "Wang",
      "referenceId" : "RGD:A417031"
    }, {
      "firstName" : "M",
      "lastName" : "Jungck",
      "authorRank" : 6,
      "name" : "Jungck",
      "referenceId" : "RGD:A251601"
    }, {
      "firstName" : "M",
      "lastName" : "Mathiak",
      "authorRank" : 7,
      "name" : "Mathiak",
      "referenceId" : "RGD:A261223"
    }, {
      "firstName" : "HR",
      "lastName" : "Malayeri",
      "authorRank" : 8,
      "name" : "Malayeri",
      "referenceId" : "RGD:A279705"
    }, {
      "firstName" : "W",
      "lastName" : "Friedl",
      "authorRank" : 9,
      "name" : "Friedl W",
      "referenceId" : "RGD:A94211"
    }, {
      "firstName" : "T",
      "lastName" : "Sauerbruch",
      "authorRank" : 10,
      "name" : "Sauerbruch T",
      "referenceId" : "RGD:A85073"
    }, {
      "firstName" : "P",
      "lastName" : "Propping",
      "authorRank" : 11,
      "name" : "Propping P",
      "referenceId" : "RGD:A52842"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071522"
    } ]
  }, {
    "primaryId" : "PMID:10325899",
    "title" : "Increased neutrophils and cytokines, TNF-alpha and IL-8, in induced sputum of non-asthmatic patients with chronic dry cough.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Jatakanon A, etal., Thorax. 1999 Mar;54(3):234-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-24T11:25:07.000-05:00",
    "volume" : "54",
    "pages" : "234-7",
    "abstract" : "BACKGROUND: The pathogenesis of non-asthmatic chronic dry cough remains unclear. METHODS: A study was undertaken to determine whether airway inflammation could be a contributing factor by analysing inflammatory cells and cytokines in induced sputum from 19 patients with chronic dry cough of varying aetiology, excluding asthma and bronchiectasis, and from 10 normal controls. The associated causes for the chronic cough were postnasal drip (n = 5), gastro-oesophageal reflux (n = 4), and idiopathic (n = 10). All patients had an enhanced cough reflex to capsaicin. RESULTS: Sputum neutrophilia (median (interquartile range)) was found in the patients with chronic cough (59.4 (27.1)%) compared with the normal controls (28.4 (22.0)%; p < 0.01, 95% CI 11.3 to 42.2). Sputum levels of interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were also significantly increased compared with normal controls (0.57 (1.08) and 0.25 (0.72) ng/ml; p < 0.05 (95% CI 0.05 to 1.75) for IL-8; 48.3 (34.4) and 12.6 (33.6) pg/ml, p < 0.01 (95% CI 8.8 to 69.8) for TNF-alpha). CONCLUSION: Neutrophils and cytokines associated with neutrophil chemotaxis and activation may contribute to the pathogenesis of non-asthmatic chronic dry cough.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Jatakanon",
      "authorRank" : 1,
      "name" : "Jatakanon A",
      "referenceId" : "RGD:A128237"
    }, {
      "firstName" : "UG",
      "lastName" : "Lalloo",
      "authorRank" : 2,
      "name" : "Lalloo UG",
      "referenceId" : "RGD:A128238"
    }, {
      "firstName" : "S",
      "lastName" : "Lim",
      "authorRank" : 3,
      "name" : "Lim S",
      "referenceId" : "RGD:A22544"
    }, {
      "firstName" : "KF",
      "lastName" : "Chung",
      "authorRank" : 4,
      "name" : "Chung KF",
      "referenceId" : "RGD:A81292"
    }, {
      "firstName" : "PJ",
      "lastName" : "Barnes",
      "authorRank" : 5,
      "name" : "Barnes PJ",
      "referenceId" : "RGD:A24970"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4143478"
    } ]
  }, {
    "primaryId" : "PMID:10325948",
    "title" : "Molecular structure of cardiac Ito channels: Kv4.2, Kv4.3, and other possibilities?",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Tseng GN Cardiovasc Res 1999 Jan;41(1):16-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-01-15T11:16:35.000-06:00",
    "volume" : "41",
    "pages" : "16-8",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GN",
      "lastName" : "Tseng",
      "authorRank" : 1,
      "name" : "Tseng GN",
      "referenceId" : "RGD:A7475"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:628469"
    } ]
  }, {
    "primaryId" : "PMID:10326749",
    "title" : "Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Casano RA, etal., Am J Otolaryngol. 1999 May-Jun;20(3):151-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:34:06.000-05:00",
    "volume" : "20",
    "pages" : "151-6",
    "abstract" : "PURPOSE: Aminoglycoside-induced ototoxicity appears to have a genetic susceptibility in some individuals, and the A1555G mutation in the mitochondrial  12S ribosomal RNA gene has been shown to be responsible for this susceptibility in all familial cases. An Italian family with 5 family members who became deaf after aminoglycoside exposure presented to us, and molecular analysis excluded the A1555G mutation. The purpose of this study is to identify the molecular basis for the aminoglycoside susceptibility in this family. PATIENTS AND METHODS: Two sisters and three of their children developed severe to profound high-frequency hearing loss after aminoglycoside exposure. DNA was extracted from the blood of these individuals and their unaffected relatives, and analyzed for mitochondrial  DNA mutations. The region around nucleotide 961 was also cloned and individual clones were sequenced. RESULTS: Sequencing of the 12S ribosomal RNA gene revealed a thymidine deletion at position 961, with a complex pattern of sequence around this mutation. Sequencing of individual clones around the 961 mutation demonstrated a varying number of inserted cytosines in different mitochondrial molecules. CONCLUSION: This family establishes the nucleotide 961 thymidine deletion associated with a varying number of inserted cytosines in the mitochondrial 12S ribosomal RNA gene as the second pathogenic mutation that can predispose to aminoglycoside ototoxicity. It demonstrates the clinical relevance  of taking a family history before administering aminoglycosides to any patient. In addition, it would be desirable for sporadic patients with aminoglycoside-induced hearing loss to be screened with molecular tests for the presence of the 1555 and 961 mutations. Such screening could significantly decrease the prevalence of aminoglycoside-induced hearing loss.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RA",
      "lastName" : "Casano",
      "authorRank" : 1,
      "name" : "Casano",
      "referenceId" : "RGD:A268539"
    }, {
      "firstName" : "DF",
      "lastName" : "Johnson",
      "authorRank" : 2,
      "name" : "Johnson",
      "referenceId" : "RGD:A268540"
    }, {
      "firstName" : "Y",
      "lastName" : "Bykhovskaya",
      "authorRank" : 3,
      "name" : "Bykhovskaya",
      "referenceId" : "RGD:A236898"
    }, {
      "firstName" : "F",
      "lastName" : "Torricelli",
      "authorRank" : 4,
      "name" : "Torricelli",
      "referenceId" : "RGD:A183429"
    }, {
      "firstName" : "M",
      "lastName" : "Bigozzi",
      "authorRank" : 5,
      "name" : "Bigozzi",
      "referenceId" : "RGD:A268541"
    }, {
      "firstName" : "N",
      "lastName" : "Fischel-Ghodsian",
      "authorRank" : 6,
      "name" : "Fischel-Ghodsian N",
      "referenceId" : "RGD:A57660"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067578"
    } ]
  }, {
    "primaryId" : "PMID:10326868",
    "title" : "Loss of HNF1alpha function in human renal cell carcinoma: frequent mutations in the VHL gene but not the HNF1alpha gene.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Lemm I, etal., Mol Carcinog. 1999 Apr;24(4):305-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:54:03.000-05:00",
    "volume" : "24",
    "pages" : "305-14",
    "abstract" : "Human renal cell carcinoma (RCC) is a common malignant disease of the kidney characterized by dedifferentiation of renal epithelial cells. Our previous experiments showed that most RCCs have a loss of function of the tissue-specific  transcription factor hepatocyte nuclear factor (HNF) 1alpha. Detailed analyses of the 10 exons encoding HNF1alpha in 32 human RCCs by single-strand conformation polymorphism analysis and direct DNA sequencing revealed no tumor-associated mutation, whereas with the same probes we frequently found mutations in the von Hippel-Lindau tumor suppressor gene. No mutation leading to loss of HNF1alpha function was detected by analyzing the integrity of the HNF1alpha transcripts in  the RNA derived from RCCs by the protein truncation test. Investigating human RCC cell lines by western blotting and gel retardation assays showed a dramatic loss  in the expression of the tissue-specific transcription factor HNF1alpha in eight  of 10 cell lines. As the HNF1alpha-related transcription factor HNF1beta was expressed in all these tumor cell lines, the loss of HNF1alpha expression was a specific event and was maintained in RCC cell lines. The loss of HNF1alpha expression in RCC cell lines on the RNA level was confirmed by reverse transcription polymerase chain reaction. We propose that tumor-associated mutations in the HNF1alpha gene do not occur in human RCC and that the loss of function is partially due to a transcriptional inactivation of the HNF1alpha gene.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Lemm",
      "authorRank" : 1,
      "name" : "Lemm",
      "referenceId" : "RGD:A236800"
    }, {
      "firstName" : "A",
      "lastName" : "Lingott",
      "authorRank" : 2,
      "name" : "Lingott",
      "referenceId" : "RGD:A270085"
    }, {
      "firstName" : "E",
      "lastName" : "Pogge v Strandmann",
      "authorRank" : 3,
      "name" : "Pogge v Strandmann",
      "referenceId" : "RGD:A270086"
    }, {
      "firstName" : "C",
      "lastName" : "Zoidl",
      "authorRank" : 4,
      "name" : "Zoidl C",
      "referenceId" : "RGD:A49895"
    }, {
      "firstName" : "MP",
      "lastName" : "Bulman",
      "authorRank" : 5,
      "name" : "Bulman MP",
      "referenceId" : "RGD:A75077"
    }, {
      "firstName" : "AT",
      "lastName" : "Hattersley",
      "authorRank" : 6,
      "name" : "Hattersley AT",
      "referenceId" : "RGD:A39907"
    }, {
      "firstName" : "WA",
      "lastName" : "Schulz",
      "authorRank" : 7,
      "name" : "Schulz WA",
      "referenceId" : "RGD:A66839"
    }, {
      "firstName" : "T",
      "lastName" : "Ebert",
      "authorRank" : 8,
      "name" : "Ebert",
      "referenceId" : "RGD:A270087"
    }, {
      "firstName" : "GU",
      "lastName" : "Ryffel",
      "authorRank" : 9,
      "name" : "Ryffel",
      "referenceId" : "RGD:A270088"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068106"
    } ]
  }, {
    "primaryId" : "PMID:10327052",
    "title" : "Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wurfel J, etal., Oncogene 1999 Apr 8;18(14):2323-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:24.000-05:00",
    "volume" : "18",
    "pages" : "2323-34",
    "abstract" : "Screening for surface molecules expressed by metastasizing rat tumors had revealed evidence for metastasis-association of a molecule also expressed on epithelial cells. The similarity to the expression profile of the panepithelial glycoprotein EGP314 prompted us to isolate and sequence the gene and to explore functional features of the molecule in transfected tumor lines. The molecule D5.7A, named according to the antibody, D5.7, used for selection, indeed, is the ortholog of EGP314 with 92% and 80% identity to the murine and the human molecules. Like EGP314, D5.7A has a particular cleavage site, a small cleavage product being resolved under reducing conditions from the membrane anchored part of the molecule. Transfection of a low metastasizing fibrosarcoma, pheochromoblastoma and adenocarcinoma revealed that expression of D5.7A facilitates tumor progression. Depending on the origin of the tumor, D5.7A transfectants either metastasized via the lymphatic system (pheochromoblastoma, adenocarcinoma) or hematogeneously (fibrosarcoma). Particularly after proteolytic cleavage, D5.7A facilitated cell - cell adhesion and provided a proliferative signal upon crosslinking. Thus, the rat ortholog of EGP314 is involved in metastasis formation. Importantly, its functional activities apparently rely on proteolytic cleavage. These findings provide a first evidence on how a panepithelial marker can be involved in tumor progression.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Wurfel",
      "authorRank" : 1,
      "name" : "Wurfel J",
      "referenceId" : "RGD:A4307"
    }, {
      "firstName" : "M",
      "lastName" : "Rosel",
      "authorRank" : 2,
      "name" : "Rosel M",
      "referenceId" : "RGD:A23476"
    }, {
      "firstName" : "S",
      "lastName" : "Seiter",
      "authorRank" : 3,
      "name" : "Seiter S",
      "referenceId" : "RGD:A23583"
    }, {
      "firstName" : "C",
      "lastName" : "Claas",
      "authorRank" : 4,
      "name" : "Claas C",
      "referenceId" : "RGD:A5227"
    }, {
      "firstName" : "M",
      "lastName" : "Herlevsen",
      "authorRank" : 5,
      "name" : "Herlevsen M",
      "referenceId" : "RGD:A5229"
    }, {
      "firstName" : "R",
      "lastName" : "Weth",
      "authorRank" : 6,
      "name" : "Weth R",
      "referenceId" : "RGD:A23478"
    }, {
      "firstName" : "M",
      "lastName" : "Zoller",
      "authorRank" : 7,
      "name" : "Zoller M",
      "referenceId" : "RGD:A121439"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634200"
    } ]
  }, {
    "primaryId" : "PMID:10327204",
    "title" : "Palmitoyl-protein thioesterase, an enzyme implicated in neurodegeneration, is localized in neurons and is developmentally regulated in rat brain.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Suopanki J, etal., Neurosci Lett. 1999 Apr 9;265(1):53-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-09-18T15:37:10.000-05:00",
    "volume" : "265",
    "pages" : "53-6",
    "abstract" : "Palmitoyl-protein thioesterase (PPT) is an enzyme involved in cleavage of palmitate residues from acylated proteins. Mutations in PPT gene cause a severe neurodegenerative disorder, infantile neuronal ceroid-lipofuscinosis (INCL), characterized by loss of cortical neurons. In order to clarify the role of PPT and palmitoylation/depalmitoylation in the development of CNS and pathogenesis of infantile neuronal ceroid-lipofuscinosis (INCL), we studied the localization and expression of PPT in developing rats. Using immunohistochemical methods, we show for the first time that PPT is truly localized in neurons. Further, using RT-PCR and Western blotting, we show that expression of PPT in rat brain is developmentally regulated, with increasing expression during the maturation of CNS, reaching the maximum in young adulthood. The presented data support the view of PPT being essential for both development and maintenance of cortical neurons.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Suopanki",
      "authorRank" : 1,
      "name" : "Suopanki J",
      "referenceId" : "RGD:A21881"
    }, {
      "firstName" : "J",
      "lastName" : "Tyynela",
      "authorRank" : 2,
      "name" : "Tyynela J",
      "referenceId" : "RGD:A21887"
    }, {
      "firstName" : "M",
      "lastName" : "Baumann",
      "authorRank" : 3,
      "name" : "Baumann M",
      "referenceId" : "RGD:A21886"
    }, {
      "firstName" : "M",
      "lastName" : "Haltia",
      "authorRank" : 4,
      "name" : "Haltia M",
      "referenceId" : "RGD:A21884"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581146"
    } ]
  }, {
    "primaryId" : "PMID:10328076",
    "title" : "Advances in molecular genetics and management of hypertrophic cardiomyopathy.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Fananapazir L JAMA. 1999 May 12;281(18):1746-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:36:43.000-05:00",
    "volume" : "281",
    "pages" : "1746-52",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Fananapazir",
      "authorRank" : 1,
      "name" : "Fananapazir L",
      "referenceId" : "RGD:A56285"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067643"
    } ]
  }, {
    "primaryId" : "PMID:10328528",
    "title" : "Increased steady state mRNA levels of DNA-repair genes XRCC1, ERCC2 and ERCC3 in brain of patients with Down syndrome.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Fang-Kircher SG, etal., Life Sci. 1999;64(18):1689-99.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-08-01T16:55:27.000-05:00",
    "volume" : "64",
    "pages" : "1689-99",
    "abstract" : "Although deficient DNA-repair was proposed for neurodegenerative disorders including Down Syndrome (DS), repair genes for nucleotide excision repair or X-ray repair have not been studied in brain yet. As one of the hypotheses for the pathogenesis of brain damage in DS is oxidative stress and cells of patients with DS are more susceptible to ionizing irradiation, we decided to study ERCC2, ERCC3 and XRCC1, representatives of repair genes known to be involved in the repair of oxidative DNA-damage. mRNA steady state levels of ERCC2, ERCC3, XRCC1, a transcription activator (TAF-DBP) and an elongation factor (EF1A) were determined and normalized versus the housekeeping gene beta-actin in five individual brain regions of nine controls and nine DS patients. Although different in the individual regions, DNA-repair genes were consistently higher in temporal, parietal and occipital lobes of patients with DS accompanied by comparable changes of TFA-DBP and EF1A. Our results are the first to describe DNA-repair gene patterns in human brain regions providing the basis for further studies in this area. We showed that DNA-repair genes ERCC2 and ERCC3 (excision-repair-cross-complementing-) for nucleotide excision repair and XRCC1 (X-ray-repair-cross-complementing-) for X-ray-repair, were increased at the transcriptional level with the possible biological meaning that this increase may be compatible with permanent (oxidative?) DNA damage.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S G",
      "lastName" : "Fang-Kircher",
      "authorRank" : 1,
      "name" : "Fang-Kircher SG",
      "referenceId" : "RGD:A448460"
    }, {
      "firstName" : "O",
      "lastName" : "Labudova",
      "authorRank" : 2,
      "name" : "Labudova O",
      "referenceId" : "RGD:A65511"
    }, {
      "firstName" : "E",
      "lastName" : "Kitzmueller",
      "authorRank" : 3,
      "name" : "Kitzmueller E",
      "referenceId" : "RGD:A102933"
    }, {
      "firstName" : "H",
      "lastName" : "Rink",
      "authorRank" : 4,
      "name" : "Rink H",
      "referenceId" : "RGD:A448461"
    }, {
      "firstName" : "N",
      "lastName" : "Cairns",
      "authorRank" : 5,
      "name" : "Cairns N",
      "referenceId" : "RGD:A46792"
    }, {
      "firstName" : "G",
      "lastName" : "Lubec",
      "authorRank" : 6,
      "name" : "Lubec G",
      "referenceId" : "RGD:A49942"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13207452"
    } ]
  }, {
    "primaryId" : "PMID:10328854",
    "title" : "Regulation of retinoid X receptor-gamma gene transcript levels in rat heart cells.",
    "datePublished" : "1000-06-01T00:00:00.000-06:00",
    "citation" : "Georgiades P and Brickell PM, Cell Biol Int. 1998;22(6):457-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-15T16:27:30.000-05:00",
    "volume" : "22",
    "pages" : "457-63",
    "abstract" : "Retinoid X receptor-gamma (RXRgamma) is a transcription factor that mediates retinoid signalling and is expressed in rat heart during adult life. However, its expression in embryonic and neonatal heart has not been investigated and it is not known whether ventricular cardiomyocytes express RXRgamma or whether all- trans -retinoic acid (tRA) and thyroid hormone (T3) could influence RXRgamma transcript levels in these cells. First, in situ hybridization experiments were used to test for any spatio-temporal correlation between RXRgamma gene expression and the previously shown requirement for retinoid signalling in embryonic ventricular cardiomyocytes. It was shown that RXRgamma transcripts are not detectable in embryonic heart at all developmental stages examined under conditions where they are detectable in other embryonic tissues. Second, Northern blotting was used to examine whether there is a difference in RXRgamma transcript levels between neonatal and adult heart. We show that levels of two RXRgamma transcripts are developmentally regulated during the postnatal period because they differ between neonatal and adult hearts. Third, it was demonstrated that primary cultures of neonatal rat ventricular cardiomyocytes express RXRgamma transcripts, making them a novel in vitro system for the study of RXRgamma gene regulation in heart-derived cells. Finally, this system was used to examine whether tRA and T3can influence levels of RXRgamma transcripts because they have been shown to have antagonistic effects in this system and to influence RXRgamma RNA levels in other systems. It was shown by Northern blot experiments, that in this system, RXRgamma transcript levels are differentially influenced by these two hormones. The significance of these findings in relation to previously published work is discussed.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Georgiades",
      "authorRank" : 1,
      "name" : "Georgiades P",
      "referenceId" : "RGD:A22714"
    }, {
      "firstName" : "PM",
      "lastName" : "Brickell",
      "authorRank" : 2,
      "name" : "Brickell PM",
      "referenceId" : "RGD:A22715"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2325975"
    } ]
  }, {
    "primaryId" : "PMID:10328880",
    "title" : "Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Martin SC, etal., Mol Cell Neurosci 1999 Mar;13(3):180-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:53.000-05:00",
    "volume" : "13",
    "pages" : "180-91",
    "abstract" : "We have identified a gene encoding a GABAB receptor, the human GABABR2, located on chromosome 9q22.1, that is distinct from the recently reported rat GABABR1. GABABR2 structurally resembles GABABR1 (35% identity), having seven transmembrane domains and a large extracellular region, but differs in having a longer carboxy-terminal tail. GABABR2 is localized to the cell surface in transfected COS cells, and negatively couples to adenylyl cyclase in response to GABA, baclofen, and 3-aminopropyl(methyl)phosphinic acid in CHO cells lacking GABABR1. Baclofen action is inhibited by the GABABR antagonist, 2-hydroxysaclofen. The human GABABR2 and GABABR1 genes are differentially expressed in the nervous system, with the greatest difference being detected in the striatum in which GABABR1 but not GABABR2 mRNA transcripts are detected. GABABR2 and GABABR1 mRNAs are also coexpressed in various brain regions such as the Purkinje cell layer of the cerebellum. Identification of a functional homomeric GABABR2 coupled to adenylyl cyclase suggests that the complexity of GABAB pharmacological data is at least in part due to the presence of more than one receptor and opens avenues for future research leading to an understanding of metabotropic GABA receptor signal transduction mechanisms.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SC",
      "lastName" : "Martin",
      "authorRank" : 1,
      "name" : "Martin SC",
      "referenceId" : "RGD:A30532"
    }, {
      "firstName" : "SJ",
      "lastName" : "Russek",
      "authorRank" : 2,
      "name" : "Russek SJ",
      "referenceId" : "RGD:A30533"
    }, {
      "firstName" : "DH",
      "lastName" : "Farb",
      "authorRank" : 3,
      "name" : "Farb DH",
      "referenceId" : "RGD:A30534"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:728744"
    } ]
  }, {
    "primaryId" : "PMID:10329019",
    "title" : "Coding sequence mutations in the alpha subunit of propionyl-CoA carboxylase in patients with propionic acidemia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Campeau E, etal., Mol Genet Metab. 1999 May;67(1):11-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:12:24.000-05:00",
    "volume" : "67",
    "pages" : "11-22",
    "abstract" : "Propionic acidemia is a rare autosomal recessive disorder of intermediary metabolism. It is caused by a deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC, EC 6.4.1.3), a heteropolymeric protein composed of two subunits, alpha and beta. PCC requires ATP and biotin as cofactors for the reaction, the latter enzymatically added onto the alpha subunit. We investigated  coding sequence mutations in the alpha subunit of PCC by analyzing fibroblast RNA from propionic acidemia patients deficient in alpha subunit function by single-strand conformation polymorphism and direct sequencing. Five missense mutations and one short in-frame deletion were found among different patients. Four mutations were located in the putative biotin carboxylase domain, whereas the two others were within the 67-amino-acid C-terminal domain previously shown to be required to obtain biotinylation of the alpha subunit. We analyzed fibroblast extracts for the presence of a biotinylated alpha subunit by Western blot analysis using streptavidin coupled to alkaline phosphatase. Four of five cell lines failed to show a biotinylated alpha subunit, regardless of the position of the mutations within the coding sequence. Two mutations located in the biotinylation domain were expressed in an Escherichia coli-based system and shown to abolish biotinylation of the domain. The results suggest that most mutations have a severe impact on the stability or the functionality of the alpha subunit.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Campeau",
      "authorRank" : 1,
      "name" : "Campeau",
      "referenceId" : "RGD:A255926"
    }, {
      "firstName" : "L",
      "lastName" : "Dupuis",
      "authorRank" : 2,
      "name" : "Dupuis L",
      "referenceId" : "RGD:A116171"
    }, {
      "firstName" : "A",
      "lastName" : "Leon-Del-Rio",
      "authorRank" : 3,
      "name" : "Leon-Del-Rio",
      "referenceId" : "RGD:A255927"
    }, {
      "firstName" : "R",
      "lastName" : "Gravel",
      "authorRank" : 4,
      "name" : "Gravel",
      "referenceId" : "RGD:A255928"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063671"
    } ]
  }, {
    "primaryId" : "PMID:10329199",
    "title" : "cDNA sequence and characterization of the gene that encodes human myotrophin/V-1 protein, a mediator of cardiac hypertrophy.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Anderson KM, etal., J Mol Cell Cardiol. 1999 Apr;31(4):705-19.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-09-12T11:16:38.000-05:00",
    "volume" : "31",
    "pages" : "705-19",
    "abstract" : "The predominant response of the heart to sustained increased work load is development of ventricular hypertrophy, principally as a result of hypertrophy of cardiomyocytes. The molecular mechanisms and factors involved in cardiomyocyte hypertrophy are poorly understood. Myotrophin is a novel 12-kilodalton protein recently implicated as a factor associated with and able to induce cardiac hypertrophy. Cloning of rat myotrophin revealed that this protein is identical to the functionally undefined rat, murine and chicken V-1 proteins. Although human myotrophin has been purified to homogeneity, its gene has not been characterized. In this report we describe the cloning, expression, purification and characterization of the human homolog of myotrophin/V-1 protein. Sequence analysis indicators high homology (>90%) between all species at both the nucleotide and amino acid levels, and Southern blot analysis of genomic DNA from diverse species verifies that myotrophin/V-1 is a highly conserved gene. Northern analysis indicates wide-spread expression of a single human transcript, and examination of mRNA distribution in 50 human tissues by dot blot analysis indicates ubiquitous expression with relatively high expressioon in adult and fetal heart. We verify that recombinant human myotrophin produces cardiomyocyte hypertrophy, and we demonstrate for the first time that elevated levels of myotrophin/V-1 protein mRNA are expressed in human dilated cardiomyopathic hearts. We report the novel findings that myotrophin expression is elevated in ischemic hearts, and that myotrophin expression correlates positively with ventricular mass in a hypoxic rat model of induced right ventricular hypertrophy.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KM",
      "lastName" : "Anderson",
      "authorRank" : 1,
      "name" : "Anderson KM",
      "referenceId" : "RGD:A85084"
    }, {
      "firstName" : "I",
      "lastName" : "Berrebi-Bertrand",
      "authorRank" : 2,
      "name" : "Berrebi-Bertrand I",
      "referenceId" : "RGD:A51334"
    }, {
      "firstName" : "RB",
      "lastName" : "Kirkpatrick",
      "authorRank" : 3,
      "name" : "Kirkpatrick RB",
      "referenceId" : "RGD:A65272"
    }, {
      "firstName" : "MS",
      "lastName" : "McQueney",
      "authorRank" : 4,
      "name" : "McQueney MS",
      "referenceId" : "RGD:A65273"
    }, {
      "firstName" : "DC",
      "lastName" : "Underwood",
      "authorRank" : 5,
      "name" : "Underwood DC",
      "referenceId" : "RGD:A65274"
    }, {
      "firstName" : "S",
      "lastName" : "Rouanet",
      "authorRank" : 6,
      "name" : "Rouanet S",
      "referenceId" : "RGD:A65275"
    }, {
      "firstName" : "M",
      "lastName" : "Chabot-Fletcher",
      "authorRank" : 7,
      "name" : "Chabot-Fletcher M",
      "referenceId" : "RGD:A65276"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581047"
    } ]
  }, {
    "primaryId" : "PMID:10329212",
    "title" : "A physiologically relevant hyperthermia selectively activates constitutive hsp70  in H9c2 cardiac myoblasts and confers oxidative protection.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Su CY, etal., J Mol Cell Cardiol. 1999 Apr;31(4):845-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-18T11:08:26.000-05:00",
    "volume" : "31",
    "pages" : "845-55",
    "abstract" : "Whole body hyperthermia (42-43 degrees C for 15-20 min) elicits the formation of  heat shock proteins (hsps) and improves cardiac recovery from subsequent ischemia/reperfusion. However, the beneficial effects of this response are compromised by initial tissue injury, which limits its clinical applicability. Using a simplified myocardial model (rat heart-derived H9c2 myoblasts) a hypothesis was tested that chronic, mild hyperthermia is as effective as acute heat shock in inducing the heat shock response. Our results indicate that 39 degrees C pre-conditioning evoked thermotolerance and oxidative resistance, but caused no detectable adverse effects. An improved survival after hydrogen peroxide (H2O2) exposure (40-54 microm for 3 h) was first observed in cells pre-conditioned at 39 degrees C for 24 h. As the duration of thermal pre-incubation increased, cells became more resistant than the control (37 degrees C) to a greater toxicity of H2O2(68 microm). An optimal oxidative protection developed by;4 days at 39 degrees C and this persisted for as long as  the cells were incubated at this temperature. Three hsps are known to modulate cellular antioxidant defenses: the constitutive-hsp70 (hsc70), its inducible counterpart (hsp70), and hsp27. The authors found that mild hyperthermia selectively induced only hsc70, which demonstrates a lower temperature threshold  for activation of hsc70. The initial protection against the milder H2O2challenge  correlated with a homogenous distribution of pre-existing hsc70. The subsequent optimal protection was associated with an identical distribution pattern and a moderate increase of hsc70. These observations suggest that mild hyperthermia induces a beneficial adaptive response, in which hsc70 plays a critical role.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CY",
      "lastName" : "Su",
      "authorRank" : 1,
      "name" : "Su CY",
      "referenceId" : "RGD:A154399"
    }, {
      "firstName" : "KY",
      "lastName" : "Chong",
      "authorRank" : 2,
      "name" : "Chong",
      "referenceId" : "RGD:A205418"
    }, {
      "firstName" : "J",
      "lastName" : "Chen",
      "authorRank" : 3,
      "name" : "Chen",
      "referenceId" : "RGD:A415147"
    }, {
      "firstName" : "S",
      "lastName" : "Ryter",
      "authorRank" : 4,
      "name" : "Ryter",
      "referenceId" : "RGD:A205420"
    }, {
      "firstName" : "R",
      "lastName" : "Khardori",
      "authorRank" : 5,
      "name" : "Khardori",
      "referenceId" : "RGD:A205421"
    }, {
      "firstName" : "CC",
      "lastName" : "Lai",
      "authorRank" : 6,
      "name" : "Lai",
      "referenceId" : "RGD:A194229"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10059424"
    } ]
  }, {
    "primaryId" : "PMID:10329375",
    "title" : "Identification of a novel kinase-like gene induced during neuronal cell death.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mayumi-Matsuda K, etal., Biochem Biophys Res Commun 1999 May 10;258(2):260-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T17:21:06.000-05:00",
    "volume" : "258",
    "pages" : "260-4",
    "abstract" : "When deprived of neurotrophic factors, neuronal cells undergo a form of programmed cell death that involves a cascade of gene expression. To better understand this cascade, we screened the genes induced during programmed cell death evoked in neuronal PC6-3 cells by NGF-depletion and discovered a novel gene, NIPK (Neuronal cell death Inducible Putative Kinase), that contains a kinase-like domain. Expression of NIPK was also induced in cultured sympathetic neurons by NGF deprivation and in cortical neurons exposed to the Ca2+ ionophore, A23187. In contrast, NIPK was not induced during non-neuronal cell death evoked by serum or growth factor deprivation, or by treatment with methyl methanesulfonate, an agent that causes cell death by damaging DNA. Taken together, these findings suggest that NIPK is involved in programmed cell death via a pathway that is present in neurons but is absent in non-neurons.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Mayumi-Matsuda",
      "authorRank" : 1,
      "name" : "Mayumi-Matsuda K",
      "referenceId" : "RGD:A43054"
    }, {
      "firstName" : "S",
      "lastName" : "Kojima",
      "authorRank" : 2,
      "name" : "Kojima S",
      "referenceId" : "RGD:A43055"
    }, {
      "firstName" : "H",
      "lastName" : "Suzuki",
      "authorRank" : 3,
      "name" : "Suzuki H",
      "referenceId" : "RGD:A299780"
    }, {
      "firstName" : "T",
      "lastName" : "Sakata",
      "authorRank" : 4,
      "name" : "Sakata T",
      "referenceId" : "RGD:A23384"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299439"
    } ]
  }, {
    "primaryId" : "PMID:10329397",
    "title" : "Localization of glutaredoxin (thioltransferase) in the rat brain and possible functional implications during focal ischemia.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Takagi Y, etal., Biochem Biophys Res Commun. 1999 May 10;258(2):390-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-28T09:44:06.000-06:00",
    "volume" : "258",
    "pages" : "390-4",
    "abstract" : "We investigated the distribution of glutaredoxin (GRX, thioltransferase) in the rat brain using the in situ hybridization and immunohistochemical methods. GRX mRNA and GRX were expressed widely in the rat brain. The endothelial cell, tanycyte and ependymal cell expressed GRX mRNA and GRX protein. Neurons in various regions also showed GRX mRNA and GRX. Among them, pyramidal neurons in hippocampal CA3 region expressed a higher level of GRX mRNA. In addition, GRX mRNA signals were reduced after middle cerebral artery occlusion. Immunohistochemical analysis for GRX also revealed that GRX was reduced after ischemia. Northern blot analysis also showed that GRX mRNA from ischemic hemispheres decreased after ischemia. This reduction was parallel with the neuronal damage. This observation indicated that the maintenance of GRX and the redox regulating system was important for neuronal survival against oxidative stress.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Takagi",
      "authorRank" : 1,
      "name" : "Takagi Y",
      "referenceId" : "RGD:A12976"
    }, {
      "firstName" : "T",
      "lastName" : "Nakamura",
      "authorRank" : 2,
      "name" : "Nakamura",
      "referenceId" : "RGD:A416904"
    }, {
      "firstName" : "A",
      "lastName" : "Nishiyama",
      "authorRank" : 3,
      "name" : "Nishiyama A",
      "referenceId" : "RGD:A13754"
    }, {
      "firstName" : "K",
      "lastName" : "Nozaki",
      "authorRank" : 4,
      "name" : "Nozaki K",
      "referenceId" : "RGD:A64032"
    }, {
      "firstName" : "T",
      "lastName" : "Tanaka",
      "authorRank" : 5,
      "name" : "Tanaka",
      "referenceId" : "RGD:A416765"
    }, {
      "firstName" : "N",
      "lastName" : "Hashimoto",
      "authorRank" : 6,
      "name" : "Hashimoto N",
      "referenceId" : "RGD:A7792"
    }, {
      "firstName" : "J",
      "lastName" : "Yodoi",
      "authorRank" : 7,
      "name" : "Yodoi J",
      "referenceId" : "RGD:A35974"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9686043"
    } ]
  }, {
    "primaryId" : "PMID:10329450",
    "title" : "Thromboxane A2 receptor linked with the Ca2+ pathway in rat colonic crypt cells.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ikari A, etal., Biochem Biophys Res Commun. 1999 May 19;258(3):708-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-18T11:15:55.000-05:00",
    "volume" : "258",
    "pages" : "708-12",
    "abstract" : "To clarify the presence of thromboxane A2 (TXA2) receptor in the colonic epithelium, we examined the effect of 9,11-epithio-11, 12-methano-thromboxane A2  (STA2), a stable analogue of TXA2, on intracellular free Ca2+ concentration ([Ca2+]i) of indo-1-loaded single cells in isolated rat colonic crypts by laser confocal microscopy. STA2 increased [Ca2+]i in a concentration-dependent manner with a transient peak phase and a subsequent plateau phase. The EC50 values at peak and plateau phases were 1 and 32 nM, respectively. The STA2-induced increase in [Ca2+]i was completely blocked by two selective TXA2 receptor antagonists, KW-3635 and ONO-3708. These antagonists did not affect both the basal [Ca2+]i and the carbaco-induced increase in [Ca2+]i. Prostaglandin E2 did not increase [Ca2+]i. These results indicate that the STA2-elicited increase in [Ca2+]i is mediated specifically by a TXA2 receptor in colonic crypt cells This is the first report showing the presence of a TXA2 receptor that is associated with Ca2+ mobilization in the colon.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Ikari",
      "authorRank" : 1,
      "name" : "Ikari A",
      "referenceId" : "RGD:A74538"
    }, {
      "firstName" : "H",
      "lastName" : "Sakai",
      "authorRank" : 2,
      "name" : "Sakai",
      "referenceId" : "RGD:A389347"
    }, {
      "firstName" : "T",
      "lastName" : "Sato",
      "authorRank" : 3,
      "name" : "Sato T",
      "referenceId" : "RGD:A9831"
    }, {
      "firstName" : "N",
      "lastName" : "Takeguchi",
      "authorRank" : 4,
      "name" : "Takeguchi N",
      "referenceId" : "RGD:A81069"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11059605"
    } ]
  }, {
    "primaryId" : "PMID:10329451",
    "title" : "Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wen Y, etal., Biochem Biophys Res Commun. 1999 May 19;258(3):713-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-10T15:07:20.000-05:00",
    "volume" : "258",
    "pages" : "713-21",
    "abstract" : "Binding of vascular endothelial growth factor (VEGF) to its receptor, VEGFR-2 (Flk-1/KDR), induces dimerization and activation of the tyrosine kinase domain of the receptor, resulting in autophosphorylation of cytoplasmic tyrosine residues used as docking sites for signaling proteins that relay the signals for cell proliferation, migration, and permeability enhancement. We explored the VEGF/receptor signaling pathway by performing a two-hybrid screen of a rat lung cDNA library in yeast using the intracellular domain of rat VEGFR-2 as bait. Two clones encoding lipocortin V were isolated. Subsequent studies with the yeast two-hybrid assay showed that the complete intracellular domain of VEGFR-2 was required for the interaction. Co-immunoprecipitation of translated proteins confirmed the interaction between the VEGF receptor and lipocortin V. VEGF induced a rapid tyrosine phosphorylation of lipocortin V in human umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with antisense oligodeoxyribonucleotide (ODN) for lipocortin V significantly inhibited VEGF-induced cell proliferation, which was accompanied by a decrease in protein synthesis and tyrosine phosphorylation of lipocortin V. Our results indicate that lipocortin V may function as a signaling protein for VEGFR-2 by directly interacting with the intracellular domain of the receptor and appears to be involved in regulation of vascular endothelial cell proliferation mediated by VEGFR-2.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Wen",
      "authorRank" : 1,
      "name" : "Wen Y",
      "referenceId" : "RGD:A4545"
    }, {
      "firstName" : "JL",
      "lastName" : "Edelman",
      "authorRank" : 2,
      "name" : "Edelman JL",
      "referenceId" : "RGD:A31420"
    }, {
      "firstName" : "T",
      "lastName" : "Kang",
      "authorRank" : 3,
      "name" : "Kang T",
      "referenceId" : "RGD:A31421"
    }, {
      "firstName" : "G",
      "lastName" : "Sachs",
      "authorRank" : 4,
      "name" : "Sachs G",
      "referenceId" : "RGD:A4548"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292112"
    } ]
  }, {
    "primaryId" : "PMID:10329507",
    "title" : "Effect of arsenite on induction of CYP1A, CYP2B, and CYP3A in primary cultures of rat hepatocytes.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Jacobs JM, etal., Toxicol Appl Pharmacol. 1999 May 15;157(1):51-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-04-30T09:57:28.000-05:00",
    "volume" : "157",
    "pages" : "51-9",
    "abstract" : "In earlier studies, sodium arsenite treatment was shown to decrease induction of enzymatic activities associated with hepatic CYPs in rats. Here we investigated the effect of sodium arsenite on induction of CYP2B, CYP1A, and CYP3A in primary cultures of rat hepatocytes. Arsenite decreased the induction of all three families of CYP, as measured enzymatically and immunochemically. These decreases in CYPs occurred at concentrations of arsenite (2.5-10 microM) at which no toxicity was observed; however, toxicity was observed at 25 microM arsenite. With 3-methylcholanthrene as inducer, 5 microM arsenite caused a 55% decrease in CYP1A1 immunoreactive protein and enzyme activity, but only a 25% decrease in CYP1A1 mRNA. With phenobarbital (PB) as the inducer, 2.5 microM arsenite decreased CYP2B enzyme activity and immunoreactive protein 50%, with only a 25% decrease in CYP2B1 mRNA. 5 microM Arsenite decreased CYP2B enzyme activity and immunoreactive protein 80%, but decreased CYP2B1 mRNA only 50%, while CYP3A protein was decreased greater than 75% with no decrease in CYP3A23 mRNA. With dexamethasone (DEX) as inducer, 5 microM sodium arsenite caused a 50% decrease in immunoreactive CYP3A and a 30% decrease in CYP3A23 mRNA. Although arsenite-mediated increases in heme oxygenase (HO) inversely correlated with decreases in CYP2B or CYP1A activity, inclusion of heme in cultures treated with inducers of CYP1A or CYP2B did not prevent the arsenite-mediated decreases in these CYPs. Even though added heme induced HO to similar levels with and without arsenite, decreases in CYPs were only observed in the presence of arsenite. These results suggest that, in rat hepatocytes, elevated levels of HO alone are not responsible for arsenite-mediated decreases in CYP.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Jacobs",
      "authorRank" : 1,
      "name" : "Jacobs JM",
      "referenceId" : "RGD:A106063"
    }, {
      "firstName" : "CE",
      "lastName" : "Nichols",
      "authorRank" : 2,
      "name" : "Nichols CE",
      "referenceId" : "RGD:A106064"
    }, {
      "firstName" : "AS",
      "lastName" : "Andrew",
      "authorRank" : 3,
      "name" : "Andrew AS",
      "referenceId" : "RGD:A106065"
    }, {
      "firstName" : "DE",
      "lastName" : "Marek",
      "authorRank" : 4,
      "name" : "Marek DE",
      "referenceId" : "RGD:A106066"
    }, {
      "firstName" : "SG",
      "lastName" : "Wood",
      "authorRank" : 5,
      "name" : "Wood SG",
      "referenceId" : "RGD:A106067"
    }, {
      "firstName" : "PR",
      "lastName" : "Sinclair",
      "authorRank" : 6,
      "name" : "Sinclair PR",
      "referenceId" : "RGD:A85889"
    }, {
      "firstName" : "SA",
      "lastName" : "Wrighton",
      "authorRank" : 7,
      "name" : "Wrighton SA",
      "referenceId" : "RGD:A106068"
    }, {
      "firstName" : "VE",
      "lastName" : "Kostrubsky",
      "authorRank" : 8,
      "name" : "Kostrubsky VE",
      "referenceId" : "RGD:A106069"
    }, {
      "firstName" : "JF",
      "lastName" : "Sinclair",
      "authorRank" : 9,
      "name" : "Sinclair JF",
      "referenceId" : "RGD:A106070"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306684"
    } ]
  }, {
    "primaryId" : "PMID:10329590",
    "title" : "Hyperglycemia-induced vasculopathy in the murine vitelline vasculature: correlation with PECAM-1/CD31 tyrosine phosphorylation state.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Pinter E, etal., Am J Pathol. 1999 May;154(5):1367-79.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-07-28T17:10:15.000-05:00",
    "volume" : "154",
    "pages" : "1367-79",
    "abstract" : "Maternal diabetes mellitus is associated with an increased incidence of congenital abnormalities as well as embryonic and perinatal lethality. In particular, a wide range of cardiovascular abnormalities have been noted in children of diabetic mothers and in the offspring of diabetic animals. The vascular system is the first organ system to develop in the embryo and is critical for normal organogenesis. The organization of mesodermal cells into endothelial and hematopoietic cells and into a complex vascular system is, in part, mediated by a series of specific cell-cell, cell-extracellular matrix, and cell-factor interactions. PECAM-1 expression has been observed during the earliest stages of vasculogenesis, and changes in PECAM-1 tyrosine phosphorylation have been associated with endothelial cell migration, vasculogenesis, and angiogenesis both in vitro and in vivo. In this report we demonstrate that exposure to hyperglycemia during gastrulation causes yolk sac and embryonic vasculopathy in cultured murine conceptuses and in the conceptuses of streptozotocin-induced diabetic pregnant mice. In addition, we correlate the presence of yolk sac and embryonic vasculopathy with the failure of PECAM-1 tyrosine dephosphorylation during the formation of blood islands/vessels from clusters of extra-embryonic and embryonic angioblasts in the murine conceptus using both in vitro and in vivo models. The importance of these findings in the development of vasculopathy in the offspring of diabetic mothers and the potential effects and benefits of glucose regulation during the periods of vasculogenesis/angiogenesis in embryonic development are discussed.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Pinter",
      "authorRank" : 1,
      "name" : "Pinter E",
      "referenceId" : "RGD:A110040"
    }, {
      "firstName" : "S",
      "lastName" : "Mahooti",
      "authorRank" : 2,
      "name" : "Mahooti S",
      "referenceId" : "RGD:A110041"
    }, {
      "firstName" : "Y",
      "lastName" : "Wang",
      "authorRank" : 3,
      "name" : "Wang Y",
      "referenceId" : "RGD:A381280"
    }, {
      "firstName" : "BA",
      "lastName" : "Imhof",
      "authorRank" : 4,
      "name" : "Imhof BA",
      "referenceId" : "RGD:A110042"
    }, {
      "firstName" : "JA",
      "lastName" : "Madri",
      "authorRank" : 5,
      "name" : "Madri JA",
      "referenceId" : "RGD:A110043"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311657"
    } ]
  }, {
    "primaryId" : "PMID:10329655",
    "title" : "Cholesterol biosynthesis from lanosterol. Molecular cloning, tissue distribution, expression, chromosomal localization, and regulation of rat 7-dehydrocholesterol reductase, a Smith-Lemli-Opitz syndrome-related protein.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Bae SH, etal., J Biol Chem 1999 May 21;274(21):14624-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-21T16:24:25.000-05:00",
    "volume" : "274",
    "pages" : "14624-31",
    "abstract" : "The cDNA encoding the 471-amino acid rat 7-dehydrocholesterol reductase (DHCR), an enzyme that has been implicated in both cholesterol biosynthesis and developmental abnormalities (e.g. Smith-Lemli-Opitz syndrome) in mammals, has been cloned and sequenced, and the primary structure of the enzyme has been deduced. The DHCR gene was mapped to chromosome 8q2.1 by fluorescence in situ hybridization. Rat DHCR, calculated molecular mass of 54.15-kDa polypeptide, shares a close amino acid identity with mouse and human DHCRs (96 and 87%, respectively) as compared with its other related proteins (e.g. fungal sterol Delta14-reductase) and exhibits high hydrophobicity (>68%) with 9 transmembrane domains. Five putative sterol-sensing domains were predicted to be localized in transmembrane domains 4-8, which are highly homologous to those found in 3-hydroxymethylglutaryl-CoA reductase, sterol regulatory element-binding protein cleavage-activating protein, and patched protein. The polypeptide encoded by DHCR cDNA was expressed in yeast as a 55.45-kDa myc-tagged fusion protein, which was recognized with anti-myc monoclonal antibody 9E10 and shown to possess full DHCR activity with respect to dependence on NADPH and sensitivity to DHCR inhibitors. Northern blot analysis indicates that the highest expression of DHCR mRNA was detected in liver, followed by kidney and brain. In rat brains, the highest level of mRNA encoding DHCR was detected in the midbrain, followed by the spinal cord and medulla. Feeding rats 5% cholestyramine plus 0.1% lovastatin in chow resulted in both approximately a 3-fold induction of DHCR mRNA and a 5-fold increase of the enzymic activity in the liver. When rats were fed 0.1% (w/w) AY-9944 (in chow) for 14-days, a complete inhibition of DHCR activity and a significant reduction in serum total cholesterol level were observed. However, the level of hepatic DHCR mRNA fell only slightly, suggesting that AY-9944 may act more rapidly at the protein level than at the level of transcription of the DHCR gene under these conditions.",
    "issueName" : "21",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SH",
      "lastName" : "Bae",
      "authorRank" : 1,
      "name" : "Bae SH",
      "referenceId" : "RGD:A12184"
    }, {
      "firstName" : "JN",
      "lastName" : "Lee",
      "authorRank" : 2,
      "name" : "Lee JN",
      "referenceId" : "RGD:A12183"
    }, {
      "firstName" : "BU",
      "lastName" : "Fitzky",
      "authorRank" : 3,
      "name" : "Fitzky BU",
      "referenceId" : "RGD:A16133"
    }, {
      "firstName" : "J",
      "lastName" : "Seong",
      "authorRank" : 4,
      "name" : "Seong J",
      "referenceId" : "RGD:A13704"
    }, {
      "firstName" : "YK",
      "lastName" : "Paik",
      "authorRank" : 5,
      "name" : "Paik YK",
      "referenceId" : "RGD:A12185"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632010"
    } ]
  }, {
    "primaryId" : "PMID:10329663",
    "title" : "Identification of rabbit reticulocyte E217K as a UBC7 homologue and functional characterization of its core domain loop.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Lin H and Wing SS, J Biol Chem 1999 May 21;274(21):14685-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:36:26.000-05:00",
    "volume" : "274",
    "pages" : "14685-91",
    "abstract" : "The structural basis by which ubiquitin (Ub)-conjugating enzymes (E2s) determine substrate specificity remains unclear. We cloned rabbit reticulocyte E217K because unlike the similarly sized class I E2s, E214K and UBC4, it is unable to support ubiquitin-protein ligase (E3)-dependent conjugation to endogenous proteins. RNA analysis revealed that this E2 was expressed in all tissues tested, with higher levels in the testis. Analysis of testis RNA from rats of different ages showed that E217K mRNA was induced from days 15 to 30. The predicted amino acid sequence indicates that E217K is a 19. 5-kDa class I E2 but differs from other class I enzymes in possessing an insertion of 13 amino acids distal to the active site cysteine. E217K shows 74% amino acid identity with Saccharomyces cerevisiae UBC7, and therefore, we rename it mammalian UBC7. Yeast UBC7 crystal structure indicates that this insertion forms a loop out of the otherwise conserved folding structure. Sequence analysis of E2s had previously suggested that this loop is a hypervariable region and may play a role in substrate specificity. We created mutant UBC7 lacking the loop (ubc7Deltaloop) and a mutant E214k with an inserted loop (E214k+loop) and characterized their biochemical functions. Ubc7Deltaloop had higher affinity for the E1-Ub thiol ester than native UBC7 and permitted conjugation of Ub to selected proteins in the testis but did not permit the broad spectrum E3-dependent conjugation to endogenous reticulocyte proteins. Surprisingly, E214k+loop was unable to accept Ub from ubiquitin-activating enzyme (E1) but was able to accept NEDD8 from E1. E214k+loop was able to support conjugation of NEDD8 to endogenous reticulocyte proteins but with much lower efficiency than E214k. Thus, the loop can influence interactions of the E2 with charged E1 as well as with E3s or substrates, but the exact nature of these interactions depends on divergent sequences in the remaining conserved core domain.",
    "issueName" : "21",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Lin",
      "authorRank" : 1,
      "name" : "Lin H",
      "referenceId" : "RGD:A23648"
    }, {
      "firstName" : "SS",
      "lastName" : "Wing",
      "authorRank" : 2,
      "name" : "Wing SS",
      "referenceId" : "RGD:A6579"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634475"
    } ]
  }, {
    "primaryId" : "PMID:10329667",
    "title" : "Molecular cloning and functional expression of the mouse gap junction gene connexin-57 in human HeLa cells.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Manthey D, etal., J Biol Chem. 1999 May 21;274(21):14716-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-21T18:08:39.000-06:00",
    "volume" : "274",
    "pages" : "14716-23",
    "abstract" : "A new mouse connexin gene has been isolated that codes for a connexin protein of 505 amino acid residues. Based on the predicted molecular mass of 57.115 kDa, it has been designated connexin-57. Similar to most other mouse connexin genes, the coding region of connexin-57 is not interrupted by introns and exists in the mouse genome as a single-copy gene. Within the connexin family, this new gene shows highest sequence identity to porcine connexin-60 in the alpha group of connexins. The connexin-57 gene was mapped to a position on mouse chromosome 4, 30 centimorgans proximal to a cluster of previously mapped connexin genes. Low levels of connexin-57 mRNA were detected in skin, heart, kidney, testis, ovary, intestine, and in the mouse embryo after 8 days post coitum, but expression was not detected in brain, sciatic nerve or liver. In order to analyze gene function, the connexin-57 coding region was expressed by transfection in human HeLa cells, where it restored homotypic intercellular transfer of microinjected neurobiotin. Heterotypic transfer was observed between HeLa connexin-57 transfectants and HeLa cells, expressing murine connexin-43, -37, or -30.3. Double whole-cell voltage clamp analyses revealed that HeLa-connexin-57 transfectants expressed about 10 times more channels than parental HeLa cells. Voltage gating by transjunctional and transmembrane voltages as well as unitary conductance ( approximately 27 picosiemens) were different from intrinsic connexin channels in parental HeLa cells.",
    "issueName" : "21",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Manthey",
      "authorRank" : 1,
      "name" : "Manthey D",
      "referenceId" : "RGD:A58904"
    }, {
      "firstName" : "F",
      "lastName" : "Bukauskas",
      "authorRank" : 2,
      "name" : "Bukauskas F",
      "referenceId" : "RGD:A58905"
    }, {
      "firstName" : "CG",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee CG",
      "referenceId" : "RGD:A56904"
    }, {
      "firstName" : "CA",
      "lastName" : "Kozak",
      "authorRank" : 4,
      "name" : "Kozak CA",
      "referenceId" : "RGD:A74637"
    }, {
      "firstName" : "K",
      "lastName" : "Willecke",
      "authorRank" : 5,
      "name" : "Willecke K",
      "referenceId" : "RGD:A7408"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578422"
    } ]
  }, {
    "primaryId" : "PMID:10329704",
    "title" : "Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "He XY, etal., J Biol Chem 1999 May 21;274(21):15014-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-10T12:27:50.000-05:00",
    "volume" : "274",
    "pages" : "15014-9",
    "abstract" : "Human brain short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) was found to catalyze the oxidation of 17beta-estradiol and dihydroandrosterone as well as alcohols. Mitochondria have been demonstrated to be the proper location of this NAD+-dependent dehydrogenase in cells, although its primary structure is identical to an amyloid beta-peptide binding protein reportedly associated with the endoplasmic reticulum (ERAB). This fatty acid beta-oxidation enzyme was identified as a novel 17beta-hydroxysteroid dehydrogenase responsible for the inactivation of sex steroid hormones. The catalytic rate constant of the purified enzyme was estimated to be 0.66 min-1 with apparent Km values of 43 and 50 microM for 17beta-estradiol and NAD+, respectively. The catalytic efficiency of this enzyme for the oxidation of 17beta-estradiol was comparable with that of peroxisomal 17beta-hydroxysteroid dehydrogenase type 4. As a result, the human SCHAD gene product, a single-domain multifunctional enzyme, appears to function in two different pathways of lipid metabolism. Because the catalytic functions of human brain short chain L-3-hydroxyacyl-CoA dehydrogenase could weaken the protective effects of estrogen and generate aldehydes in neurons, it is proposed that a high concentration of this enzyme in brain is a potential risk factor for Alzheimer's disease.",
    "issueName" : "21",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "XY",
      "lastName" : "He",
      "authorRank" : 1,
      "name" : "He XY",
      "referenceId" : "RGD:A137754"
    }, {
      "firstName" : "G",
      "lastName" : "Merz",
      "authorRank" : 2,
      "name" : "Merz G",
      "referenceId" : "RGD:A5903"
    }, {
      "firstName" : "P",
      "lastName" : "Mehta",
      "authorRank" : 3,
      "name" : "Mehta P",
      "referenceId" : "RGD:A5907"
    }, {
      "firstName" : "H",
      "lastName" : "Schulz",
      "authorRank" : 4,
      "name" : "Schulz H",
      "referenceId" : "RGD:A5908"
    }, {
      "firstName" : "SY",
      "lastName" : "Yang",
      "authorRank" : 5,
      "name" : "Yang SY",
      "referenceId" : "RGD:A5909"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358377"
    } ]
  }, {
    "primaryId" : "PMID:10329733",
    "title" : "p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor.",
    "datePublished" : "1999-05-21T00:00:00.000-05:00",
    "citation" : "Budhram-Mahadeo V, etal., J Biol Chem. 1999 May 21;274(21):15237-44. doi: 10.1074/jbc.274.21.15237.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-08-03T07:17:38.000-05:00",
    "volume" : "274",
    "pages" : "15237-44",
    "abstract" : "The Brn-3a POU family transcription factor has been shown to strongly activate expression of the Bcl-2 proto-oncogene and thereby protect neuronal cells from programmed cell death (apoptosis). This activation of the Bcl-2 promoter by Brn-3a is strongly inhibited by the p53 anti-oncogene protein. This inhibitory effect of p53 on Brn-3a-mediated transactivation is observed with nonoverlapping gene fragments containing either the Bcl-2 p1 or p2 promoters but is not observed with other Brn-3a-activated promoters such as in the gene encoding alpha-internexin or with an isolated Brn-3a binding site from the Bcl-2 promoter linked to a heterologous promoter. In contrast, p53 mutants, which are incapable of binding to DNA, do not affect Brn-3a-mediated activation of the Bcl-2 p1 and p2 promoters. Moreover, Brn-3a and p53 have been shown to bind to adjacent sites in the p2 promoter and to directly interact with one another, both in vitro and in vivo, with this interaction being mediated by the POU domain of Brn-3a and the DNA binding domain of p53. The significance of these effects is discussed in terms of the antagonistic effects of Bcl-2 and p53 on the rate of apoptosis and the overexpression of Brn-3a in specific tumor cell types.",
    "issueName" : "21",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Budhram-Mahadeo",
      "authorRank" : 1,
      "name" : "Budhram-Mahadeo V",
      "referenceId" : "RGD:A464003"
    }, {
      "firstName" : "P J",
      "lastName" : "Morris",
      "authorRank" : 2,
      "name" : "Morris PJ",
      "referenceId" : "RGD:A472142"
    }, {
      "firstName" : "M D",
      "lastName" : "Smith",
      "authorRank" : 3,
      "name" : "Smith MD",
      "referenceId" : "RGD:A472143"
    }, {
      "firstName" : "C A",
      "lastName" : "Midgley",
      "authorRank" : 4,
      "name" : "Midgley CA",
      "referenceId" : "RGD:A472144"
    }, {
      "firstName" : "L M",
      "lastName" : "Boxer",
      "authorRank" : 5,
      "name" : "Boxer LM",
      "referenceId" : "RGD:A472145"
    }, {
      "firstName" : "D S",
      "lastName" : "Latchman",
      "authorRank" : 6,
      "name" : "Latchman DS",
      "referenceId" : "RGD:A472146"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14697712"
    } ]
  }, {
    "primaryId" : "PMID:10329919",
    "title" : "Quantitative analysis of CD79b, CD5 and CD19 in mature B-cell lymphoproliferative disorders.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Cabezudo E, etal., Haematologica. 1999 May;84(5):413-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-29T12:23:48.000-05:00",
    "volume" : "84",
    "pages" : "413-8",
    "abstract" : "BACKGROUND AND OBJECTIVE: Distinction between B-cell chronic leukemias can be difficult due to overlap in cell morphology and immunologic features. We investigated, by quantitative flow cytometry, the expression of CD79b, CD5 and CD19 in cells from a variety of B-cell disorders to see whether this analysis adds further information useful to the diagnosis and characterization of these diseases. DESIGN AND METHODS: Peripheral blood cells from 6 normal individuals were used as reference controls. The diseases of the 63 patients investigated comprised: 29 chronic lymphocytic leukemia (CLL), six of them with atypical morphology, 6 B-cell prolymphocytic leukemia (PLL), 12 splenic lymphoma with villous lymphocytes (SLVL) and 16 mantle-cell (Mc) lymphoma in leukemic phase. The study was carried out by triple immunostaining with directly conjugated monoclonal antibodies (MoAb) against CD79b, CD5 and CD19 and quantitative estimation of the antigens per cell assessed with standard microbeads (Quantum Simply Cellular). RESULTS: Compared to normal B-cells, the number of CD19 molecules was significantly lower in cells from all of the B-cell disorders except PLL. The intensity of CD5 in leukemic B-cells was significantly higher in  CLL cells, including atypical cases, and Mc lymphoma than in normal B-cells, whilst PLL and SLVL had values similar to those of normal B-lymphocytes. CD79b was expressed at lower levels in all types of leukemic cells compared to normal B-lymphocytes but differences were statistically significant in CLL, Mc lymphoma  and SLVL. The number of CD79b molecules per cell was significantly lower in typical CLL than in the remaining B-cell diseases whilst the comparison of CD5 and CD19 intensity between CLL and non-CLL samples failed to show any statistically significant difference. INTERPRETATION AND CONCLUSIONS: Distinct antigen density patterns for the various conditions emerged from this analysis: Typical CLL was characterized by moderate CD5 and weak or negative CD79b expression. Mc lymphoma showed an homogeneous pattern, characterized by similar expression of CD5 than CLL but significantly stronger expression of CD79b whilst  PLL and SLVL had weak CD5 and moderate CD79b expression. Atypical CLL had an intermediate pattern of CD79b antigen expression ranging from weak to moderate with bright CD5. Unlike CD5 and CD79b, CD19 did not discriminate the various B-cell disorders but only between normal and leukemic cells.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Cabezudo",
      "authorRank" : 1,
      "name" : "Cabezudo",
      "referenceId" : "RGD:A374422"
    }, {
      "firstName" : "P",
      "lastName" : "Carrara",
      "authorRank" : 2,
      "name" : "Carrara",
      "referenceId" : "RGD:A374423"
    }, {
      "firstName" : "R",
      "lastName" : "Morilla",
      "authorRank" : 3,
      "name" : "Morilla",
      "referenceId" : "RGD:A374424"
    }, {
      "firstName" : "E",
      "lastName" : "Matutes",
      "authorRank" : 4,
      "name" : "Matutes",
      "referenceId" : "RGD:A211037"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11531139"
    } ]
  }, {
    "primaryId" : "PMID:10330043",
    "title" : "Genetic disruption of atrial natriuretic peptide causes pulmonary hypertension in normoxic and hypoxic mice.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Klinger JR, etal., Am J Physiol. 1999 May;276(5 Pt 1):L868-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-06T15:58:10.000-06:00",
    "volume" : "276",
    "pages" : "L868-74",
    "abstract" : "To determine whether atrial natriuretic peptide (ANP) plays a physiological role in modulating pulmonary hypertensive responses, we studied mice with gene-targeted disruption of the ANP gene under normoxic and chronically hypoxic conditions. Right ventricular peak pressure (RVPP), right ventricle weight- and left ventricle plus septum weight-to-body weight ratios [RV/BW and (LV+S)/BW, respectively], and muscularization of pulmonary vessels were measured in wild-type mice (+/+) and in mice heterozygous (+/-) and homozygous (-/-) for a disrupted proANP gene after 3 wk of normoxia or hypobaric hypoxia (0.5 atm). Under normoxic conditions, homozygous mutants had higher RVPP (22 +/- 2 vs. 15 +/- 1 mmHg; P < 0.05) than wild-type mice and greater RV/BW (1.22 +/- 0.08 vs. 0.94 +/- 0.07 and 0.76 +/- 0.04 mg/g; P < 0.05) and (LV+S)/BW (4.74 +/- 0. 42 vs. 3.53 +/- 0.14 and 3.18 +/- 0.18 mg/g; P < 0.05) than heterozygous or wild-type mice, respectively. Three weeks of hypoxia increased RVPP in heterozygous and wild-type mice and increased RV/BW and RV/(LV+S) in all genotypes compared with their normoxic control animals but had no effect on (LV+S)/BW. After 3 wk of hypoxia, homozygous mutants had higher RVPP (29 +/- 3 vs. 23 +/- 1 and 22 +/- 2 mmHg; P < 0.05), RV/BW (2.03 +/- 0.14 vs. 1.46 +/- 0.04 and 1.33 +/- 0.08 mg/g; P < 0.05), and (LV+S)/BW (4.76 +/- 0.23 vs. 3.82 +/- 0.09 and 3.44 +/- 0.14 mg/g; P < 0.05) than heterozygous or wild-type mice, respectively. The percent muscularization of peripheral pulmonary vessels was greater in homozygous mutants than that in heterozygous or wild-type mice under both normoxic and hypoxic conditions. We conclude that endogenous ANP plays a physiological role in modulating pulmonary arterial pressure, cardiac hypertrophy, and pulmonary vascular remodeling under normoxic and hypoxic conditions.",
    "issueName" : "5 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JR",
      "lastName" : "Klinger",
      "authorRank" : 1,
      "name" : "Klinger JR",
      "referenceId" : "RGD:A6407"
    }, {
      "firstName" : "RR",
      "lastName" : "Warburton",
      "authorRank" : 2,
      "name" : "Warburton RR",
      "referenceId" : "RGD:A58581"
    }, {
      "firstName" : "LA",
      "lastName" : "Pietras",
      "authorRank" : 3,
      "name" : "Pietras LA",
      "referenceId" : "RGD:A58582"
    }, {
      "firstName" : "O",
      "lastName" : "Smithies",
      "authorRank" : 4,
      "name" : "Smithies O",
      "referenceId" : "RGD:A15324"
    }, {
      "firstName" : "R",
      "lastName" : "Swift",
      "authorRank" : 5,
      "name" : "Swift R",
      "referenceId" : "RGD:A58583"
    }, {
      "firstName" : "NS",
      "lastName" : "Hill",
      "authorRank" : 6,
      "name" : "Hill NS",
      "referenceId" : "RGD:A6408"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578330"
    } ]
  }, {
    "primaryId" : "PMID:10330122",
    "title" : "Comparative mapping of the region of human chromosome 7 deleted in williams syndrome.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "DeSilva U, etal., Genome Res 1999 May;9(5):428-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-06T13:37:53.000-05:00",
    "volume" : "9",
    "pages" : "428-36",
    "abstract" : "Williams syndrome (WS) is a complex developmental disorder resulting from the deletion of a large (approximately 1.5-2 Mb) segment of human chromosome 7q11.23. Physical mapping studies have revealed that this deleted region, which contains a number of known genes, is flanked by several large, nearly identical blocks of DNA. The presence of such highly related DNA segments in close physical proximity to one another has hampered efforts to elucidate the precise long-range organization of this segment of chromosome 7. To gain insight about the structure and evolutionary origins of this important and complex genomic region, we have constructed a fully contiguous bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) contig map encompassing the corresponding region on mouse chromosome 5. In contrast to the difficulties encountered in constructing a clone-based physical map of the human WS region, the BAC/PAC-based map of the mouse WS region was straightforward to construct, with no evidence of large duplicated segments, such as those encountered in the human WS region. To confirm this difference, representative human and mouse BACs were used as probes for performing fluorescence in situ hybridization (FISH) to metaphase and interphase chromosomes. Human BACs derived from the nonunique portion of the WS region hybridized to multiple, closely spaced regions on human chromosome 7q11.23. In contrast, corresponding mouse BACs hybridized to a single site on mouse chromosome 5. Furthermore, FISH analysis revealed the presence of duplicated segments within the WS region of various nonhuman primates (chimpanzee, gorilla, orangutan, and gibbon). Hybridization was also noted at the genomic locations corresponding to human chromosome 7p22 and 7q22 in human, chimpanzee, and gorilla, but not in the other animal species examined. Together, these results indicate that the WS region is associated with large, duplicated blocks of DNA on human chromosome 7q11.23 as well as the corresponding genomic regions of other nonhuman primates. However, such duplications are not present in the mouse.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "U",
      "lastName" : "DeSilva",
      "authorRank" : 1,
      "name" : "DeSilva U",
      "referenceId" : "RGD:A55673"
    }, {
      "firstName" : "H",
      "lastName" : "Massa",
      "authorRank" : 2,
      "name" : "Massa H",
      "referenceId" : "RGD:A55786"
    }, {
      "firstName" : "BJ",
      "lastName" : "Trask",
      "authorRank" : 3,
      "name" : "Trask BJ",
      "referenceId" : "RGD:A47789"
    }, {
      "firstName" : "ED",
      "lastName" : "Green",
      "authorRank" : 4,
      "name" : "Green ED",
      "referenceId" : "RGD:A7697"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549664"
    } ]
  }, {
    "primaryId" : "PMID:10330132",
    "title" : "Mouse molecular cytogenetic resource: 157 BACs link the chromosomal and genetic maps.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Korenberg JR, etal., Genome Res 1999 May;9(5):514-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-01T15:11:53.000-05:00",
    "volume" : "9",
    "pages" : "514-23",
    "abstract" : "We have established a collection of strong molecular cytogenetic markers that span the mouse autosomes and X chromosome at an average spacing of one per 19 Mb and identify 127 distinct band landmarks. In addition, this Mouse Molecular Cytogenetic Resource relates the ends of the genetic maps to their chromosomal locations. The resource consists of 157 bacterial artificial chromosome (BAC) clones, each of which identifies specific mouse chromosome bands or band borders, and 42 of which are linked to genetic markers that define the centromeric and telomeric ends of the Whitehead/MIT recombinational maps. In addition, 108 randomly selected and 6 STS-linked BACs have been assigned to single chromosome bands. We have also developed a high-resolution fluorescent reverse-banding technique for mouse chromosomes that allows simultaneous localization of probes by fluorescence in situ hybridization (FISH) with respect to the cytogenetic landmarks. This approach integrates studies of the entire mouse genome. Moreover, these reagents will simplify gene mapping and analyses of genomic fragments in fetal and adult mouse models. As shown with the MMU16 telomeric marker for the trisomy 16 mouse model of Down syndrome, these clones can obviate the need for metaphase analyses. The potential contribution of this resource and associated methods extends well beyond mapping and includes clues to understanding mouse chromosomes and their rearrangements in cancers and evolution. Finally it will facilitate the development of an integrated view of the mouse genome by providing anchor points from the genetic to the cytogenetic and functional maps of the mouse as we attempt to understand mutations, their biological consequences, and gene function.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JR",
      "lastName" : "Korenberg",
      "authorRank" : 1,
      "name" : "Korenberg JR",
      "referenceId" : "RGD:A28738"
    }, {
      "firstName" : "XN",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen XN",
      "referenceId" : "RGD:A36040"
    }, {
      "firstName" : "KL",
      "lastName" : "Devon",
      "authorRank" : 3,
      "name" : "Devon KL",
      "referenceId" : "RGD:A55293"
    }, {
      "firstName" : "D",
      "lastName" : "Noya",
      "authorRank" : 4,
      "name" : "Noya D",
      "referenceId" : "RGD:A55294"
    }, {
      "firstName" : "ML",
      "lastName" : "Oster-Granite",
      "authorRank" : 5,
      "name" : "Oster-Granite ML",
      "referenceId" : "RGD:A55295"
    }, {
      "firstName" : "BW",
      "lastName" : "Birren",
      "authorRank" : 6,
      "name" : "Birren BW",
      "referenceId" : "RGD:A20254"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549524"
    } ]
  }, {
    "primaryId" : "PMID:10330176",
    "title" : "Cooperative interaction between GATA-4 and GATA-6 regulates myocardial gene expression.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Charron F, etal., Mol Cell Biol. 1999 Jun;19(6):4355-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:35:22.000-05:00",
    "volume" : "19",
    "pages" : "4355-65",
    "abstract" : "Two members of the GATA family of transcription factors, GATA-4 and GATA-6, are expressed in the developing and postnatal myocardium and are equally potent transactivators of several cardiac promoters. However, several in vitro and in vivo lines of evidence suggest distinct roles for the two factors in the heart. Since identification of the endogenous downstream targets of GATA factors would greatly help to elucidate their exact functions, we have developed an adenovirus-mediated antisense strategy to specifically inhibit GATA-4 and GATA-6  protein production in postnatal cardiomyocytes. Expression of several endogenous  cardiac genes was significantly down-regulated in cells lacking GATA-4 or GATA-6, indicating that these factors are required for the maintenance of the cardiac genetic program. Interestingly, transcription of some genes like the alpha- and beta-myosin heavy-chain (alpha- and beta-MHC) genes was preferentially regulated  by GATA-4 due, in part, to higher affinity of GATA-4 for their promoter GATA element. However, transcription of several other genes, including the atrial natriuretic factor and B-type natriuretic peptide (ANF and BNP) genes, was similarly down-regulated in cardiomyocytes lacking one or both GATA factors, suggesting that GATA-4 and GATA-6 could act through the same transcriptional pathway. Consistent with this, GATA-4 and GATA-6 were found to colocalize in postnatal cardiomyocytes and to interact functionally and physically to provide cooperative activation of the ANF and BNP promoters. The results identify for the first time bona fide in vivo targets for GATA-4 and GATA-6 in the myocardium. The data also show that GATA factors act in concert to regulate distinct subsets of genes, suggesting that combinatorial interactions among GATA factors may differentially control various cellular processes.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Charron",
      "authorRank" : 1,
      "name" : "Charron F",
      "referenceId" : "RGD:A58936"
    }, {
      "firstName" : "P",
      "lastName" : "Paradis",
      "authorRank" : 2,
      "name" : "Paradis P",
      "referenceId" : "RGD:A39449"
    }, {
      "firstName" : "O",
      "lastName" : "Bronchain",
      "authorRank" : 3,
      "name" : "Bronchain",
      "referenceId" : "RGD:A184563"
    }, {
      "firstName" : "G",
      "lastName" : "Nemer",
      "authorRank" : 4,
      "name" : "Nemer G",
      "referenceId" : "RGD:A58934"
    }, {
      "firstName" : "M",
      "lastName" : "Nemer",
      "authorRank" : 5,
      "name" : "Nemer M",
      "referenceId" : "RGD:A9035"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553656"
    } ]
  }, {
    "primaryId" : "PMID:10330181",
    "title" : "DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Kishida S, etal., Mol Cell Biol. 1999 Jun;19(6):4414-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-07-30T13:36:20.000-05:00",
    "volume" : "19",
    "pages" : "4414-22",
    "abstract" : "The N-terminal region of Dvl-1 (a mammalian Dishevelled homolog) shares 37% identity with the C-terminal region of Axin, and this related region is named the DIX domain. The functions of the DIX domains of Dvl-1 and Axin were investigated. By yeast two-hybrid screening, the DIX domain of Dvl-1 was found to interact with Dvl-3, a second mammalian Dishevelled relative. The DIX domains of Dvl-1 and Dvl-3 directly bound one another. Furthermore, Dvl-1 formed a homo-oligomer. Axin also formed a homo-oligomer, and its DIX domain was necessary. The N-terminal region of Dvl-1, including its DIX domain, bound to Axin directly. Dvl-1 inhibited Axin-promoted glycogen synthase kinase 3beta-dependent phosphorylation of beta-catenin, and the DIX domain of Dvl-1 was required for this inhibitory activity. Expression of Dvl-1 in L cells induced the nuclear accumulation of beta-catenin, and deletion of the DIX domain abolished this activity. Although expression of Axin in SW480 cells caused the degradation of beta-catenin and reduced the cell growth rate, expression of an Axin mutant that lacks the DIX domain did not affect the level of beta-catenin or the growth rate. These results indicate that the DIX domains of Dvl-1 and Axin are important for protein-protein interactions and that they are necessary for the ability of Dvl-1 and Axin to regulate the stability of beta-catenin.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kishida",
      "authorRank" : 1,
      "name" : "Kishida S",
      "referenceId" : "RGD:A5603"
    }, {
      "firstName" : "H",
      "lastName" : "Yamamoto",
      "authorRank" : 2,
      "name" : "Yamamoto H",
      "referenceId" : "RGD:A158691"
    }, {
      "firstName" : "S",
      "lastName" : "Hino",
      "authorRank" : 3,
      "name" : "Hino S",
      "referenceId" : "RGD:A5920"
    }, {
      "firstName" : "S",
      "lastName" : "Ikeda",
      "authorRank" : 4,
      "name" : "Ikeda S",
      "referenceId" : "RGD:A5605"
    }, {
      "firstName" : "M",
      "lastName" : "Kishida",
      "authorRank" : 5,
      "name" : "Kishida M",
      "referenceId" : "RGD:A15935"
    }, {
      "firstName" : "A",
      "lastName" : "Kikuchi",
      "authorRank" : 6,
      "name" : "Kikuchi A",
      "referenceId" : "RGD:A5608"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4108508"
    } ]
  }, {
    "primaryId" : "PMID:10330244",
    "title" : "Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Wickenden AD, etal., Am J Physiol 1999 May;276(5 Pt 2):H1599-607.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-01-15T11:16:35.000-06:00",
    "volume" : "276",
    "pages" : "H1599-607",
    "abstract" : "The aim of the present study was to assess differences in transient outward potassium current (Ito) between the right ventricular free wall and the interventricular septum of the adult rat ventricle and to evaluate the relative contributions of Kv4.2, Kv4.3, and Kv1.4 to Ito in these regions. The results show that Ito is composed of both rapidly and slowly recovering components in the right wall and septum. The fast component had a significantly higher density in the right free wall than in the septum, whereas the slow component did not differ between the two sites. Kv4.2 mRNA and protein levels were also highest in the right wall and correlated with Ito density, whereas Kv4.3 was expressed uniformly in these regions. The kinetics of the rapidly recovering component of Ito in myocytes was similar to that recorded in tsa-201 cells expressing Kv4.2 and Kv4.3 channels. Kv1.4 mRNA and protein expression correlated well with the density of the slowly recovering Ito, whereas the recovery kinetics of the slow component were identical to Kv1.4 expressed in tsa-201 cells. In conclusion, expression of Kv1.4, Kv4.2, and Kv4.3 differs between regions in rat hearts. Regionally specific differences in the genetic composition of Ito can account for the region-specific properties of this current.",
    "issueName" : "5 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AD",
      "lastName" : "Wickenden",
      "authorRank" : 1,
      "name" : "Wickenden AD",
      "referenceId" : "RGD:A13807"
    }, {
      "firstName" : "TJ",
      "lastName" : "Jegla",
      "authorRank" : 2,
      "name" : "Jegla TJ",
      "referenceId" : "RGD:A13808"
    }, {
      "firstName" : "R",
      "lastName" : "Kaprielian",
      "authorRank" : 3,
      "name" : "Kaprielian R",
      "referenceId" : "RGD:A13809"
    }, {
      "firstName" : "PH",
      "lastName" : "Backx",
      "authorRank" : 4,
      "name" : "Backx PH",
      "referenceId" : "RGD:A13755"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:628470"
    } ]
  }, {
    "primaryId" : "PMID:10330252",
    "title" : "Effects of aminopeptidase P inhibition on kinin-mediated vasodepressor responses.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kitamura S, etal., Am J Physiol. 1999 May;276(5 Pt 2):H1664-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-07-12T17:21:57.000-05:00",
    "volume" : "276",
    "pages" : "H1664-71",
    "abstract" : "We studied in anesthetized rats whether aminopeptidase P (AMP) may be involved in bradykinin (BK) metabolism and responses. For this we inhibited AMP with the specific inhibitor apstatin (Aps). Studies were done with Aps alone or together with the angiotensin-converting enzyme inhibitor lisinopril (Lis). Aps increased the vasodepressor response to an intravenous bolus of BK (400 ng/kg): vehicle, -3.0 +/- 0.7 mmHg; Aps, -7.8 +/- 0.7 mmHg (P < 0.01 vs. vehicle); Lis, -23.8 +/- 1.8 mmHg; Aps + Lis, -37.5 +/- 1.9 mmHg (P < 0.01 vs. Lis). Aps did not affect the vasodepressor response to BK given into the descending aorta. Plasma BK increased only in Aps + Lis-treated rats (in pg/ml): control, 48.0 +/- 1.4; Lis, 57.5 +/- 7.6; Aps + Lis, 121. 8 +/- 30.6 (P < 0.05 vs. control or Lis), whereas in rats infused with BK (400 ng. kg-1. min-1 for 5 min), Aps increased plasma BK (in pg/ml): control, 51.9 +/- 2.5; Aps, 83.5 +/- 20.5; Lis, 725 +/- 225; Aps + Lis, 1,668 +/- 318 (P < 0.05, Aps vs. control and Lis vs. Aps + Lis). In rats with aortic coarctation hypertension, the acute antihypertensive effects of Aps plus Lis were greater than Lis alone (P < 0.01). Hoe-140, a BK B2-receptor antagonist, abolished the difference. We concluded that in the rat AMP contributes to regulation of BK metabolism and responses.",
    "issueName" : "5 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kitamura",
      "authorRank" : 1,
      "name" : "Kitamura S",
      "referenceId" : "RGD:A87364"
    }, {
      "firstName" : "L A",
      "lastName" : "Carbini",
      "authorRank" : 2,
      "name" : "Carbini LA",
      "referenceId" : "RGD:A447085"
    }, {
      "firstName" : "W H",
      "lastName" : "Simmons",
      "authorRank" : 3,
      "name" : "Simmons WH",
      "referenceId" : "RGD:A447086"
    }, {
      "firstName" : "A G",
      "lastName" : "Scicli",
      "authorRank" : 4,
      "name" : "Scicli AG",
      "referenceId" : "RGD:A447087"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12914784"
    } ]
  }, {
    "primaryId" : "PMID:10330338",
    "title" : "Human mitochondrial complex I in health and disease.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Smeitink J and van den Heuvel L, Am J Hum Genet. 1999 Jun;64(6):1505-10. doi: 10.1086/302432.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:24:43.000-05:00",
    "volume" : "64",
    "pages" : "1505-10",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Smeitink",
      "authorRank" : 1,
      "name" : "Smeitink J",
      "referenceId" : "RGD:A77673"
    }, {
      "firstName" : "L",
      "lastName" : "van den Heuvel",
      "authorRank" : 2,
      "name" : "van den Heuvel L",
      "referenceId" : "RGD:A566903"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118047"
    } ]
  }, {
    "primaryId" : "PMID:10330339",
    "title" : "Mutational analysis of the defective protease in classic late-infantile neuronal  ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Sleat DE, etal., Am J Hum Genet. 1999 Jun;64(6):1511-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:04:56.000-05:00",
    "volume" : "64",
    "pages" : "1511-23",
    "abstract" : "The late-infantile form of neuronal ceroid lipofuscinosis (LINCL) is a progressive and ultimately fatal neurodegenerative disease of childhood. The defective gene in this hereditary disorder, CLN2, encodes a recently identified lysosomal pepstatin-insensitive acid protease. To better understand the molecular pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families. In 14 patients, CLN2 protease activities were normal and no mutations were identified, suggesting other forms of NCL. Both pathogenic alleles were identified in 57 of the other 60 LINCL families studied. In total, 24 mutations were associated with LINCL, comprising six splice-junction mutations, 11 missense mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide insertion. Two mutations were particularly common: an intronic G-->C transversion in the invariant AG of a 3' splice junction, found in 38 of 115 alleles, and a C-->T transition in 32 of 115 alleles, which prematurely terminates translation at amino acid 208 of 563. An Arg-->His substitution was identified, which was associated with a late age at onset and protracted clinical phenotype, in a number of other patients originally diagnosed with juvenile NCL.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DE",
      "lastName" : "Sleat",
      "authorRank" : 1,
      "name" : "Sleat DE",
      "referenceId" : "RGD:A37695"
    }, {
      "firstName" : "RM",
      "lastName" : "Gin",
      "authorRank" : 2,
      "name" : "Gin RM",
      "referenceId" : "RGD:A37696"
    }, {
      "firstName" : "I",
      "lastName" : "Sohar",
      "authorRank" : 3,
      "name" : "Sohar I",
      "referenceId" : "RGD:A37694"
    }, {
      "firstName" : "K",
      "lastName" : "Wisniewski",
      "authorRank" : 4,
      "name" : "Wisniewski",
      "referenceId" : "RGD:A254930"
    }, {
      "firstName" : "S",
      "lastName" : "Sklower-Brooks",
      "authorRank" : 5,
      "name" : "Sklower-Brooks",
      "referenceId" : "RGD:A254931"
    }, {
      "firstName" : "RK",
      "lastName" : "Pullarkat",
      "authorRank" : 6,
      "name" : "Pullarkat RK",
      "referenceId" : "RGD:A53657"
    }, {
      "firstName" : "DN",
      "lastName" : "Palmer",
      "authorRank" : 7,
      "name" : "Palmer DN",
      "referenceId" : "RGD:A66026"
    }, {
      "firstName" : "TJ",
      "lastName" : "Lerner",
      "authorRank" : 8,
      "name" : "Lerner TJ",
      "referenceId" : "RGD:A52818"
    }, {
      "firstName" : "RM",
      "lastName" : "Boustany",
      "authorRank" : 9,
      "name" : "Boustany RM",
      "referenceId" : "RGD:A52810"
    }, {
      "firstName" : "P",
      "lastName" : "Uldall",
      "authorRank" : 10,
      "name" : "Uldall",
      "referenceId" : "RGD:A200089"
    }, {
      "firstName" : "AN",
      "lastName" : "Siakotos",
      "authorRank" : 11,
      "name" : "Siakotos",
      "referenceId" : "RGD:A251265"
    }, {
      "firstName" : "RJ",
      "lastName" : "Donnelly",
      "authorRank" : 12,
      "name" : "Donnelly RJ",
      "referenceId" : "RGD:A37697"
    }, {
      "firstName" : "P",
      "lastName" : "Lobel",
      "authorRank" : 13,
      "name" : "Lobel P",
      "referenceId" : "RGD:A37698"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063387"
    } ]
  }, {
    "primaryId" : "PMID:10330340",
    "title" : "Calpainopathy-a survey of mutations and polymorphisms.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Richard I, etal., Am J Hum Genet. 1999 Jun;64(6):1524-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:23:15.000-05:00",
    "volume" : "64",
    "pages" : "1524-40",
    "abstract" : "Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder characterized mainly by symmetrical and selective atrophy of the proximal limb muscles. It derives from defects in the human CAPN3 gene, which encodes the skeletal muscle-specific member of the calpain family. This report represents a compilation of the mutations and variants identified so far in this  gene. To date, 97 distinct pathogenic calpain 3 mutations have been identified (4 nonsense mutations, 32 deletions/insertions, 8 splice-site mutations, and 53 missense mutations), 56 of which have not been described previously, together with 12 polymorphisms and 5 nonclassified variants. The mutations are distributed along the entire length of the CAPN3 gene. Thus far, most mutations identified represent private variants, although particular mutations have been found more frequently. Knowledge of the mutation spectrum occurring in the CAPN3 gene may contribute significantly to structure/function and pathogenesis studies. It may also help in the design of efficient mutation-screening strategies for calpainopathies.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Richard",
      "authorRank" : 1,
      "name" : "Richard I",
      "referenceId" : "RGD:A71877"
    }, {
      "firstName" : "C",
      "lastName" : "Roudaut",
      "authorRank" : 2,
      "name" : "Roudaut C",
      "referenceId" : "RGD:A78394"
    }, {
      "firstName" : "A",
      "lastName" : "Saenz",
      "authorRank" : 3,
      "name" : "Saenz",
      "referenceId" : "RGD:A206733"
    }, {
      "firstName" : "R",
      "lastName" : "Pogue",
      "authorRank" : 4,
      "name" : "Pogue",
      "referenceId" : "RGD:A257130"
    }, {
      "firstName" : "JE",
      "lastName" : "Grimbergen",
      "authorRank" : 5,
      "name" : "Grimbergen",
      "referenceId" : "RGD:A257131"
    }, {
      "firstName" : "LV",
      "lastName" : "Anderson",
      "authorRank" : 6,
      "name" : "Anderson LV",
      "referenceId" : "RGD:A24010"
    }, {
      "firstName" : "C",
      "lastName" : "Beley",
      "authorRank" : 7,
      "name" : "Beley",
      "referenceId" : "RGD:A257132"
    }, {
      "firstName" : "AM",
      "lastName" : "Cobo",
      "authorRank" : 8,
      "name" : "Cobo",
      "referenceId" : "RGD:A231500"
    }, {
      "firstName" : "C",
      "lastName" : "De Diego",
      "authorRank" : 9,
      "name" : "De Diego",
      "referenceId" : "RGD:A257133"
    }, {
      "firstName" : "B",
      "lastName" : "Eymard",
      "authorRank" : 10,
      "name" : "Eymard B",
      "referenceId" : "RGD:A62861"
    }, {
      "firstName" : "P",
      "lastName" : "Gallano",
      "authorRank" : 11,
      "name" : "Gallano",
      "referenceId" : "RGD:A257134"
    }, {
      "firstName" : "HB",
      "lastName" : "Ginjaar",
      "authorRank" : 12,
      "name" : "Ginjaar",
      "referenceId" : "RGD:A250304"
    }, {
      "firstName" : "A",
      "lastName" : "Lasa",
      "authorRank" : 13,
      "name" : "Lasa",
      "referenceId" : "RGD:A250447"
    }, {
      "firstName" : "C",
      "lastName" : "Pollitt",
      "authorRank" : 14,
      "name" : "Pollitt C",
      "referenceId" : "RGD:A71876"
    }, {
      "firstName" : "H",
      "lastName" : "Topaloglu",
      "authorRank" : 15,
      "name" : "Topaloglu H",
      "referenceId" : "RGD:A53426"
    }, {
      "firstName" : "JA",
      "lastName" : "Urtizberea",
      "authorRank" : 16,
      "name" : "Urtizberea JA",
      "referenceId" : "RGD:A71529"
    }, {
      "firstName" : "M",
      "lastName" : "De Visser",
      "authorRank" : 17,
      "name" : "De Visser M",
      "referenceId" : "RGD:A52772"
    }, {
      "firstName" : "A",
      "lastName" : "Van der Kooi",
      "authorRank" : 18,
      "name" : "Van der Kooi",
      "referenceId" : "RGD:A256695"
    }, {
      "firstName" : "K",
      "lastName" : "Bushby",
      "authorRank" : 19,
      "name" : "Bushby K",
      "referenceId" : "RGD:A71878"
    }, {
      "firstName" : "E",
      "lastName" : "Bakker",
      "authorRank" : 20,
      "name" : "Bakker E",
      "referenceId" : "RGD:A40724"
    }, {
      "firstName" : "A",
      "lastName" : "Lopez de Munain",
      "authorRank" : 21,
      "name" : "Lopez de Munain A",
      "referenceId" : "RGD:A142992"
    }, {
      "firstName" : "M",
      "lastName" : "Fardeau",
      "authorRank" : 22,
      "name" : "Fardeau M",
      "referenceId" : "RGD:A37513"
    }, {
      "firstName" : "JS",
      "lastName" : "Beckmann",
      "authorRank" : 23,
      "name" : "Beckmann",
      "referenceId" : "RGD:A397798"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064016"
    } ]
  }, {
    "primaryId" : "PMID:10330342",
    "title" : "The spectrum of mutations in TBX3: Genotype/Phenotype relationship in ulnar-mammary syndrome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Bamshad M, etal., Am J Hum Genet. 1999 Jun;64(6):1550-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-19T15:43:34.000-05:00",
    "volume" : "64",
    "pages" : "1550-62",
    "abstract" : "Ulnar-mammary syndrome (UMS) is a pleiotropic disorder affecting limb, apocrine-gland, tooth, hair, and genital development. Mutations that disrupt the DNA-binding domain of the T-box gene, TBX3, have been demonstrated to cause UMS. However, the 3' terminus of the open reading frame (ORF) of TBX3 was not identified, and mutations were detected in only two families with UMS. Furthermore, no substantial homology outside the T-box was found among TBX3 and its orthologues. The subsequent cloning of new TBX3 cDNAs allowed us to complete the characterization of TBX3 and to identify alternatively transcribed TBX3 transcripts, including one that interrupts the T-box. The complete ORF of TBX3 is predicted to encode a 723-residue protein, of which 255 amino acids are encoded by newly identified exons. Comparison of other T-box genes to TBX3 indicates regions of substantial homology outside the DNA-binding domain. Novel mutations have been found in all of eight newly reported families with UMS, including five mutations downstream of the region encoding the T-box. This suggests that a domain(s) outside the T-box is highly conserved and important for the function of TBX3. We found no obvious phenotypic differences between those who have missense mutations and those who have deletions or frameshifts.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Bamshad",
      "authorRank" : 1,
      "name" : "Bamshad M",
      "referenceId" : "RGD:A47460"
    }, {
      "firstName" : "T",
      "lastName" : "Le",
      "authorRank" : 2,
      "name" : "Le T",
      "referenceId" : "RGD:A80896"
    }, {
      "firstName" : "WS",
      "lastName" : "Watkins",
      "authorRank" : 3,
      "name" : "Watkins WS",
      "referenceId" : "RGD:A80897"
    }, {
      "firstName" : "ME",
      "lastName" : "Dixon",
      "authorRank" : 4,
      "name" : "Dixon ME",
      "referenceId" : "RGD:A80898"
    }, {
      "firstName" : "BE",
      "lastName" : "Kramer",
      "authorRank" : 5,
      "name" : "Kramer BE",
      "referenceId" : "RGD:A12378"
    }, {
      "firstName" : "AD",
      "lastName" : "Roeder",
      "authorRank" : 6,
      "name" : "Roeder AD",
      "referenceId" : "RGD:A80899"
    }, {
      "firstName" : "JC",
      "lastName" : "Carey",
      "authorRank" : 7,
      "name" : "Carey JC",
      "referenceId" : "RGD:A74040"
    }, {
      "firstName" : "S",
      "lastName" : "Root",
      "authorRank" : 8,
      "name" : "Root S",
      "referenceId" : "RGD:A80900"
    }, {
      "firstName" : "A",
      "lastName" : "Schinzel",
      "authorRank" : 9,
      "name" : "Schinzel A",
      "referenceId" : "RGD:A47469"
    }, {
      "firstName" : "L",
      "lastName" : "Van Maldergem",
      "authorRank" : 10,
      "name" : "Van Maldergem L",
      "referenceId" : "RGD:A9687"
    }, {
      "firstName" : "RJ",
      "lastName" : "Gardner",
      "authorRank" : 11,
      "name" : "Gardner RJ",
      "referenceId" : "RGD:A80901"
    }, {
      "firstName" : "RC",
      "lastName" : "Lin",
      "authorRank" : 12,
      "name" : "Lin RC",
      "referenceId" : "RGD:A86674"
    }, {
      "firstName" : "CE",
      "lastName" : "Seidman",
      "authorRank" : 13,
      "name" : "Seidman CE",
      "referenceId" : "RGD:A32532"
    }, {
      "firstName" : "JG",
      "lastName" : "Seidman",
      "authorRank" : 14,
      "name" : "Seidman JG",
      "referenceId" : "RGD:A32536"
    }, {
      "firstName" : "R",
      "lastName" : "Wallerstein",
      "authorRank" : 15,
      "name" : "Wallerstein R",
      "referenceId" : "RGD:A36800"
    }, {
      "firstName" : "E",
      "lastName" : "Moran",
      "authorRank" : 16,
      "name" : "Moran E",
      "referenceId" : "RGD:A80903"
    }, {
      "firstName" : "R",
      "lastName" : "Sutphen",
      "authorRank" : 17,
      "name" : "Sutphen R",
      "referenceId" : "RGD:A80904"
    }, {
      "firstName" : "CE",
      "lastName" : "Campbell",
      "authorRank" : 18,
      "name" : "Campbell CE",
      "referenceId" : "RGD:A56719"
    }, {
      "firstName" : "LB",
      "lastName" : "Jorde",
      "authorRank" : 19,
      "name" : "Jorde LB",
      "referenceId" : "RGD:A47470"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601419"
    } ]
  }, {
    "primaryId" : "PMID:10330343",
    "title" : "Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Seppala R, etal., Am J Hum Genet. 1999 Jun;64(6):1563-9. doi: 10.1086/302411.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:10:58.000-05:00",
    "volume" : "64",
    "pages" : "1563-9",
    "abstract" : "Sialuria is a rare inborn error of metabolism characterized by cytoplasmic accumulation and increased urinary excretion of free N-acetylneuraminic acid (NeuAc, sialic acid). Overproduction of NeuAc is believed to result from loss of feedback inhibition of uridinediphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac). We report the cloning and characterization of human UDP-GlcNAc 2-epimerase cDNA, with mutation analysis of three patients with sialuria. Their heterozygote mutations, R266W, R266Q, and R263L, indicate that the allosteric site of the epimerase resides in the region of codons 263-266. The heterozygous nature of the mutant allele in all three patients reveals a dominant mechanism of inheritance for sialuria.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Seppala",
      "authorRank" : 1,
      "name" : "Seppala R",
      "referenceId" : "RGD:A600003"
    }, {
      "firstName" : "V P",
      "lastName" : "Lehto",
      "authorRank" : 2,
      "name" : "Lehto VP",
      "referenceId" : "RGD:A600004"
    }, {
      "firstName" : "W A",
      "lastName" : "Gahl",
      "authorRank" : 3,
      "name" : "Gahl WA",
      "referenceId" : "RGD:A446164"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119417"
    } ]
  }, {
    "primaryId" : "PMID:10330345",
    "title" : "A unique point mutation in the PMP22 gene is associated with Charcot-Marie-Tooth disease and deafness.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kovach MJ, etal., Am J Hum Genet. 1999 Jun;64(6):1580-93. doi: 10.1086/302420.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:45:21.000-05:00",
    "volume" : "64",
    "pages" : "1580-93",
    "abstract" : "Charcot-Marie-Tooth disease (CMT) with deafness is clinically distinct among the genetically heterogeneous group of CMT disorders. Molecular studies in a large family with autosomal dominant CMT and deafness have not been reported. The present molecular study involves a family with progressive features of CMT and deafness, originally reported by Kousseff et al. Genetic analysis of 70 individuals (31 affected, 28 unaffected, and 11 spouses) revealed linkage to markers on chromosome 17p11.2-p12, with a maximum LOD score of 9.01 for marker D17S1357 at a recombination fraction of .03. Haplotype analysis placed the CMT-deafness locus between markers D17S839 and D17S122, a approximately 0.6-Mb interval. This critical region lies within the CMT type 1A duplication region and excludes MYO15, a gene coding an unconventional myosin that causes a form of autosomal recessive deafness called DFNB3. Affected individuals from this family do not have the common 1.5-Mb duplication of CMT type 1A. Direct sequencing of the candidate peripheral myelin protein 22 (PMP22) gene detected a unique G-->C transversion in the heterozygous state in all affected individuals, at position 248 in coding exon 3, predicted to result in an Ala67Pro substitution in the second transmembrane domain of PMP22.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M J",
      "lastName" : "Kovach",
      "authorRank" : 1,
      "name" : "Kovach MJ",
      "referenceId" : "RGD:A605426"
    }, {
      "firstName" : "J P",
      "lastName" : "Lin",
      "authorRank" : 2,
      "name" : "Lin JP",
      "referenceId" : "RGD:A566075"
    }, {
      "firstName" : "S",
      "lastName" : "Boyadjiev",
      "authorRank" : 3,
      "name" : "Boyadjiev S",
      "referenceId" : "RGD:A605427"
    }, {
      "firstName" : "K",
      "lastName" : "Campbell",
      "authorRank" : 4,
      "name" : "Campbell K",
      "referenceId" : "RGD:A22903"
    }, {
      "firstName" : "L",
      "lastName" : "Mazzeo",
      "authorRank" : 5,
      "name" : "Mazzeo L",
      "referenceId" : "RGD:A605428"
    }, {
      "firstName" : "K",
      "lastName" : "Herman",
      "authorRank" : 6,
      "name" : "Herman K",
      "referenceId" : "RGD:A605429"
    }, {
      "firstName" : "L A",
      "lastName" : "Rimer",
      "authorRank" : 7,
      "name" : "Rimer LA",
      "referenceId" : "RGD:A605430"
    }, {
      "firstName" : "W",
      "lastName" : "Frank",
      "authorRank" : 8,
      "name" : "Frank W",
      "referenceId" : "RGD:A605431"
    }, {
      "firstName" : "B",
      "lastName" : "Llewellyn",
      "authorRank" : 9,
      "name" : "Llewellyn B",
      "referenceId" : "RGD:A605432"
    }, {
      "firstName" : "E W",
      "lastName" : "Jabs",
      "authorRank" : 10,
      "name" : "Jabs EW",
      "referenceId" : "RGD:A441580"
    }, {
      "firstName" : "D",
      "lastName" : "Gelber",
      "authorRank" : 11,
      "name" : "Gelber D",
      "referenceId" : "RGD:A605433"
    }, {
      "firstName" : "V E",
      "lastName" : "Kimonis",
      "authorRank" : 12,
      "name" : "Kimonis VE",
      "referenceId" : "RGD:A572214"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598120389"
    } ]
  }, {
    "primaryId" : "PMID:10330348",
    "title" : "Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Teraoka SN, etal., Am J Hum Genet. 1999 Jun;64(6):1617-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:05:51.000-05:00",
    "volume" : "64",
    "pages" : "1617-31",
    "abstract" : "Mutations resulting in defective splicing constitute a significant proportion (30/62 [48%]) of a new series of mutations in the ATM gene in patients with ataxia-telangiectasia (AT) that were detected by the protein-truncation assay followed by sequence analysis of genomic DNA. Fewer than half of the splicing mutations involved the canonical AG splice-acceptor site or GT splice-donor site. A higher percentage of mutations occurred at less stringently conserved sites, including silent mutations of the last nucleotide of exons, mutations in nucleotides other than the conserved AG and GT in the consensus splice sites, and creation of splice-acceptor or splice-donor sites in either introns or exons. These splicing mutations led to a variety of consequences, including exon skipping and, to a lesser degree, intron retention, activation of cryptic splice  sites, or creation of new splice sites. In addition, 5 of 12 nonsense mutations and 1 missense mutation were associated with deletion in the cDNA of the exons in which the mutations occurred. No ATM protein was detected by western blotting in  any AT cell line in which splicing mutations were identified. Several cases of exon skipping in both normal controls and patients for whom no underlying defect  could be found in genomic DNA were also observed, suggesting caution in the interpretation of exon deletions observed in ATM cDNA when there is no accompanying identification of genomic mutations.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SN",
      "lastName" : "Teraoka",
      "authorRank" : 1,
      "name" : "Teraoka",
      "referenceId" : "RGD:A252426"
    }, {
      "firstName" : "M",
      "lastName" : "Telatar",
      "authorRank" : 2,
      "name" : "Telatar M",
      "referenceId" : "RGD:A110605"
    }, {
      "firstName" : "S",
      "lastName" : "Becker-Catania",
      "authorRank" : 3,
      "name" : "Becker-Catania",
      "referenceId" : "RGD:A262042"
    }, {
      "firstName" : "T",
      "lastName" : "Liang",
      "authorRank" : 4,
      "name" : "Liang T",
      "referenceId" : "RGD:A15428"
    }, {
      "firstName" : "S",
      "lastName" : "Onengut",
      "authorRank" : 5,
      "name" : "Onengut",
      "referenceId" : "RGD:A239661"
    }, {
      "firstName" : "A",
      "lastName" : "Tolun",
      "authorRank" : 6,
      "name" : "Tolun",
      "referenceId" : "RGD:A228783"
    }, {
      "firstName" : "L",
      "lastName" : "Chessa",
      "authorRank" : 7,
      "name" : "Chessa",
      "referenceId" : "RGD:A254410"
    }, {
      "firstName" : "O",
      "lastName" : "Sanal",
      "authorRank" : 8,
      "name" : "Sanal O",
      "referenceId" : "RGD:A71677"
    }, {
      "firstName" : "E",
      "lastName" : "Bernatowska",
      "authorRank" : 9,
      "name" : "Bernatowska",
      "referenceId" : "RGD:A256041"
    }, {
      "firstName" : "RA",
      "lastName" : "Gatti",
      "authorRank" : 10,
      "name" : "Gatti RA",
      "referenceId" : "RGD:A76615"
    }, {
      "firstName" : "P",
      "lastName" : "Concannon",
      "authorRank" : 11,
      "name" : "Concannon P",
      "referenceId" : "RGD:A35676"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065475"
    } ]
  }, {
    "primaryId" : "PMID:10330349",
    "title" : "High rate of mosaicism in tuberous sclerosis complex.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Verhoef S, etal., Am J Hum Genet. 1999 Jun;64(6):1632-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:01:34.000-05:00",
    "volume" : "64",
    "pages" : "1632-7",
    "abstract" : "Six families with mosaicism are identified in a series of 62 unrelated families with a mutation in one of the two tuberous sclerosis complex (TSC) genes, TSC1 or TSC2. In five families, somatic mosaicism was present in a mildly affected parent of an index patient. In one family with clinically unaffected parents, gonadal mosaicism was detected after TSC was found in three children. The detection of mosaicism has consequences for genetic counseling of the families involved, as changed risks apply to individuals with mosaicism, both siblings and parents. Clinical investigation of parents of patients with seemingly sporadic mutations is essential to determine their residual chance of gonadal and/or somatic mosaicism, unless a mosaic pattern is detected in the index patient, proving a de novo event. In our data set, the exclusion of signs of TSC in the parents of a patient with TSC reduced the chance of one of the parents to be a (mosaic) mutation carrier from 10% to 2%. In the five families with somatic mosaicism, the parent was given the diagnosis after the diagnosis was made in the child.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Verhoef",
      "authorRank" : 1,
      "name" : "Verhoef S",
      "referenceId" : "RGD:A81999"
    }, {
      "firstName" : "L",
      "lastName" : "Bakker",
      "authorRank" : 2,
      "name" : "Bakker",
      "referenceId" : "RGD:A251809"
    }, {
      "firstName" : "AM",
      "lastName" : "Tempelaars",
      "authorRank" : 3,
      "name" : "Tempelaars",
      "referenceId" : "RGD:A254327"
    }, {
      "firstName" : "AL",
      "lastName" : "Hesseling-Janssen",
      "authorRank" : 4,
      "name" : "Hesseling-Janssen",
      "referenceId" : "RGD:A254328"
    }, {
      "firstName" : "T",
      "lastName" : "Mazurczak",
      "authorRank" : 5,
      "name" : "Mazurczak",
      "referenceId" : "RGD:A254329"
    }, {
      "firstName" : "S",
      "lastName" : "Jozwiak",
      "authorRank" : 6,
      "name" : "Jozwiak S",
      "referenceId" : "RGD:A82019"
    }, {
      "firstName" : "A",
      "lastName" : "Fois",
      "authorRank" : 7,
      "name" : "Fois",
      "referenceId" : "RGD:A254330"
    }, {
      "firstName" : "G",
      "lastName" : "Bartalini",
      "authorRank" : 8,
      "name" : "Bartalini",
      "referenceId" : "RGD:A254331"
    }, {
      "firstName" : "BA",
      "lastName" : "Zonnenberg",
      "authorRank" : 9,
      "name" : "Zonnenberg",
      "referenceId" : "RGD:A250902"
    }, {
      "firstName" : "AJ",
      "lastName" : "Van Essen",
      "authorRank" : 10,
      "name" : "Van Essen AJ",
      "referenceId" : "RGD:A71349"
    }, {
      "firstName" : "D",
      "lastName" : "Lindhout",
      "authorRank" : 11,
      "name" : "Lindhout D",
      "referenceId" : "RGD:A81725"
    }, {
      "firstName" : "DJ",
      "lastName" : "Halley",
      "authorRank" : 12,
      "name" : "Halley DJ",
      "referenceId" : "RGD:A126470"
    }, {
      "firstName" : "AM",
      "lastName" : "Van den Ouweland",
      "authorRank" : 13,
      "name" : "Van den Ouweland AM",
      "referenceId" : "RGD:A101725"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063243"
    } ]
  }, {
    "primaryId" : "PMID:10330357",
    "title" : "An extreme-sib-pair genome scan for genes regulating blood pressure.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Xu X, etal., Am J Hum Genet 1999 Jun;64(6):1694-701.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:46.000-05:00",
    "volume" : "64",
    "pages" : "1694-701",
    "abstract" : "Hypertension, a risk factor for many cardiovascular, cerebrovascular, and renal diseases, affects one in four Americans, at an annual cost of>$30 billion. Although genetic mutations have been identified in rare forms of hypertension, including Liddle syndrome and glucocorticoid-remediable aldosteronism, the abundance of plausible candidate genes and potential environmental risk factors has complicated the genetic dissection of more prevalent essential hypertension. To search systematically for chromosomal regions containing genes that regulate blood pressure, we scanned the entire autosomal genome by using 367 polymorphic markers. Our study population, selected from a blood-pressure screen of >200,000 Chinese adults, comprises rare but highly efficient extreme sib pairs (207 discordant, 258 high concordant, and 99 low concordant) and all but a single parent of these sibs. By virtue of the sampling design, the number of sib pairs, and the availability of genotyped parents, this study represents one of the most powerful of its kind. Although no regions achieved a 5% genomewide significance level, maximum LOD-score values were >2.0 (unadjusted P<.001) for regions containing five markers (D3S2387, D11S2019, D15S657, D16S3396, and D17S1303), in our primary analysis. Other promising regions identified through secondary analyses include loci near D4S3248, D7S2195, D10S1423, D20S470, D20S482, D21S2052, PAH, and AGT.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Xu",
      "authorRank" : 1,
      "name" : "Xu X",
      "referenceId" : "RGD:A161911"
    }, {
      "firstName" : "JJ",
      "lastName" : "Rogus",
      "authorRank" : 2,
      "name" : "Rogus JJ",
      "referenceId" : "RGD:A40195"
    }, {
      "firstName" : "HA",
      "lastName" : "Terwedow",
      "authorRank" : 3,
      "name" : "Terwedow HA",
      "referenceId" : "RGD:A40196"
    }, {
      "firstName" : "J",
      "lastName" : "Yang",
      "authorRank" : 4,
      "name" : "Yang J",
      "referenceId" : "RGD:A161907"
    }, {
      "firstName" : "Z",
      "lastName" : "Wang",
      "authorRank" : 5,
      "name" : "Wang Z",
      "referenceId" : "RGD:A161162"
    }, {
      "firstName" : "C",
      "lastName" : "Chen",
      "authorRank" : 6,
      "name" : "Chen C",
      "referenceId" : "RGD:A161909"
    }, {
      "firstName" : "T",
      "lastName" : "Niu",
      "authorRank" : 7,
      "name" : "Niu T",
      "referenceId" : "RGD:A40199"
    }, {
      "firstName" : "B",
      "lastName" : "Wang",
      "authorRank" : 8,
      "name" : "Wang B",
      "referenceId" : "RGD:A13107"
    }, {
      "firstName" : "H",
      "lastName" : "Xu",
      "authorRank" : 9,
      "name" : "Xu H",
      "referenceId" : "RGD:A14579"
    }, {
      "firstName" : "S",
      "lastName" : "Weiss",
      "authorRank" : 10,
      "name" : "Weiss S",
      "referenceId" : "RGD:A161331"
    }, {
      "firstName" : "NJ",
      "lastName" : "Schork",
      "authorRank" : 11,
      "name" : "Schork NJ",
      "referenceId" : "RGD:A159787"
    }, {
      "firstName" : "Z",
      "lastName" : "Fang",
      "authorRank" : 12,
      "name" : "Fang Z",
      "referenceId" : "RGD:A40202"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298213"
    } ]
  }, {
    "primaryId" : "PMID:10330413",
    "title" : "Critical role for cholesterol in Lyn-mediated tyrosine phosphorylation of FcepsilonRI and their association with detergent-resistant membranes.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Sheets ED, etal., J Cell Biol. 1999 May 17;145(4):877-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-02-23T07:54:49.000-06:00",
    "volume" : "145",
    "pages" : "877-87",
    "abstract" : "Tyrosine phosphorylation of the high affinity immunoglobulin (Ig)E receptor (FcepsilonRI) by the Src family kinase Lyn is the first known biochemical step that occurs during activation of mast cells and basophils after cross-linking of FcepsilonRI by antigen. The hypothesis that specialized regions in the plasma membrane, enriched in sphingolipids and cholesterol, facilitate the coupling of Lyn and FcepsilonRI was tested by investigating functional and structural effects of cholesterol depletion on Lyn/FcepsilonRI interactions. We find that cholesterol depletion with methyl-beta-cyclodextrin substantially reduces stimulated tyrosine phosphorylation of FcepsilonRI and other proteins while enhancing more downstream events that lead to stimulated exocytosis. In parallel to its inhibition of tyrosine phosphorylation, cholesterol depletion disrupts the interactions of aggregated FcepsilonRI and Lyn on intact cells and also disrupts those interactions with detergent-resistant membranes that are isolated by sucrose gradient ultracentrifugation of lysed cells. Importantly, cholesterol repletion restores receptor phosphorylation together with the structural interactions. These results provide strong evidence that membrane structure, maintained by cholesterol, plays a critical role in the initiation of FcepsilonRI signaling.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ED",
      "lastName" : "Sheets",
      "authorRank" : 1,
      "name" : "Sheets ED",
      "referenceId" : "RGD:A103879"
    }, {
      "firstName" : "D",
      "lastName" : "Holowka",
      "authorRank" : 2,
      "name" : "Holowka D",
      "referenceId" : "RGD:A103862"
    }, {
      "firstName" : "B",
      "lastName" : "Baird",
      "authorRank" : 3,
      "name" : "Baird B",
      "referenceId" : "RGD:A103863"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303706"
    } ]
  }, {
    "primaryId" : "PMID:10330430",
    "title" : "Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Mogensen J, etal., J Clin Invest 1999 May 15;103(10):R39-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-10-25T14:50:51.000-05:00",
    "volume" : "103",
    "pages" : "R39-43",
    "abstract" : "We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Mogensen",
      "authorRank" : 1,
      "name" : "Mogensen J",
      "referenceId" : "RGD:A40784"
    }, {
      "firstName" : "IC",
      "lastName" : "Klausen",
      "authorRank" : 2,
      "name" : "Klausen IC",
      "referenceId" : "RGD:A56194"
    }, {
      "firstName" : "AK",
      "lastName" : "Pedersen",
      "authorRank" : 3,
      "name" : "Pedersen AK",
      "referenceId" : "RGD:A56195"
    }, {
      "firstName" : "H",
      "lastName" : "Egeblad",
      "authorRank" : 4,
      "name" : "Egeblad H",
      "referenceId" : "RGD:A56196"
    }, {
      "firstName" : "P",
      "lastName" : "Bross",
      "authorRank" : 5,
      "name" : "Bross P",
      "referenceId" : "RGD:A56197"
    }, {
      "firstName" : "TA",
      "lastName" : "Kruse",
      "authorRank" : 6,
      "name" : "Kruse TA",
      "referenceId" : "RGD:A40785"
    }, {
      "firstName" : "N",
      "lastName" : "Gregersen",
      "authorRank" : 7,
      "name" : "Gregersen N",
      "referenceId" : "RGD:A28402"
    }, {
      "firstName" : "PS",
      "lastName" : "Hansen",
      "authorRank" : 8,
      "name" : "Hansen PS",
      "referenceId" : "RGD:A56198"
    }, {
      "firstName" : "U",
      "lastName" : "Baandrup",
      "authorRank" : 9,
      "name" : "Baandrup U",
      "referenceId" : "RGD:A56199"
    }, {
      "firstName" : "AD",
      "lastName" : "Borglum",
      "authorRank" : 10,
      "name" : "Borglum AD",
      "referenceId" : "RGD:A40786"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556464"
    } ]
  }, {
    "primaryId" : "PMID:10330440",
    "title" : "A human immunoglobulin lambda locus is similarly well expressed in mice and humans.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Popov AV, etal., J Exp Med. 1999 May 17;189(10):1611-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:15:33.000-05:00",
    "volume" : "189",
    "pages" : "1611-20",
    "abstract" : "Transgenic mice carrying a 380-kb region of the human immunoglobulin (Ig) lambda  light (L) chain locus in germline configuration were created. The introduced translocus on a yeast artificial chromosome (YAC) accommodates the most proximal  Iglambda variable region (V) gene cluster, including 15 Vlambda genes that contribute to >60% of lambda L chains in humans, all Jlambda-Clambda segments, and the 3' enhancer. HuIglambdaYAC mice were bred with animals in which mouse Igkappa production was silenced by gene targeting. In the kappa-/- background, human Iglambda was expressed by approximately 84% of splenic B cells. A striking  result was that human Iglambda was also produced at high levels in mice with normal kappa locus. Analysis of bone marrow cells showed that human Iglambda and  mouse Igkappa were expressed at similar levels throughout B cell development, suggesting that the Iglambda translocus and the endogenous kappa locus rearrange  independently and with equal efficiency at the same developmental stage. This is  further supported by the finding that in hybridomas expressing human Iglambda the endogenous L chain loci were in germline configuration. The presence of somatic hypermutation in the human Vlambda genes indicated that the Iglambda-expressing cells function normally. The finding that human lambda genes can be utilized with similar efficiency in mice and humans implies that L chain expression is critically dependent on the configuration of the locus.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AV",
      "lastName" : "Popov",
      "authorRank" : 1,
      "name" : "Popov",
      "referenceId" : "RGD:A231959"
    }, {
      "firstName" : "X",
      "lastName" : "Zou",
      "authorRank" : 2,
      "name" : "Zou X",
      "referenceId" : "RGD:A125741"
    }, {
      "firstName" : "J",
      "lastName" : "Xian",
      "authorRank" : 3,
      "name" : "Xian",
      "referenceId" : "RGD:A175591"
    }, {
      "firstName" : "IC",
      "lastName" : "Nicholson",
      "authorRank" : 4,
      "name" : "Nicholson",
      "referenceId" : "RGD:A231960"
    }, {
      "firstName" : "M",
      "lastName" : "Bruggemann",
      "authorRank" : 5,
      "name" : "Bruggemann M",
      "referenceId" : "RGD:A19811"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11055857"
    } ]
  }, {
    "primaryId" : "PMID:10330441",
    "title" : "Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "De Sanctis GT, etal., J Exp Med. 1999 May 17;189(10):1621-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-06-02T09:28:46.000-05:00",
    "volume" : "189",
    "pages" : "1621-30",
    "abstract" : "Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GT",
      "lastName" : "De Sanctis",
      "authorRank" : 1,
      "name" : "De Sanctis GT",
      "referenceId" : "RGD:A13484"
    }, {
      "firstName" : "JA",
      "lastName" : "MacLean",
      "authorRank" : 2,
      "name" : "MacLean JA",
      "referenceId" : "RGD:A26297"
    }, {
      "firstName" : "K",
      "lastName" : "Hamada",
      "authorRank" : 3,
      "name" : "Hamada K",
      "referenceId" : "RGD:A43031"
    }, {
      "firstName" : "S",
      "lastName" : "Mehta",
      "authorRank" : 4,
      "name" : "Mehta S",
      "referenceId" : "RGD:A42566"
    }, {
      "firstName" : "JA",
      "lastName" : "Scott",
      "authorRank" : 5,
      "name" : "Scott JA",
      "referenceId" : "RGD:A24267"
    }, {
      "firstName" : "A",
      "lastName" : "Jiao",
      "authorRank" : 6,
      "name" : "Jiao A",
      "referenceId" : "RGD:A140381"
    }, {
      "firstName" : "CN",
      "lastName" : "Yandava",
      "authorRank" : 7,
      "name" : "Yandava CN",
      "referenceId" : "RGD:A35844"
    }, {
      "firstName" : "L",
      "lastName" : "Kobzik",
      "authorRank" : 8,
      "name" : "Kobzik L",
      "referenceId" : "RGD:A8131"
    }, {
      "firstName" : "WW",
      "lastName" : "Wolyniec",
      "authorRank" : 9,
      "name" : "Wolyniec WW",
      "referenceId" : "RGD:A140580"
    }, {
      "firstName" : "AJ",
      "lastName" : "Fabian",
      "authorRank" : 10,
      "name" : "Fabian AJ",
      "referenceId" : "RGD:A140581"
    }, {
      "firstName" : "CS",
      "lastName" : "Venugopal",
      "authorRank" : 11,
      "name" : "Venugopal CS",
      "referenceId" : "RGD:A126676"
    }, {
      "firstName" : "H",
      "lastName" : "Grasemann",
      "authorRank" : 12,
      "name" : "Grasemann H",
      "referenceId" : "RGD:A127887"
    }, {
      "firstName" : "PL",
      "lastName" : "Huang",
      "authorRank" : 13,
      "name" : "Huang PL",
      "referenceId" : "RGD:A69711"
    }, {
      "firstName" : "JM",
      "lastName" : "Drazen",
      "authorRank" : 14,
      "name" : "Drazen JM",
      "referenceId" : "RGD:A35843"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5132861"
    } ]
  }, {
    "primaryId" : "PMID:10330443",
    "title" : "A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Chan OT, etal., J Exp Med. 1999 May 17;189(10):1639-48.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T20:09:09.000-05:00",
    "volume" : "189",
    "pages" : "1639-48",
    "abstract" : "The precise role of B cells in systemic autoimmunity is incompletely understood.  Although B cells are necessary for expression of disease (Chan, O., and M.J. Shlomchik. 1998. J. Immunol. 160:51-59, and Shlomchik, M.J., M.P. Madaio, D. Ni,  M. Trounstine, and D. Huszar. 1994. J. Exp. Med. 180:1295-1306), it is unclear whether autoantibody production, antigen presentation, and/or other B cell functions are required for the complete pathologic phenotype. To address this issue, two experimental approaches were used. In the first, the individual contributions of circulating antibodies and B cells were analyzed using MRL/MpJ-Faslpr (MRL/lpr) mice that expressed a mutant transgene encoding surface  immunoglobulin (Ig), but which did not permit the secretion of circulating Ig. These mice developed nephritis, characterized by cellular infiltration within the kidney, indicating that B cells themselves, without soluble autoantibody production, exert a pathogenic role. The results indicate that, independent of serum autoantibody, functional B cells expressing surface Ig are essential for disease expression, either by serving as antigen-presenting cells for antigen-specific, autoreactive T cells, or by contributing directly to local inflammation.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "OT",
      "lastName" : "Chan",
      "authorRank" : 1,
      "name" : "Chan OT",
      "referenceId" : "RGD:A160604"
    }, {
      "firstName" : "LG",
      "lastName" : "Hannum",
      "authorRank" : 2,
      "name" : "Hannum",
      "referenceId" : "RGD:A330727"
    }, {
      "firstName" : "AM",
      "lastName" : "Haberman",
      "authorRank" : 3,
      "name" : "Haberman",
      "referenceId" : "RGD:A333996"
    }, {
      "firstName" : "MP",
      "lastName" : "Madaio",
      "authorRank" : 4,
      "name" : "Madaio MP",
      "referenceId" : "RGD:A145690"
    }, {
      "firstName" : "MJ",
      "lastName" : "Shlomchik",
      "authorRank" : 5,
      "name" : "Shlomchik",
      "referenceId" : "RGD:A170803"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11341616"
    } ]
  }, {
    "primaryId" : "PMID:10330993",
    "title" : "Rat genetic map and a rat/mouse/human comparative gene map.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Serikawa T, etal., Transplant Proc 1999 May;31(3):1537-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-02-19T16:10:40.000-06:00",
    "volume" : "31",
    "pages" : "1537-40",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Serikawa",
      "authorRank" : 1,
      "name" : "Serikawa T",
      "referenceId" : "RGD:A130780"
    }, {
      "firstName" : "T",
      "lastName" : "Kuramoto",
      "authorRank" : 2,
      "name" : "Kuramoto T",
      "referenceId" : "RGD:A130779"
    }, {
      "firstName" : "N",
      "lastName" : "Yokoi",
      "authorRank" : 3,
      "name" : "Yokoi N",
      "referenceId" : "RGD:A1150"
    }, {
      "firstName" : "Y",
      "lastName" : "Andoh",
      "authorRank" : 4,
      "name" : "Andoh Y",
      "referenceId" : "RGD:A1151"
    }, {
      "firstName" : "Z",
      "lastName" : "Cui",
      "authorRank" : 5,
      "name" : "Cui Z",
      "referenceId" : "RGD:A1152"
    }, {
      "firstName" : "Y",
      "lastName" : "Kondo",
      "authorRank" : 6,
      "name" : "Kondo Y",
      "referenceId" : "RGD:A1153"
    }, {
      "firstName" : "K",
      "lastName" : "Omeda K",
      "authorRank" : 7,
      "name" : "Omeda K K",
      "referenceId" : "RGD:A1154"
    }, {
      "firstName" : "K",
      "lastName" : "Itada K",
      "authorRank" : 8,
      "name" : "Itada K K",
      "referenceId" : "RGD:A1155"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61504"
    } ]
  }, {
    "primaryId" : "PMID:10330994",
    "title" : "Gene-based anchoring of the rat genetic linkage and cytogenetic maps.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Szpirer C, etal., Transplant Proc 1999 May;31(3):1541-3",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-01T15:50:45.000-06:00",
    "volume" : "31",
    "pages" : "1541-3",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Szpirer",
      "authorRank" : 1,
      "name" : "Szpirer C",
      "referenceId" : "RGD:A135942"
    }, {
      "firstName" : "J",
      "lastName" : "Szpirer",
      "authorRank" : 2,
      "name" : "Szpirer J",
      "referenceId" : "RGD:A135941"
    }, {
      "firstName" : "P",
      "lastName" : "Van Vooren",
      "authorRank" : 3,
      "name" : "Van Vooren P",
      "referenceId" : "RGD:A54971"
    }, {
      "firstName" : "F",
      "lastName" : "Tissir",
      "authorRank" : 4,
      "name" : "Tissir F",
      "referenceId" : "RGD:A123363"
    }, {
      "firstName" : "JS",
      "lastName" : "Simon",
      "authorRank" : 5,
      "name" : "Simon JS",
      "referenceId" : "RGD:A51018"
    }, {
      "firstName" : "G",
      "lastName" : "Koike",
      "authorRank" : 6,
      "name" : "Koike G",
      "referenceId" : "RGD:A51179"
    }, {
      "firstName" : "HJ",
      "lastName" : "Jacob",
      "authorRank" : 7,
      "name" : "Jacob HJ",
      "referenceId" : "RGD:A160476"
    }, {
      "firstName" : "ES",
      "lastName" : "Lander",
      "authorRank" : 8,
      "name" : "Lander ES",
      "referenceId" : "RGD:A144400"
    }, {
      "firstName" : "K",
      "lastName" : "Helou",
      "authorRank" : 9,
      "name" : "Helou K",
      "referenceId" : "RGD:A123303"
    }, {
      "firstName" : "K",
      "lastName" : "Linga-Levan K",
      "authorRank" : 10,
      "name" : "Linga-Levan K K",
      "referenceId" : "RGD:A1188"
    }, {
      "firstName" : "G",
      "lastName" : "Levan",
      "authorRank" : 11,
      "name" : "Levan G",
      "referenceId" : "RGD:A123304"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61511"
    } ]
  }, {
    "primaryId" : "PMID:10330996",
    "title" : "An integrated rat genetic map: analysis of linkage conservation with the mouse and human maps.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Remmers EF, etal., Transplant Proc 1999 May;31(3):1549-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-02-20T16:58:04.000-06:00",
    "volume" : "31",
    "pages" : "1549-54",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EF",
      "lastName" : "Remmers",
      "authorRank" : 1,
      "name" : "Remmers EF",
      "referenceId" : "RGD:A153565"
    }, {
      "firstName" : "MM",
      "lastName" : "Griffiths",
      "authorRank" : 2,
      "name" : "Griffiths MM",
      "referenceId" : "RGD:A54317"
    }, {
      "firstName" : "RE",
      "lastName" : "Longman",
      "authorRank" : 3,
      "name" : "Longman RE",
      "referenceId" : "RGD:A30287"
    }, {
      "firstName" : "PS",
      "lastName" : "Gulko",
      "authorRank" : 4,
      "name" : "Gulko PS",
      "referenceId" : "RGD:A148715"
    }, {
      "firstName" : "Y",
      "lastName" : "Kawahito",
      "authorRank" : 5,
      "name" : "Kawahito Y",
      "referenceId" : "RGD:A147123"
    }, {
      "firstName" : "S",
      "lastName" : "Chen",
      "authorRank" : 6,
      "name" : "Chen S",
      "referenceId" : "RGD:A157966"
    }, {
      "firstName" : "L",
      "lastName" : "Chang",
      "authorRank" : 7,
      "name" : "Chang L",
      "referenceId" : "RGD:A140967"
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      "name" : "Markholst H",
      "referenceId" : "RGD:A1164"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61506"
    } ]
  }, {
    "primaryId" : "PMID:10331024",
    "title" : "Linkage mapping of rat hypodactyly locus to chromosome 10.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Krenova D, etal., Transplant Proc 1999 May;31(3):1620.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:49:29.000-05:00",
    "volume" : "31",
    "pages" : "1620",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Krenova",
      "authorRank" : 1,
      "name" : "Krenova D",
      "referenceId" : "RGD:A123484"
    }, {
      "firstName" : "M",
      "lastName" : "Pravenec",
      "authorRank" : 2,
      "name" : "Pravenec M",
      "referenceId" : "RGD:A157908"
    }, {
      "firstName" : "D",
      "lastName" : "Housa",
      "authorRank" : 3,
      "name" : "Housa D",
      "referenceId" : "RGD:A43902"
    }, {
      "firstName" : "F",
      "lastName" : "Liska",
      "authorRank" : 4,
      "name" : "Liska F",
      "referenceId" : "RGD:A43903"
    }, {
      "firstName" : "V",
      "lastName" : "Bila",
      "authorRank" : 5,
      "name" : "Bila V",
      "referenceId" : "RGD:A100021"
    }, {
      "firstName" : "R",
      "lastName" : "Kasparek",
      "authorRank" : 6,
      "name" : "Kasparek R",
      "referenceId" : "RGD:A16987"
    }, {
      "firstName" : "V",
      "lastName" : "Kren",
      "authorRank" : 7,
      "name" : "Kren V",
      "referenceId" : "RGD:A138191"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300053"
    } ]
  }, {
    "primaryId" : "PMID:10331026",
    "title" : "Contribution of the TNF alpha gene region of rat chromosome 20 to the body temperature response to endotoxin.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Pausova Z, etal., Transplant Proc 1999 May;31(3):1622-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-02-19T16:10:40.000-06:00",
    "volume" : "31",
    "pages" : "1622-3",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Pausova",
      "authorRank" : 1,
      "name" : "Pausova Z",
      "referenceId" : "RGD:A48058"
    }, {
      "firstName" : "J",
      "lastName" : "Kunes",
      "authorRank" : 2,
      "name" : "Kunes J",
      "referenceId" : "RGD:A1157"
    }, {
      "firstName" : "V",
      "lastName" : "Kren",
      "authorRank" : 3,
      "name" : "Kren V",
      "referenceId" : "RGD:A138191"
    }, {
      "firstName" : "D",
      "lastName" : "Krenova",
      "authorRank" : 4,
      "name" : "Krenova D",
      "referenceId" : "RGD:A123484"
    }, {
      "firstName" : "M",
      "lastName" : "Pravenec",
      "authorRank" : 5,
      "name" : "Pravenec M",
      "referenceId" : "RGD:A157908"
    }, {
      "firstName" : "J",
      "lastName" : "Tremblay",
      "authorRank" : 6,
      "name" : "Tremblay J",
      "referenceId" : "RGD:A72583"
    }, {
      "firstName" : "P",
      "lastName" : "Hamet",
      "authorRank" : 7,
      "name" : "Hamet P",
      "referenceId" : "RGD:A84211"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61505"
    } ]
  }, {
    "primaryId" : "PMID:10331392",
    "title" : "A family of mammalian Na+-dependent L-ascorbic acid transporters.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Tsukaguchi H, etal., Nature 1999 May 6;399(6731):70-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:58.000-05:00",
    "volume" : "399",
    "pages" : "70-5",
    "abstract" : "Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in which it serves to maintain prosthetic metal ions in their reduced forms (for example, Fe2+, Cu+), and for scavenging free radicals in order to protect tissues from oxidative damage. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid, but these transporters are unlikely to allow significant physiological amounts of vitamin C to be taken up in the presence of normal glucose concentrations, because the vitamin is present in plasma essentially only in its reduced form. Here we describe the isolation of two L-ascorbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA libraries, as the first step in investigating the importance of L-ascorbic acid transport in regulating the supply and metabolism of vitamin C. We find that SVCT1 and SVCT2 each mediate concentrative, high-affinity L-ascorbic acid transport that is stereospecific and is driven by the Na+ electrochemical gradient. Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs.",
    "issueName" : "6731",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Tsukaguchi",
      "authorRank" : 1,
      "name" : "Tsukaguchi H",
      "referenceId" : "RGD:A23434"
    }, {
      "firstName" : "T",
      "lastName" : "Tokui",
      "authorRank" : 2,
      "name" : "Tokui T",
      "referenceId" : "RGD:A8000"
    }, {
      "firstName" : "B",
      "lastName" : "Mackenzie",
      "authorRank" : 3,
      "name" : "Mackenzie B",
      "referenceId" : "RGD:A4651"
    }, {
      "firstName" : "UV",
      "lastName" : "Berger",
      "authorRank" : 4,
      "name" : "Berger UV",
      "referenceId" : "RGD:A63295"
    }, {
      "firstName" : "XZ",
      "lastName" : "Chen",
      "authorRank" : 5,
      "name" : "Chen XZ",
      "referenceId" : "RGD:A159956"
    }, {
      "firstName" : "Y",
      "lastName" : "Wang",
      "authorRank" : 6,
      "name" : "Wang Y",
      "referenceId" : "RGD:A381280"
    }, {
      "firstName" : "RF",
      "lastName" : "Brubaker",
      "authorRank" : 7,
      "name" : "Brubaker RF",
      "referenceId" : "RGD:A23437"
    }, {
      "firstName" : "MA",
      "lastName" : "Hediger",
      "authorRank" : 8,
      "name" : "Hediger MA",
      "referenceId" : "RGD:A63297"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634186"
    } ]
  }, {
    "primaryId" : "PMID:10331393",
    "title" : "Regulation of alternative splicing by RNA editing.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Rueter SM, etal., Nature. 1999 May 6;399(6731):75-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-22T18:20:32.000-06:00",
    "volume" : "399",
    "pages" : "75-80",
    "abstract" : "The enzyme ADAR2 is a double-stranded RNA-specific adenosine deaminase which is involved in the editing of mammalian messenger RNAs by the site-specific conversion of adenosine to inosine. Here we identify several rat ADAR2 mRNAs produced as a result of two distinct alternative splicing events. One such splicing event uses a proximal 3' acceptor site, adding 47 nucleotides to the ADAR2 coding region, changing the predicted reading frame of the mature ADAR2 transcript. Nucleotide-sequence analysis of ADAR2 genomic DNA revealed the presence of adenosine-adenosine (AA) and adenosine-guanosine (AG) dinucleotides at these proximal and distal alternative 3' acceptor sites, respectively. Use of  the proximal 3' acceptor depends upon the ability of ADAR2 to edit its own pre-mRNA, converting the intronic AA to an adenosine-inosine (AI) dinucleotide which effectively mimics the highly conserved AG sequence normally found at 3' splice junctions. Our observations indicate that RNA editing can serve as a mechanism for regulating alternative splicing and they suggest a novel strategy by which ADAR2 can modulate its own expression.",
    "issueName" : "6731",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SM",
      "lastName" : "Rueter",
      "authorRank" : 1,
      "name" : "Rueter SM",
      "referenceId" : "RGD:A38834"
    }, {
      "firstName" : "TR",
      "lastName" : "Dawson",
      "authorRank" : 2,
      "name" : "Dawson TR",
      "referenceId" : "RGD:A51997"
    }, {
      "firstName" : "RB",
      "lastName" : "Emeson",
      "authorRank" : 3,
      "name" : "Emeson RB",
      "referenceId" : "RGD:A31841"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10450893"
    } ]
  }, {
    "primaryId" : "PMID:10331426",
    "title" : "A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Elbein SC, etal., Diabetes. 1999 May;48(5):1175-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-12-15T11:23:24.000-06:00",
    "volume" : "48",
    "pages" : "1175-82",
    "abstract" : "Considerable evidence supports a major inherited component of type 2 diabetes. We initially conducted a genome-wide scan with 440 microsatellite markers at 10-cM intervals in 19 multigenerational families of Northern European ancestry with at least two diabetic siblings. Initial two-point analyses of these families directed marker typing of 23 additional families. Subsequently, all available marker data on the total of 42 families were analyzed using both parametric and nonparametric multipoint methods to test for linkage to type 2 diabetes. One locus on chromosome 1q21-1q23 met genome-wide criteria for significant linkage under a model of recessive inheritance with a common diabetes allele (logarithm of odds [LOD] = 4.295). Both pedigree-based nonparametric linkage (NPL) analysis and affected sib pair (MAPMAKER/SIBS) nonparametric methods also showed the highest genome-wide scores at this region, near markers CRP and APOA2, but failed to meet levels of genome-wide significance. The risk of type 2 diabetes to siblings of a diabetic person when compared with the population (lambdaS) was estimated from MAPMAKER/SIBS to be 2.8 in these 42 families. Simulation studies using study data confirmed a genome-wide significance level of P<0.05 (95% CI 0.005-0.0466). However, analysis of 20 similarly ascertained but smaller families failed to confirm this linkage. The LOD score with 50% heterogeneity for all 62 families considered together was only 2.25, with an estimated lambdaS of 1.87. Our data suggest a novel diabetes susceptibility locus near APOA2 on chromosome 1 in a region with many transcribed genes.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SC",
      "lastName" : "Elbein",
      "authorRank" : 1,
      "name" : "Elbein SC",
      "referenceId" : "RGD:A57220"
    }, {
      "firstName" : "MD",
      "lastName" : "Hoffman",
      "authorRank" : 2,
      "name" : "Hoffman MD",
      "referenceId" : "RGD:A116308"
    }, {
      "firstName" : "K",
      "lastName" : "Teng",
      "authorRank" : 3,
      "name" : "Teng K",
      "referenceId" : "RGD:A116309"
    }, {
      "firstName" : "MF",
      "lastName" : "Leppert",
      "authorRank" : 4,
      "name" : "Leppert MF",
      "referenceId" : "RGD:A10823"
    }, {
      "firstName" : "SJ",
      "lastName" : "Hasstedt",
      "authorRank" : 5,
      "name" : "Hasstedt SJ",
      "referenceId" : "RGD:A57221"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2315040"
    } ]
  }, {
    "primaryId" : "PMID:10331432",
    "title" : "Induction of apoptosis signal regulating kinase 1 (ASK1) after spinal cord injury in rats: possible involvement of ASK1-JNK and -p38 pathways in neuronal apoptosis.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Nakahara S, etal., J Neuropathol Exp Neurol. 1999 May;58(5):442-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-11-18T10:57:12.000-06:00",
    "volume" : "58",
    "pages" : "442-50",
    "abstract" : "The aims of this study were to clarify the mechanism of cell death by apoptosis in the spinal cord after traumatic injury, and to examine the role of the mitogen-activated protein kinase (MAPK) pathways in the transmission of apoptosis signals. The rat spinal cord, experimentally injured by extradural static weight-compression, was studied by hematoxylin and eosin staining, Nissl-staining, terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) staining, and immunostaining using polyclonal antibodies against Apoptosis Signal-regulating Kinase 1 (ASK1), c-Jun N-terminal  kinase (JNK), and p38 MAPK. TUNEL-positive cells were present at all stages studied until 7 days after injury, and percentage positivity for these cells was  maximal at 3 days after injury. Electron microscopic analysis revealed the occurrence of apoptosis in both neuronal cells and glial cells. TUNEL-positive glial cells were stained by oligodendrocyte-specific maker. Expression of ASK1 was maximal at 24 h after injury in the gray matter and at 3 days after injury in the white matter. Following the expression of ASK1, activated forms of JNK and p38 were observed in apoptotic cells detected by the TUNEL method. Colocalization of ASK1 and activated JNK or activated p38 was observed in the same cell. These findings suggest the involvement of the stress-activated MAPK pathways including  ASK1 in the transmission of apoptosis signals after spinal cord injury.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Nakahara",
      "authorRank" : 1,
      "name" : "Nakahara S",
      "referenceId" : "RGD:A32410"
    }, {
      "firstName" : "K",
      "lastName" : "Yone",
      "authorRank" : 2,
      "name" : "Yone K",
      "referenceId" : "RGD:A32411"
    }, {
      "firstName" : "T",
      "lastName" : "Sakou",
      "authorRank" : 3,
      "name" : "Sakou T",
      "referenceId" : "RGD:A90335"
    }, {
      "firstName" : "S",
      "lastName" : "Wada",
      "authorRank" : 4,
      "name" : "Wada S",
      "referenceId" : "RGD:A31749"
    }, {
      "firstName" : "T",
      "lastName" : "Nagamine",
      "authorRank" : 5,
      "name" : "Nagamine T",
      "referenceId" : "RGD:A90333"
    }, {
      "firstName" : "T",
      "lastName" : "Niiyama",
      "authorRank" : 6,
      "name" : "Niiyama",
      "referenceId" : "RGD:A208461"
    }, {
      "firstName" : "H",
      "lastName" : "Ichijo",
      "authorRank" : 7,
      "name" : "Ichijo H",
      "referenceId" : "RGD:A9710"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10412645"
    } ]
  }, {
    "primaryId" : "PMID:10331485",
    "title" : "Modulation of cellular annexin I in human leukocytes infiltrating DTH skin reactions.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Perretti M, etal., J Leukoc Biol. 1999 May;65(5):583-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-11-21T14:18:49.000-06:00",
    "volume" : "65",
    "pages" : "583-9",
    "abstract" : "Based on our previous studies showing endogenous annexin I being depleted from migrated neutrophils (PMN) in vitro, we have tested whether the levels of this glucocorticoid-regulated protein in PMN and mononuclear cells (PBMC) were modified after adhesion to endothelial monolayers in vitro and extravasation into skin blisters in vivo. In vitro, annexin I levels were depleted more significantly (-70%) in post-adherent PMNs than in monocytes (-25%) and lymphocytes (-50%, only in the positive fraction). In vivo, a significant time-dependent increase (approximately threefold, P < 0.05) in cell-associated annexin I was measured in PBMCs recovered from the blisters, whereas no significant changes were detected in extravasated PMNs. This was associated with  annexin I release in the blister fluids (approximately 35 ng/mL), whereas no detectable protein was found in matched-paired plasmas. In conclusion, we report  for the first time an activation of the annexin I pathway during an ongoing experimental inflammatory response in humans, which is differently regulated between PMNs and PBMCs.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Perretti",
      "authorRank" : 1,
      "name" : "Perretti M",
      "referenceId" : "RGD:A8271"
    }, {
      "firstName" : "SK",
      "lastName" : "Wheller",
      "authorRank" : 2,
      "name" : "Wheller",
      "referenceId" : "RGD:A176019"
    }, {
      "firstName" : "RJ",
      "lastName" : "Flower",
      "authorRank" : 3,
      "name" : "Flower RJ",
      "referenceId" : "RGD:A8270"
    }, {
      "firstName" : "S",
      "lastName" : "Wahid",
      "authorRank" : 4,
      "name" : "Wahid",
      "referenceId" : "RGD:A176020"
    }, {
      "firstName" : "C",
      "lastName" : "Pitzalis",
      "authorRank" : 5,
      "name" : "Pitzalis",
      "referenceId" : "RGD:A176021"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7421575"
    } ]
  }, {
    "primaryId" : "PMID:10331746",
    "title" : "Involvement of mutations in the DPC4 promoter in endometrial carcinoma development.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Zhou Y, etal., Mol Carcinog. 1999 May;25(1):64-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-08-29T12:47:14.000-05:00",
    "volume" : "25",
    "pages" : "64-72",
    "abstract" : "To define the target of chromosome 18q loss of heterozygosity, which is prevalent in endometrial carcinomas, we made a deletion map from 64 tumors. Loss of heterozygosity on 18q was found in 20 tumors. Among these, 14 tumors carried deletions at the 18q21.1 region, where the DPC4 gene is located. DPC4 transcription was disturbed in all six of the tumors with deletions at 18q21.1 examined, which sharply contrasted with the positive transcription in 12 tumors that retained heterozygosity at the 18q21.1 region. However, in the 14 tumors with the 18q21.1 deletions, the remaining allele had the wild-type sequence of the DPC4 coding region instead of somatic mutations in the DPC4 coding region. We found a one- and two-base substitutions in the DPC4 promoter in two of the six tumors that showed disturbed DPC4 transcription. Chloramphenicol acetyltransferase assays clearly demonstrated that the mutant promoters had the potential to suppress or silence DPC4 transcription, implicating the DPC4 gene in endometrial carcinoma.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Zhou",
      "authorRank" : 1,
      "name" : "Zhou Y",
      "referenceId" : "RGD:A31411"
    }, {
      "firstName" : "H",
      "lastName" : "Kato",
      "authorRank" : 2,
      "name" : "Kato H",
      "referenceId" : "RGD:A158249"
    }, {
      "firstName" : "D",
      "lastName" : "Shan",
      "authorRank" : 3,
      "name" : "Shan D",
      "referenceId" : "RGD:A99422"
    }, {
      "firstName" : "R",
      "lastName" : "Minami",
      "authorRank" : 4,
      "name" : "Minami R",
      "referenceId" : "RGD:A99423"
    }, {
      "firstName" : "S",
      "lastName" : "Kitazawa",
      "authorRank" : 5,
      "name" : "Kitazawa S",
      "referenceId" : "RGD:A98029"
    }, {
      "firstName" : "T",
      "lastName" : "Matsuda",
      "authorRank" : 6,
      "name" : "Matsuda T",
      "referenceId" : "RGD:A21320"
    }, {
      "firstName" : "T",
      "lastName" : "Arima",
      "authorRank" : 7,
      "name" : "Arima T",
      "referenceId" : "RGD:A52314"
    }, {
      "firstName" : "JC",
      "lastName" : "Barrett",
      "authorRank" : 8,
      "name" : "Barrett JC",
      "referenceId" : "RGD:A6240"
    }, {
      "firstName" : "N",
      "lastName" : "Wake",
      "authorRank" : 9,
      "name" : "Wake N",
      "referenceId" : "RGD:A99384"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2300009"
    } ]
  }, {
    "primaryId" : "PMID:10331871",
    "title" : "Structural basis of autoregulation of phenylalanine hydroxylase.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kobe B, etal., Nat Struct Biol. 1999 May;6(5):442-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-24T15:16:01.000-05:00",
    "volume" : "6",
    "pages" : "442-8",
    "abstract" : "Phenylalanine hydroxylase converts phenylalanine to tyrosine, a rate-limiting step in phenylalanine catabolism and protein and neurotransmitter biosynthesis. It is tightly regulated by the substrates phenylalanine and tetrahydrobiopterin and by phosphorylation. We present the crystal structures of dephosphorylated and phosphorylated forms of a dimeric enzyme with catalytic and regulatory properties of the wild-type protein. The structures reveal a catalytic domain flexibly linked to a regulatory domain. The latter consists of an N-terminal autoregulatory sequence (containing Ser 16, which is the site of phosphorylation) that extends over the active site pocket, and an alpha-beta sandwich core that is, unexpectedly, structurally related to both pterin dehydratase and the regulatory domains of metabolic enzymes. Phosphorylation has no major structural effects in the absence of phenylalanine, suggesting that phenylalanine and phosphorylation act in concert to activate the enzyme through a combination of intrasteric and possibly allosteric mechanisms.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Kobe",
      "authorRank" : 1,
      "name" : "Kobe B",
      "referenceId" : "RGD:A81383"
    }, {
      "firstName" : "IG",
      "lastName" : "Jennings",
      "authorRank" : 2,
      "name" : "Jennings IG",
      "referenceId" : "RGD:A81384"
    }, {
      "firstName" : "CM",
      "lastName" : "House",
      "authorRank" : 3,
      "name" : "House CM",
      "referenceId" : "RGD:A7734"
    }, {
      "firstName" : "BJ",
      "lastName" : "Michell",
      "authorRank" : 4,
      "name" : "Michell BJ",
      "referenceId" : "RGD:A7732"
    }, {
      "firstName" : "KE",
      "lastName" : "Goodwill",
      "authorRank" : 5,
      "name" : "Goodwill KE",
      "referenceId" : "RGD:A81385"
    }, {
      "firstName" : "BD",
      "lastName" : "Santarsiero",
      "authorRank" : 6,
      "name" : "Santarsiero BD",
      "referenceId" : "RGD:A81386"
    }, {
      "firstName" : "RC",
      "lastName" : "Stevens",
      "authorRank" : 7,
      "name" : "Stevens RC",
      "referenceId" : "RGD:A29769"
    }, {
      "firstName" : "RG",
      "lastName" : "Cotton",
      "authorRank" : 8,
      "name" : "Cotton RG",
      "referenceId" : "RGD:A81387"
    }, {
      "firstName" : "BE",
      "lastName" : "Kemp",
      "authorRank" : 9,
      "name" : "Kemp BE",
      "referenceId" : "RGD:A7738"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601548"
    } ]
  }, {
    "primaryId" : "PMID:10331975",
    "title" : "The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Clark TG, etal., Development. 1999 Jun;126(12):2631-42. doi: 10.1242/dev.126.12.2631.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-01-31T15:22:01.000-06:00",
    "volume" : "126",
    "pages" : "2631-42",
    "abstract" : "Mammalian Tolloid-like 1 (mTLL-1) is an astacin-like metalloprotease, highly similar in domain structure to the morphogenetically important proteases bone morphogenetic protein-1 (BMP-1) and Drosophila Tolloid. To investigate possible roles for mTLL-1 in mammalian development, we have used gene targeting in ES cells to produce mice with a disrupted allele for the corresponding gene, Tll1. Homozygous mutants were embryonic lethal, with death at mid-gestation from cardiac failure and a unique constellation of developmental defects that were apparently confined solely to the heart. Constant features were incomplete formation of the muscular interventricular septum and an abnormal and novel positioning of the heart and aorta. Consistent with roles in cardiac development, Tll1 expression was specific to precardiac tissue and endocardium in 7.5 and 8.5 days p.c. embryos, respectively. Tll1 expression was also high in the developing interventricular septum, where expression of the BMP-1 gene, Bmp1, was not observed. Cardiac structures that were not affected in Tll1-/- embryos either showed no Tll1 expression (atrio-ventricular cushions) or showed overlapping expression of Tll1 and Bmp1 (aortico-pulmonary septum), suggesting that products of the Bmp1 gene may be capable of functionally substituting for mTLL-1 at sites in which they are co-expressed. Together, the various data show that mTLL-1 plays multiple roles in formation of the mammalian heart and is essential for formation of the interventricular septum.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T G",
      "lastName" : "Clark",
      "authorRank" : 1,
      "name" : "Clark TG",
      "referenceId" : "RGD:A524702"
    }, {
      "firstName" : "S J",
      "lastName" : "Conway",
      "authorRank" : 2,
      "name" : "Conway SJ",
      "referenceId" : "RGD:A524703"
    }, {
      "firstName" : "I C",
      "lastName" : "Scott",
      "authorRank" : 3,
      "name" : "Scott IC",
      "referenceId" : "RGD:A524704"
    }, {
      "firstName" : "P A",
      "lastName" : "Labosky",
      "authorRank" : 4,
      "name" : "Labosky PA",
      "referenceId" : "RGD:A524705"
    }, {
      "firstName" : "G",
      "lastName" : "Winnier",
      "authorRank" : 5,
      "name" : "Winnier G",
      "referenceId" : "RGD:A524706"
    }, {
      "firstName" : "J",
      "lastName" : "Bundy",
      "authorRank" : 6,
      "name" : "Bundy J",
      "referenceId" : "RGD:A524707"
    }, {
      "firstName" : "B L",
      "lastName" : "Hogan",
      "authorRank" : 7,
      "name" : "Hogan BL",
      "referenceId" : "RGD:A524708"
    }, {
      "firstName" : "D S",
      "lastName" : "Greenspan",
      "authorRank" : 8,
      "name" : "Greenspan DS",
      "referenceId" : "RGD:A524709"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:155882595"
    } ]
  }, {
    "primaryId" : "PMID:10332026",
    "title" : "Dentatorubral-pallidoluysian atrophy protein interacts through a proline-rich region near polyglutamine with the SH3 domain of an insulin receptor tyrosine kinase substrate.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Okamura-Oho Y, etal., Hum Mol Genet. 1999 Jun;8(6):947-57.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-12-12T17:03:04.000-06:00",
    "volume" : "8",
    "pages" : "947-57",
    "abstract" : "Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neuro degrees enerative disorder associated with CAG/glutamine repeat expansion. While  the DRPLA gene is ubiquitously expressed, neuron death occurs in specific anatomical areas of the brain. This predicts that the DRPLA protein interacts with other proteins and that these interactions may play a role in pathogenesis.  Here, we describe a protein that binds to the DRPLA product. One of the clones isolated with a yeast two-hybrid system was identified as a human homolog of the  insulin receptor tyrosine kinase substrate protein of 53 kDa (IRSp53). The gene produced two mRNA forms by differential splicing and encoded 552 and 521 amino acids, respectively. The longer form was mainly expressed in the brain and the shorter one in other tissues. The products were phosphorylated upon stimulation of cultured cells with insulin or insulin-like growth factor 1. Binding of the DRPLA protein to IRSp53 was ascertained by co-immunoprecipitation with antibodies and also by co-localization in perinuclear oval dots in cells expressing engineered constructs. A proline-rich region near the polyglutamine tract of the  DRPLA protein and the SH3 domain of IRSp53 were involved in the binding. An extended polyglutamine tract significantly reduced binding ability in yeast cells, but not in in vitro binding assays. The identification of IRSp53 and other proteins detected by the yeast hybrid system predicts that DRPLA functions in a signal transduction pathway coupled with insulin/IGF-1.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Okamura-Oho",
      "authorRank" : 1,
      "name" : "Okamura-Oho Y",
      "referenceId" : "RGD:A49554"
    }, {
      "firstName" : "T",
      "lastName" : "Miyashita",
      "authorRank" : 2,
      "name" : "Miyashita T",
      "referenceId" : "RGD:A49555"
    }, {
      "firstName" : "K",
      "lastName" : "Ohmi",
      "authorRank" : 3,
      "name" : "Ohmi",
      "referenceId" : "RGD:A197511"
    }, {
      "firstName" : "M",
      "lastName" : "Yamada",
      "authorRank" : 4,
      "name" : "Yamada",
      "referenceId" : "RGD:A398379"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9684992"
    } ]
  }, {
    "primaryId" : "PMID:10332027",
    "title" : "T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-binding protein implicated in spermatogenesis.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Venables JP, etal., Hum Mol Genet. 1999 Jun;8(6):959-69.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-15T17:08:42.000-06:00",
    "volume" : "8",
    "pages" : "959-69",
    "abstract" : "RBM is an RNA-binding protein encoded on the Y chromosome in mammals and is expressed only in the nuclei of male germ cells. Genetic evidence from infertile men implicates it in spermatogenesis, but its function is unknown. Of a number of potential partners for RBM identified by a yeast two-hybrid screen with testis cDNA, the most frequent isolates encoded a novel RNA-binding protein, termed T-STAR, that is closely related to SAM68, an Src-associated protein of unknown function. The mouse homologue was also cloned and designated etoile. It mapped to chromosome 15, while T-STAR mapped to the syntenic region on human chromosome 8. T-STAR/etoile is expressed primarily in the testis; in rat germ cells, the expression of both T-STAR/etoile and SAM68 is regulated during meiosis. Transfection of T-STAR/etoile fused with green fluorescent protein into HeLa cells caused an accumulation of protein in a novel compartment of the nucleus, adjacent to the nucleolus but distinct from the peri-nucleolar compartment. RBM and other hnRNP G family members are candidate downstream targets for regulation by T-STAR/ETOILE and SAM68.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JP",
      "lastName" : "Venables",
      "authorRank" : 1,
      "name" : "Venables JP",
      "referenceId" : "RGD:A119230"
    }, {
      "firstName" : "C",
      "lastName" : "Vernet",
      "authorRank" : 2,
      "name" : "Vernet C",
      "referenceId" : "RGD:A119231"
    }, {
      "firstName" : "SL",
      "lastName" : "Chew",
      "authorRank" : 3,
      "name" : "Chew SL",
      "referenceId" : "RGD:A119232"
    }, {
      "firstName" : "DJ",
      "lastName" : "Elliott",
      "authorRank" : 4,
      "name" : "Elliott DJ",
      "referenceId" : "RGD:A119233"
    }, {
      "firstName" : "RB",
      "lastName" : "Cowmeadow",
      "authorRank" : 5,
      "name" : "Cowmeadow RB",
      "referenceId" : "RGD:A119234"
    }, {
      "firstName" : "J",
      "lastName" : "Wu",
      "authorRank" : 6,
      "name" : "Wu J",
      "referenceId" : "RGD:A160329"
    }, {
      "firstName" : "HJ",
      "lastName" : "Cooke",
      "authorRank" : 7,
      "name" : "Cooke HJ",
      "referenceId" : "RGD:A57007"
    }, {
      "firstName" : "K",
      "lastName" : "Artzt",
      "authorRank" : 8,
      "name" : "Artzt K",
      "referenceId" : "RGD:A32440"
    }, {
      "firstName" : "IC",
      "lastName" : "Eperon",
      "authorRank" : 9,
      "name" : "Eperon IC",
      "referenceId" : "RGD:A119236"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316541"
    } ]
  }, {
    "primaryId" : "PMID:10332028",
    "title" : "N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin disease striate palmoplantar keratoderma.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Rickman L, etal., Hum Mol Genet. 1999 Jun;8(6):971-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-19T14:05:47.000-06:00",
    "volume" : "8",
    "pages" : "971-6",
    "abstract" : "The N-terminal extracellular domain of the cadherins, calcium-dependent cell adhesion molecules, has been shown by X-ray crystallography to be involved in two types of interaction: lateral strand dimers and adhesive dimers. Here we describe the first human mutation in a cadherin present in desmosome cell junctions that removes a portion of this highly conserved first extracellular domain. The mutation, in the DSG1 gene coding for a desmoglein (Dsg1), results in the deletion of the first and much of the second beta-strand of the first cadherin repeat and part of the first Ca2+-binding site, and would be expected to compromise strand dimer formation. It causes a dominantly inherited skin disease, striate palmoplantar keratoderma (SPPK), mapping to chromosome 18q12.1, in which affected individuals have marked hyperkeratotic bands on the palms and soles. In a three generation Dutch family with SPPK, we have found a G-->A transition in the 3\" splice acceptor site of intron 2 of the DSG1 gene which segregated with the disease phenotype. This causes aberrant splicing of exon 2 to exon 4, which are in-frame, with the consequent removal of exon 3 encoding part of the prosequence, the mature protein cleavage site and part of the first extracellular domain. This mutation emphasizes the importance of this part of the molecule for cadherin function, and of the Dsg1 protein and hence desmosomes in epidermal function.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Rickman",
      "authorRank" : 1,
      "name" : "Rickman L",
      "referenceId" : "RGD:A71489"
    }, {
      "firstName" : "D",
      "lastName" : "Simrak",
      "authorRank" : 2,
      "name" : "Simrak D",
      "referenceId" : "RGD:A71490"
    }, {
      "firstName" : "HP",
      "lastName" : "Stevens",
      "authorRank" : 3,
      "name" : "Stevens HP",
      "referenceId" : "RGD:A64546"
    }, {
      "firstName" : "DM",
      "lastName" : "Hunt",
      "authorRank" : 4,
      "name" : "Hunt DM",
      "referenceId" : "RGD:A71491"
    }, {
      "firstName" : "IA",
      "lastName" : "King",
      "authorRank" : 5,
      "name" : "King IA",
      "referenceId" : "RGD:A71492"
    }, {
      "firstName" : "SP",
      "lastName" : "Bryant",
      "authorRank" : 6,
      "name" : "Bryant SP",
      "referenceId" : "RGD:A71493"
    }, {
      "firstName" : "RA",
      "lastName" : "Eady",
      "authorRank" : 7,
      "name" : "Eady RA",
      "referenceId" : "RGD:A38061"
    }, {
      "firstName" : "IM",
      "lastName" : "Leigh",
      "authorRank" : 8,
      "name" : "Leigh IM",
      "referenceId" : "RGD:A56411"
    }, {
      "firstName" : "J",
      "lastName" : "Arnemann",
      "authorRank" : 9,
      "name" : "Arnemann J",
      "referenceId" : "RGD:A71494"
    }, {
      "firstName" : "AI",
      "lastName" : "Magee",
      "authorRank" : 10,
      "name" : "Magee AI",
      "referenceId" : "RGD:A67079"
    }, {
      "firstName" : "DP",
      "lastName" : "Kelsell",
      "authorRank" : 11,
      "name" : "Kelsell DP",
      "referenceId" : "RGD:A59181"
    }, {
      "firstName" : "RS",
      "lastName" : "Buxton",
      "authorRank" : 12,
      "name" : "Buxton RS",
      "referenceId" : "RGD:A71495"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598781"
    } ]
  }, {
    "primaryId" : "PMID:10332035",
    "title" : "Correlations of genotype and phenotype in hypophosphatasia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Zurutuza L, etal., Hum Mol Genet. 1999 Jun;8(6):1039-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:34:43.000-05:00",
    "volume" : "8",
    "pages" : "1039-46",
    "abstract" : "Hypophosphatasia, a rare inherited disorder characterized by defective bone mineralization, is highly variable in its clinical expression. The disease is due to various mutations in the tissue-non-specific alkaline phosphatase ( TNSALP ) gene. We report here the use of clinical data, site-directed mutagenesis and computer-assisted modelling to propose a classification of 32 TNSALP gene mutations found in 23 European patients, 17 affected with lethal hypophosphatasia and six with non-lethal hypophosphatasia. Transfection studies of the missense mutations found in non-lethal hypophosphatasia showed that six of them allowed significant residual in vitro enzymatic activity, suggesting that these mutations corresponded to moderate alleles. Each of the six patients with non-lethal hypophosphatasia carried at least one of these alleles. The three-dimensional model study showed that moderate mutations were not found in the active site, and that most of the severe missense mutations were localized in crucial domains such as the active site, the vicinity of the active site and homodimer interface. Some mutations appeared to be organized in clusters on the surface of the molecule that may represent possible candidates for regions interacting with the C-terminal end involved in glycosylphosphatidylinositol (GPI) attachment or with  other dimers to form tetramers. Finally, our results show a good correlation between clinical forms of the disease, mutagenesis experiments and the three-dimensional structure study, and allowed us to clearly distinguish moderate alleles from severe alleles. They also confirm that the extremely high phenotypic heterogeneity observed in patients with hypophosphatasia was due mainly to variable residual enzymatic activities allowed by missense mutations found in the human TNSALP gene.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Zurutuza",
      "authorRank" : 1,
      "name" : "Zurutuza",
      "referenceId" : "RGD:A258653"
    }, {
      "firstName" : "F",
      "lastName" : "Muller",
      "authorRank" : 2,
      "name" : "Muller F",
      "referenceId" : "RGD:A9848"
    }, {
      "firstName" : "JF",
      "lastName" : "Gibrat",
      "authorRank" : 3,
      "name" : "Gibrat",
      "referenceId" : "RGD:A258654"
    }, {
      "firstName" : "A",
      "lastName" : "Taillandier",
      "authorRank" : 4,
      "name" : "Taillandier",
      "referenceId" : "RGD:A253315"
    }, {
      "firstName" : "B",
      "lastName" : "Simon-Bouy",
      "authorRank" : 5,
      "name" : "Simon-Bouy",
      "referenceId" : "RGD:A375539"
    }, {
      "firstName" : "JL",
      "lastName" : "Serre",
      "authorRank" : 6,
      "name" : "Serre",
      "referenceId" : "RGD:A253316"
    }, {
      "firstName" : "E",
      "lastName" : "Mornet",
      "authorRank" : 7,
      "name" : "Mornet E",
      "referenceId" : "RGD:A35870"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064447"
    } ]
  }, {
    "primaryId" : "PMID:10332085",
    "title" : "Protein kinase C activators induce membrane retrieval of type II Na+-phosphate cotransporters expressed in Xenopus oocytes.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Forster IC, etal., J Physiol. 1999 Jun 1;517 ( Pt 2):327-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-13T15:27:39.000-05:00",
    "volume" : "517 ( Pt 2)",
    "pages" : "327-40",
    "abstract" : "1. The rate of inorganic phosphate (Pi) reabsorption in the mammalian kidney is determined by the amount of type II sodium-coupled inorganic phosphate (Na+-Pi) cotransport protein present in the brush border membrane. Under physiological conditions, parathyroid hormone (PTH) leads to an inhibition of Na+-Pi cotransport activity, most probably mediated by the protein kinase A (PKA) and/or C (PKC) pathways. 2. In this study, PKC-induced inhibition of type II Na+-Pi cotransport activity was characterized in Xenopus laevis oocytes using electrophysiological and immunodetection techniques. Transport function was quantified in terms of Pi-activated current. 3. Oocytes expressing the type IIa rat renal, type IIb flounder renal or type IIb mouse intestinal Na+-Pi cotransporters lost > 50 % of Pi-activated transport function when exposed to the PKC activators DOG (1,2-dioctanoyl-sn-glycerol) or PMA (phorbol 12-myristate 13-acetate). DOG-induced inhibition was partially reduced with the PKC inhibitors staurosporine and bisindolylmaleimide I. Oocytes exposed to the inactive phorbol  ester 4alpha-PDD (4alpha-phorbol 12,13-didecanoate) showed no significant loss of cotransporter function. 4. Oocytes expressing the rat renal Na+-SO42- cotransporter alone, or coexpressing this with the type IIa rat renal Na+-Pi cotransporter, showed no downregulation of SO42--activated cotransport activity by DOG. 5. Steady-state and presteady-state voltage-dependent kinetics of type II Na+-Pi cotransporter function were unaffected by DOG. 6. DOG induced a decrease in membrane capacitance which indicated a reduction in membrane area, thereby providing evidence for PKC-mediated endocytosis. 7. Immunocytochemical studies showed a redistribution of type II Na+-Pi cotransporters from the oolemma to the  submembrane region after DOG treatment. Surface biotinylation confirmed a DOG-induced internalization of the transport protein. 8. These findings document  a specific retrieval of exogenous type II Na+-Pi cotransporters induced by activation of a PKC pathway in the Xenopus oocyte.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "IC",
      "lastName" : "Forster",
      "authorRank" : 1,
      "name" : "Forster",
      "referenceId" : "RGD:A169696"
    }, {
      "firstName" : "M",
      "lastName" : "Traebert",
      "authorRank" : 2,
      "name" : "Traebert",
      "referenceId" : "RGD:A169472"
    }, {
      "firstName" : "M",
      "lastName" : "Jankowski",
      "authorRank" : 3,
      "name" : "Jankowski M",
      "referenceId" : "RGD:A6658"
    }, {
      "firstName" : "G",
      "lastName" : "Stange",
      "authorRank" : 4,
      "name" : "Stange",
      "referenceId" : "RGD:A216490"
    }, {
      "firstName" : "J",
      "lastName" : "Biber",
      "authorRank" : 5,
      "name" : "Biber",
      "referenceId" : "RGD:A403617"
    }, {
      "firstName" : "H",
      "lastName" : "Murer",
      "authorRank" : 6,
      "name" : "Murer",
      "referenceId" : "RGD:A341576"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7243183"
    } ]
  }, {
    "primaryId" : "PMID:10332146",
    "title" : "[Molecular cloning, expression of rat Msx-1 and Msx-2 during early embryo genesis and roles for mandibular chondrogenesis]",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ishiguro S Kokubyo Gakkai Zasshi. 1999 Mar;66(1):33-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-09T10:49:36.000-06:00",
    "volume" : "66",
    "pages" : "33-45",
    "abstract" : "Quail-chick chimera experiments have shown a contribution of carnial neural crest cells to the craniofacial skeletal elements. Moreover, tissue interactions between epithelial-mesenchymal interaction during early facial process development are required for both skeletal differentiation and morphogenesis. In this study, it was observed that Msx homeobox containing genes expressed in the facial process were important molecules of cartilage morphogenesis. Rat cDNAs were isolated and encoded by Msx-1 and -2, and then the expression patterns using in situ hybridization were investigated during early rat face development. These genes were correlatively expressed in the cranial neural crest forming area (E 9.5 dpc) and the facial process (E 12.5 dpc). Antisence inhibition of Msx genes in the E 12.5 mandibular process exhibited the alteration of their gene expression and cartilage patterns. Antisence inhibition of Msx-1 induced lack of the medial portion of cartilage, and antisence inhibition of Msx-2 enhanced chondrogenesis of mandibular process under the organ culture condition. Thus it was concluded that expression of Msx genes during mandibular process development comprises important signals of chondrogenesis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Ishiguro",
      "authorRank" : 1,
      "name" : "Ishiguro S",
      "referenceId" : "RGD:A67379"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600462"
    } ]
  }, {
    "primaryId" : "PMID:10332679",
    "title" : "Factor VIII and other hemostasis variables are related to incident diabetes in adults. The Atherosclerosis Risk in Communities (ARIC) Study.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Duncan BB, etal., Diabetes Care. 1999 May;22(5):767-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-08-11T12:01:12.000-05:00",
    "volume" : "22",
    "pages" : "767-72",
    "abstract" : "OBJECTIVE: Our objective was to evaluate whether selected hemostasis variables, some of which may reflect inflammation or endothelial dysfunction, are independently associated with the development of diabetes. RESEARCH DESIGN AND METHODS: We studied a biethnic cohort of 12,330 men and women, 45-64 years of age, of the Atherosclerosis Risk in Communities Study. New cases of diabetes were diagnosed by a reported physician diagnosis, hypoglycemic medication use, or a casual or fasting serum glucose level of > or = 11.1 or > or = 7 mmol/l, respectively. RESULTS: Over an average follow-up of 7 years, 1,335 new cases of diabetes were detected. The odds ratios (4th versus 1st quartile) of developing diabetes, adjusted by logistic regression for age, sex, race, study center, family history of diabetes, fasting glucose, physical activity, and smoking, were 1.2 (95% CI 1.0-1.5) for fibrinogen and 1.4 (1.1-1.6) for factor VII. Associations for factor VIII, von Willebrand factor, and activated partial thromboplastin time were found to be 1.8 (1.3-2.3), 1.4 (1.1-1.8), and 0.63 (0.49-0.82), respectively, in women. Although further adjustment for BMI and waist-to-hip ratio diminished the relationships, a highly statistically significant association (P = 0.001) remained for factor VIII (1.6 [1.2-2.1]) in women. CONCLUSIONS: Factor VIII and other hemostasis variables are associated with the development of diabetes in middle-aged adults. These findings support a role for inflammation and, particularly in women, endothelial dysfunction in the pathogenesis of type 2 diabetes.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BB",
      "lastName" : "Duncan",
      "authorRank" : 1,
      "name" : "Duncan BB",
      "referenceId" : "RGD:A110594"
    }, {
      "firstName" : "MI",
      "lastName" : "Schmidt",
      "authorRank" : 2,
      "name" : "Schmidt MI",
      "referenceId" : "RGD:A110595"
    }, {
      "firstName" : "S",
      "lastName" : "Offenbacher",
      "authorRank" : 3,
      "name" : "Offenbacher S",
      "referenceId" : "RGD:A107406"
    }, {
      "firstName" : "KK",
      "lastName" : "Wu",
      "authorRank" : 4,
      "name" : "Wu KK",
      "referenceId" : "RGD:A59300"
    }, {
      "firstName" : "PJ",
      "lastName" : "Savage",
      "authorRank" : 5,
      "name" : "Savage PJ",
      "referenceId" : "RGD:A25071"
    }, {
      "firstName" : "G",
      "lastName" : "Heiss",
      "authorRank" : 6,
      "name" : "Heiss G",
      "referenceId" : "RGD:A39783"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2312388"
    } ]
  }, {
    "primaryId" : "PMID:10333057",
    "title" : "Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Yoshiuchi I, etal., Diabetologia. 1999 May;42(5):621-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:09:18.000-05:00",
    "volume" : "42",
    "pages" : "621-6",
    "abstract" : "AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of the type 3 form of maturity-onset diabetes of the young. We examined the clinical features and molecular basis of hepatocyte nuclear factor-1alpha (HNF-1alpha) diabetes. METHODS: Thirty-seven Japanese subjects with early onset Type II (non-insulin-dependent) diabetes mellitus and 45 with Type I  (insulin-dependent) diabetes mellitus were screened for mutations in this gene. Functional properties of mutant HNF-1alpha were also investigated. RESULTS: Three new mutations [G415R, R272C and A site of the promoter (+ 102G-to-C)] were found. Insulin secretion was impaired in the three subjects. Insulin and glucagon secretory responses to arginine in the subject with the R272C mutation were also  diminished. Molecular biological studies indicated that the G415R mutation generated a protein with about 50% of the activity of wild-type HNF-1alpha. The R272C mutation had no transactivating or DNA binding activity and acted in a dominant negative manner. The + 102 G-to-C mutation in the A site of the promoter activity was associated with an increase in promoter activity and it had 42-75% more activity than the wild-type sequence. CONCLUSION/INTERPRETATION: Mutations in the HNF-1alpha gene may affect the normal islet function by different molecular mechanisms.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Yoshiuchi",
      "authorRank" : 1,
      "name" : "Yoshiuchi I",
      "referenceId" : "RGD:A112093"
    }, {
      "firstName" : "K",
      "lastName" : "Yamagata",
      "authorRank" : 2,
      "name" : "Yamagata",
      "referenceId" : "RGD:A331984"
    }, {
      "firstName" : "Q",
      "lastName" : "Yang",
      "authorRank" : 3,
      "name" : "Yang Q",
      "referenceId" : "RGD:A15596"
    }, {
      "firstName" : "H",
      "lastName" : "Iwahashi",
      "authorRank" : 4,
      "name" : "Iwahashi H",
      "referenceId" : "RGD:A117554"
    }, {
      "firstName" : "K",
      "lastName" : "Okita",
      "authorRank" : 5,
      "name" : "Okita K",
      "referenceId" : "RGD:A124528"
    }, {
      "firstName" : "K",
      "lastName" : "Yamamoto",
      "authorRank" : 6,
      "name" : "Yamamoto K",
      "referenceId" : "RGD:A5107"
    }, {
      "firstName" : "T",
      "lastName" : "Oue",
      "authorRank" : 7,
      "name" : "Oue T",
      "referenceId" : "RGD:A29647"
    }, {
      "firstName" : "A",
      "lastName" : "Imagawa",
      "authorRank" : 8,
      "name" : "Imagawa A",
      "referenceId" : "RGD:A101771"
    }, {
      "firstName" : "T",
      "lastName" : "Hamaguchi",
      "authorRank" : 9,
      "name" : "Hamaguchi T",
      "referenceId" : "RGD:A20435"
    }, {
      "firstName" : "T",
      "lastName" : "Yamasaki",
      "authorRank" : 10,
      "name" : "Yamasaki T",
      "referenceId" : "RGD:A21404"
    }, {
      "firstName" : "Y",
      "lastName" : "Horikawa",
      "authorRank" : 11,
      "name" : "Horikawa Y",
      "referenceId" : "RGD:A30253"
    }, {
      "firstName" : "T",
      "lastName" : "Satoh",
      "authorRank" : 12,
      "name" : "Satoh T",
      "referenceId" : "RGD:A22193"
    }, {
      "firstName" : "H",
      "lastName" : "Nakajima",
      "authorRank" : 13,
      "name" : "Nakajima",
      "referenceId" : "RGD:A401655"
    }, {
      "firstName" : "J",
      "lastName" : "Miyazaki",
      "authorRank" : 14,
      "name" : "Miyazaki J",
      "referenceId" : "RGD:A18997"
    }, {
      "firstName" : "S",
      "lastName" : "Higashiyama",
      "authorRank" : 15,
      "name" : "Higashiyama S",
      "referenceId" : "RGD:A18582"
    }, {
      "firstName" : "J",
      "lastName" : "Miyagawa",
      "authorRank" : 16,
      "name" : "Miyagawa J",
      "referenceId" : "RGD:A30254"
    }, {
      "firstName" : "M",
      "lastName" : "Namba",
      "authorRank" : 17,
      "name" : "Namba M",
      "referenceId" : "RGD:A25153"
    }, {
      "firstName" : "T",
      "lastName" : "Hanafusa",
      "authorRank" : 18,
      "name" : "Hanafusa",
      "referenceId" : "RGD:A321611"
    }, {
      "firstName" : "Y",
      "lastName" : "Matsuzawa",
      "authorRank" : 19,
      "name" : "Matsuzawa",
      "referenceId" : "RGD:A366205"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071974"
    } ]
  }, {
    "primaryId" : "PMID:10333267",
    "title" : "Pax-6 is required for thalamocortical pathway formation in fetal rats.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kawano H, etal., J Comp Neurol 1999 May 31;408(2):147-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-08-23T10:29:55.000-05:00",
    "volume" : "408",
    "pages" : "147-60",
    "abstract" : "Pax-6, a transcription regulatory factor, has been demonstrated to play important roles in eye, nose, and brain development by analyzing mice, rats, and humans with a Pax-6 gene mutation. We examined the role of Pax-6 with special attention to the formation of efferent and afferent pathways of the cerebral cortex by using the rat Small eye (rSey2), which has a mutation in the Pax-6 gene. In rSey2/rSey2 fetuses, cortical efferent axons develop with normal trajectory, at least within the cortical anlage, when examined with immunohistochemistry of the neuronal cell adhesion molecule TAG-1 and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) labeling from the cortical surface. A remarkable disorder was found in the trajectory of dorsal thalamic axons by immunostaining of the neurofilament and the neural cell adhesion molecule L1 and DiI labeling from the dorsal thalamus. In normal rat fetuses, dorsal thalamic axons curved laterally in the ventral thalamus without invading a Pax-6-immunoreactive cell cluster in the ventral part of the ventral thalamus. These axons then coursed up to the cortical anlage, passing just dorsal to another Pax-6-immunoreactive cell cluster in the amygdaloid region. In contrast, in rSey2/rSey2 fetuses, dorsal thalamic axons extended downward to converge in the ventrolateral corner of the ventral thalamus and fanned out in the amygdaloid region without reaching the cortical anlage. These results suggest that Pax-6-expressing cell clusters along the thalamocortical pathway (ventral part of the ventral thalamus and amygdala) are responsible for the determination of the axonal pathfinding of the thalamocortical pathway.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Kawano",
      "authorRank" : 1,
      "name" : "Kawano H",
      "referenceId" : "RGD:A34918"
    }, {
      "firstName" : "T",
      "lastName" : "Fukuda",
      "authorRank" : 2,
      "name" : "Fukuda T",
      "referenceId" : "RGD:A9510"
    }, {
      "firstName" : "K",
      "lastName" : "Kubo",
      "authorRank" : 3,
      "name" : "Kubo K",
      "referenceId" : "RGD:A35426"
    }, {
      "firstName" : "M",
      "lastName" : "Horie",
      "authorRank" : 4,
      "name" : "Horie M",
      "referenceId" : "RGD:A17058"
    }, {
      "firstName" : "K",
      "lastName" : "Uyemura",
      "authorRank" : 5,
      "name" : "Uyemura K",
      "referenceId" : "RGD:A20901"
    }, {
      "firstName" : "K",
      "lastName" : "Takeuchi",
      "authorRank" : 6,
      "name" : "Takeuchi K",
      "referenceId" : "RGD:A5272"
    }, {
      "firstName" : "N",
      "lastName" : "Osumi",
      "authorRank" : 7,
      "name" : "Osumi N",
      "referenceId" : "RGD:A16783"
    }, {
      "firstName" : "K",
      "lastName" : "Eto",
      "authorRank" : 8,
      "name" : "Eto K",
      "referenceId" : "RGD:A35425"
    }, {
      "firstName" : "K",
      "lastName" : "Kawamura",
      "authorRank" : 9,
      "name" : "Kawamura K",
      "referenceId" : "RGD:A87232"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:731243"
    } ]
  }, {
    "primaryId" : "PMID:10333405",
    "title" : "Immunocytochemical detection of structural and regulatory proteins in rat adrenal nuclear matrix.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Neves D, etal., Biotech Histochem. 1999 Mar;74(2):85-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-02-04T18:35:56.000-06:00",
    "volume" : "74",
    "pages" : "85-91",
    "abstract" : "The nuclear matrix is a specific cell structure consisting of a residual nucleoskeleton that extends from the nucleoli to the nuclear envelope. The nuclear matrix of steroidogenic cells was isolated previously from a purified nuclear fraction. We present here an in situ extraction method, modified Lutz's method, for rat glandular adrenal cell nuclear matrix. This residual organelle was characterized and studied using immunocytochemical methods. The adrenal glands were removed, the cells prepared in suspension and deposited by cytospin onto Poly-L-lysine glass slides. The nuclear matrix was extracted with Nonidet P-40, DNase I and high and low ionic strength buffers. Structural proteins, nuclear lamins, coilin and fibrillarin were detected immunocytochemically. The adrenal fasciculata cells were easily identified by this method because of their  large nuclei and abundant lipid droplets in the cytoplasm. After immunocytochemical detection by antibodies against lamins A and C, a marked brown layer at the periphery of the nucleus was observed. The intensity of the staining was lower using the antibody against nuclear lamin B. Immunocytochemical detection of the protein coilin revealed punctuated stained areas, 2-6 per nucleus, that probably correspond to the coiled bodies. The protein fibrillarin was detected at the nucleolus and coiled bodies. Our technique is simple, reveals well preserved adrenal nuclear matrices, and may be a useful method for immunocytochemical analysis and in situ hybridization.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Neves",
      "authorRank" : 1,
      "name" : "Neves",
      "referenceId" : "RGD:A211691"
    }, {
      "firstName" : "MM",
      "lastName" : "Magalhaes",
      "authorRank" : 2,
      "name" : "Magalhaes",
      "referenceId" : "RGD:A211692"
    }, {
      "firstName" : "MC",
      "lastName" : "Magalhaes",
      "authorRank" : 3,
      "name" : "Magalhaes",
      "referenceId" : "RGD:A211693"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10755764"
    } ]
  }, {
    "primaryId" : "PMID:10333487",
    "title" : "Functional expression of rat thioredoxin reductase: selenocysteine insertion sequence element is essential for the active enzyme.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Fujiwara N, etal., Biochem J 1999 Jun 1;340 ( Pt 2):439-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:32:35.000-05:00",
    "volume" : "340 ( Pt 2)",
    "pages" : "439-44",
    "abstract" : "Mammalian thioredoxin reductase (TR) is a flavoprotein catalysing reduction of oxidized thioredoxin in an NADPH-dependent manner, and contains a selenocysteine (Sec) residue near the C-terminus. We observed that TR activity was decreased in A549 cells by the lowering of the fetal bovine serum content in the culture medium and was recovered by the addition of selenium. To study the role of Sec in TR activity, we have isolated a full-length clone of the rat TR cDNA (3.3 kb) and have expressed it in COS-1 cells in a transient-expression system. TR activities in COS-1 cells expressing rat TR were increased in accordance with supplemented sodium selenite concentrations, whereas levels of TR protein, examined by Western blotting, were not affected by sodium selenite concentrations. We introduced various deletions into the 3'-untranslated region of the TR cDNA to localize and examine the role of a Sec insertion-sequence (SECIS) element in the functional expression of TR. TR activities were observed only in COS-1 cells transfected with the TR cDNAs containing the putative SECIS element located between 1856 and 1915 bp in the correct orientation. We also carried out radiolabelling of proteins by incubation of the cDNA-transfected cells with sodium [75Se]selenite. 75Se was incorporated into the expressed TR protein of the cells transfected with the SECIS element-containing cDNAs, but not into those without the SECIS element or with an inverted SECIS element. These data clearly showed a requirement of selenium for the formation of functional TR protein.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Fujiwara",
      "authorRank" : 1,
      "name" : "Fujiwara N",
      "referenceId" : "RGD:A23775"
    }, {
      "firstName" : "T",
      "lastName" : "Fujii",
      "authorRank" : 2,
      "name" : "Fujii T",
      "referenceId" : "RGD:A297692"
    }, {
      "firstName" : "J",
      "lastName" : "Fujii",
      "authorRank" : 3,
      "name" : "Fujii J",
      "referenceId" : "RGD:A4630"
    }, {
      "firstName" : "N",
      "lastName" : "Taniguchi",
      "authorRank" : 4,
      "name" : "Taniguchi N",
      "referenceId" : "RGD:A4634"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634383"
    } ]
  }, {
    "primaryId" : "PMID:10333503",
    "title" : "Identification of peroxisomal proteins by using M13 phage protein VI phage display: molecular evidence that mammalian peroxisomes contain a 2,4-dienoyl-CoA reductase.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Fransen M, etal., Biochem J 1999 Jun 1;340 ( Pt 2):561-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:27:20.000-05:00",
    "volume" : "340 ( Pt 2)",
    "pages" : "561-8",
    "abstract" : "To elucidate unknown mammalian peroxisomal enzymes and functions, we subjected M13 phage expressing fusions between the gene encoding protein VI and a rat liver cDNA library to an immunoaffinity selection process in vitro (biopanning) with the use of antibodies raised against peroxisomal subfractions. In an initial series of biopanning experiments, four different cDNA clones were obtained. These cDNA species encoded two previously identified peroxisomal enzymes, catalase and urate oxidase, and two novel proteins that contained a C-terminal peroxisomal targeting signal (PTS1). A primary structure analysis of these novel proteins revealed that one, ending in the tripeptide AKL, is homologous to the yeast peroxisomal 2,4-dienoyl-CoA reductase (EC 1.3.1.34; DCR), an enzyme required for the degradation of unsaturated fatty acids, and that the other, ending in the tripeptide SRL, is a putative member of the short-chain dehydrogenase/reductase (SDR) family, with three isoforms. Green fluorescent protein (GFP) fusions encoding GFP-DCR-AKL, GFP-DCR, GFP-SDR-SRL and GFP-SDR were expressed in mammalian cells. The analysis of the subcellular location of the recombinant fusion proteins confirmed the peroxisomal localization of GFP-DCR-AKL and GFP-SDR-SRL, as well as the functionality of the PTS1. That the AKL protein is indeed an NADPH-dependent DCR was demonstrated by showing DCR activity of the bacterially expressed protein. These results demonstrate at the molecular level that mammalian peroxisomes do indeed contain a DCR. In addition, the results presented here indicate that the protein VI display system is suitable for the isolation of rare cDNA clones from cDNA libraries and that this technology facilitates the identification of novel peroxisomal proteins.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Fransen",
      "authorRank" : 1,
      "name" : "Fransen M",
      "referenceId" : "RGD:A5610"
    }, {
      "firstName" : "PP",
      "lastName" : "Van Veldhoven",
      "authorRank" : 2,
      "name" : "Van Veldhoven PP",
      "referenceId" : "RGD:A5617"
    }, {
      "firstName" : "S",
      "lastName" : "Subramani",
      "authorRank" : 3,
      "name" : "Subramani S",
      "referenceId" : "RGD:A9891"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70713"
    } ]
  }, {
    "primaryId" : "PMID:10333942",
    "title" : "Phenotypic characteristics of early-onset autosomal-dominant type 2 diabetes unlinked to known maturity-onset diabetes of the young (MODY) genes.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Doria A, etal., Diabetes Care. 1999 Feb;22(2):253-61. doi: 10.2337/diacare.22.2.253.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-06-26T13:36:07.000-05:00",
    "volume" : "22",
    "pages" : "253-61",
    "abstract" : "<br><b>OBJECTIVE: </b>To investigate whether there are forms of early-onset autosomal-dominant type 2 diabetes that are distinct from typical maturity-onset diabetes of the young (MODY) and to characterize their phenotypic characteristics.<br><b>RESEARCH DESIGN AND METHODS: </b>The study included 220 affected subjects from 29 families in which early-onset type 2 diabetes occurred in multiple generations and was not linked to known MODY genes (MODY gene-negative families). All individuals underwent an oral glucose tolerance test and other clinical measurements aimed at investigating the underlying metabolic defect and the presence of diabetic complications. For comparison, 79 affected carriers of MODY3 (hepatocyte nuclear factor [HNF]-1 alpha) mutations were similarly examined.<br><b>RESULTS: </b>Subjects from MODY gene-negative pedigrees were diagnosed with diabetes at an older age (36 +/- 17 vs. 21 +/- 10 years, P = 0.0001) and were more frequently obese (52 vs. 18%, P = 0.0001) than MODY3 individuals. MODY gene-negative patients who were insulin treated required more exogenous insulin than did MODY3 subjects (0.7 +/- 0.4 vs. 0.45 +/- 0.2 U.kg-1.day-1, P = 0.04), despite similar C-peptide levels. Among subjects not treated with insulin, MODY gene-negative subjects had significantly higher serum insulin levels, both fasting (16.5 +/- 15 vs. 6.5 +/- 5 microU/ml, P = 0.027) and 2 h after a glucose load (53 +/- 44 vs. 11 +/- 10, P = 0.002). They also had higher serum triglycerides (P = 0.02), higher cholesterol levels (P = 0.02), more hypertension (P = 0.0001), and more nephropathy (P = 0.001). Differences persisted when families were matched for age at diagnosis.<br><b>CONCLUSIONS: </b>Our findings indicate the existence of forms of early-onset autosomal-dominant type 2 diabetes that are distinct from MODY and are frequently characterized by insulin resistance, similar to later-onset type 2 diabetes. Because of the Mendelian pattern of inheritance, the goal of identifying the genes involved in these forms of diabetes appears to be particularly feasible.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Doria",
      "authorRank" : 1,
      "name" : "Doria A",
      "referenceId" : "RGD:A26596"
    }, {
      "firstName" : "Y",
      "lastName" : "Yang",
      "authorRank" : 2,
      "name" : "Yang Y",
      "referenceId" : "RGD:A10922"
    }, {
      "firstName" : "M",
      "lastName" : "Malecki",
      "authorRank" : 3,
      "name" : "Malecki M",
      "referenceId" : "RGD:A88600"
    }, {
      "firstName" : "S",
      "lastName" : "Scotti",
      "authorRank" : 4,
      "name" : "Scotti S",
      "referenceId" : "RGD:A529342"
    }, {
      "firstName" : "J",
      "lastName" : "Dreyfus",
      "authorRank" : 5,
      "name" : "Dreyfus J",
      "referenceId" : "RGD:A529343"
    }, {
      "firstName" : "C",
      "lastName" : "O'Keeffe",
      "authorRank" : 6,
      "name" : "O'Keeffe C",
      "referenceId" : "RGD:A529344"
    }, {
      "firstName" : "T",
      "lastName" : "Orban",
      "authorRank" : 7,
      "name" : "Orban T",
      "referenceId" : "RGD:A164083"
    }, {
      "firstName" : "J H",
      "lastName" : "Warram",
      "authorRank" : 8,
      "name" : "Warram JH",
      "referenceId" : "RGD:A529345"
    }, {
      "firstName" : "A S",
      "lastName" : "Krolewski",
      "authorRank" : 9,
      "name" : "Krolewski AS",
      "referenceId" : "RGD:A529346"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:329901808"
    } ]
  }, {
    "primaryId" : "PMID:10334320",
    "title" : "A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Clement K, etal., Diabetes 1999 Feb;48(2):398-402.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-04-23T16:53:19.000-05:00",
    "volume" : "48",
    "pages" : "398-402",
    "abstract" : "As part of an ongoing search for susceptibility genes in obese families, we performed linkage analyses in 101 French families between qualitative and quantitative traits related to morbid obesity and polymorphisms located in or near 15 candidate genes whose products are involved in body weight regulation. These included cholecystokinin A and B receptors (CCK-AR and CCK-BR), glucagon-like peptide 1 receptor (GLP-1R), the LIM/homeodomain islet-1 gene (Isl-1), the caudal-type homeodomain 3 (CDX-3), the uncoupling protein 1 (UCP-1), the beta3-adrenoceptor (beta3-AR), the fatty acid-binding protein 2 (FABP-2), the hormone-sensitive lipase (HSL), the lipoprotein lipase (LPL), the apoprotein-C2 (apo-C2), the insulin receptor substrate-1 (IRS-1), the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and the liver carnitine palmitoyltransferase-1 (CPT-1). Phenotypes related to obesity such as BMI, adult life body weight gain, fasting leptin, insulin, fasting glycerol, and free fatty acids were used for nonparametric sib-pair analyses. A weak indication for linkage was obtained between the Isl-1 locus and obesity status defined by a z score over one SD of BMI (n = 226 sib pairs, pi = 0.54 +/- 0.02, P = 0.03). Moreover, a suggestive indication for linkage was found between the Isl-1 locus and BMI and leptin values (P = 0.001 and 0.0003, respectively) and leptin adjusted for BMI (P = 0.0001). Multipoint analyses for leptin trait with Isl-1 and two flanking markers (D5S418 and D5S407) showed that the logarithm of odds (LOD) score is 1.73, coinciding with the Isl-1 locus. Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity. Whether an obesity susceptibility gene (Isl-1 itself or another nearby gene) lies on chromosome 5q should be determined by further analyses.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Clement",
      "authorRank" : 1,
      "name" : "Clement K",
      "referenceId" : "RGD:A40125"
    }, {
      "firstName" : "C",
      "lastName" : "Dina",
      "authorRank" : 2,
      "name" : "Dina C",
      "referenceId" : "RGD:A40117"
    }, {
      "firstName" : "A",
      "lastName" : "Basdevant",
      "authorRank" : 3,
      "name" : "Basdevant A",
      "referenceId" : "RGD:A40124"
    }, {
      "firstName" : "N",
      "lastName" : "Chastang",
      "authorRank" : 4,
      "name" : "Chastang N",
      "referenceId" : "RGD:A40150"
    }, {
      "firstName" : "V",
      "lastName" : "Pelloux",
      "authorRank" : 5,
      "name" : "Pelloux V",
      "referenceId" : "RGD:A40151"
    }, {
      "firstName" : "N",
      "lastName" : "Lahlou",
      "authorRank" : 6,
      "name" : "Lahlou N",
      "referenceId" : "RGD:A40152"
    }, {
      "firstName" : "M",
      "lastName" : "Berlan",
      "authorRank" : 7,
      "name" : "Berlan M",
      "referenceId" : "RGD:A40153"
    }, {
      "firstName" : "D",
      "lastName" : "Langin",
      "authorRank" : 8,
      "name" : "Langin D",
      "referenceId" : "RGD:A31833"
    }, {
      "firstName" : "B",
      "lastName" : "Guy-Grand",
      "authorRank" : 9,
      "name" : "Guy-Grand B",
      "referenceId" : "RGD:A40126"
    }, {
      "firstName" : "P",
      "lastName" : "Froguel",
      "authorRank" : 10,
      "name" : "Froguel P",
      "referenceId" : "RGD:A119724"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298039"
    } ]
  }, {
    "primaryId" : "PMID:10334910",
    "title" : "Developmentally regulated expression of a nonmuscle myosin heavy chain IIB inserted isoform in rat brain.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Takahashi M, etal., Biochem Biophys Res Commun 1999 May 27;259(1):29-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:58.000-05:00",
    "volume" : "259",
    "pages" : "29-33",
    "abstract" : "The alternatively spliced isoform of the nonmuscle myosin II heavy chain B (MHC-B) with an insert of 21 amino acids at the 50- to 20-kDa junction of the globular region of myosin has been demonstrated to be expressed specifically in the central nervous system (CNS) in chicken. To explore the role of this B2 inserted isoform (MHC-B(B2)), immunoblot and immunoprecipitation analyses were performed using specific antibodies and extracts from rat tissues. MHC-B(B2) is present throughout the CNS, but is less abundant in the cerebrum and not expressed in the olfactory lobe at all. In the developing rat brain, MHC-B(B2) is expressed from postnatal day 10 (P10) in the cerebellum and increases markedly from P14. The appearance of MHC-B(B2) in the cerebrum (P28) is later than in the cerebellum. Additionally, we show that myosin IIB(B2) is homodimeric in its heavy chain subunit composition. These results suggest that myosin IIB(B2) might participate in cell motility in the neuronal cells of the mature CNS.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Takahashi",
      "authorRank" : 1,
      "name" : "Takahashi M",
      "referenceId" : "RGD:A4629"
    }, {
      "firstName" : "T",
      "lastName" : "Hirano",
      "authorRank" : 2,
      "name" : "Hirano T",
      "referenceId" : "RGD:A18629"
    }, {
      "firstName" : "K",
      "lastName" : "Uchida",
      "authorRank" : 3,
      "name" : "Uchida K",
      "referenceId" : "RGD:A20920"
    }, {
      "firstName" : "A",
      "lastName" : "Yamagishi",
      "authorRank" : 4,
      "name" : "Yamagishi A",
      "referenceId" : "RGD:A20921"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633431"
    } ]
  }, {
    "primaryId" : "PMID:10334992",
    "title" : "Identification of a nuclear receptor for bile acids.",
    "datePublished" : "1999-05-21T00:00:00.000-05:00",
    "citation" : "Makishima M, etal., Science. 1999 May 21;284(5418):1362-5. doi: 10.1126/science.284.5418.1362.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-12-20T13:03:17.000-06:00",
    "volume" : "284",
    "pages" : "1362-5",
    "abstract" : "Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.",
    "issueName" : "5418",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Makishima",
      "authorRank" : 1,
      "name" : "Makishima M",
      "referenceId" : "RGD:A48358"
    }, {
      "firstName" : "A Y",
      "lastName" : "Okamoto",
      "authorRank" : 2,
      "name" : "Okamoto AY",
      "referenceId" : "RGD:A477643"
    }, {
      "firstName" : "J J",
      "lastName" : "Repa",
      "authorRank" : 3,
      "name" : "Repa JJ",
      "referenceId" : "RGD:A477644"
    }, {
      "firstName" : "H",
      "lastName" : "Tu",
      "authorRank" : 4,
      "name" : "Tu H",
      "referenceId" : "RGD:A5421"
    }, {
      "firstName" : "R M",
      "lastName" : "Learned",
      "authorRank" : 5,
      "name" : "Learned RM",
      "referenceId" : "RGD:A477645"
    }, {
      "firstName" : "A",
      "lastName" : "Luk",
      "authorRank" : 6,
      "name" : "Luk A",
      "referenceId" : "RGD:A5423"
    }, {
      "firstName" : "M V",
      "lastName" : "Hull",
      "authorRank" : 7,
      "name" : "Hull MV",
      "referenceId" : "RGD:A477646"
    }, {
      "firstName" : "K D",
      "lastName" : "Lustig",
      "authorRank" : 8,
      "name" : "Lustig KD",
      "referenceId" : "RGD:A477647"
    }, {
      "firstName" : "D J",
      "lastName" : "Mangelsdorf",
      "authorRank" : 9,
      "name" : "Mangelsdorf DJ",
      "referenceId" : "RGD:A477648"
    }, {
      "firstName" : "B",
      "lastName" : "Shan",
      "authorRank" : 10,
      "name" : "Shan B",
      "referenceId" : "RGD:A5422"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:15090836"
    } ]
  }, {
    "primaryId" : "PMID:10334995",
    "title" : "UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation.",
    "datePublished" : "1999-05-21T00:00:00.000-05:00",
    "citation" : "Keppler OT, etal., Science. 1999 May 21;284(5418):1372-6. doi: 10.1126/science.284.5418.1372.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-12-06T01:55:50.000-06:00",
    "volume" : "284",
    "pages" : "1372-6",
    "abstract" : "Modification of cell surface molecules with sialic acid is crucial for their function in many biological processes, including cell adhesion and signal transduction. Uridine diphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) is an enzyme that catalyzes an early, rate-limiting step in the sialic acid biosynthetic pathway. UDP-GlcNAc 2-epimerase was found to be a major determinant of cell surface sialylation in human hematopoietic cell lines and a critical regulator of the function of specific cell surface adhesion molecules.",
    "issueName" : "5418",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O T",
      "lastName" : "Keppler",
      "authorRank" : 1,
      "name" : "Keppler OT",
      "referenceId" : "RGD:A536184"
    }, {
      "firstName" : "S",
      "lastName" : "Hinderlich",
      "authorRank" : 2,
      "name" : "Hinderlich S",
      "referenceId" : "RGD:A5851"
    }, {
      "firstName" : "J",
      "lastName" : "Langner",
      "authorRank" : 3,
      "name" : "Langner J",
      "referenceId" : "RGD:A140491"
    }, {
      "firstName" : "R",
      "lastName" : "Schwartz-Albiez",
      "authorRank" : 4,
      "name" : "Schwartz-Albiez R",
      "referenceId" : "RGD:A536185"
    }, {
      "firstName" : "W",
      "lastName" : "Reutter",
      "authorRank" : 5,
      "name" : "Reutter W",
      "referenceId" : "RGD:A5856"
    }, {
      "firstName" : "M",
      "lastName" : "Pawlita",
      "authorRank" : 6,
      "name" : "Pawlita M",
      "referenceId" : "RGD:A536186"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401901215"
    } ]
  }, {
    "primaryId" : "PMID:10335358",
    "title" : "Junctional plaque proteins shift to the apical surface of uterine epithelial cells during early pregnancy in the rat.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Orchard MD, etal., Acta Histochem. 1999 Apr;101(2):147-56.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-03T16:36:11.000-05:00",
    "volume" : "101",
    "pages" : "147-56",
    "abstract" : "Antibodies against the cytoplasmic plaque molecules, plectin and plakoglobin, and cytokeratin, the molecular component of intermediate filaments (IFs), were used to examine the distribution of these molecules in rat uterine epithelial cells during early pregnancy including the period of blastocyst implantation. On day 1 of pregnancy plectin was detected in concentrated bands along the apical and basal plasma membranes, and diffusely throughout the cytoplasm. Plakoglobin was found along the entire lateral plasma membrane on day 1. By day 6, the time of blastocyst implantation, plectin was localised along the apical and basal membranes and reduced in the basal cytoplasm, and plakoglobin was seen exclusively at the apical-most quarter of the lateral plasma membrane. Cytokeratin was detected throughout the cytoplasm on day 1, but by day 6, was localised to the apical region of the cytoplasm only. These results show a redistribution of plectin, plakoglobin and cytokeratin away from the basal region of the uterine epithelial cells. The change in distribution of these molecules may contribute to the adhesion of the blastocyst to the apical and lateral surfaces of uterine epithelial cells and the subsequent detachment of the uterine epithelium from the basal lamina.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MD",
      "lastName" : "Orchard",
      "authorRank" : 1,
      "name" : "Orchard MD",
      "referenceId" : "RGD:A93798"
    }, {
      "firstName" : "TJ",
      "lastName" : "Shaw",
      "authorRank" : 2,
      "name" : "Shaw TJ",
      "referenceId" : "RGD:A93799"
    }, {
      "firstName" : "CR",
      "lastName" : "Murphy",
      "authorRank" : 3,
      "name" : "Murphy CR",
      "referenceId" : "RGD:A67072"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2291899"
    } ]
  }, {
    "primaryId" : "PMID:10335523",
    "title" : "Chromosome 19 locus apolipoprotein C-II association with multiple sclerosis.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Zouali H, etal., Mult Scler 1999 Apr;5(2):134-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-10T14:50:49.000-05:00",
    "volume" : "5",
    "pages" : "134-6",
    "abstract" : "We have used a PCR based method to analyze allelic frequencies in a (TG)n(AG)m microsatellite marker located in the first intron of the apolipoprotein C-II gene in French MS patients and controls. Samples were collected from 74 MS patients and from 102 controls. The distribution of microsatellite alleles differed between patients and controls (chi 2 = 7.82), showing a significant effect (P < 0.04) with MS due to the increased frequency of the allele 6 and a decrease frequency (P < 0.03) of allele I. Our study confirms that the apolipoprotein C-II region may influence susceptibility to MS.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Zouali",
      "authorRank" : 1,
      "name" : "Zouali H",
      "referenceId" : "RGD:A52358"
    }, {
      "firstName" : "L",
      "lastName" : "Faure-Delanef",
      "authorRank" : 2,
      "name" : "Faure-Delanef L",
      "referenceId" : "RGD:A52359"
    }, {
      "firstName" : "G",
      "lastName" : "Lucotte",
      "authorRank" : 3,
      "name" : "Lucotte G",
      "referenceId" : "RGD:A52360"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358408"
    } ]
  }, {
    "primaryId" : "PMID:10335651",
    "title" : "Molecular evolution of the nuclear von Willebrand factor gene in mammals and the phylogeny of rodents.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Huchon D, etal., Mol Biol Evol 1999 May;16(5):577-89.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:06.000-05:00",
    "volume" : "16",
    "pages" : "577-89",
    "abstract" : "Nucleotide sequences of exon 28 of the von Willebrand Factor (vWF) were analyzed for a representative sampling of rodent families and eutherian orders, with one marsupial sequence as outgroup. The aim of this study was to test if inclusion of an increased taxonomic diversity in molecular analyses would shed light on three uncertainties concerning rodent phylogeny: (1) relationships between rodent families, (2) Rodentia monophyly, and (3) the sister group relationship of rodents and lagomorphs. The results did not give evidence of any particular rodent pattern of molecular evolution relative to a general eutherian pattern. Base compositions and rates of evolution of vWF sequences of rodents were in the range of placental variation. The 10 rodent families studied here cluster in five clades: Hystricognathi, Sciuridae and Aplodontidae (Sciuroidea), Muridae, Dipodidae, and Gliridae. Among hystricognaths, the following conclusions are drawn: a single colonization event in South America by Caviomorpha, a paraphyly of Old World and New World porcupines, and an African origin for Old World porcupines. Despite a broader taxonomic sampling diversity, we did not obtain a robust answer to the question of Rodentia monophyly, but in the absence of any other alternative, we cannot reject the hypothesis of a single origin of rodents. Moreover, the phylogenetic position of Lagomorpha remains totally unsettled.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Huchon",
      "authorRank" : 1,
      "name" : "Huchon D",
      "referenceId" : "RGD:A24237"
    }, {
      "firstName" : "FM",
      "lastName" : "Catzeflis",
      "authorRank" : 2,
      "name" : "Catzeflis FM",
      "referenceId" : "RGD:A7849"
    }, {
      "firstName" : "EJ",
      "lastName" : "Douzery",
      "authorRank" : 3,
      "name" : "Douzery EJ",
      "referenceId" : "RGD:A24238"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634526"
    } ]
  }, {
    "primaryId" : "PMID:10335943",
    "title" : "Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Lekmine F, etal., Virchows Arch. 1999 Apr;434(4):325-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-02T14:48:39.000-06:00",
    "volume" : "434",
    "pages" : "325-32",
    "abstract" : "Medullary thyroid carcinoma (MTC) originates from C cells, which secrete calcitonin (CT), their specific marker. C cells are located in contact with the basement membrane (BM) of the thyroid follicles, which is partly made up of the laminin-2 isoform synthesized by thyrocytes. During oncogenesis, proliferation of the C cells, invading the centre of the follicles, leads to a break in their normal contact with the BM. As specific interactions of cells with BM components, especially laminins, are important for proliferation and differentiation, we investigated the relationships of normal and neoplastic C cells with laminin in the Wag/Rij rat model of human MTC. Immunocytochemical studies showed a progressive loss of the laminin layer underlying the hyperplastic C cell nodules around the large dedifferentiated tumours. The alpha2, beta1 and gamma1 chains of the laminin-2 isoform were synthesized and secreted by rat MTC 6-23 cell cultures and the tumours induced by subcutaneous injection of these cells. In situ hybridization combined with anti-CT immunocytochemistry showed a low expression of alpha2 mRNA on differentiated C cells and thyrocytes, but an overexpression on immunonegative spontaneous MTC and induced intrathyroid tumours. The high level of alpha2 gene expression, together with tumour dedifferentiation, suggests a relationship with malignancy.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Lekmine",
      "authorRank" : 1,
      "name" : "Lekmine F",
      "referenceId" : "RGD:A76537"
    }, {
      "firstName" : "H",
      "lastName" : "Feracci",
      "authorRank" : 2,
      "name" : "Feracci H",
      "referenceId" : "RGD:A17459"
    }, {
      "firstName" : "G",
      "lastName" : "Milhaud",
      "authorRank" : 3,
      "name" : "Milhaud G",
      "referenceId" : "RGD:A16325"
    }, {
      "firstName" : "F",
      "lastName" : "Treilhou-Lahille",
      "authorRank" : 4,
      "name" : "Treilhou-Lahille F",
      "referenceId" : "RGD:A76538"
    }, {
      "firstName" : "N",
      "lastName" : "Jeanne",
      "authorRank" : 5,
      "name" : "Jeanne N",
      "referenceId" : "RGD:A76539"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600207"
    } ]
  }, {
    "primaryId" : "PMID:10335989",
    "title" : "Hb Siriraj: a G-->A substitution at codon 7 of the beta-globin chain creates an MboII cutting site.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Chang JG, etal., Hemoglobin. 1999 May;23(2):197-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:32:19.000-05:00",
    "volume" : "23",
    "pages" : "197-9",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JG",
      "lastName" : "Chang",
      "authorRank" : 1,
      "name" : "Chang JG",
      "referenceId" : "RGD:A66796"
    }, {
      "firstName" : "TY",
      "lastName" : "Yang",
      "authorRank" : 2,
      "name" : "Yang",
      "referenceId" : "RGD:A203721"
    }, {
      "firstName" : "LI",
      "lastName" : "Perng",
      "authorRank" : 3,
      "name" : "Perng",
      "referenceId" : "RGD:A363071"
    }, {
      "firstName" : "NM",
      "lastName" : "Wang",
      "authorRank" : 4,
      "name" : "Wang",
      "referenceId" : "RGD:A349627"
    }, {
      "firstName" : "CT",
      "lastName" : "Peng",
      "authorRank" : 5,
      "name" : "Peng CT",
      "referenceId" : "RGD:A59570"
    }, {
      "firstName" : "CH",
      "lastName" : "Tsai",
      "authorRank" : 6,
      "name" : "Tsai CH",
      "referenceId" : "RGD:A58671"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11527252"
    } ]
  }, {
    "primaryId" : "PMID:10336070",
    "title" : "Up-regulation of Eph tyrosine kinase receptors after excitotoxic injury in adult  hippocampus.",
    "datePublished" : "1000-03-01T00:00:00.000-06:00",
    "citation" : "Moreno-Flores MT and Wandosell F, Neuroscience. 1999;91(1):193-201.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-03-05T15:16:56.000-06:00",
    "volume" : "91",
    "pages" : "193-201",
    "abstract" : "The molecular mechanisms underlying the response to injury in the central nervous system are incompletely understood. Many cell activation systems may be involved. Tyrosine kinase receptors and their ligands play key roles in cell activation throughout life. The Eph family of tyrosine kinase receptors/ ligands are developmentally regulated and have been implicated in neural pathfinding. However, nothing is known about their role in the adult brain. We have used a model of central nervous system lesion in the rat, in which intraventricular injection of kainate was performed. This produced neuronal death in the CA3-CA4 fields and glial activation in the hippocampus. Highly degenerate primers, corresponding to the catalytic domain of the tyrosine kinase family, were used for reverse transcription-polymerase chain reaction of pooled RNA extracted from  injured hippocampi. The amplified products were cloned and 100 clones (arbitrarily named TK1-TK100) were examined and inserts sequenced. We obtained four clones containing inserts which belong to the Eph receptor family. Two of these inserts (TK17 and TK63) were EphA4 and the other were EphB2 (TK25) and EphA5 (TK23). We performed in situ hybridization, and we found our clones to be present in all fields of the hippocampus, their expression being mainly neuronal. Three days after lesion, prominent expression appeared in CA1 as compared to the  same field in the non-treated contralateral hippocampus. We performed northern blot analysis for quantification, and found that, three days after injury, the values decreased to 33 +/- 4%, 33 +/- 1% and 46 +/- 1% of control values for TK63 (EphA4), TK25 (EphB2) and TK23 (EphA5), respectively. Neuronal death in CA3-CA4 might account for this fact. Later, five days post-injury, the expression increased to 63 +/- 3%, 71 +/- 1% and 111 +/- 5% of control values, respectively. This increase was due to an up-regulation of these genes in the hippocampal neurons that survive after the injury, as indicated by in situ hybridization.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MT",
      "lastName" : "Moreno-Flores",
      "authorRank" : 1,
      "name" : "Moreno-Flores MT",
      "referenceId" : "RGD:A27650"
    }, {
      "firstName" : "F",
      "lastName" : "Wandosell",
      "authorRank" : 2,
      "name" : "Wandosell F",
      "referenceId" : "RGD:A27654"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5688752"
    } ]
  }, {
    "primaryId" : "PMID:10336418",
    "title" : "A rat RuvB-like protein, TIP49a, is a germ cell-enriched novel DNA helicase.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Makino Y, etal., J Biol Chem 1999 May 28;274(22):15329-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:16.000-05:00",
    "volume" : "274",
    "pages" : "15329-35",
    "abstract" : "We have isolated a novel nuclear protein with a molecular mass of 49 kDa (TIP49a) from rat liver. The rat TIP49a showed structural resemblance to several bacterial RuvBs and also displayed Walker A and B motifs. We overproduced the recombinant TIP49a in Escherichia coli and purified it to near homogeneity. Biochemical investigations demonstrated that TIP49a possessed ATPase activity that was stimulated by single-stranded DNA but neither by double-stranded DNA nor by any forms of RNA polymers tested. Moreover, a UV cross-linking assay indicated TIP49a specifically interacted with ATP. Interestingly, we found that DNA duplex was unwound by the recombinant TIP49a in the presence of ATP or dATP. Optimal concentrations of ATP and Mg2+ for the helicase activity were 1-2 mM and 0.25-1 mM, respectively. Displacement of the DNA strand occurred in the 3' to 5' direction with respect to the single-stranded DNA flanking the duplex. Western blot analysis revealed that TIP49a was abundantly expressed in testes and moderately in spleen, thymus, and lung. In mouse seminiferous tubules, the protein was restrictively observed in germ lineages from late pachytene spermatocytes to round spermatids. From these observations, we propose that TIP49a is a novel DNA helicase and may play a role in nuclear processes such as recombination and transcription.",
    "issueName" : "22",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Makino",
      "authorRank" : 1,
      "name" : "Makino Y",
      "referenceId" : "RGD:A5103"
    }, {
      "firstName" : "M",
      "lastName" : "Kanemaki",
      "authorRank" : 2,
      "name" : "Kanemaki M",
      "referenceId" : "RGD:A5102"
    }, {
      "firstName" : "Y",
      "lastName" : "Kurokawa",
      "authorRank" : 3,
      "name" : "Kurokawa Y",
      "referenceId" : "RGD:A25656"
    }, {
      "firstName" : "T",
      "lastName" : "Koji",
      "authorRank" : 4,
      "name" : "Koji T",
      "referenceId" : "RGD:A33729"
    }, {
      "firstName" : "T",
      "lastName" : "Tamura",
      "authorRank" : 5,
      "name" : "Tamura T",
      "referenceId" : "RGD:A156706"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:729809"
    } ]
  }, {
    "primaryId" : "PMID:10336434",
    "title" : "Mixed and non-cognate SNARE complexes. Characterization of assembly and biophysical properties.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Fasshauer D, etal., J Biol Chem 1999 May 28;274(22):15440-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:16.000-05:00",
    "volume" : "274",
    "pages" : "15440-6",
    "abstract" : "Assembly of soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) proteins between two opposing membranes is thought to be the key event that initiates membrane fusion. Many new SNARE proteins have recently been localized to distinct intracellular compartments, supporting the view that sets of specific SNAREs are specialized for distinct trafficking steps. We have now investigated whether other SNAREs can form complexes with components of the synaptic SNARE complex including synaptobrevin/VAMP 2, SNAP-25, and syntaxin 1. When the Q-SNAREs syntaxin 2, 3, and 4, and the R-SNARE endobrevin/VAMP 8 were used in various combinations, heat-resistant complexes were formed. Limited proteolysis revealed that these complexes contained a protease-resistant core similar to that of the synaptic complex. All complexes were disassembled by the ATPase N-ethylmaleimide-sensitive fusion protein and its cofactor alpha-SNAP. Circular dichroism spectroscopy showed that major conformational changes occur during assembly, which are associated with induction of structure from unstructured monomers. Furthermore, no preference for synaptobrevin was observed during the assembly of the synaptic complex when endobrevin/VAMP 8 was present in equal concentrations. We conclude that cognate and non-cognate SNARE complexes are very similar with respect to biophysical properties, assembly, and disassembly, suggesting that specificity of membrane fusion in intracellular membrane traffic is not due to intrinsic specificity of SNARE pairing.",
    "issueName" : "22",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Fasshauer",
      "authorRank" : 1,
      "name" : "Fasshauer D",
      "referenceId" : "RGD:A23376"
    }, {
      "firstName" : "W",
      "lastName" : "Antonin",
      "authorRank" : 2,
      "name" : "Antonin W",
      "referenceId" : "RGD:A23373"
    }, {
      "firstName" : "M",
      "lastName" : "Margittai",
      "authorRank" : 3,
      "name" : "Margittai M",
      "referenceId" : "RGD:A23619"
    }, {
      "firstName" : "S",
      "lastName" : "Pabst",
      "authorRank" : 4,
      "name" : "Pabst S",
      "referenceId" : "RGD:A23371"
    }, {
      "firstName" : "R",
      "lastName" : "Jahn",
      "authorRank" : 5,
      "name" : "Jahn R",
      "referenceId" : "RGD:A160905"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634238"
    } ]
  }, {
    "primaryId" : "PMID:10336460",
    "title" : "A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Lu PJ, etal., J Biol Chem. 1999 May 28;274(22):15633-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-10-16T12:50:14.000-05:00",
    "volume" : "274",
    "pages" : "15633-45",
    "abstract" : "A novel human gene (PLU-1) has been identified which shows a highly restricted expression in normal adult tissues but which is consistently expressed in breast  cancers. A fragment of the PLU-1 cDNA was identified by differentially screening  a fetal brain library with cDNAs prepared from ce-1 cells (a human mammary epithelial cell line overexpressing c-ErbB2) treated or untreated with the antibody 4D5, which inhibits c-ErbB2 phosphorylation. Clones covering the full cDNA sequence of 6.4 kilobases were isolated from a breast cancer cDNA library. Although expression of PLU-1 in ce-1 cells is regulated by signaling from c-ErbB2, the gene is expressed in all the breast cancer cell lines examined, in cells cultured from primary breast cancers, and in the invasive and in situ components of primary breast cancers. Translation of the open reading frame predicts a protein of 1544 amino acids, which contains three PHD/LAP motifs, a specific DNA-binding domain found in a Drosophila protein (dri) and novel domains showing extensive homology with other human and non human gene products. Transient transfection of cell lines with MYC-tagged PLU-1 showed the protein to  be localized in the nucleus and associated with discrete foci. The presence of the dri motif and PHD/LAP fingers together with the clear nuclear localization and consistent expression in breast cancers, suggest a role for PLU-1 in regulating gene expression in breast cancers.",
    "issueName" : "22",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PJ",
      "lastName" : "Lu",
      "authorRank" : 1,
      "name" : "Lu PJ",
      "referenceId" : "RGD:A115413"
    }, {
      "firstName" : "K",
      "lastName" : "Sundquist",
      "authorRank" : 2,
      "name" : "Sundquist",
      "referenceId" : "RGD:A195137"
    }, {
      "firstName" : "D",
      "lastName" : "Baeckstrom",
      "authorRank" : 3,
      "name" : "Baeckstrom",
      "referenceId" : "RGD:A195138"
    }, {
      "firstName" : "R",
      "lastName" : "Poulsom",
      "authorRank" : 4,
      "name" : "Poulsom R",
      "referenceId" : "RGD:A34141"
    }, {
      "firstName" : "A",
      "lastName" : "Hanby",
      "authorRank" : 5,
      "name" : "Hanby A",
      "referenceId" : "RGD:A91966"
    }, {
      "firstName" : "S",
      "lastName" : "Meier-Ewert",
      "authorRank" : 6,
      "name" : "Meier-Ewert",
      "referenceId" : "RGD:A195139"
    }, {
      "firstName" : "T",
      "lastName" : "Jones",
      "authorRank" : 7,
      "name" : "Jones T",
      "referenceId" : "RGD:A24923"
    }, {
      "firstName" : "M",
      "lastName" : "Mitchell",
      "authorRank" : 8,
      "name" : "Mitchell",
      "referenceId" : "RGD:A195140"
    }, {
      "firstName" : "P",
      "lastName" : "Pitha-Rowe",
      "authorRank" : 9,
      "name" : "Pitha-Rowe",
      "referenceId" : "RGD:A195141"
    }, {
      "firstName" : "P",
      "lastName" : "Freemont",
      "authorRank" : 10,
      "name" : "Freemont P",
      "referenceId" : "RGD:A21048"
    }, {
      "firstName" : "J",
      "lastName" : "Taylor-Papadimitriou",
      "authorRank" : 11,
      "name" : "Taylor-Papadimitriou",
      "referenceId" : "RGD:A195142"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9587743"
    } ]
  }, {
    "primaryId" : "PMID:10336464",
    "title" : "Splice variants of intersectin are components of the endocytic machinery in neurons and nonneuronal cells.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Hussain NK, etal., J Biol Chem. 1999 May 28;274(22):15671-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:18:08.000-05:00",
    "volume" : "274",
    "pages" : "15671-7",
    "abstract" : "We recently identified and cloned intersectin, a protein containing two Eps15 homology (EH) domains and five Src homology 3 (SH3) domains. Using a newly developed intersectin antibody, we demonstrate that endogenous COS-7 cell intersectin localizes to clathrin-coated pits, and transfection studies suggest that the EH domains may direct this localization. Through alternative splicing in a stop codon, a long form of intersectin is generated with a C-terminal extension containing Dbl homology (DH), pleckstrin homology (PH), and C2 domains. Western blots reveal that the long form of intersectin is expressed specifically in neurons, whereas the short isoform is expressed at lower levels in glia and other nonneuronal cells. Immunofluorescence analysis of cultured hippocampal neurons reveals that intersectin is found at the plasma membrane where it is co-localized with clathrin. Ibp2, a protein identified based on its interactions with the EH domains of intersectin, binds to clathrin through the N terminus of the heavy chain, suggesting a mechanism for the localization of intersectin at clathrin-coated pits. Ibp2 also binds to the clathrin adaptor AP2, and antibodies against intersectin co-immunoprecipitate clathrin, AP2, and dynamin from brain extracts. These data suggest that the long and short forms of intersectin are components of the endocytic machinery in neurons and nonneuronal cells.",
    "issueName" : "22",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NK",
      "lastName" : "Hussain",
      "authorRank" : 1,
      "name" : "Hussain NK",
      "referenceId" : "RGD:A38828"
    }, {
      "firstName" : "M",
      "lastName" : "Yamabhai",
      "authorRank" : 2,
      "name" : "Yamabhai M",
      "referenceId" : "RGD:A38829"
    }, {
      "firstName" : "AR",
      "lastName" : "Ramjaun",
      "authorRank" : 3,
      "name" : "Ramjaun AR",
      "referenceId" : "RGD:A27366"
    }, {
      "firstName" : "AM",
      "lastName" : "Guy",
      "authorRank" : 4,
      "name" : "Guy",
      "referenceId" : "RGD:A214046"
    }, {
      "firstName" : "D",
      "lastName" : "Baranes",
      "authorRank" : 5,
      "name" : "Baranes D",
      "referenceId" : "RGD:A5277"
    }, {
      "firstName" : "JP",
      "lastName" : "O'Bryan",
      "authorRank" : 6,
      "name" : "O'Bryan JP",
      "referenceId" : "RGD:A49313"
    }, {
      "firstName" : "CJ",
      "lastName" : "Der",
      "authorRank" : 7,
      "name" : "Der CJ",
      "referenceId" : "RGD:A11906"
    }, {
      "firstName" : "BK",
      "lastName" : "Kay",
      "authorRank" : 8,
      "name" : "Kay BK",
      "referenceId" : "RGD:A38832"
    }, {
      "firstName" : "PS",
      "lastName" : "McPherson",
      "authorRank" : 9,
      "name" : "McPherson PS",
      "referenceId" : "RGD:A5279"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041034"
    } ]
  }, {
    "primaryId" : "PMID:10336471",
    "title" : "Localization of functional prostaglandin E2 receptors EP3 and EP4 in the nuclear  envelope.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Bhattacharya M, etal., J Biol Chem. 1999 May 28;274(22):15719-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-04-02T10:48:53.000-05:00",
    "volume" : "274",
    "pages" : "15719-24",
    "abstract" : "The effects of prostaglandin E2 are thought to be mediated via G protein-coupled  plasma membrane receptors, termed EP. However recent data implied that prostanoids may also act intracellularly. We investigated if the ubiquitous EP3 and the EP4 receptors are localized in nuclear membranes. Radioligand binding studies on isolated nuclear membrane fractions of neonatal porcine brain and adult rat liver revealed the presence of EP3 and EP4. A perinuclear localization  of EP3alpha and EP4 receptors was visualized by indirect immunocytofluorescence and confocal microscopy in porcine cerebral microvascular endothelial cells and in transfected HEK 293 cells that stably overexpress these receptors. Immunoelectron microscopy clearly revealed EP3alpha and EP4 receptors localization in the nuclear envelope of endothelial cells; this is the first demonstration of the nuclear localization of these receptors. Data also reveal that nuclear EP receptors are functional as they affect transcription of genes such as inducible nitric-oxide synthase and intranuclear calcium transients; this appears to involve pertussis toxin-sensitive G proteins. These results define a possible molecular mechanism of action of nuclear EP3 receptors.",
    "issueName" : "22",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Bhattacharya",
      "authorRank" : 1,
      "name" : "Bhattacharya M",
      "referenceId" : "RGD:A99264"
    }, {
      "firstName" : "K",
      "lastName" : "Peri",
      "authorRank" : 2,
      "name" : "Peri K",
      "referenceId" : "RGD:A68025"
    }, {
      "firstName" : "A",
      "lastName" : "Ribeiro-da-Silva",
      "authorRank" : 3,
      "name" : "Ribeiro-da-Silva A",
      "referenceId" : "RGD:A68024"
    }, {
      "firstName" : "G",
      "lastName" : "Almazan",
      "authorRank" : 4,
      "name" : "Almazan G",
      "referenceId" : "RGD:A25296"
    }, {
      "firstName" : "H",
      "lastName" : "Shichi",
      "authorRank" : 5,
      "name" : "Shichi",
      "referenceId" : "RGD:A200527"
    }, {
      "firstName" : "X",
      "lastName" : "Hou",
      "authorRank" : 6,
      "name" : "Hou X",
      "referenceId" : "RGD:A61831"
    }, {
      "firstName" : "DR",
      "lastName" : "Varma",
      "authorRank" : 7,
      "name" : "Varma DR",
      "referenceId" : "RGD:A99658"
    }, {
      "firstName" : "S",
      "lastName" : "Chemtob",
      "authorRank" : 8,
      "name" : "Chemtob S",
      "referenceId" : "RGD:A49818"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9850259"
    } ]
  }, {
    "primaryId" : "PMID:10336634",
    "title" : "Structures and co-regulated expression of the genes encoding mouse cytosolic chaperonin CCT subunits.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Kubota H, etal., Eur J Biochem 1999 Jun;262(2):492-500.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:44:00.000-05:00",
    "volume" : "262",
    "pages" : "492-500",
    "abstract" : "The chaperonin-containing TCP-1 (CCT) is a hetero-oligomeric molecular chaperone that mediates protein folding in the cytosol of eukaryotes. Eight (or nine in testis) subunit species are assembled in the CCT hexadecamer complex. We have cloned seven CCT subunit genes, Cctb, Cctd, Ccte, Cctz-1, Cctz-2 (testis specific), Ccth and Cctq, from mouse genomic DNA libraries, in addition to the Ccta and Cctg genes reported previously, and the entire nucleotide sequences of these DNA clones were determined. These genes are approximately 15-20 kb in length except for Cctz-2 which is longer than 35 kb, and all the Cct genes consist of 11-16 exons. Primer extension analyses of testis RNA indicate one to several potential transcription start sites 50-150 bp upstream from the translation start codon of each Cct gene. There are several possible Sp1-binding sequences, but no obvious TATA box was observed around the potential start sites. From 5'-flanking regions to the first introns, the Cct genes are rich in CpG dinucleotides. In reporter gene assays using these regions, five of eight Cct genes showed strong transcriptional activity comparable with the combination of SV40 promoter and enhancer in HeLa cells. We also show, by Western and Northern blot analyses, that CCT expression levels vary widely among different tissues but the expression patterns are very similar among the eight subunit species. It is likely that expression levels of the eight different subunits are tightly co-regulated to maintain a constant ratio of these subunits which constitute the CCT hexadecamer complex with a fixed subunit arrangement.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Kubota",
      "authorRank" : 1,
      "name" : "Kubota H",
      "referenceId" : "RGD:A23795"
    }, {
      "firstName" : "S",
      "lastName" : "Yokota",
      "authorRank" : 2,
      "name" : "Yokota S",
      "referenceId" : "RGD:A161486"
    }, {
      "firstName" : "H",
      "lastName" : "Yanagi",
      "authorRank" : 3,
      "name" : "Yanagi H",
      "referenceId" : "RGD:A20643"
    }, {
      "firstName" : "T",
      "lastName" : "Yura",
      "authorRank" : 4,
      "name" : "Yura T",
      "referenceId" : "RGD:A47133"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302594"
    } ]
  }, {
    "primaryId" : "PMID:10336669",
    "title" : "Raf-1 and B-Raf proteins have similar regional distributions but differential subcellular localization in adult rat brain.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Morice C, etal., Eur J Neurosci. 1999 Jun;11(6):1995-2006.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-01-14T14:26:40.000-06:00",
    "volume" : "11",
    "pages" : "1995-2006",
    "abstract" : "The Raf kinases play an important and specific role in the activation of extracellular signal-regulated kinases (ERK) cascade. Beside its role in the control of proliferation and differentiation, the ERK cascade has also been implicated in neuron-specific functions. In order to gain clues on the function of Raf kinases in the adult central nervous system (CNS), we performed a comparative analysis of the distribution and subcellular localization of the different Raf kinases in rat brain with antibodies specific for the different Raf kinases. We show that B-Raf and Raf-1 proteins are present in most brain areas, whereas A-Raf is not detected. Interestingly, the two Raf proteins have an approximately similar pattern of distribution with a rostro-caudal decreasing gradient of expression. These two kinases are colocalized in neurons but they are differentially located in subcellular compartments. Raf-1 is localized mainly in the cytosolic fraction around the nucleus, whereas B-Raf is widely distributed in the cell bodies and in the neuritic processes. In addition, we demonstrated that numerous B-Raf isoforms are present in the brain. These isoforms have a differential pattern of distribution, some of them being ubiquitously expressed whereas others are localized to specific brain areas. These isoforms also have a clear differential subcellular localization, specially in Triton-insoluble fractions, but also in synaptosomal, membrane and cytosolic compartments. Altogether these results suggest that each Raf protein could have a distinct signalling regulatory function in the brain with regard to its subcellular localization.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Morice",
      "authorRank" : 1,
      "name" : "Morice C",
      "referenceId" : "RGD:A117733"
    }, {
      "firstName" : "F",
      "lastName" : "Nothias",
      "authorRank" : 2,
      "name" : "Nothias F",
      "referenceId" : "RGD:A98949"
    }, {
      "firstName" : "S",
      "lastName" : "Konig",
      "authorRank" : 3,
      "name" : "Konig S",
      "referenceId" : "RGD:A102597"
    }, {
      "firstName" : "P",
      "lastName" : "Vernier",
      "authorRank" : 4,
      "name" : "Vernier P",
      "referenceId" : "RGD:A26850"
    }, {
      "firstName" : "M",
      "lastName" : "Baccarini",
      "authorRank" : 5,
      "name" : "Baccarini M",
      "referenceId" : "RGD:A117734"
    }, {
      "firstName" : "JD",
      "lastName" : "Vincent",
      "authorRank" : 6,
      "name" : "Vincent JD",
      "referenceId" : "RGD:A117735"
    }, {
      "firstName" : "JV",
      "lastName" : "Barnier",
      "authorRank" : 7,
      "name" : "Barnier JV",
      "referenceId" : "RGD:A8084"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2315873"
    } ]
  }, {
    "primaryId" : "PMID:10336672",
    "title" : "Differential interaction of the tSXV motifs of the NR1 and NR2A NMDA receptor subunits with PSD-95 and SAP97.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Bassand P, etal., Eur J Neurosci. 1999 Jun;11(6):2031-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:39:26.000-05:00",
    "volume" : "11",
    "pages" : "2031-43",
    "abstract" : "The NR1 and NR2 subunits of the N-methyl-D-aspartate (NMDA) receptor are encoded  by distinct genes. In the rat brain, four C-terminal variants of the NR1 subunit  (NR1-1 to NR1-4) are encoded by a single gene, and are generated by alternative splicing of the C1 and C2 exon cassettes, while four different genes encode the NR2 subunits (NR2 A-D). Functional NMDA receptors result from the heteromultimeric assembly of NR1 variants with distinct NR2 subunits. The NR2B subunit interacts with post-synaptic density protein 95 (PSD-95), SAP97 and members of the membrane-associated guanylate-like kinase (MAGUK) family of proteins. This interaction occurs through the binding of the C-terminal tSXV intracellular motif of the NR2B subunit to the N-terminal PDZ (PSD-95, discs-large, ZO-1) domains of the PSD-95 and SAP97 proteins. Both NR1-3 and NR1-4 also display a consensus C-terminal tSXV motif. Using the two-hybrid genetic system in yeast and site-directed mutagenesis, we compared the binding of the NR2A, NR1-3 and NR1-4 tSXV motifs with the PDZ domains of PSD-95 and SAP97. The main conclusions of the present report are that: (i) while NR2A displays a strong interaction with PSD-95 and SAP97, the NR1-3 and NR1-4 NMDA receptor subunits do  not display any interaction despite the presence of tSXV motifs; (ii) the C-terminal tSXV motif of the NR2A subunit is mandatory but not sufficient for efficient interaction with the PSD-95 and SAP97 proteins; (iii) as yet unidentified upstream sequences of the receptor subunits determine whether the tSXV motifs will bind to the PSD-95 and SAP97 PDZ domains; (iv) different tSXV motifs elicit interactions of variable strengths; and (v) residues in positions -3 and -4 modulate the binding affinity of the C-terminal tSXV motifs. Using immunohistochemistry, we also compared the distribution of the PSD-95, NR2A and SAP97 proteins in adult rat brain, and we show that in the cortex, hippocampus and cerebellum, there is evidence for colocalization of these proteins.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Bassand",
      "authorRank" : 1,
      "name" : "Bassand P",
      "referenceId" : "RGD:A33988"
    }, {
      "firstName" : "A",
      "lastName" : "Bernard",
      "authorRank" : 2,
      "name" : "Bernard A",
      "referenceId" : "RGD:A9474"
    }, {
      "firstName" : "A",
      "lastName" : "Rafiki",
      "authorRank" : 3,
      "name" : "Rafiki A",
      "referenceId" : "RGD:A19234"
    }, {
      "firstName" : "D",
      "lastName" : "Gayet",
      "authorRank" : 4,
      "name" : "Gayet",
      "referenceId" : "RGD:A185515"
    }, {
      "firstName" : "M",
      "lastName" : "Khrestchatisky",
      "authorRank" : 5,
      "name" : "Khrestchatisky M",
      "referenceId" : "RGD:A20324"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554042"
    } ]
  }, {
    "primaryId" : "PMID:10336779",
    "title" : "Analysis of CpG C-to-T mutations in neurofibromatosis type 1. Mutations in brief  no. 129. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Krkljus S, etal., Hum Mutat. 1998;11(5):411.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:15:28.000-05:00",
    "volume" : "11",
    "pages" : "411",
    "abstract" : "Neurofibromatosis type 1 (NF1) is a dominant disorder caused by mutations in the  NF1 gene; approximately 100 NF1 gene mutations have been published. The CpG C-to-T transition is a frequent mutation mechanism in genetic disorders. To estimate its frequency in NF1, we employed a PCR-restriction digestion method to  examine 17 CpGs in 65 patients, and also screened for a CpG nonsense transition (R1947X) that occurs in 1-2% of patients. The analysis revealed disease-related CpG C-to-T transitions (including a nonsense mutation that may be as frequent as  R1947X) as well as a benign variant and another mutation at a CpG. Four patients  showed CpG mutations in analysis of 18 sites (17 surveyed by restriction digest,  plus the R1947X assay), including three C-to-T transitions and one C-to-G transversion. These 18 sites represent one-fifth of the 91 CpGs at which a C-to-T transition would result in a nonsense or nonconservative missense mutation. Thus, it is feasible that the CpG mutation rate at NF1 might be similar to that seen in other disorders with a high mutation rate, and that recurrent NF1 mutations may frequently reside at CpG sites.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Krkljus",
      "authorRank" : 1,
      "name" : "Krkljus",
      "referenceId" : "RGD:A262930"
    }, {
      "firstName" : "CR",
      "lastName" : "Abernathy",
      "authorRank" : 2,
      "name" : "Abernathy",
      "referenceId" : "RGD:A262931"
    }, {
      "firstName" : "JS",
      "lastName" : "Johnson",
      "authorRank" : 3,
      "name" : "Johnson",
      "referenceId" : "RGD:A204752"
    }, {
      "firstName" : "CA",
      "lastName" : "Williams",
      "authorRank" : 4,
      "name" : "Williams CA",
      "referenceId" : "RGD:A51950"
    }, {
      "firstName" : "DJ",
      "lastName" : "Driscoll",
      "authorRank" : 5,
      "name" : "Driscoll DJ",
      "referenceId" : "RGD:A51951"
    }, {
      "firstName" : "R",
      "lastName" : "Zori",
      "authorRank" : 6,
      "name" : "Zori",
      "referenceId" : "RGD:A262932"
    }, {
      "firstName" : "HJ",
      "lastName" : "Stalker",
      "authorRank" : 7,
      "name" : "Stalker HJ",
      "referenceId" : "RGD:A61918"
    }, {
      "firstName" : "SA",
      "lastName" : "Rasmussen",
      "authorRank" : 8,
      "name" : "Rasmussen",
      "referenceId" : "RGD:A262933"
    }, {
      "firstName" : "FS",
      "lastName" : "Collins",
      "authorRank" : 9,
      "name" : "Collins FS",
      "referenceId" : "RGD:A18919"
    }, {
      "firstName" : "BG",
      "lastName" : "Kousseff",
      "authorRank" : 10,
      "name" : "Kousseff",
      "referenceId" : "RGD:A262934"
    }, {
      "firstName" : "L",
      "lastName" : "Baumbach",
      "authorRank" : 11,
      "name" : "Baumbach",
      "referenceId" : "RGD:A258063"
    }, {
      "firstName" : "MR",
      "lastName" : "Wallace",
      "authorRank" : 12,
      "name" : "Wallace MR",
      "referenceId" : "RGD:A44916"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065771"
    } ]
  }, {
    "primaryId" : "PMID:10336852",
    "title" : "Effect of transient ischemia on the expression of glucose transporters GLUT-1 and GLUT-4 in rat myocardium.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Tardy-Cantalupi I, etal., J Mol Cell Cardiol. 1999 May;31(5):1143-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-04-27T14:54:17.000-05:00",
    "volume" : "31",
    "pages" : "1143-55",
    "abstract" : "A number of observations indicate that myocardial glucose utilization is increased late during post-ischemic reperfusion. The present study was designed to examine whether transient ischemia elicits altered expression of glucose transporters GLUT-1 and GLUT-4. In rats, the left anterior descending coronary artery was occluded for 20 min followed by reperfusion for 1, 3 or 7 days. Regional myocardial uptake and phosphorylation of glucose was determined based on myocardial accumulation of 2-deoxy-D-[2, 6-3H]glucose-6-phosphate. In hearts from fasted rats, after 3 days of reperfusion, myocardial uptake and phosphorylation of glucose was 48% higher in the reperfused region compared to a remote control region. No regional difference in myocardial glucose uptake and phosphorylation was detectable in hearts from fed rats. After 1 day of reperfusion, expression of myocardial glucose transporter GLUT-1 mRNA was increased to 195+/-24% (mean+/-SEM) of the value measured in the remote region and the expression of GLUT-4 mRNA was decreased to 58+/-7%. After 3 days of reperfusion both mRNA and protein of GLUT-1 were higher in the reperfused region, averaging 133+/-23% and 249+/-36%, respectively. The corresponding values for GLUT-4 mRNA and protein were 77+/-7% and 62+/-6%, respectively. The results indicate that a short period of ischemia alters the expression of glucose transporter isoforms GLUT-1 and GLUT-4. Observed changes may be involved in the mechanisms underlying late changes of substrate metabolism during reperfusion.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Tardy-Cantalupi",
      "authorRank" : 1,
      "name" : "Tardy-Cantalupi I",
      "referenceId" : "RGD:A442827"
    }, {
      "firstName" : "C",
      "lastName" : "Montessuit",
      "authorRank" : 2,
      "name" : "Montessuit C",
      "referenceId" : "RGD:A442828"
    }, {
      "firstName" : "I",
      "lastName" : "Papageorgiou",
      "authorRank" : 3,
      "name" : "Papageorgiou I",
      "referenceId" : "RGD:A442829"
    }, {
      "firstName" : "A",
      "lastName" : "Remondino-Müller",
      "authorRank" : 4,
      "name" : "Remondino-Müller A",
      "referenceId" : "RGD:A442830"
    }, {
      "firstName" : "F",
      "lastName" : "Assimacopoulos-Jeannet",
      "authorRank" : 5,
      "name" : "Assimacopoulos-Jeannet F",
      "referenceId" : "RGD:A49031"
    }, {
      "firstName" : "D R",
      "lastName" : "Morel",
      "authorRank" : 6,
      "name" : "Morel DR",
      "referenceId" : "RGD:A442831"
    }, {
      "firstName" : "R",
      "lastName" : "Lerch",
      "authorRank" : 7,
      "name" : "Lerch R",
      "referenceId" : "RGD:A442832"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12879857"
    } ]
  }, {
    "primaryId" : "PMID:10337614",
    "title" : "Sequence-ready physical map of the mouse chromosome 16 region with conserved synteny to the human velocardiofacial syndrome region on 22q11.2.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Lund J, etal., Mamm Genome. 1999 May;10(5):438-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T20:06:26.000-05:00",
    "volume" : "10",
    "pages" : "438-43",
    "abstract" : "Proximal mouse Chromosome (Chr) 16 shows conserved synteny with human Chrs 16, 8, 22, and 3. The mouse Chr 16/human Chr 22 conserved synteny region includes the DiGeorge/Velocardiofacial syndrome region of human Chr 22q11.2. A physical map of the entire mouse Chr 16/human Chr 22 region of conserved synteny has been constructed to provide a substrate for gene discovery, genomic sequencing, and animal model development. A YAC contig was constructed that extends ca. 5.4 Mb from a region of conserved synteny with human Chr 8 at Prkdc through the region conserved with human Chr 3 at DVL3. Sixty-one markers including 37 genes are mapped with average marker spacing of 90 kb. Physical distance was determined across the 2.6-Mb region from D16Mit74 to Hira with YAC fragmentation. The central region from D16Jhu28 to Igl-C1 was converted into BAC and PAC clones, further refining the physical map and providing sequence-ready template. The gene content and borders of three blocks of conserved linkage between human Chr 22q11.2 mouse Chr 16 are refined.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Lund",
      "authorRank" : 1,
      "name" : "Lund J",
      "referenceId" : "RGD:A33828"
    }, {
      "firstName" : "B",
      "lastName" : "Roe",
      "authorRank" : 2,
      "name" : "Roe B",
      "referenceId" : "RGD:A64004"
    }, {
      "firstName" : "F",
      "lastName" : "Chen",
      "authorRank" : 3,
      "name" : "Chen F",
      "referenceId" : "RGD:A13746"
    }, {
      "firstName" : "M",
      "lastName" : "Budarf",
      "authorRank" : 4,
      "name" : "Budarf",
      "referenceId" : "RGD:A331225"
    }, {
      "firstName" : "N",
      "lastName" : "Galili",
      "authorRank" : 5,
      "name" : "Galili",
      "referenceId" : "RGD:A210851"
    }, {
      "firstName" : "R",
      "lastName" : "Riblet",
      "authorRank" : 6,
      "name" : "Riblet",
      "referenceId" : "RGD:A241082"
    }, {
      "firstName" : "RD",
      "lastName" : "Miller",
      "authorRank" : 7,
      "name" : "Miller RD",
      "referenceId" : "RGD:A29974"
    }, {
      "firstName" : "BS",
      "lastName" : "Emanuel",
      "authorRank" : 8,
      "name" : "Emanuel BS",
      "referenceId" : "RGD:A61132"
    }, {
      "firstName" : "RH",
      "lastName" : "Reeves",
      "authorRank" : 9,
      "name" : "Reeves RH",
      "referenceId" : "RGD:A90536"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11341497"
    } ]
  }, {
    "primaryId" : "PMID:10337620",
    "title" : "A high-resolution radiation hybrid map of the proximal region of rat chromosome 4.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "al-Majali KM, etal., Mamm Genome 1999 May;10(5):471-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-07-01T10:40:41.000-05:00",
    "volume" : "10",
    "pages" : "471-6",
    "abstract" : "Radiation hybrid (RH) mapping has been used to produce genome maps in the human and mouse, but as yet the technique has been applied little to other species. We describe the use of RH mapping in the rat, using a newly available rat/hamster RH panel, to construct an RH map of the proximal part of rat Chromosome (Chr) 4. This region is of interest because quantitative trait loci (QTLs) for defective insulin and catecholamine action, hypertension, and dyslipidemia map to this region. The RH map includes 23 rat genes or microsatellites previously mapped to this part of Chr 4, one rat gene not previously mapped in the rat, and markers for four new genes, homologs of which map to the syntenic region of the mouse genome. The RH map integrates genetic markers previously mapped on several rat crosses, increases the resolution of existing maps, and may provide a suitable basis for physical map construction and gene identification in this chromosomal region. Our results demonstrate the utility of RH mapping in the rat genome and show that RH mapping can be used to localize, in the rat genome, the homologs of genes from other species such as the mouse. This will facilitate identification of candidate genes underlying QTLs on this chromosomal segment.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KM",
      "lastName" : "Al-Majali",
      "authorRank" : 1,
      "name" : "Al-Majali KM",
      "referenceId" : "RGD:A10430"
    }, {
      "firstName" : "AM",
      "lastName" : "Glazier",
      "authorRank" : 2,
      "name" : "Glazier AM",
      "referenceId" : "RGD:A6478"
    }, {
      "firstName" : "PJ",
      "lastName" : "Norsworthy",
      "authorRank" : 3,
      "name" : "Norsworthy PJ",
      "referenceId" : "RGD:A9139"
    }, {
      "firstName" : "FN",
      "lastName" : "Wahid",
      "authorRank" : 4,
      "name" : "Wahid FN",
      "referenceId" : "RGD:A10431"
    }, {
      "firstName" : "LD",
      "lastName" : "Cooper",
      "authorRank" : 5,
      "name" : "Cooper LD",
      "referenceId" : "RGD:A10432"
    }, {
      "firstName" : "CA",
      "lastName" : "Wallace",
      "authorRank" : 6,
      "name" : "Wallace CA",
      "referenceId" : "RGD:A111039"
    }, {
      "firstName" : "J",
      "lastName" : "Scott",
      "authorRank" : 7,
      "name" : "Scott J",
      "referenceId" : "RGD:A124566"
    }, {
      "firstName" : "B",
      "lastName" : "Lausen",
      "authorRank" : 8,
      "name" : "Lausen B",
      "referenceId" : "RGD:A10435"
    }, {
      "firstName" : "TJ",
      "lastName" : "Aitman",
      "authorRank" : 9,
      "name" : "Aitman TJ",
      "referenceId" : "RGD:A664"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70850"
    } ]
  }, {
    "primaryId" : "PMID:10337870",
    "title" : "Variation of the fatty acid binding protein 2 gene is not associated with obesity and insulin resistance in Japanese subjects.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Hayakawa T, etal., Metabolism. 1999 May;48(5):655-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-08-07T12:08:16.000-05:00",
    "volume" : "48",
    "pages" : "655-7",
    "abstract" : "An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians. We investigated whether this polymorphism contributes to obesity and insulin resistance in 258 Japanese subjects. Thirty-six subjects (13.9%) were homozygous for the Thr54 allele, 106 (41.1%) were heterozygous for the Ala54/Thr54 allele, and 116 (45.0%) were homozygous for the Ala54 allele. The frequency of the Thr54 allele was 0.34 and did not differ significantly between men and women. The incidence of non-insulin-dependent diabetes mellitus (NIDDM) was not different among the three genotypes. The variation at codon 54 of the FABP2 gene was not associated with obesity, hypertension, dyslipidemia, hyperuricemia, or hyperinsulinemia. These results suggest that the polymorphism at codon 54 of the FABP2 gene is not a major contributing factor to obesity and insulin resistance in Japanese subjects.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Hayakawa",
      "authorRank" : 1,
      "name" : "Hayakawa T",
      "referenceId" : "RGD:A4681"
    }, {
      "firstName" : "Y",
      "lastName" : "Nagai",
      "authorRank" : 2,
      "name" : "Nagai Y",
      "referenceId" : "RGD:A9016"
    }, {
      "firstName" : "E",
      "lastName" : "Nohara",
      "authorRank" : 3,
      "name" : "Nohara E",
      "referenceId" : "RGD:A86067"
    }, {
      "firstName" : "H",
      "lastName" : "Yamashita",
      "authorRank" : 4,
      "name" : "Yamashita H",
      "referenceId" : "RGD:A23379"
    }, {
      "firstName" : "T",
      "lastName" : "Takamura",
      "authorRank" : 5,
      "name" : "Takamura T",
      "referenceId" : "RGD:A86068"
    }, {
      "firstName" : "T",
      "lastName" : "Abe",
      "authorRank" : 6,
      "name" : "Abe T",
      "referenceId" : "RGD:A8476"
    }, {
      "firstName" : "G",
      "lastName" : "Nomura",
      "authorRank" : 7,
      "name" : "Nomura G",
      "referenceId" : "RGD:A86069"
    }, {
      "firstName" : "K",
      "lastName" : "Kobayashi",
      "authorRank" : 8,
      "name" : "Kobayashi K",
      "referenceId" : "RGD:A314641"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1626414"
    } ]
  }, {
    "primaryId" : "PMID:10338089",
    "title" : "Congenital hyperinsulinism: molecular basis of a heterogeneous disease.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Meissner T, etal., Hum Mutat. 1999;13(5):351-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:17:30.000-05:00",
    "volume" : "13",
    "pages" : "351-61",
    "abstract" : "Congenital hyperinsulinism (CHI) is a disease phenotype characterized by increased, usually irregular, insulin secretion leading to hypoglycemia, coma, and severe brain damage, left untreated. Hyperinsulinism may be caused by a range of biochemical disturbances and molecular defects. In pancreatic beta cells, insulin secretion is stimulated by closure of the ATP-dependent potassium channel (K(ATP) channel). K(ATP) channel is a complex composed of at least two subunits:  the sulfonylurea receptor SUR1 and Kir6.2, an inward rectifier K+ channel member. Mutations in both subunits have been identified in patients with the autosomal recessive form of hyperinsulinism, including 28 different mutations in the SUR1 gene and two mutations in the Kir6.2 gene. These mutations co-segregated with disease phenotype, also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI), and with attenuated K(ATP) channel function. Inadequately high insulin secretion in one family with an autosomal dominant mode of inheritance is caused by a mutation in the glucokinase gene, resulting in increased affinity of  the enzyme for glucose. Five different mutations have been identified in the glutamate dehydrogenase gene, resulting in overactivity of this enzyme and causing a syndrome of hyperinsulinism and hyperammonemia. In 13 cases, hyperinsulinism was caused by one or more focal pancreatic lesions with specific  loss of maternal alleles of the imprinted chromosome region 11p15. In five patients, this loss of heterozygosity unmasked a paternally inherited recessive SUR1 mutation. The new molecular approaches in PHHI give further insight into the mechanism of pancreatic beta cell insulin secretion. The heterogeneous group of patients with CHI may now be classified according to their basic defects in the four different genes, with potential implications for a more specific treatment.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Meissner",
      "authorRank" : 1,
      "name" : "Meissner",
      "referenceId" : "RGD:A217969"
    }, {
      "firstName" : "B",
      "lastName" : "Beinbrech",
      "authorRank" : 2,
      "name" : "Beinbrech",
      "referenceId" : "RGD:A281321"
    }, {
      "firstName" : "E",
      "lastName" : "Mayatepek",
      "authorRank" : 3,
      "name" : "Mayatepek",
      "referenceId" : "RGD:A217970"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072146"
    } ]
  }, {
    "primaryId" : "PMID:10338090",
    "title" : "Cystathionine beta-synthase mutations in homocystinuria.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Kraus JP, etal., Hum Mutat. 1999;13(5):362-75.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:11:18.000-05:00",
    "volume" : "13",
    "pages" : "362-75",
    "abstract" : "The major cause of homocystinuria is mutation of the gene encoding the enzyme cystathionine beta-synthase (CBS). Deficiency of CBS activity results in elevated levels of homocysteine as well as methionine in plasma and urine and decreased levels of cystathionine and cysteine. Ninety-two different disease-associated mutations have been identified in the CBS gene in 310 examined homocystinuric alleles in more than a dozen laboratories around the world. Most of these mutations are missense, and the vast majority of these are private mutations. The two most frequently encountered of these mutations are the pyridoxine-responsive  I278T and the pyridoxine-nonresponsive G307S. Mutations due to deaminations of methylcytosines represent 53% of all point substitutions in the coding region of  the CBS gene.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JP",
      "lastName" : "Kraus",
      "authorRank" : 1,
      "name" : "Kraus JP",
      "referenceId" : "RGD:A15066"
    }, {
      "firstName" : "M",
      "lastName" : "Janosik",
      "authorRank" : 2,
      "name" : "Janosik",
      "referenceId" : "RGD:A269131"
    }, {
      "firstName" : "V",
      "lastName" : "Kozich",
      "authorRank" : 3,
      "name" : "Kozich V",
      "referenceId" : "RGD:A61876"
    }, {
      "firstName" : "R",
      "lastName" : "Mandell",
      "authorRank" : 4,
      "name" : "Mandell",
      "referenceId" : "RGD:A278008"
    }, {
      "firstName" : "V",
      "lastName" : "Shih",
      "authorRank" : 5,
      "name" : "Shih",
      "referenceId" : "RGD:A278009"
    }, {
      "firstName" : "MP",
      "lastName" : "Sperandeo",
      "authorRank" : 6,
      "name" : "Sperandeo",
      "referenceId" : "RGD:A229506"
    }, {
      "firstName" : "G",
      "lastName" : "Sebastio",
      "authorRank" : 7,
      "name" : "Sebastio",
      "referenceId" : "RGD:A253532"
    }, {
      "firstName" : "R",
      "lastName" : "De Franchis",
      "authorRank" : 8,
      "name" : "De Franchis",
      "referenceId" : "RGD:A253531"
    }, {
      "firstName" : "G",
      "lastName" : "Andria",
      "authorRank" : 9,
      "name" : "Andria G",
      "referenceId" : "RGD:A73040"
    }, {
      "firstName" : "LA",
      "lastName" : "Kluijtmans",
      "authorRank" : 10,
      "name" : "Kluijtmans LA",
      "referenceId" : "RGD:A77953"
    }, {
      "firstName" : "H",
      "lastName" : "Blom",
      "authorRank" : 11,
      "name" : "Blom",
      "referenceId" : "RGD:A171664"
    }, {
      "firstName" : "GH",
      "lastName" : "Boers",
      "authorRank" : 12,
      "name" : "Boers",
      "referenceId" : "RGD:A266650"
    }, {
      "firstName" : "RB",
      "lastName" : "Gordon",
      "authorRank" : 13,
      "name" : "Gordon",
      "referenceId" : "RGD:A278010"
    }, {
      "firstName" : "P",
      "lastName" : "Kamoun",
      "authorRank" : 14,
      "name" : "Kamoun",
      "referenceId" : "RGD:A278011"
    }, {
      "firstName" : "MY",
      "lastName" : "Tsai",
      "authorRank" : 15,
      "name" : "Tsai MY",
      "referenceId" : "RGD:A38400"
    }, {
      "firstName" : "WD",
      "lastName" : "Kruger",
      "authorRank" : 16,
      "name" : "Kruger WD",
      "referenceId" : "RGD:A99679"
    }, {
      "firstName" : "HG",
      "lastName" : "Koch",
      "authorRank" : 17,
      "name" : "Koch HG",
      "referenceId" : "RGD:A46649"
    }, {
      "firstName" : "T",
      "lastName" : "Ohura",
      "authorRank" : 18,
      "name" : "Ohura T",
      "referenceId" : "RGD:A21436"
    }, {
      "firstName" : "M",
      "lastName" : "Gaustadnes",
      "authorRank" : 19,
      "name" : "Gaustadnes",
      "referenceId" : "RGD:A256582"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070864"
    } ]
  }, {
    "primaryId" : "PMID:10338092",
    "title" : "Molecular genetic study of Pompe disease in Chinese patients in Taiwan.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Ko TM, etal., Hum Mutat. 1999;13(5):380-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:20:52.000-05:00",
    "volume" : "13",
    "pages" : "380-4",
    "abstract" : "Pompe disease is caused by mutations in the acid alpha-glucosidase (GAA) gene. Multiple kinds of mutations in the GAA gene have been reported worldwide. In order to elucidate the molecular basis of the disease in Taiwanese patients of Chinese origin, we have recruited 11 unrelated families who had at least one member with Pompe disease for study. We used 16 pairs of oligonucleotide primers  to amplify all the coding regions from exon 2 to 20 in the family members. The coding regions were sequenced on both the sense and antisense strands. We identified 7 different mutations in 17 alleles but failed to identify the defects in the other 5 alleles. The most common defect was D645E (Asp645Glu), accounting  for 36% (8/22 alleles) of mutations, followed by G615R (Gly615Arg) (3 alleles); 1411del4 (Glu471-shift) (2 alleles); and one allele each of R600H (Arg600His); deltaN675 (deltaAsn675); 2380delC (Arg794-shift) and 2815delGT (Val939-shift). The molecular defects of Pompe disease are highly heterogeneous in Chinese. Characterization of the molecular defects of the disease is useful for a genotype-phenotype correlation and for genetic counseling and prenatal diagnosis.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TM",
      "lastName" : "Ko",
      "authorRank" : 1,
      "name" : "Ko",
      "referenceId" : "RGD:A254503"
    }, {
      "firstName" : "WL",
      "lastName" : "Hwu",
      "authorRank" : 2,
      "name" : "Hwu WL",
      "referenceId" : "RGD:A136561"
    }, {
      "firstName" : "YW",
      "lastName" : "Lin",
      "authorRank" : 3,
      "name" : "Lin YW",
      "referenceId" : "RGD:A84577"
    }, {
      "firstName" : "LH",
      "lastName" : "Tseng",
      "authorRank" : 4,
      "name" : "Tseng",
      "referenceId" : "RGD:A272008"
    }, {
      "firstName" : "HL",
      "lastName" : "Hwa",
      "authorRank" : 5,
      "name" : "Hwa",
      "referenceId" : "RGD:A254502"
    }, {
      "firstName" : "TR",
      "lastName" : "Wang",
      "authorRank" : 6,
      "name" : "Wang",
      "referenceId" : "RGD:A205819"
    }, {
      "firstName" : "SM",
      "lastName" : "Chuang",
      "authorRank" : 7,
      "name" : "Chuang",
      "referenceId" : "RGD:A212269"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068762"
    } ]
  }, {
    "primaryId" : "PMID:10338095",
    "title" : "Six novel beta-galactosidase gene mutations in Brazilian patients with GM1-gangliosidosis.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Silva CM, etal., Hum Mutat. 1999;13(5):401-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:58:07.000-05:00",
    "volume" : "13",
    "pages" : "401-9",
    "abstract" : "GM1-gangliosidosis is a lysosomal storage disease caused by a deficiency of acid  beta-galactosidase. Three clinical forms are recognized-infantile, juvenile, and  adult-based on age of onset and severity of the symptoms. We have performed molecular analysis of a large cohort of GM1 patients (19 Brazilian and one Uruguayan), using nonradioactive single-strand conformation polymorphism (SSCP) and restriction enzyme analysis of genomic DNA. Six novel mutations (R121S, V240M, D491N, 638-641insT, 895-896insC, 1622-1627insG) and two previously described point mutations (R59H, R208C) were identified. Together they accounted  for 90% of the disease alleles of the patients. Two mutations, 1622-1627insG and  R59H, were present in 18 of 20 patients. In addition, four polymorphisms (L10P, L12L, R521C, S532G) were identified. All cases reported are infantile GM1 gangliosidosis. This report constitutes the most comprehensive molecular study to date of this disorder in infantile patients. Since GM1-gangliosidosis is the most common lysosomal storage disorder in Southern Brazil, molecular diagnosis will be important for genetic counseling, carrier detection and prenatal diagnosis in index families.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CM",
      "lastName" : "Silva",
      "authorRank" : 1,
      "name" : "Silva",
      "referenceId" : "RGD:A169182"
    }, {
      "firstName" : "MH",
      "lastName" : "Severini",
      "authorRank" : 2,
      "name" : "Severini",
      "referenceId" : "RGD:A265604"
    }, {
      "firstName" : "A",
      "lastName" : "Sopelsa",
      "authorRank" : 3,
      "name" : "Sopelsa",
      "referenceId" : "RGD:A265605"
    }, {
      "firstName" : "JC",
      "lastName" : "Coelho",
      "authorRank" : 4,
      "name" : "Coelho",
      "referenceId" : "RGD:A265606"
    }, {
      "firstName" : "A",
      "lastName" : "Zaha",
      "authorRank" : 5,
      "name" : "Zaha",
      "referenceId" : "RGD:A265607"
    }, {
      "firstName" : "A",
      "lastName" : "D'Azzo",
      "authorRank" : 6,
      "name" : "D'Azzo A",
      "referenceId" : "RGD:A72053"
    }, {
      "firstName" : "R",
      "lastName" : "Giugliani",
      "authorRank" : 7,
      "name" : "Giugliani R",
      "referenceId" : "RGD:A145289"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066655"
    } ]
  }, {
    "primaryId" : "PMID:10338331",
    "title" : "Melanoma development in relation to non-functional p16/INK4A protein and dysplastic naevus syndrome in Swedish melanoma kindreds.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hashemi J, etal., Melanoma Res. 1999 Feb;9(1):21-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-04-17T15:02:01.000-05:00",
    "volume" : "9",
    "pages" : "21-30",
    "abstract" : "The CDKN2A gene encodes the cell cycle inhibitor p16/ INK4A, which is involved in familial cutaneous melanoma. We have studied five Swedish familial melanoma kindreds characterized by germline mutations in CDKN2A and dysplastic naevus syndrome (DNS). We found significant correlations between germline CDKN2A mutations and melanoma and between DNS phenotype and melanoma, respectively. There was also a correlation between mutation status and the presence of DNS. In  CDKN2A mutation carriers, all cases of early-onset melanoma occurred in DNS individuals, and the mean age at melanoma diagnosis was significantly lower in individuals with DNS than in those without a confirmed DNS phenotype. In one family where the proband had a P48L mutation in CDKN2A exon 1, the DNS phenotype  was studied in detail. In vitro binding experiments established that the P48L mutant protein does not bind to cdk4 or cdk6 and thus is functionally abnormal. Furthermore, we demonstrated loss of heterozygosity at markers on chromosome 9p flanking the CDKN2A locus in a primary melanoma and a metastasis from the proband. Our results are consistent with the hypothesis that germline CDKN2A mutations and DNS both contribute to the predisposition to melanoma and may lead  to the development of early-onset melanoma when present in the same individual.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Hashemi",
      "authorRank" : 1,
      "name" : "Hashemi",
      "referenceId" : "RGD:A182592"
    }, {
      "firstName" : "S",
      "lastName" : "Linder",
      "authorRank" : 2,
      "name" : "Linder S",
      "referenceId" : "RGD:A78551"
    }, {
      "firstName" : "A",
      "lastName" : "Platz",
      "authorRank" : 3,
      "name" : "Platz A",
      "referenceId" : "RGD:A78547"
    }, {
      "firstName" : "J",
      "lastName" : "Hansson",
      "authorRank" : 4,
      "name" : "Hansson J",
      "referenceId" : "RGD:A78548"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8552302"
    } ]
  }, {
    "primaryId" : "PMID:10338516",
    "title" : "Citrobacter rodentium infection in mice elicits a mucosal Th1 cytokine response and lesions similar to those in murine inflammatory bowel disease.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Higgins LM, etal., Infect Immun. 1999 Jun;67(6):3031-9. doi: 10.1128/IAI.67.6.3031-3039.1999.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-06-01T15:35:07.000-05:00",
    "volume" : "67",
    "pages" : "3031-9",
    "abstract" : "Citrobacter rodentium is a classically noninvasive pathogen of mice that is similar to enteropathogenic Escherichia coli (EPEC) in man. Following oral infection of young mice, the organism colonizes the distal colon, and within 1 week the colonic mucosa doubles in thickness and there is massive epithelial cell hyperplasia. Since T-cell responses in mouse models of inflammatory bowel disease (IBD) also cause epithelial hyperplasia, we have investigated the possibility that C. rodentium promotes similar T-cell responses in the mucosa, thereby increasing epithelial shedding, transmission, and replication of the organism. Beginning 6 days after infection, bacteria were observed to be in close association with the epithelial surface and were also visible scattered throughout the lamina propria and in the submucosa. There was a CD3(+)-cell infiltrate into the colonic lamina propria and epithelium as well as mucosal thickening and crypt hyperplasia. The majority of CD3(+) cells were CD4(+) and were not gammadelta+. Reverse transcription-PCR analysis of cytokines also revealed a highly polarized Th1 response (interleukin-12, gamma interferon, and tumor necrosis factor alpha) in the mucosa and a large increase in the epithelial cell mitogen keratinocyte growth factor. None of the changes were seen in mice inoculated with bacteria lacking intimin (which is necessary for colonization), but they were seen in mice inoculated with C. rodentium complemented with intimin from EPEC. This is the first example of a classically noninvasive bacterial pathogen which elicits a strong mucosal Th1 response and which produces pathology similar to that seen in mouse models of IBD, which is also characterized by a strong Th1 response. These results also suggest that the colonic mucosa responds in a stereotypic way to Th1 responses.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L M",
      "lastName" : "Higgins",
      "authorRank" : 1,
      "name" : "Higgins LM",
      "referenceId" : "RGD:A500061"
    }, {
      "firstName" : "G",
      "lastName" : "Frankel",
      "authorRank" : 2,
      "name" : "Frankel G",
      "referenceId" : "RGD:A500062"
    }, {
      "firstName" : "G",
      "lastName" : "Douce",
      "authorRank" : 3,
      "name" : "Douce G",
      "referenceId" : "RGD:A500063"
    }, {
      "firstName" : "G",
      "lastName" : "Dougan",
      "authorRank" : 4,
      "name" : "Dougan G",
      "referenceId" : "RGD:A485074"
    }, {
      "firstName" : "T T",
      "lastName" : "MacDonald",
      "authorRank" : 5,
      "name" : "MacDonald TT",
      "referenceId" : "RGD:A500060"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:126928149"
    } ]
  }, {
    "primaryId" : "PMID:10339406",
    "title" : "Genetic and structural characterization of the human mitochondrial inner membrane translocase.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Bauer MF, etal., J Mol Biol 1999 May 28;289(1):69-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-22T21:57:05.000-06:00",
    "volume" : "289",
    "pages" : "69-82",
    "abstract" : "Translocation of nuclear-encoded mitochondrial preproteins is mediated by translocases in the outer and inner membranes. In the yeast Saccharomyces cerevisiae, translocation of preproteins into the matrix requires the membrane proteins Tim23, Tim17 and Tim44, which drive translocation in cooperation with mtHsp70 and its co-chaperone Mge1p. We have cloned and functionally analyzed the human homologues of Tim17, Tim23 and Tim44. In contrast to yeast, two TIM17 genes were found to be expressed in humans. TIM44, TIM23 and TIM17a genes were mapped to chromosomes 19p13.2-p13.3, 10q11. 21-q11.23 and 1q32. The TIM17b gene mapped to Xp11.23, near the fusion point where an autosomal region was proposed to have been added to the \"ancient\" part of the X chromosome about 80-130 MY ago. The primary sequences of the two proteins, hTim17a and hTim17b, are essentially identical, significant differences being restricted to their C termini. They are ubiquitously expressed in fetal and adult tissues, and both show expression levels comparable to that of hTim23. Biochemical characterization of the human Tim components revealed that hTim44 is localized in the matrix and, in contrast to yeast, only loosely associated with the inner membrane. hTim23 is organized into two distinct complexes in the inner membrane, one containing hTim17a and one containing hTim17b. Both TIM complexes display a native molecular mass of 110 kDa. We suggest that the structural organization of TIM23.17 preprotein translocases is conserved from low to high eukaryotes.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MF",
      "lastName" : "Bauer",
      "authorRank" : 1,
      "name" : "Bauer MF",
      "referenceId" : "RGD:A4609"
    }, {
      "firstName" : "K",
      "lastName" : "Gempel",
      "authorRank" : 2,
      "name" : "Gempel K",
      "referenceId" : "RGD:A38861"
    }, {
      "firstName" : "AS",
      "lastName" : "Reichert",
      "authorRank" : 3,
      "name" : "Reichert AS",
      "referenceId" : "RGD:A38862"
    }, {
      "firstName" : "GA",
      "lastName" : "Rappold",
      "authorRank" : 4,
      "name" : "Rappold GA",
      "referenceId" : "RGD:A38863"
    }, {
      "firstName" : "P",
      "lastName" : "Lichtner",
      "authorRank" : 5,
      "name" : "Lichtner P",
      "referenceId" : "RGD:A38864"
    }, {
      "firstName" : "KD",
      "lastName" : "Gerbitz",
      "authorRank" : 6,
      "name" : "Gerbitz KD",
      "referenceId" : "RGD:A38865"
    }, {
      "firstName" : "W",
      "lastName" : "Neupert",
      "authorRank" : 7,
      "name" : "Neupert W",
      "referenceId" : "RGD:A4614"
    }, {
      "firstName" : "M",
      "lastName" : "Brunner",
      "authorRank" : 8,
      "name" : "Brunner M",
      "referenceId" : "RGD:A4615"
    }, {
      "firstName" : "S",
      "lastName" : "Hofmann",
      "authorRank" : 9,
      "name" : "Hofmann S",
      "referenceId" : "RGD:A4616"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:737677"
    } ]
  }, {
    "primaryId" : "PMID:10339581",
    "title" : "Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Triggs-Raine B, etal., Proc Natl Acad Sci U S A. 1999 May 25;96(11):6296-300.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-15T15:28:36.000-06:00",
    "volume" : "96",
    "pages" : "6296-300",
    "abstract" : "Hyaluronan (HA), a large glycosaminoglycan abundant in the extracellular matrix, is important in cell migration during embryonic development, cellular proliferation, and differentiation and has a structural role in connective tissues. The turnover of HA requires endoglycosidic breakdown by lysosomal hyaluronidase, and a congenital deficiency of hyaluronidase has been thought to be incompatible with life. However, a patient with a deficiency of serum hyaluronidase, now designated as mucopolysaccharidosis IX, was recently described. This patient had a surprisingly mild clinical phenotype, including notable periarticular soft tissue masses, mild short stature, an absence of neurological or visceral involvement, and histological and ultrastructural evidence of a lysosomal storage disease. To determine the molecular basis of mucopolysaccharidosis IX, we analyzed two candidate genes tandemly distributed on human chromosome 3p21.3 and encoding proteins with homology to a sperm protein with hyaluronidase activity. These genes, HYAL1 and HYAL2, encode two distinct lysosomal hyaluronidases with different substrate specificities. We identified two mutations in the HYAL1 alleles of the patient, a 1412G --> A mutation that introduces a nonconservative amino acid substitution (Glu268Lys) in a putative active site residue and a complex intragenic rearrangement, 1361del37ins14, that results in a premature termination codon. We further show that these two hyaluronidase genes, as well as a third recently discovered adjacent hyaluronidase gene, HYAL3, have markedly different tissue expression patterns, consistent with differing roles in HA metabolism. These data provide an explanation for the unexpectedly mild phenotype in mucopolysaccharidosis IX and predict the existence of other hyaluronidase deficiency disorders.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Triggs-Raine",
      "authorRank" : 1,
      "name" : "Triggs-Raine B",
      "referenceId" : "RGD:A72383"
    }, {
      "firstName" : "TJ",
      "lastName" : "Salo",
      "authorRank" : 2,
      "name" : "Salo TJ",
      "referenceId" : "RGD:A75214"
    }, {
      "firstName" : "H",
      "lastName" : "Zhang",
      "authorRank" : 3,
      "name" : "Zhang H",
      "referenceId" : "RGD:A6284"
    }, {
      "firstName" : "BA",
      "lastName" : "Wicklow",
      "authorRank" : 4,
      "name" : "Wicklow BA",
      "referenceId" : "RGD:A50650"
    }, {
      "firstName" : "MR",
      "lastName" : "Natowicz",
      "authorRank" : 5,
      "name" : "Natowicz MR",
      "referenceId" : "RGD:A75215"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599811"
    } ]
  }, {
    "primaryId" : "PMID:10340301",
    "title" : "The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Dev KK, etal., Neuropharmacology. 1999 May;38(5):635-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:35:48.000-05:00",
    "volume" : "38",
    "pages" : "635-44",
    "abstract" : "Here we report an interaction between AMPA receptor subunits and a single PDZ domain-containing protein called PICK1 which is known to bind protein kinase C alpha (PKC alpha). The interaction occurs within the last ten amino acid residues containing a novel PDZ binding motif (E S V/I K I) of the short C-terminal alternative splice variants of AMPA receptor subunits. No interaction occurs with the corresponding long splice variants which do not contain the E S V/I K I motif. The PDZ domain of PICK1 is required for the interaction and the mutation of a single amino acid in this region (Lys-27 to Glu) prevents interaction between PICK1 and GluR2 in the yeast two-hybrid assay. A similar mutation has been reported to prevent the binding of PICK1 to PKC alpha indicating that the same domain of PICK1 binds both PKC alpha and GluRs. Flag-tagged PICK1 is retained by a glutathione S-transferase (GST) fusion of the C-terminal of GluR2 (GST-ct-GluR2; short splice variant) but not by GST-ct-GluR1 (long splice variant). Recombinant full length GluR2 is coimmunoprecipitated with flag-PICK1 using an anti-flag antibody and flag-PICK1 is coimmunoprecipitated with an N-terminal directed anti-GluR2 antibody. Transient expression of both proteins in COS cells reveals colocalization and an altered pattern of distribution for each  protein from when they are expressed individually. This novel interaction provides a possible regulatory mechanism to specifically modulate distinct splice variants and may be involved in targeting the phosphorylation of short form GluRs by PKC alpha.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KK",
      "lastName" : "Dev",
      "authorRank" : 1,
      "name" : "Dev KK",
      "referenceId" : "RGD:A90201"
    }, {
      "firstName" : "A",
      "lastName" : "Nishimune",
      "authorRank" : 2,
      "name" : "Nishimune A",
      "referenceId" : "RGD:A88166"
    }, {
      "firstName" : "JM",
      "lastName" : "Henley",
      "authorRank" : 3,
      "name" : "Henley JM",
      "referenceId" : "RGD:A42390"
    }, {
      "firstName" : "S",
      "lastName" : "Nakanishi",
      "authorRank" : 4,
      "name" : "Nakanishi",
      "referenceId" : "RGD:A238315"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553694"
    } ]
  }, {
    "primaryId" : "PMID:10340377",
    "title" : "Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Cabannes E, etal., Oncogene. 1999 May 20;18(20):3063-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-07-31T11:19:51.000-05:00",
    "volume" : "18",
    "pages" : "3063-70",
    "abstract" : "The NF-kappaB/Rel family of transcription factors regulates a wide variety of genes whose products play a fundamental role in inflammatory and immune responses. The implication of NF-kappaB/Rel proteins and their IkappaB regulatory subunits in the control of cellular growth and oncogenesis, was suggested by the induction of fatal lymphomas in birds by the v-rel oncoprotein, and the rearrangement and amplification of several genes encoding the NF-kappaB/Rel/IkappaB signal transduction factors in human malignancies, primarily of lymphoid origin. Hodgkin's disease (HD) is a lymphoma characterized by a low frequency of malignant Hodgkin and Reed-Sternberg (H/RS) cells in a reactive background of non-neoplastic cells. The peculiar activated phenotype of Hodgkin and Reed-Sternberg cells and their pattern of cytokine secretion are believed to be a consequence of constitutive activation of the NF-kappaB transcription factor. Here, we report the detection of mutations of the IkBa gene, in two HD-derived cell lines and in two out of eight biopsy samples from patients with relapsed Hodgkin's disease. The presence of defective IkappaBalpha is thus likely to explain the constitutive activation of NF-kappaB in these cells and suggests that IkappaBalpha is a tumour suppressor controlling the oncogenic activation of NF-kappaB in Hodgkin and Reed-Sternberg cells.",
    "issueName" : "20",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Cabannes",
      "authorRank" : 1,
      "name" : "Cabannes E",
      "referenceId" : "RGD:A98510"
    }, {
      "firstName" : "G",
      "lastName" : "Khan",
      "authorRank" : 2,
      "name" : "Khan G",
      "referenceId" : "RGD:A74117"
    }, {
      "firstName" : "F",
      "lastName" : "Aillet",
      "authorRank" : 3,
      "name" : "Aillet F",
      "referenceId" : "RGD:A98511"
    }, {
      "firstName" : "RF",
      "lastName" : "Jarrett",
      "authorRank" : 4,
      "name" : "Jarrett RF",
      "referenceId" : "RGD:A98512"
    }, {
      "firstName" : "RT",
      "lastName" : "Hay",
      "authorRank" : 5,
      "name" : "Hay RT",
      "referenceId" : "RGD:A98513"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2298893"
    } ]
  }, {
    "primaryId" : "PMID:10340381",
    "title" : "Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis.",
    "datePublished" : "1999-05-20T00:00:00.000-05:00",
    "citation" : "Miyaki M, etal., Oncogene. 1999 May 20;18(20):3098-103. doi: 10.1038/sj.onc.1202642.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-02-10T10:54:47.000-06:00",
    "volume" : "18",
    "pages" : "3098-103",
    "abstract" : "We have previously detected an increased frequency of loss of heterozygosity (LOH) on chromosome 18q during progression of colorectal carcinomas. To clarify the target of 18qLOH, mutation of Smad4 and Smad2 genes was analysed in 176 colorectal tumors with different stages, including liver metastasis, from 111 sporadic, 52 familial adenomatous polyposis (FAP) and nine hereditary nonpolyposis colorectal cancer (HNPCC) patients. Mutation of other Smad gene families in the TGF-beta signaling pathway was also examined. Twenty-one Smad4 mutations and one Smad2 mutation were detected, whereas mutation of Smad3, 6 and 7 genes was not detected. Smad4 mutations included seven frameshift, one inframe deletion, four nonsense and nine missense mutations, 95% of which resulted in alteration of Smad4 protein regions included in homo-oligomer and hetero-oligomer formation. Frequencies of tumors with Smad4 mutation were 0/40 (0%) in adenoma, 4/39 (10%) in intramucosal carcinoma, 3/44 (7%) in primary invasive carcinoma without distant metastasis, 6/17 (35%) in primary invasive carcinoma with distant metastasis, and 11/36 (31%) in distant metastasis (metastatic/non-metastatic: P=0.006 approximately 0.01). Loss of the other allele was observed in 19 of 20 (95%) invasive and metastasized carcinomas with Smad4 mutations. In four cases both primary and metastasized carcinomas in the same patients showed the same mutations. The present results suggest that Smad4 gene is one of true targets of 18qLOH, and that its inactivation is involved in advanced stages, such as distant metastasis, in human colorectal carcinogenesis.",
    "issueName" : "20",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Miyaki",
      "authorRank" : 1,
      "name" : "Miyaki M",
      "referenceId" : "RGD:A479127"
    }, {
      "firstName" : "T",
      "lastName" : "Iijima",
      "authorRank" : 2,
      "name" : "Iijima T",
      "referenceId" : "RGD:A34884"
    }, {
      "firstName" : "M",
      "lastName" : "Konishi",
      "authorRank" : 3,
      "name" : "Konishi M",
      "referenceId" : "RGD:A7338"
    }, {
      "firstName" : "K",
      "lastName" : "Sakai",
      "authorRank" : 4,
      "name" : "Sakai K",
      "referenceId" : "RGD:A162498"
    }, {
      "firstName" : "A",
      "lastName" : "Ishii",
      "authorRank" : 5,
      "name" : "Ishii A",
      "referenceId" : "RGD:A58361"
    }, {
      "firstName" : "M",
      "lastName" : "Yasuno",
      "authorRank" : 6,
      "name" : "Yasuno M",
      "referenceId" : "RGD:A479128"
    }, {
      "firstName" : "T",
      "lastName" : "Hishima",
      "authorRank" : 7,
      "name" : "Hishima T",
      "referenceId" : "RGD:A479129"
    }, {
      "firstName" : "M",
      "lastName" : "Koike",
      "authorRank" : 8,
      "name" : "Koike M",
      "referenceId" : "RGD:A37197"
    }, {
      "firstName" : "N",
      "lastName" : "Shitara",
      "authorRank" : 9,
      "name" : "Shitara N",
      "referenceId" : "RGD:A479130"
    }, {
      "firstName" : "T",
      "lastName" : "Iwama",
      "authorRank" : 10,
      "name" : "Iwama T",
      "referenceId" : "RGD:A17034"
    }, {
      "firstName" : "J",
      "lastName" : "Utsunomiya",
      "authorRank" : 11,
      "name" : "Utsunomiya J",
      "referenceId" : "RGD:A35965"
    }, {
      "firstName" : "T",
      "lastName" : "Kuroki",
      "authorRank" : 12,
      "name" : "Kuroki T",
      "referenceId" : "RGD:A19644"
    }, {
      "firstName" : "T",
      "lastName" : "Mori",
      "authorRank" : 13,
      "name" : "Mori T",
      "referenceId" : "RGD:A151972"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:21066333"
    } ]
  }, {
    "primaryId" : "PMID:10340516",
    "title" : "Presynaptic cytomatrix protein bassoon is localized at both excitatory and inhibitory synapses of rat brain.",
    "datePublished" : "1999-06-07T00:00:00.000-05:00",
    "citation" : "Richter K, etal., J Comp Neurol. 1999 Jun 7;408(3):437-48.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T01:58:37.000-05:00",
    "volume" : "408",
    "pages" : "437-48",
    "abstract" : "Bassoon is a 420-kDa protein specifically localized at the active zone of presynaptic nerve terminals. It is thought to be involved in the structural organization of the neurotransmitter release site. We studied the distribution of Bassoon transcripts and protein in rat brain and assessed which types of presynaptic terminals contain the protein. As shown by in situ hybridization, Bassoon transcripts are widely distributed in the brain and occur primarily in excitatory neurons. In addition, examples of gamma-aminobutyric acid (GABA)-ergic neurons expressing Bassoon are detected. At the light microscopic level, Bassoon immunoreactivity is found in synaptic neuropil regions throughout the brain, with the strongest expression in the hippocampus, the cerebellar cortex, and the olfactory bulb. Immunoelectron microscopy showed that Bassoon immunoreactivity is found in both asymmetric type 1 and symmetric type 2 synapses. Immunopositive asymmetric synapses include mossy fiber boutons and various spine and shaft synapses in the hippocampus and mossy fiber terminals and parallel fiber terminals in the cerebellum. Bassoon-containing symmetric synapses are observed, e.g., between basket and granule cells in the hippocampus, between Golgi cells and granule cells, and between basket cells and Purkinje cells in the cerebellum. Within synaptic terminals, Bassoon appears highly concentrated at sites opposite to postsynaptic densities. In cultured hippocampal neurons, Bassoon was found to colocalize with GABA(A) and glutamate (GluR1) receptors. These data indicate that Bassoon is a component of the presynaptic apparatus of both excitatory glutamatergic and inhibitory GABAergic synapses.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Richter",
      "authorRank" : 1,
      "name" : "Richter K",
      "referenceId" : "RGD:A7105"
    }, {
      "firstName" : "K",
      "lastName" : "Langnaese",
      "authorRank" : 2,
      "name" : "Langnaese K",
      "referenceId" : "RGD:A7104"
    }, {
      "firstName" : "M R",
      "lastName" : "Kreutz",
      "authorRank" : 3,
      "name" : "Kreutz MR",
      "referenceId" : "RGD:A437099"
    }, {
      "firstName" : "G",
      "lastName" : "Olias",
      "authorRank" : 4,
      "name" : "Olias G",
      "referenceId" : "RGD:A36251"
    }, {
      "firstName" : "R",
      "lastName" : "Zhai",
      "authorRank" : 5,
      "name" : "Zhai R",
      "referenceId" : "RGD:A6540"
    }, {
      "firstName" : "H",
      "lastName" : "Scheich",
      "authorRank" : 6,
      "name" : "Scheich H",
      "referenceId" : "RGD:A460258"
    }, {
      "firstName" : "C C",
      "lastName" : "Garner",
      "authorRank" : 7,
      "name" : "Garner CC",
      "referenceId" : "RGD:A460259"
    }, {
      "firstName" : "E D",
      "lastName" : "Gundelfinger",
      "authorRank" : 8,
      "name" : "Gundelfinger ED",
      "referenceId" : "RGD:A437100"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702152"
    } ]
  }, {
    "primaryId" : "PMID:10340649",
    "title" : "Novel 23-base-pair duplication mutation in TSC1 exon 15 in an infant presenting with cardiac rhabdomyomas.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Smith M and Sperling D, Am J Med Genet. 1999 Jun 4;84(4):346-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:31:34.000-05:00",
    "volume" : "84",
    "pages" : "346-9",
    "abstract" : "Tuberous sclerosis (TSC) is a dominantly inherited disorder due to mutations at two gene loci, the TSC1 locus on chromosome 9q34 and the TSC2 locus on chromosome 16p13.3. The TSC2 and the TSC1 genes have now been cloned, enabling mutation analysis. We report results of mutation analysis in a sporadic case of TSC first  identified in intra-uterine life on the basis of the presence of cardiac rhabdomyomas. Postnatally this infant was also found to have subependymal nodules on brain computed tomographic scan. Hypomelanotic macules were not detected neonatally or at 12 months of age. The specific TSC1 exon 15 mutation found in our patient has not previously been reported in cases of TSC. This mutation involves duplication of a 23-bp segment of DNA between two 9-bp repeated sequence elements within exon 15. These repeat elements are located between nucleotides 1892-1900 and between nucleotides 1915-1923 within the TSC1 gene sequence. It is  likely that the presence of these two repeated elements predisposes to misalignment of DNA strands and unequal crossing over. The mechanism of origin of rhabdomyomas in TSC is reviewed. Loss of heterozygosity in the TSC gene regions has been reported in cardiac rhabdomyomas; however, these lesions are self-limiting in their growth. The basis for this self limiting proliferation is  not clear. One interesting postulation is that cardiac rhabdomyomas may be due to delay or failure of apoptosis which occurs as part of the normal remodeling process in the heart.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Smith",
      "authorRank" : 1,
      "name" : "Smith",
      "referenceId" : "RGD:A359038"
    }, {
      "firstName" : "D",
      "lastName" : "Sperling",
      "authorRank" : 2,
      "name" : "Sperling",
      "referenceId" : "RGD:A258217"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064339"
    } ]
  }, {
    "primaryId" : "PMID:10340764",
    "title" : "A plethora of presynaptic proteins associated with ATP-storing organelles in cultured astrocytes.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Maienschein V, etal., Glia. 1999 May;26(3):233-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-02-24T10:48:44.000-06:00",
    "volume" : "26",
    "pages" : "233-44",
    "abstract" : "Cultured astrocytes can release a variety of messenger substances via receptor-mediated mechanisms, implicating their potential for regulated exocytosis and the participation of proteins of the SNARE complex. Here we demonstrate the astrocytic expression and organellar association of a large variety of synaptic proteins (synaptobrevin II, synaptotagmin I, synaptophysin, rab3a, synapsin I, SNAP-25, and syntaxin I) and also of the ubiquitous cellubrevin. As revealed by immunoblotting the expression of synaptic proteins was highest within the first few days after plating. Synaptophysin and SNAP-25 showed the most significant decline with prolonged culture time. Rab3a and synaptobrevin II were retained at a high level and synaptotagmin I, synapsin I, and syntaxin I at a lower level until 20 DIV. The immunoreaction for cellubrevin was low at the beginning and increased with prolonged culture time. As revealed by light microscopical immunocytochemistry the proteins are expressed by GFAP-positive astrocytes and associated with organelles of varying size. Immunoelectron microscopical analysis allocates synaptobrevin II and synaptophysin to the membranes of vesicular organelles. Double labeling experiments for pairs of synaptic proteins reveal that individual synaptic proteins can be entirely colocalized or partly reside on different organelles. Subcellular fractionation of astrocyte cultures by sucrose density gradient centrifugation after 2, 6, 13, and 20 DIV showed that the proteins sediment with ATP containing organelles of a broad density range. Our data suggest that messenger substances may be released from cultured astrocytes via receptor-mediated, Ca2+-dependent exocytosis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Maienschein",
      "authorRank" : 1,
      "name" : "Maienschein V",
      "referenceId" : "RGD:A135110"
    }, {
      "firstName" : "M",
      "lastName" : "Marxen",
      "authorRank" : 2,
      "name" : "Marxen M",
      "referenceId" : "RGD:A135111"
    }, {
      "firstName" : "W",
      "lastName" : "Volknandt",
      "authorRank" : 3,
      "name" : "Volknandt W",
      "referenceId" : "RGD:A9667"
    }, {
      "firstName" : "H",
      "lastName" : "Zimmermann",
      "authorRank" : 4,
      "name" : "Zimmermann H",
      "referenceId" : "RGD:A5722"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892571"
    } ]
  }, {
    "primaryId" : "PMID:10340789",
    "title" : "Expression of stress-response protein 60 in lens epithelial cells in atopic cataract.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Ishikura R, etal., Jpn J Ophthalmol. 1999 Mar-Apr;43(2):89-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-11-02T14:58:04.000-06:00",
    "volume" : "43",
    "pages" : "89-96",
    "abstract" : "PURPOSE: To clarify the pathogenesis of atopic cataract, especially to determine  if there is any relationship between autoimmunity and atopic cataract. METHODS: We investigated the lens epithelia obtained at surgery from 12 patients (12 eyes) with atopic cataract: from 8 patients (8 eyes) with nonatopic cataract (5 with senile cataract, 2 with juvenile cataract, and one with secondary cataract due to anterior uveitis); and from 4 autopsy eyes as controls. RESULTS: Histopathological findings in the lens epithelial cells from atopic and nonatopic cataract patients were essentially the same: atrophy of the cells, presence of the superimposed cells, migration of cells into the lens cortex, cytoplasmic vacuolation, and loss of cells. In an immunohistochemical study, the expression of stress-response protein 60 (srp 60), srp 27, and srp 72 was examined in the lens epithelial cells. In atopic cataract specimens, 71%-87% of the lens epithelial cells were stained with the antibody against srp 60, but the cells in  nonatopic cataract and control specimens were not stained. CONCLUSIONS: Srp 27 and srp 72 were not expressed in any observed epithelial cells. The expression of srp 60 may reflect a protective mechanism of the epithelial cells against injury  triggered by immunorelated agents. These findings suggest that the pathogenesis of degeneration of the lens epithelial cells in patients with atopic cataract may be related to autoimmunity.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Ishikura",
      "authorRank" : 1,
      "name" : "Ishikura",
      "referenceId" : "RGD:A207954"
    }, {
      "firstName" : "S",
      "lastName" : "Kato",
      "authorRank" : 2,
      "name" : "Kato S",
      "referenceId" : "RGD:A17686"
    }, {
      "firstName" : "M",
      "lastName" : "Nagata",
      "authorRank" : 3,
      "name" : "Nagata M",
      "referenceId" : "RGD:A5370"
    }, {
      "firstName" : "A",
      "lastName" : "Tamai",
      "authorRank" : 4,
      "name" : "Tamai",
      "referenceId" : "RGD:A207955"
    }, {
      "firstName" : "E",
      "lastName" : "Ohama",
      "authorRank" : 5,
      "name" : "Ohama",
      "referenceId" : "RGD:A207956"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10402844"
    } ]
  }, {
    "primaryId" : "PMID:10340890",
    "title" : "Significance of Fas and retinoblastoma protein expression during the progression  of Barrett's metaplasia to adenocarcinoma.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Coppola D, etal., Ann Surg Oncol. 1999 Apr-May;6(3):298-304.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-23T16:51:38.000-05:00",
    "volume" : "6",
    "pages" : "298-304",
    "abstract" : "BACKGROUND: Barrett's esophagus (BE) is a premalignant lesion characterized by replacement of normal squamous epithelium with columnar epithelium. This lesion can progress to dysplasia and adenocarcinoma. Recently, the Fas receptor and retinoblastoma (Rb) protein have been described as important mediators of apoptosis and tumor suppression, respectively. This study was undertaken to examine their expression during the progression of metaplasia to adenocarcinoma in BE. METHODS: In a review of 56 adenocarcinomas arising in BE, the specimen blocks were examined using the immunohistochemical avidin-biotin-peroxidase complex technique. For each specimen, areas of normal epithelium were compared with areas of metaplasia, dysplasia, or carcinoma (when present). Monoclonal mouse anti-human antibodies were used to identify Rb protein (Rb-Ab5, 1/50 dilution; Oncogene Science) and the 40-50-kDa cell membrane Fas protein (APO-1/Fas, 1/5 dilution; DAKO Corp.). RESULTS: Loss of Rb staining was observed  as the metaplasia progressed to dysplasia and carcinoma, indicating accumulation  of unstainable aberrant protein. Conversely, Fas protein staining was undetectable or weak in normal or metaplastic epithelium, increasing in the areas of high-grade dysplasia and carcinoma. These differences were statistically significant (P < .001). CONCLUSIONS: The accumulation of abnormal Rb protein during the progression of Barrett's metaplasia to carcinoma leads to unsuppressed tumor growth. Fas overexpression may represent a cellular attempt to balance the  uncontrolled tumor proliferation by promoting apoptosis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Coppola",
      "authorRank" : 1,
      "name" : "Coppola D",
      "referenceId" : "RGD:A80722"
    }, {
      "firstName" : "RH",
      "lastName" : "Schreiber",
      "authorRank" : 2,
      "name" : "Schreiber",
      "referenceId" : "RGD:A190384"
    }, {
      "firstName" : "L",
      "lastName" : "Mora",
      "authorRank" : 3,
      "name" : "Mora",
      "referenceId" : "RGD:A190385"
    }, {
      "firstName" : "W",
      "lastName" : "Dalton",
      "authorRank" : 4,
      "name" : "Dalton",
      "referenceId" : "RGD:A190386"
    }, {
      "firstName" : "RC",
      "lastName" : "Karl",
      "authorRank" : 5,
      "name" : "Karl",
      "referenceId" : "RGD:A190387"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662425"
    } ]
  }, {
    "primaryId" : "PMID:10340905",
    "title" : "Trichloroethylene exposure and specific somatic mutations in patients with renal  cell carcinoma.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Brauch H, etal., J Natl Cancer Inst. 1999 May 19;91(10):854-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:43:20.000-05:00",
    "volume" : "91",
    "pages" : "854-61",
    "abstract" : "BACKGROUND: The development of renal cell carcinoma (RCC) has been associated with both genetic and environmental factors-with mutations in the von Hippel-Lindau (VHL) tumor suppressor gene for clear-cell RCC specifically and with long-term exposure to high doses of trichloroethylene (TRI), an industrially important solvent, for RCC generally. We investigated whether TRI exposure produces RCC through a specific mutational effect on the VHL gene by analyzing VHL sequences in the RCCs of patients exposed to high, cumulative doses of TRI. METHODS: The level of exposure for each of 44 patients with RCC who had known industrial exposure to TRI was classified according to the duration, frequency, and mode of exposure. Samples of normal and cancerous tissues were microdissected from paraffin-embedded tissue. DNA was isolated from these samples, and somatic VHL mutations were identified by polymerase chain reaction analysis, single-strand conformation polymorphism analysis, DNA sequencing, and restriction enzyme digestion. Control samples included RCC DNA from 107 patients without known TRI exposure and lymphocyte DNA from 97 healthy subjects. RESULTS: RCCs of  TRI-exposed patients showed somatic VHL mutations in 33 (75%) of 44 cases. The mutations were frequently multiple and accompanied by loss of heterozygosity, and there was an association between the number of mutations and the severity of TRI  exposure. We observed a specific mutational hot spot at VHL nucleotide 454 in the RCCs of 13 (39%) of the patients, and this mutation was present in adjacent non-neoplastic kidney parenchyma in four of these patients. The nucleotide 454 mutation was neither detected in any of the RCCs from patients without TRI exposure nor in any of the healthy subjects. CONCLUSION: Our results suggest that RCC in patients with high, cumulative TRI exposure is associated with a unique mutation pattern in the VHL gene.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Brauch",
      "authorRank" : 1,
      "name" : "Brauch H",
      "referenceId" : "RGD:A76258"
    }, {
      "firstName" : "G",
      "lastName" : "Weirich",
      "authorRank" : 2,
      "name" : "Weirich G",
      "referenceId" : "RGD:A116967"
    }, {
      "firstName" : "MA",
      "lastName" : "Hornauer",
      "authorRank" : 3,
      "name" : "Hornauer",
      "referenceId" : "RGD:A279589"
    }, {
      "firstName" : "S",
      "lastName" : "Storkel",
      "authorRank" : 4,
      "name" : "Storkel S",
      "referenceId" : "RGD:A76263"
    }, {
      "firstName" : "T",
      "lastName" : "Wohl",
      "authorRank" : 5,
      "name" : "Wohl",
      "referenceId" : "RGD:A279590"
    }, {
      "firstName" : "T",
      "lastName" : "Bruning",
      "authorRank" : 6,
      "name" : "Bruning T",
      "referenceId" : "RGD:A118108"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071478"
    } ]
  }, {
    "primaryId" : "PMID:10340909",
    "title" : "Prevalence of mutations in the BRCA1 gene among Chinese patients with breast cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Tang NL, etal., J Natl Cancer Inst. 1999 May 19;91(10):882-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:57:09.000-05:00",
    "volume" : "91",
    "pages" : "882-5",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NL",
      "lastName" : "Tang",
      "authorRank" : 1,
      "name" : "Tang NL",
      "referenceId" : "RGD:A130860"
    }, {
      "firstName" : "CP",
      "lastName" : "Pang",
      "authorRank" : 2,
      "name" : "Pang CP",
      "referenceId" : "RGD:A112202"
    }, {
      "firstName" : "W",
      "lastName" : "Yeo",
      "authorRank" : 3,
      "name" : "Yeo",
      "referenceId" : "RGD:A274175"
    }, {
      "firstName" : "KW",
      "lastName" : "Choy",
      "authorRank" : 4,
      "name" : "Choy KW",
      "referenceId" : "RGD:A112196"
    }, {
      "firstName" : "PK",
      "lastName" : "Lam",
      "authorRank" : 5,
      "name" : "Lam",
      "referenceId" : "RGD:A274176"
    }, {
      "firstName" : "M",
      "lastName" : "Suen",
      "authorRank" : 6,
      "name" : "Suen",
      "referenceId" : "RGD:A274177"
    }, {
      "firstName" : "LK",
      "lastName" : "Law",
      "authorRank" : 7,
      "name" : "Law",
      "referenceId" : "RGD:A261008"
    }, {
      "firstName" : "WW",
      "lastName" : "King",
      "authorRank" : 8,
      "name" : "King",
      "referenceId" : "RGD:A274178"
    }, {
      "firstName" : "P",
      "lastName" : "Johnson",
      "authorRank" : 9,
      "name" : "Johnson P",
      "referenceId" : "RGD:A28913"
    }, {
      "firstName" : "M",
      "lastName" : "Hjelm",
      "authorRank" : 10,
      "name" : "Hjelm",
      "referenceId" : "RGD:A274179"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069527"
    } ]
  }, {
    "primaryId" : "PMID:10341223",
    "title" : "Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Jo K, etal., J Neurosci. 1999 Jun 1;19(11):4189-99.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:17:53.000-05:00",
    "volume" : "19",
    "pages" : "4189-99",
    "abstract" : "Protein assembly at the postsynaptic density (PSD) of neuronal synapses is mediated in part by protein interactions with PSD-95/discs large/zona occludens-1 (PDZ) motifs. Here, we identify MALS-1, -2, -3, a family of small synaptic proteins containing little more than a single PDZ domain. MALS-1, -2, and -3 are  mammalian homologs LIN-7, a Caenorhabditis elegans protein essential for vulval development. In contrast to functions for LIN-7 in epithelial cells, MALS-1 and -2 are selectively expressed in specific neuronal populations in brain and are enriched in PSD fractions. In cultured hippocampal neurons, MALS proteins are clustered together with PSD-95 and NMDA type glutamate receptors, consistent with a postsynaptic localization for MALS proteins. Immunoprecipitation and affinity chromatography studies readily identify association of MALS with PSD-95 and an NMDA receptor subunit. The PDZ domain of MALS selectively binds to peptides terminating in E-T/S-R/X-V/I/L, which corresponds to the C terminus of NMDA type  2 receptors and numerous other ion channels at the PSD. This work suggests a role for MALS proteins in regulating recruitment of neurotransmitter receptors to the  PSD.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Jo",
      "authorRank" : 1,
      "name" : "Jo",
      "referenceId" : "RGD:A207198"
    }, {
      "firstName" : "R",
      "lastName" : "Derin",
      "authorRank" : 2,
      "name" : "Derin R",
      "referenceId" : "RGD:A11935"
    }, {
      "firstName" : "M",
      "lastName" : "Li",
      "authorRank" : 3,
      "name" : "Li M",
      "referenceId" : "RGD:A5679"
    }, {
      "firstName" : "DS",
      "lastName" : "Bredt",
      "authorRank" : 4,
      "name" : "Bredt",
      "referenceId" : "RGD:A405890"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041013"
    } ]
  }, {
    "primaryId" : "PMID:10341365",
    "title" : "The immune-inflammatory pathophysiology of fibromyalgia: increased serum soluble  gp130, the common signal transducer protein of various neurotrophic cytokines.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Maes M, etal., Psychoneuroendocrinology. 1999 May;24(4):371-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-04-07T10:54:33.000-05:00",
    "volume" : "24",
    "pages" : "371-83",
    "abstract" : "Fibromyalgia is a chronic, painful musculoskeletal disorder characterized by widespread pain, pressure hyperalgesia, morning stiffness and by an increased incidence of depressive symptoms. The etiology, however, has remained elusive. The aim of the present study was to examine the inflammatory response system (IRS) in fibromyalgia. Serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sgp130, sIL-1R antagonist (IL-1RA) and sCD8 were determined in 33 healthy volunteers and in 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Severity of illness was measured with  several pain scales, dolorimetry and the Hamilton Depression Rating Scale (HDRS). Serum sgp130 was significantly higher and serum sCD8 significantly lower in fibromyalgia patients than in healthy volunteers. Serum sIL-6R and sIL-1RA were significantly higher in fibromyalgia patients with an increased HDRS score (> or  = 16) than in normal volunteers and fibromyalgia patients with a HDRS score < 16. In fibromyalgia patients, an important part of the variance in sCD8 (50.3%) and IL-1RA (19.3%) could be explained by the HDRS score; 74.3% of the variance in sIL-6R was explained by the combined effects of pain symptoms and the HDRS score; and 25.9% of the variance in serum sgp130 was explained by stiffness. The results support the contention that pain and stiffness in fibromyalgia may be accompanied by a suppression of some aspects of the IRS and that the presence of clinically significant depressive symptoms in fibromyalgia is associated with some signs of  IRS activation.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Maes",
      "authorRank" : 1,
      "name" : "Maes M",
      "referenceId" : "RGD:A153773"
    }, {
      "firstName" : "I",
      "lastName" : "Libbrecht",
      "authorRank" : 2,
      "name" : "Libbrecht",
      "referenceId" : "RGD:A182204"
    }, {
      "firstName" : "F",
      "lastName" : "Van Hunsel",
      "authorRank" : 3,
      "name" : "Van Hunsel",
      "referenceId" : "RGD:A182205"
    }, {
      "firstName" : "AH",
      "lastName" : "Lin",
      "authorRank" : 4,
      "name" : "Lin AH",
      "referenceId" : "RGD:A122515"
    }, {
      "firstName" : "L",
      "lastName" : "De Clerck",
      "authorRank" : 5,
      "name" : "De Clerck",
      "referenceId" : "RGD:A182206"
    }, {
      "firstName" : "W",
      "lastName" : "Stevens",
      "authorRank" : 6,
      "name" : "Stevens W",
      "referenceId" : "RGD:A117567"
    }, {
      "firstName" : "G",
      "lastName" : "Kenis",
      "authorRank" : 7,
      "name" : "Kenis",
      "referenceId" : "RGD:A182207"
    }, {
      "firstName" : "R",
      "lastName" : "De Jongh",
      "authorRank" : 8,
      "name" : "De Jongh",
      "referenceId" : "RGD:A182208"
    }, {
      "firstName" : "E",
      "lastName" : "Bosmans",
      "authorRank" : 9,
      "name" : "Bosmans",
      "referenceId" : "RGD:A182209"
    }, {
      "firstName" : "H",
      "lastName" : "Neels",
      "authorRank" : 10,
      "name" : "Neels",
      "referenceId" : "RGD:A182210"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8549787"
    } ]
  }, {
    "primaryId" : "PMID:10342292",
    "title" : "Cold-induced mRNA expression of angiogenic factors in rat brown adipose tissue.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Asano A, etal., J Vet Med Sci. 1999 Apr;61(4):403-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-11-11T10:57:09.000-06:00",
    "volume" : "61",
    "pages" : "403-9",
    "abstract" : "Brown adipose tissue (BAT) is the major site of non-shivering thermogenesis in rodents. Rapid angiogenesis is induced in association with adaptive hyperplasia of this tissue when the animal is exposed to cold. We demonstrated previously adrenergic activation of mRNA expression of vascular endothelial growth factor (VEGF) in rat BAT and its possible contribution to the cold-induced angiogenesis in this tissue. In the present study, we examined the effect of cold exposure on mRNA expression of other two angiogenic factors, VEGF-B and basic fibroblast growth factor (bFGF), in rats. Conventional Northern blot analysis revealed abundant mRNA expression of VEGF-B as well as VEGF, but not bFGF, in BAT. When rats were exposed to cold at 4 degrees C, the VEGF mRNA level was increased by 2.7-fold in 1-4 hr and returned to the basal level within 24 hr. In contrast, the VEGF-B mRNA level did not change throughout the course of cold exposure. A significant expression of bFGF mRNA was detected in BAT by reverse transcription-polymerase chain reaction (RT-PCR). To evaluate the tissue bFGF mRNA level quantitatively, a competitive RT-PCR method was developed using a shorter RNA fragment as a competitor. The bFGF mRNA level in BAT was found to increase by 2.3-fold in 4 hr and decreased to the basal level within 24 hr after cold exposure. These results suggest that cold exposure leads to induce VEGF and bFGF rapidly and transiently in BAT, which in turn stimulate the proliferation of vascular endothelial cells in this tissue.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Asano",
      "authorRank" : 1,
      "name" : "Asano A",
      "referenceId" : "RGD:A104909"
    }, {
      "firstName" : "K",
      "lastName" : "Kimura",
      "authorRank" : 2,
      "name" : "Kimura K",
      "referenceId" : "RGD:A8857"
    }, {
      "firstName" : "M",
      "lastName" : "Saito",
      "authorRank" : 3,
      "name" : "Saito M",
      "referenceId" : "RGD:A24865"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2314329"
    } ]
  }, {
    "primaryId" : "PMID:10342378",
    "title" : "Alterations in protein tyrosine kinase pathways following retinal vein occlusion  in the rat.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Hayashi A, etal., Curr Eye Res. 1999 Mar;18(3):231-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-16T15:55:28.000-05:00",
    "volume" : "18",
    "pages" : "231-9",
    "abstract" : "PURPOSE: To determine whether an experimental retinal vein occlusion in the rat activates protein tyrosine kinase pathways and increases angiogenic growth factors in the retina. METHODS: Retinal vein occlusion (RVO) was induced in the rat retina with argon laser photocoagulation. Retinas were collected at 2 days, 1, 2, and 4 weeks after RVO and divided into halves: one half represented an area within the distribution of the occluded vein [RVO(IN)] and the other half represented an area outside the distribution of the occluded vein [RVO(OUT)]. RVO(IN) and (OUT) were examined by western blot analysis of tyrosine-phosphorylated proteins, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and 3 signal proteins in the tyrosine kinase pathways: phospholipase Cgamma (PLCgamma), phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK). RESULTS: RVO caused a severe capillary nonperfusion in RVO(IN). Overall tyrosine-phosphorylated proteins were  increased after RVO, especially in RVO(IN) at 2 days and 1 week. VEGF and bFGF were markedly increased in RVO(IN) at 2 days and 1 week. Tyrosine-phosphorylated  PLCgamma, PI3K, and MAPK were also increased in RVO(IN) at these time points. CONCLUSIONS: RVO caused an increase in overall protein tyrosine phosphorylation in the rat retina. This increase was associated with an increase in angiogenic growth factors (VEGF and bFGF). These results suggest that protein tyrosine kinase pathways are activated during retinal ischemia and may play a role in mitogenesis of vascular endothelial cells and other responses in the retina after RVO.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Hayashi",
      "authorRank" : 1,
      "name" : "Hayashi A",
      "referenceId" : "RGD:A36588"
    }, {
      "firstName" : "HC",
      "lastName" : "Kim",
      "authorRank" : 2,
      "name" : "Kim HC",
      "referenceId" : "RGD:A36973"
    }, {
      "firstName" : "JR",
      "lastName" : "De Juan E",
      "authorRank" : 3,
      "name" : "De Juan E",
      "referenceId" : "RGD:A188015"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8655593"
    } ]
  }, {
    "primaryId" : "PMID:10342836",
    "title" : "Gap junction connexin genes cx26 and cx43 are differentially regulated by ovarian steroid hormones in rat endometrium.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Grummer R, etal., Endocrinology. 1999 Jun;140(6):2509-16.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-09-24T14:34:12.000-05:00",
    "volume" : "140",
    "pages" : "2509-16",
    "abstract" : "In rat endometrium, expression of gap junction connexin-26 (cx26) in the epithelium and cx43 in the uterine stroma is suppressed by progesterone before implantation. For further study of connexin gene regulation we analyzed expression of cx26, cx43, and cx32 in the endometrium of ovariectomized rats treated with different ratios of 17beta-estradiol (E2) and progesterone (P). A hormonal ratio of E2 to P that mimics conditions during pregnancy (0.1 microg E2  and 4 mg P) suppressed expression of cx26 and cx43. By changing the ratio to higher E2 levels (1 microg E2), cx26, in contrast to cx43, was not suppressed even by application of a high P concentration (10 mg). Time-course experiments supplying E2 alone led to an early gene response of cx26 within 3 h, whereas induction of cx43 transcripts was not detected until 14 h after E2 treatment. Simultaneous application of the antiestrogen ICI 182780 abolished E2-mediated induction of both connexins. No hormonal regulation of cx32 could be detected. As already shown for cx43 gene induction in the myometrium, E2-mediated induction of cx26 expression in the endometrium also required newly synthesized transcription  factors. It can be concluded that only a hormonal ratio resembling conditions during pregnancy is able to suppress the expression of both cx26 and cx43 and that cx26 gene expression is induced earlier by E2 and is likely to be more sensitive to a shift in the E2 to P ratio than cx43.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Grummer",
      "authorRank" : 1,
      "name" : "Grummer R",
      "referenceId" : "RGD:A137493"
    }, {
      "firstName" : "O",
      "lastName" : "Traub",
      "authorRank" : 2,
      "name" : "Traub O",
      "referenceId" : "RGD:A75045"
    }, {
      "firstName" : "E",
      "lastName" : "Winterhager",
      "authorRank" : 3,
      "name" : "Winterhager E",
      "referenceId" : "RGD:A64936"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7349386"
    } ]
  }, {
    "primaryId" : "PMID:10342838",
    "title" : "Tachykinin receptor and neutral endopeptidase gene expression in the rat uterus: characterization and regulation in response to ovarian steroid treatment.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Pinto FM, etal., Endocrinology. 1999 Jun;140(6):2526-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-08-08T12:47:30.000-05:00",
    "volume" : "140",
    "pages" : "2526-32",
    "abstract" : "Tachykinin neuropeptides, such as substance P, are localized to a population of sensory fibers that innervate the mammalian female reproductive tract. In the present study, we have characterized tachykinin NK1 receptor (NK1R), NK2 receptor (NK2R), and NK3 receptor (NK3R) gene expression by semiquantitative RT-PCR in uteri from ovariectomized rats and studied their regulation in response to 17beta-estradiol (E2), progesterone (P4), or a combination of both. In addition, we analyzed the expression and regulation of the neutral endopeptidase 24.11 (NEP), the most important enzyme involved in tachykinin degradation in the rat uterus. In uteri from control (olive oil-treated) rats, RT-PCR assays revealed single bands corresponding to the expected product sizes encoding complementary DNA for NK1R (232 bp), NK2R (491 bp), NK3R (325 bp), and NEP (221 bp). The identity of the amplified fragments was confirmed by DNA sequence analysis. Compared with control rats, NK1R messenger RNA (mRNA) was increased by 2-fold in uteri from rats treated with E2, was decreased by 3.3-fold in rats treated with P4, and was decreased by 1.8-fold in rats treated with both E2 and P4. Uterine NK2R mRNA levels were not altered by any steroid treatment. E2 treatment decreased by 15-fold NK3R mRNA. P4 was without effect if administered alone and did not influence the E2-induced decrease in NK3R mRNA. NEP mRNA levels were about 4-fold lower in E2-treated than in P4-treated rats. Functional studies were carried out in uteri from E2- or P4-treated ovariectomized rats to characterize the contractile response evoked by the selective tachykinin receptor agonists [Sar9Met(O2)11]substance P (NK1R selective), [Nle10]NKA-(4-10) (NK2R selective), and [MePhe7]NKB (NK3R selective) in the presence of the NEP inhibitor phosphoramidon (1 microM). A marked correlation was observed between the magnitude of the contractile response to each agonist and the level of expression determined by RT-PCR for each tachykinin receptor. The present findings show that tachykinin NK1R, NK2R, NK3R, and NEP are expressed in the rat uterus and that ovarian steroids differentially regulate their expression.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FM",
      "lastName" : "Pinto",
      "authorRank" : 1,
      "name" : "Pinto FM",
      "referenceId" : "RGD:A34488"
    }, {
      "firstName" : "CP",
      "lastName" : "Armesto",
      "authorRank" : 2,
      "name" : "Armesto CP",
      "referenceId" : "RGD:A142751"
    }, {
      "firstName" : "J",
      "lastName" : "Magraner",
      "authorRank" : 3,
      "name" : "Magraner J",
      "referenceId" : "RGD:A142752"
    }, {
      "firstName" : "M",
      "lastName" : "Trujillo",
      "authorRank" : 4,
      "name" : "Trujillo M",
      "referenceId" : "RGD:A142753"
    }, {
      "firstName" : "JD",
      "lastName" : "Martin",
      "authorRank" : 5,
      "name" : "Martin JD",
      "referenceId" : "RGD:A142754"
    }, {
      "firstName" : "ML",
      "lastName" : "Candenas",
      "authorRank" : 6,
      "name" : "Candenas ML",
      "referenceId" : "RGD:A34482"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5147482"
    } ]
  }, {
    "primaryId" : "PMID:10342845",
    "title" : "Expression of estrogen receptor-beta protein in rodent ovary.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Fitzpatrick SL, etal., Endocrinology. 1999 Jun;140(6):2581-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-07-25T13:00:58.000-05:00",
    "volume" : "140",
    "pages" : "2581-91",
    "abstract" : "Estrogen is an essential hormone for the LH surge and ovulation. The primary source of estrogen is from ovarian granulosa cells and in rats, estrogen, in turn, increases granulosa cell number and enhances FSH-stimulated gene expression in these cells. Thus, rat granulosa cells both respond to and synthesize estrogen. To further elucidate the mechanisms mediating the actions of estrogen in granulosa cells, we have identified and characterized the estrogen receptor-beta (ER-beta) subtype in rodent granulosa cells. ER-beta protein was localized to the nuclei of rat granulosa cells in preantral and antral follicles  by immunocytochemistry, coincident with the location of ER-beta messenger RNA (mRNA). Immunoprecipitation and Western blot analysis using ER-beta specific antisera demonstrated a protein of approximately 60 kDa in granulosa cells prepared from PMSG-primed immature mice and estrogen-treated immature rats. Extracts from granulosa cells specifically bound an estrogen response element and the complex was recognized by antisera to ER-beta. A synthetic steroid estrogen radioligand, [125I]-17alpha-iodovinyl-11beta-methoxyestradiol ([125I]-VME2), bound to cytosolic granulosa cell preparations with high affinity (estimated K(D) value of 401 +/- 83 pM, and Bmax value of 102 +/- 9 fmol/mg protein). ER-beta protein levels rapidly declined following hCG treatment consistent with the reported decrease in binding activity and ER-beta mRNA levels by high levels of gonadotropins. Overall, we have demonstrated that 1) ER-beta protein is the dominant estrogen receptor subtype present in rodent granulosa cells, 2) this receptor is functional, and 3) it is regulated by ovulatory doses of gonadotropins. Thus, ER-beta is likely to be a mediator of estrogen action in rodent granulosa cells during follicular development.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SL",
      "lastName" : "Fitzpatrick",
      "authorRank" : 1,
      "name" : "Fitzpatrick",
      "referenceId" : "RGD:A191883"
    }, {
      "firstName" : "JM",
      "lastName" : "Funkhouser",
      "authorRank" : 2,
      "name" : "Funkhouser",
      "referenceId" : "RGD:A191884"
    }, {
      "firstName" : "DM",
      "lastName" : "Sindoni",
      "authorRank" : 3,
      "name" : "Sindoni",
      "referenceId" : "RGD:A191885"
    }, {
      "firstName" : "PE",
      "lastName" : "Stevis",
      "authorRank" : 4,
      "name" : "Stevis",
      "referenceId" : "RGD:A191886"
    }, {
      "firstName" : "DC",
      "lastName" : "Deecher",
      "authorRank" : 5,
      "name" : "Deecher DC",
      "referenceId" : "RGD:A82642"
    }, {
      "firstName" : "AR",
      "lastName" : "Bapat",
      "authorRank" : 6,
      "name" : "Bapat",
      "referenceId" : "RGD:A191887"
    }, {
      "firstName" : "I",
      "lastName" : "Merchenthaler",
      "authorRank" : 7,
      "name" : "Merchenthaler I",
      "referenceId" : "RGD:A68273"
    }, {
      "firstName" : "DE",
      "lastName" : "Frail",
      "authorRank" : 8,
      "name" : "Frail DE",
      "referenceId" : "RGD:A43426"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8694156"
    } ]
  }, {
    "primaryId" : "PMID:10342874",
    "title" : "Genetic bases of estrogen-induced pituitary growth in an intercross between the ACI and Copenhagen rat strains: dominant mendelian inheritance of the ACI phenotype.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Spady TJ, etal., Endocrinology 1999 Jun;140(6):2828-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-07-19T08:23:34.000-05:00",
    "volume" : "140",
    "pages" : "2828-35",
    "abstract" : "Estrogens stimulate cell proliferation in a variety of tissues and are widely believed to be contributing factors in the etiology of certain cancer types in humans. The molecular mechanisms through which estrogens regulate cell proliferation are currently unknown. Estrogens stimulate proliferation of the PRL-producing lactotroph of the rat anterior pituitary gland and induce development of PRL-producing pituitary tumors in several inbred rat strains. Therefore, the lactotroph provides a well defined model for identifying the mechanisms through which estrogens regulate cell proliferation and/or survival. Data from our laboratory and others indicate that the relative sensitivity to the pituitary growth-promoting actions of estrogens is highly strain specific. This allows genetics-based approaches to be used to address the molecular mechanisms through which estrogens stimulate lactotroph proliferation and induce pituitary tumor development. In the present study we have examined the ability of diethylstilbestrol (DES) to induce pituitary growth in the genetically related AxC-Irish (ACI) and Copenhagen (COP) strains and their derived F1, F2, and backcross progeny. The data presented herein indicate that the anterior pituitary gland of the ACI strain displays approximately a 2-fold greater growth response to administered DES than does the pituitary gland of the COP strain. The average pituitary weight in male ACI rats was increased from 9.2 +/- 0.2 mg (mean +/- SD in untreated rats to 63.7 +/- 12.6 mg in rats treated with DES for 12 weeks, whereas in male COP rats, DES increased pituitary weight from 12.7 +/- 0.9 to 38.1 +/- 8.2 mg. The ACI phenotype was inherited in the F1, F2, and backcross progeny of an ACI x COP intercross as a dominant genetic trait, and the approximately 30 mg of additional pituitary growth displayed by the DES-treated ACI rat, relative to that of the treated COP rat, appeared to result from the actions of a single locus. Moreover, in F1 progeny from an ACI x Brown Norway intercross, the ACI phenotype was inherited as a dominant or incompletely dominant genetic trait. These data, when compared with findings of previous studies using the Fischer 344 rat strain, provide the first indication that distinct genetic pathways contribute to regulation of estrogen-induced pituitary growth and induction of PRL-producing pituitary tumors in the ACI and F344 rat strains.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TJ",
      "lastName" : "Spady",
      "authorRank" : 1,
      "name" : "Spady TJ",
      "referenceId" : "RGD:A50704"
    }, {
      "firstName" : "KL",
      "lastName" : "Pennington",
      "authorRank" : 2,
      "name" : "Pennington KL",
      "referenceId" : "RGD:A20810"
    }, {
      "firstName" : "RD",
      "lastName" : "McComb",
      "authorRank" : 3,
      "name" : "McComb RD",
      "referenceId" : "RGD:A54125"
    }, {
      "firstName" : "JD",
      "lastName" : "Shull",
      "authorRank" : 4,
      "name" : "Shull JD",
      "referenceId" : "RGD:A20809"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358974"
    } ]
  }, {
    "primaryId" : "PMID:10343609",
    "title" : "Correlation between androgen receptor expression and FGF8 mRNA levels in patients with prostate cancer and benign prostatic hypertrophy.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Wang Q, etal., J Clin Pathol. 1999 Jan;52(1):29-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-01-29T15:22:20.000-06:00",
    "volume" : "52",
    "pages" : "29-34",
    "abstract" : "AIM: To investigate the correlation between androgen receptor expression and fibroblast growth factor 8 (FGF8) mRNA levels. METHODS: 39 human prostate cancers and 14 benign prostatic hypertrophy specimens were examined immunohistochemically for androgen receptor expression and by in situ hybridisation and reverse transcription polymerase chain reaction for FGF8 expression. RESULTS: In 39 tumours there was a statistically significant negative correlation between tumour grade and FGF8 expression and a positive correlation between FGF8 and androgen receptor expression. All 14 benign hypertrophy specimens expressed moderate to high levels of FGF8 and androgen receptor. CONCLUSIONS: Loss of FGF8 may be a factor involved in the development of prostatic cancer.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang Q",
      "referenceId" : "RGD:A162778"
    }, {
      "firstName" : "GW",
      "lastName" : "Stamp",
      "authorRank" : 2,
      "name" : "Stamp GW",
      "referenceId" : "RGD:A91001"
    }, {
      "firstName" : "S",
      "lastName" : "Powell",
      "authorRank" : 3,
      "name" : "Powell S",
      "referenceId" : "RGD:A91002"
    }, {
      "firstName" : "P",
      "lastName" : "Abel",
      "authorRank" : 4,
      "name" : "Abel P",
      "referenceId" : "RGD:A91003"
    }, {
      "firstName" : "M",
      "lastName" : "Laniado",
      "authorRank" : 5,
      "name" : "Laniado M",
      "referenceId" : "RGD:A91004"
    }, {
      "firstName" : "C",
      "lastName" : "Mahony",
      "authorRank" : 6,
      "name" : "Mahony C",
      "referenceId" : "RGD:A91005"
    }, {
      "firstName" : "EN",
      "lastName" : "Lalani",
      "authorRank" : 7,
      "name" : "Lalani EN",
      "referenceId" : "RGD:A34731"
    }, {
      "firstName" : "J",
      "lastName" : "Waxman",
      "authorRank" : 8,
      "name" : "Waxman J",
      "referenceId" : "RGD:A91006"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289343"
    } ]
  }, {
    "primaryId" : "PMID:10347091",
    "title" : "EVEC, a novel epidermal growth factor-like repeat-containing protein upregulated in embryonic and diseased adult vasculature.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kowal RC, etal., Circ Res 1999 May 28;84(10):1166-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:17.000-05:00",
    "volume" : "84",
    "pages" : "1166-76",
    "abstract" : "A hallmark of vascular lesions is the phenotypic modulation of vascular smooth muscle cells (VSMCs) from a quiescent, contractile state to a more primitive, proliferative phenotype with a more fetal pattern of gene expression. Using subtraction hybridization to identify genes that may regulate this transition, we cloned a novel gene named EVEC, an acronym for its expression in the embryonic vasculature and the presence of Ca2+ binding epidermal growth factor-like repeats contained in the predicted protein structure. Although these repeats are characteristic of the extracellular matrix proteins, fibrillin, fibulin, and the latent transforming growth factor-beta binding proteins, EVEC most closely resembles the H411 and T16/S1-5 gene products, the latter of which are believed to regulate DNA synthesis in quiescent fibroblasts. Using in situ hybridization, we demonstrated that EVEC is expressed predominantly in the VSMCs of developing arteries in E11.5 through E16.5 mouse embryos. Lower levels of expression are also observed in endothelial cells, perichondrium, intestine, and mesenchyme of the face and kidney. EVEC mRNA expression is dramatically downregulated in adult arteries, except in the uterus, where cyclic angiogenesis continues; however, EVEC expression is reactivated in 2 independent rodent models of vascular injury. EVEC mRNA is observed in cellular elements of atherosclerotic plaques of LDL receptor-deficient, human apolipoprotein B transgenic mice and in VSMCs of the media and neointima of balloon-injured rat carotid arteries. These data suggest that EVEC may play an important role in the regulation of vascular growth and maturation during development and in lesions of injured vessels.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RC",
      "lastName" : "Kowal",
      "authorRank" : 1,
      "name" : "Kowal RC",
      "referenceId" : "RGD:A18686"
    }, {
      "firstName" : "JA",
      "lastName" : "Richardson",
      "authorRank" : 2,
      "name" : "Richardson JA",
      "referenceId" : "RGD:A14041"
    }, {
      "firstName" : "JM",
      "lastName" : "Miano",
      "authorRank" : 3,
      "name" : "Miano JM",
      "referenceId" : "RGD:A56"
    }, {
      "firstName" : "EN",
      "lastName" : "Olson",
      "authorRank" : 4,
      "name" : "Olson EN",
      "referenceId" : "RGD:A18687"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632806"
    } ]
  }, {
    "primaryId" : "PMID:10347113",
    "title" : "Failure to detect genetic alteration of the mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) gene in hepatocellular carcinomas in Japan.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Wada I, etal., Hepatology. 1999 Jun;29(6):1718-21. doi: 10.1002/hep.510290635.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-10-10T10:18:15.000-05:00",
    "volume" : "29",
    "pages" : "1718-21",
    "abstract" : "The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) suppresses cell growth through binding to the insulin-like growth factor 2 (IGF2) and latent complex of the transforming growth factor-beta (TGF-beta). Recently, it was reported in the United States that loss of heterozygosity (LOH) and mutations in exons 27, 28, and 31 of the M6P/IGF2R gene are frequent in hepatocellular carcinomas (HCCs) and adenomas. In view of the possible importance of this finding, especially for differential diagnosis of small hepatic lesions, we analyzed 43 primary HCCs, 2 adenomatous hyperplasias (AHs), and 3 regenerative nodules (RNs) developing in 42 Japanese patients in Japan for LOH using the polymorphic locus and for mutations by both single strand conformation polymorphism (SSCP) and direct sequencing methods. In the LOH study, 21 out of 22 informative HCCs and all of the informative AHs and RNs showed no allelic loss. In mutational studies of exons 27, 28, and 31, no mutations were detected either by SSCP or direct sequencing analysis in any of the 48 lesions. Thus inactivation of the M6P/IGF2R gene because of genetic alteration does not appear to be essential for hepatocarcinogenesis in Japan.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Wada",
      "authorRank" : 1,
      "name" : "Wada I",
      "referenceId" : "RGD:A156714"
    }, {
      "firstName" : "H",
      "lastName" : "Kanada",
      "authorRank" : 2,
      "name" : "Kanada H",
      "referenceId" : "RGD:A475270"
    }, {
      "firstName" : "K",
      "lastName" : "Nomura",
      "authorRank" : 3,
      "name" : "Nomura K",
      "referenceId" : "RGD:A131735"
    }, {
      "firstName" : "Y",
      "lastName" : "Kato",
      "authorRank" : 4,
      "name" : "Kato Y",
      "referenceId" : "RGD:A12978"
    }, {
      "firstName" : "R",
      "lastName" : "Machinami",
      "authorRank" : 5,
      "name" : "Machinami R",
      "referenceId" : "RGD:A76529"
    }, {
      "firstName" : "T",
      "lastName" : "Kitagawa",
      "authorRank" : 6,
      "name" : "Kitagawa T",
      "referenceId" : "RGD:A4878"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14985220"
    } ]
  }, {
    "primaryId" : "PMID:10347153",
    "title" : "A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Lopez-Coronado JM, etal., J Biol Chem 1999 Jun 4;274(23):16034-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T08:35:03.000-05:00",
    "volume" : "274",
    "pages" : "16034-9",
    "abstract" : "We report the molecular cloning in Rattus norvegicus of a novel mammalian enzyme (RnPIP), which shows both 3'-phosphoadenosine 5'-phosphate (PAP) phosphatase and inositol-polyphosphate 1-phosphatase activities. This enzyme is the first PAP phosphatase characterized at the molecular level in mammals, and it represents the first member of a novel family of dual specificity enzymes. The phosphatase activity is strictly dependent on Mg2+, and it is inhibited by Ca2+ and Li+ ions. Lithium chloride inhibits the hydrolysis of both PAP and inositol-1,4-bisphosphate at submillimolar concentration; therefore, it is possible that the inhibition of the human homologue of RnPIP by lithium ions is related to the pharmacological action of lithium. We propose that the PAP phosphatase activity of RnPIP is crucial for the function of enzymes sensitive to inhibition by PAP, such as sulfotransferase and RNA processing enzymes. Finally, an unexpected connection between PAP and inositol-1,4-bisphosphate metabolism emerges from this work.",
    "issueName" : "23",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Lopez-Coronado",
      "authorRank" : 1,
      "name" : "Lopez-Coronado JM",
      "referenceId" : "RGD:A16968"
    }, {
      "firstName" : "JM",
      "lastName" : "Belles",
      "authorRank" : 2,
      "name" : "Belles JM",
      "referenceId" : "RGD:A16969"
    }, {
      "firstName" : "F",
      "lastName" : "Lesage",
      "authorRank" : 3,
      "name" : "Lesage F",
      "referenceId" : "RGD:A16970"
    }, {
      "firstName" : "R",
      "lastName" : "Serrano",
      "authorRank" : 4,
      "name" : "Serrano R",
      "referenceId" : "RGD:A16971"
    }, {
      "firstName" : "PL",
      "lastName" : "Rodriguez",
      "authorRank" : 5,
      "name" : "Rodriguez PL",
      "referenceId" : "RGD:A16972"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632277"
    } ]
  }, {
    "primaryId" : "PMID:10347194",
    "title" : "Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Mount DB, etal., J Biol Chem 1999 Jun 4;274(23):16355-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-10-31T09:11:23.000-06:00",
    "volume" : "274",
    "pages" : "16355-62",
    "abstract" : "The K+-Cl- cotransporters (KCCs) belong to the gene family of electroneutral cation-chloride cotransporters, which also includes two bumetanide-sensitive Na+-K+-2Cl- cotransporters and a thiazide-sensitive Na+-Cl- cotransporter. We have cloned cDNAs encoding mouse KCC3, human KCC3, and human KCC4, three new members of this gene family. The KCC3 and KCC4 cDNAs predict proteins of 1083 and 1150 amino acids, respectively. The KCC3 and KCC4 proteins are 65-71% identical to the previously characterized transporters KCC1 and KCC2, with which they share a predicted membrane topology. The four KCC proteins differ at amino acid residues within key transmembrane domains and in the distribution of putative phosphorylation sites within the amino- and carboxyl-terminal cytoplasmic domains. The expression of mouse KCC3 in Xenopus laevis oocytes reveals the expected functional characteristics of a K+Cl- cotransporter: Cl--dependent uptake of 86Rb+ which is strongly activated by cell swelling and weakly sensitive to furosemide. A direct functional comparison of mouse KCC3 to rabbit KCC1 indicates that KCC3 has a much greater volume sensitivity. The human KCC3 and KCC4 genes are located on chromosomes 5p15 and 15q14, respectively. Although widely expressed, KCC3 transcripts are the most abundant in heart and kidney, and KCC4 is expressed in muscle, brain, lung, heart, and kidney. The unexpected molecular heterogeneity of K+-Cl- cotransport has implications for the physiology and pathophysiology of a number of tissues.",
    "issueName" : "23",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DB",
      "lastName" : "Mount",
      "authorRank" : 1,
      "name" : "Mount DB",
      "referenceId" : "RGD:A56337"
    }, {
      "firstName" : "A",
      "lastName" : "Mercado",
      "authorRank" : 2,
      "name" : "Mercado A",
      "referenceId" : "RGD:A56338"
    }, {
      "firstName" : "L",
      "lastName" : "Song",
      "authorRank" : 3,
      "name" : "Song L",
      "referenceId" : "RGD:A15519"
    }, {
      "firstName" : "J",
      "lastName" : "Xu",
      "authorRank" : 4,
      "name" : "Xu J",
      "referenceId" : "RGD:A162581"
    }, {
      "firstName" : "JR",
      "lastName" : "George AL",
      "authorRank" : 5,
      "name" : "George AL JR",
      "referenceId" : "RGD:A39394"
    }, {
      "firstName" : "E",
      "lastName" : "Delpire",
      "authorRank" : 6,
      "name" : "Delpire E",
      "referenceId" : "RGD:A6103"
    }, {
      "firstName" : "G",
      "lastName" : "Gamba",
      "authorRank" : 7,
      "name" : "Gamba G",
      "referenceId" : "RGD:A7993"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556494"
    } ]
  }, {
    "primaryId" : "PMID:10347249",
    "title" : "Stoichiometry of sulfonylurea-induced ATP-sensitive potassium channel closure.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Dorschner H, etal., Mol Pharmacol. 1999 Jun;55(6):1060-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-09T14:31:15.000-06:00",
    "volume" : "55",
    "pages" : "1060-6",
    "abstract" : "Hypoglycemic sulfonylureas (e.g., glibenclamide, glipizide, and tolbutamide) exert their stimulatory effect on excitatory cells by closure of ATP-sensitive potassium (KATP) channels. These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K+ channel (KIR) subunit 6.x plus a sulfonylurea receptor (SUR). SUR1/KIR6.2 reconstitutes the neuronal/pancreatic beta-cell channel, whereas SUR2A/KIR6.2 and SUR2B/KIR6.1 (or KIR6.2) are proposed to reconstitute the cardiac and the vascular smooth muscle-type KATP channels, respectively. SUR2A and SUR2B are splice variants of a single gene differing only in their C-terminal 42 amino acids. Affinities of sulfonylureas for rat SUR2A, rat or human SUR2B, and a SUR2 chimera containing the C-terminal 42 amino acids of SUR1 did not differ significantly, implying that the C terminus does not form part of the binding pocket. Consistent with these findings, reconstituted SUR2A/KIR6.2 and SUR2B/KIR6.2 channels revealed similar sensitivities for glibenclamide and tolbutamide. Dissociation constants of sulfonylureas for SUR2A and SUR2B were 10- to 400-fold higher than for SUR1, however, amazingly the benzoic acid derivative meglitinide did not show lower affinity for SUR2 isoforms. Potencies of glibenclamide, glipizide, tolbutamide, and meglitinide to inhibit activity of SUR1/KIR6.2 and SUR2B/KIR6.2 channels were 3- to 6-fold higher than binding affinities of these drugs with concentration-inhibition relations being significantly steeper (Hill coefficients 1.23-1.32) than binding curves (Hill coefficients 0.93-1.06). The data establish that the C terminus of SURs does not affect sulfonylurea affinity and sensitivity. We conclude that occupation of one of the four SUR sites per channel complex is sufficient to induce KATP channel closure.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Dorschner",
      "authorRank" : 1,
      "name" : "Dorschner H",
      "referenceId" : "RGD:A71077"
    }, {
      "firstName" : "E",
      "lastName" : "Brekardin",
      "authorRank" : 2,
      "name" : "Brekardin E",
      "referenceId" : "RGD:A71078"
    }, {
      "firstName" : "I",
      "lastName" : "Uhde",
      "authorRank" : 3,
      "name" : "Uhde I",
      "referenceId" : "RGD:A71079"
    }, {
      "firstName" : "C",
      "lastName" : "Schwanstecher",
      "authorRank" : 4,
      "name" : "Schwanstecher C",
      "referenceId" : "RGD:A71080"
    }, {
      "firstName" : "M",
      "lastName" : "Schwanstecher",
      "authorRank" : 5,
      "name" : "Schwanstecher M",
      "referenceId" : "RGD:A71081"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598651"
    } ]
  }, {
    "primaryId" : "PMID:10347250",
    "title" : "Differential regulation of peptide alpha-amidation by dexamethasone and disulfiram.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Driscoll WJ, etal., Mol Pharmacol. 1999 Jun;55(6):1067-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-12-18T17:00:51.000-06:00",
    "volume" : "55",
    "pages" : "1067-76",
    "abstract" : "alpha-Amidation is essential for the function of many peptides in intercellular communication. This C-terminal modification is mediated in a two-step process by the hydroxylase and lyase activities of the bifunctional enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The first step, catalyzed by peptidylglycine-alpha-hydroxylating monooxygenase (PHM; EC 1.14.17. 3), is rate limiting in the process, and therefore subject to regulation. Dexamethasone and disulfiram (tetraethylthiuram disulfide; Antabuse) were used as in vivo treatments to study the regulation of PHM expression and activity in cardiac atrium. Our findings show that both dexamethasone and disulfiram treatment increase the activity of PHM in atrial tissue but that they do so by distinctly different mechanisms. Dexamethasone elevated tissue levels of PAM mRNA and protein concurrently, suggesting that glucocorticoids regulate PAM expression at the level of gene transcription. In contrast, disulfiram treatment, which depletes stores of alpha-amidated peptides, increased the specific activity of PHM without affecting the level of PAM expression. The catalytic efficiency of PHM was enhanced by raising the Vmax of the enzyme. Importantly, this increase in Vmax was retained through purification to homogeneity, indicating that either a covalent modification or a stable conformational change had occurred in the protein. These novel findings demonstrate that the rate-limiting enzyme in the bioactivation of peptide messengers is differentially regulated by transcriptional and post-transcriptional mechanisms in vivo. It is proposed that regulation of PHM's expression and catalytic efficiency serve as coordinated physiologic mechanisms for maintaining appropriate levels of alpha-amidating activity under changing conditions in vivo.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WJ",
      "lastName" : "Driscoll",
      "authorRank" : 1,
      "name" : "Driscoll WJ",
      "referenceId" : "RGD:A102606"
    }, {
      "firstName" : "SA",
      "lastName" : "Mueller",
      "authorRank" : 2,
      "name" : "Mueller SA",
      "referenceId" : "RGD:A102607"
    }, {
      "firstName" : "BA",
      "lastName" : "Eipper",
      "authorRank" : 3,
      "name" : "Eipper BA",
      "referenceId" : "RGD:A7816"
    }, {
      "firstName" : "GP",
      "lastName" : "Mueller",
      "authorRank" : 4,
      "name" : "Mueller GP",
      "referenceId" : "RGD:A102608"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2302424"
    } ]
  }, {
    "primaryId" : "PMID:10348793",
    "title" : "Dihydropyrimidine dehydrogenase activity and fluorouracil pharmacokinetics with liver damage induced by bile duct ligation in rats.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Tateishi T, etal., Drug Metab Dispos. 1999 Jun;27(6):651-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-15T08:35:30.000-06:00",
    "volume" : "27",
    "pages" : "651-4",
    "abstract" : "Hepatic metabolism is the main determinant in the pharmacokinetics of 5-fluorouracil (5-FU). Its disposition might be affected with liver dysfunction. In the present study, the influence of liver damage induced by bile duct ligation on dihydropyrimidine dehydrogenase (DPD), a rate-limiting enzyme in 5-FU catabolism, CYP2B, and 5-FU pharmacokinetics were compared in male Sprague-Dawley rats. After 3 weeks of the ligation in two different groups of animals for in vitro and pharmacokinetic experiments, significant increases in serum bilirubin level and spleen weight were found in both groups. No significant differences were noted in bilirubin level or spleen weight of the bile duct ligation group between the two experiment groups. In the in vitro experiment, DPD activity and protein levels determined by Western blot analysis in the bile duct ligation group were slightly but significantly greater than those of a sham-operated group, whereas CYP2B activity and protein level were significantly reduced. These findings were supported by mRNA levels of CYP2B and DPD. When 40 mg/kg 5-FU was administered i.v. in the pharmacokinetic experiment, no significant differences in pharmacokinetic parameters were found between the bile duct ligation and sham-operated groups. These results suggested that DPD activity and protein level were maintained and that 5-FU pharmacokinetics was not altered in the presence of liver damage accompanied by a significant reduction in CYP2B activity and protein level, supporting previous clinical studies showing that mild to moderate liver dysfunction does not affect 5-FU disposition.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Tateishi",
      "authorRank" : 1,
      "name" : "Tateishi T",
      "referenceId" : "RGD:A75132"
    }, {
      "firstName" : "M",
      "lastName" : "Watanabe",
      "authorRank" : 2,
      "name" : "Watanabe M",
      "referenceId" : "RGD:A161340"
    }, {
      "firstName" : "H",
      "lastName" : "Nakura",
      "authorRank" : 3,
      "name" : "Nakura H",
      "referenceId" : "RGD:A75134"
    }, {
      "firstName" : "M",
      "lastName" : "Tanaka",
      "authorRank" : 4,
      "name" : "Tanaka M",
      "referenceId" : "RGD:A159970"
    }, {
      "firstName" : "T",
      "lastName" : "Kumai",
      "authorRank" : 5,
      "name" : "Kumai T",
      "referenceId" : "RGD:A61162"
    }, {
      "firstName" : "SF",
      "lastName" : "Sakata",
      "authorRank" : 6,
      "name" : "Sakata SF",
      "referenceId" : "RGD:A16001"
    }, {
      "firstName" : "N",
      "lastName" : "Tamaki",
      "authorRank" : 7,
      "name" : "Tamaki N",
      "referenceId" : "RGD:A4790"
    }, {
      "firstName" : "K",
      "lastName" : "Ogura",
      "authorRank" : 8,
      "name" : "Ogura K",
      "referenceId" : "RGD:A161259"
    }, {
      "firstName" : "T",
      "lastName" : "Nishiyama",
      "authorRank" : 9,
      "name" : "Nishiyama T",
      "referenceId" : "RGD:A161260"
    }, {
      "firstName" : "T",
      "lastName" : "Watabe",
      "authorRank" : 10,
      "name" : "Watabe T",
      "referenceId" : "RGD:A161266"
    }, {
      "firstName" : "S",
      "lastName" : "Kobayashi",
      "authorRank" : 11,
      "name" : "Kobayashi S",
      "referenceId" : "RGD:A159680"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599789"
    } ]
  }, {
    "primaryId" : "PMID:10348814",
    "title" : "Mutations of RegIalpha are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Higham AD, etal., Gastroenterology. 1999 Jun;116(6):1310-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-03-30T13:48:58.000-05:00",
    "volume" : "116",
    "pages" : "1310-8",
    "abstract" : "BACKGROUND & AIMS: The RegIalpha gene (Reg) encodes a secretory protein proposed  to regulate islet beta-cell and gastric mucous cell growth. Reg is expressed in rat gastric enterochromaffin-like (ECL) cells. The aim of this study was to examine Reg expression in human corpus and to determine the identity of Reg in ECL cell carcinoid tumors in hypergastrinemic patients. METHODS: Reg messenger RNA (mRNA) abundance was quantified by Northern blot in extracts of gastric corpus from patients with and without ECL cell tumors and in AR4-2J cells stimulated by gastrin; cellular origins were determined by immunocytochemistry. Mutations of Reg were determined by reverse-transcription polymerase chain reaction, cloning, and sequencing, and the mutated protein was expressed in HIT-T15 cells. RESULTS: Reg mRNA abundance was increased approximately threefold  in the corpus of hypergastrinemic patients compared with controls, and was enriched in 3 of 7 ECL cell carcinoid tumors but not in non-endocrine cell gastric polyps. In AR4-2J cells, gastrin stimulated Reg mRNA abundance; this was  eliminated by the gastrin/cholecystokinin B antagonist L-740,093 (10(-9) mol/L).  Immunocytochemistry indicated that Reg was located in both chief cells and ECL cells in human corpus. Mutations of Reg were identified in 3 of 5 patients with ECL cell carcinoid tumors; in 2 cases, mutation of the initiator methionine residue led to exclusion of the protein from the secretory pathway. CONCLUSIONS:  Gastrin regulates Reg mRNA abundance in human corpus. Mutations of Reg that prevent secretion are associated with ECL cell carcinoids, suggesting a function  as an autocrine or paracrine tumor suppressor.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AD",
      "lastName" : "Higham",
      "authorRank" : 1,
      "name" : "Higham",
      "referenceId" : "RGD:A200418"
    }, {
      "firstName" : "LA",
      "lastName" : "Bishop",
      "authorRank" : 2,
      "name" : "Bishop",
      "referenceId" : "RGD:A200419"
    }, {
      "firstName" : "R",
      "lastName" : "Dimaline",
      "authorRank" : 3,
      "name" : "Dimaline",
      "referenceId" : "RGD:A200420"
    }, {
      "firstName" : "CG",
      "lastName" : "Blackmore",
      "authorRank" : 4,
      "name" : "Blackmore",
      "referenceId" : "RGD:A200421"
    }, {
      "firstName" : "AC",
      "lastName" : "Dobbins",
      "authorRank" : 5,
      "name" : "Dobbins",
      "referenceId" : "RGD:A200422"
    }, {
      "firstName" : "A",
      "lastName" : "Varro",
      "authorRank" : 6,
      "name" : "Varro A",
      "referenceId" : "RGD:A115999"
    }, {
      "firstName" : "DG",
      "lastName" : "Thompson",
      "authorRank" : 7,
      "name" : "Thompson",
      "referenceId" : "RGD:A200423"
    }, {
      "firstName" : "GJ",
      "lastName" : "Dockray",
      "authorRank" : 8,
      "name" : "Dockray",
      "referenceId" : "RGD:A200424"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9850135"
    } ]
  }, {
    "primaryId" : "PMID:10348829",
    "title" : "New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Vasen HF, etal., Gastroenterology. 1999 Jun;116(6):1453-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:59:20.000-05:00",
    "volume" : "116",
    "pages" : "1453-6",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HF",
      "lastName" : "Vasen",
      "authorRank" : 1,
      "name" : "Vasen HF",
      "referenceId" : "RGD:A72640"
    }, {
      "firstName" : "P",
      "lastName" : "Watson",
      "authorRank" : 2,
      "name" : "Watson P",
      "referenceId" : "RGD:A97441"
    }, {
      "firstName" : "JP",
      "lastName" : "Mecklin",
      "authorRank" : 3,
      "name" : "Mecklin JP",
      "referenceId" : "RGD:A36419"
    }, {
      "firstName" : "HT",
      "lastName" : "Lynch",
      "authorRank" : 4,
      "name" : "Lynch HT",
      "referenceId" : "RGD:A93750"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068245"
    } ]
  }, {
    "primaryId" : "PMID:10348902",
    "title" : "Molecular cloning of Ca2+/calmodulin-dependent protein kinase phosphatase.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kitani T, etal., J Biochem (Tokyo) 1999 Jun;125(6):1022-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:41.000-05:00",
    "volume" : "125",
    "pages" : "1022-8",
    "abstract" : "Calmodulin-dependent protein kinase (CaM-kinase) phosphatase dephosphorylates and concomitantly deactivates CaM-kinase II activated upon autophosphorylation, and CaM-kinases IV and I activated upon phosphorylation by CaM-kinase kinase [Ishida, I., Okuno, S., Kitani, T., Kameshita, I., and Fujisawa, H. (1998) Biochem. Biophys. Res. Commun. 253, 159-163], suggesting that CaM-kinase phosphatase plays important roles in the function of Ca2+ in the cell, because the three multifunctional CaM-kinases (CaM-kinases I, II, and IV) are thought to be the key enzymes in the Ca2+-signaling system. In the present study, cDNA for CaM-kinase phosphatase was cloned from a rat brain cDNA library. The coded protein consisted of 450 amino acids with a molecular weight of 49, 165. Western blot analysis showed the ubiquitous tissue distribution of CaM-kinase phosphatase. Immunocytochemical analysis revealed that CaM-kinase phosphatase is evenly distributed outside the nucleus in a cell.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kitani",
      "authorRank" : 1,
      "name" : "Kitani T",
      "referenceId" : "RGD:A43615"
    }, {
      "firstName" : "A",
      "lastName" : "Ishida",
      "authorRank" : 2,
      "name" : "Ishida A",
      "referenceId" : "RGD:A17117"
    }, {
      "firstName" : "S",
      "lastName" : "Okuno",
      "authorRank" : 3,
      "name" : "Okuno S",
      "referenceId" : "RGD:A162349"
    }, {
      "firstName" : "M",
      "lastName" : "Takeuchi",
      "authorRank" : 4,
      "name" : "Takeuchi M",
      "referenceId" : "RGD:A4760"
    }, {
      "firstName" : "I",
      "lastName" : "Kameshita",
      "authorRank" : 5,
      "name" : "Kameshita I",
      "referenceId" : "RGD:A17119"
    }, {
      "firstName" : "H",
      "lastName" : "Fujisawa",
      "authorRank" : 6,
      "name" : "Fujisawa H",
      "referenceId" : "RGD:A155305"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632383"
    } ]
  }, {
    "primaryId" : "PMID:10348921",
    "title" : "Transmembrane topology of the peroxin, Pex2p, an essential component for the peroxisome assembly.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Harano T, etal., J Biochem (Tokyo). 1999 Jun;125(6):1168-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-06-07T13:00:23.000-05:00",
    "volume" : "125",
    "pages" : "1168-74",
    "abstract" : "The peroxisome biogenesis factor, peroxin Pex2p, is an integral membrane protein of peroxisomes [Tsukamoto, T., Miura, S., and Fujiki, Y. (1991) Nature 350, 77-81]. As a step toward elucidating the structure and biological function of Pex2p, we determined the transmembrane topology of Pex2p by expressing epitope-tagged rat Pex2p in COS-7 cells. Pex2p tagged with myc at the C-terminus was detected as a punctate staining pattern, when the cells were permeabilized with 50 microg/ml of digitonin, under which conditions intra-peroxisomal proteins such as PTS1-proteins are inaccessible to exogenous antibodies. N-terminally flag-tagged Pex2p was likewise detected upon the same treatment. These results strongly suggest that both the N- and C-terminal parts of Pex2p are exposed to the cytosol. The transmembrane orientation of Pex2p was also assessed by using rat liver peroxisomes and Pex2p region-specific antibodies. The two types of antibodies used, raised to the N- (amino acid residues 1-131) and C-terminal part (residues 226 to the C-terminus), respectively, specifically recognized Pex2p and immunoprecipitated intact, whole peroxisomes. Pex2p was not recognized by the antibodies when the peroxisomes were treated with Proteinase K. Furthermore, in situ crosslinking studies involving bifunctional reagents revealed an apparently dimeric form of Pex2p. Therefore, Pex2p is anchored to the peroxisomal membrane by two membrane-spanning segments, with its N- and C-terminal regions exposed to the cytosol.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Harano",
      "authorRank" : 1,
      "name" : "Harano T",
      "referenceId" : "RGD:A5032"
    }, {
      "firstName" : "N",
      "lastName" : "Shimizu",
      "authorRank" : 2,
      "name" : "Shimizu N",
      "referenceId" : "RGD:A5024"
    }, {
      "firstName" : "H",
      "lastName" : "Otera",
      "authorRank" : 3,
      "name" : "Otera H",
      "referenceId" : "RGD:A5027"
    }, {
      "firstName" : "Y",
      "lastName" : "Fujiki",
      "authorRank" : 4,
      "name" : "Fujiki Y",
      "referenceId" : "RGD:A161490"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1625412"
    } ]
  }, {
    "primaryId" : "PMID:10349196",
    "title" : "Chédiak-Higashi syndrome: presentation of seven cases.",
    "datePublished" : "1998-12-01T00:00:00.000-06:00",
    "citation" : "Carnide EM, etal., Sao Paulo Med J. 1998 Nov-Dec;116(6):1873-8. doi: 10.1590/s1516-31801998000600008.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:09:35.000-05:00",
    "volume" : "116",
    "pages" : "1873-8",
    "abstract" : "<br><b>CONTEXT: </b>Chédiak-Higashi Syndrome (CHS) is a rare autosomal recessive disease characterized by recurrent infections, giant cytoplasmic granules, and oculocutaneous albinism.<br><b>OBJECTIVE: </b>To describe clinical and laboratory findings from CHS patients.<br><b>DESIGN: </b>Case report.<br><b>SETTING: </b>The patients were admitted into the Allergy and Immunology Unit of the Instituto da Criança, a tertiary public care institution.<br><b>CASES REPORT: </b>Seven patients had oculocutaneous albinism, recurrent infections and giant cytoplasmic granules in the leukocytes. One patient had low IgG levels and three showed impaired bactericidal activity of neutrophils. Six patients died of infectious complications during the accelerated phase. Therapy included ascorbic acid and antibiotics. Chemotherapy was used for the accelerated phase in two patients. Bone marrow transplantation (BMT) was proposed for one patient.<br><b>DISCUSSION: </b>The authors emphasize the need for early diagnosis and therapy of CHS. BMT should be indicated before the accelerated phase of the disease has developed.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E M",
      "lastName" : "Carnide",
      "authorRank" : 1,
      "name" : "Carnide EM",
      "referenceId" : "RGD:A575695"
    }, {
      "firstName" : "C M",
      "lastName" : "Jacob",
      "authorRank" : 2,
      "name" : "Jacob CM",
      "referenceId" : "RGD:A575696"
    }, {
      "firstName" : "A C",
      "lastName" : "Pastorino",
      "authorRank" : 3,
      "name" : "Pastorino AC",
      "referenceId" : "RGD:A575697"
    }, {
      "firstName" : "R",
      "lastName" : "Bellinati-Pires",
      "authorRank" : 4,
      "name" : "Bellinati-Pires R",
      "referenceId" : "RGD:A575698"
    }, {
      "firstName" : "M B",
      "lastName" : "Costa",
      "authorRank" : 5,
      "name" : "Costa MB",
      "referenceId" : "RGD:A575699"
    }, {
      "firstName" : "A S",
      "lastName" : "Grumach",
      "authorRank" : 6,
      "name" : "Grumach AS",
      "referenceId" : "RGD:A575700"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598115821"
    } ]
  }, {
    "primaryId" : "PMID:10349467",
    "title" : "Self-injurious behavior and Prader-Willi syndrome: behavioral forms and body locations.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Symons FJ, etal., Am J Ment Retard. 1999 May;104(3):260-9. doi: 10.1352/0895-8017(1999)104<0260:SBAPSB>2.0.CO;2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:05:43.000-05:00",
    "volume" : "104",
    "pages" : "260-9",
    "abstract" : "With few exceptions (e.g., Lesch-Nyhan syndrome), the specific nature of self-injury in relation to identified genetic syndromes associated with mental retardation is poorly understood. In the present study we surveyed the families of 62 persons with Prader-Willi syndrome to determine the prevalence, topographies, and specific body locations of self-injurious behavior. Self-injury was reported for 81% of the participants. Skin-picking was the most prevalent form, with the front of the legs and head being disproportionately targeted as preferred self-injury body sites. Individuals with the 15q11-q13 deletion injured significantly more body sites than did individuals with maternal disomy 15. Results are discussed in relation to previous self-injury body site findings and implications for the relevance of syndrome-specific behavioral phenotypes.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F J",
      "lastName" : "Symons",
      "authorRank" : 1,
      "name" : "Symons FJ",
      "referenceId" : "RGD:A599074"
    }, {
      "firstName" : "M G",
      "lastName" : "Butler",
      "authorRank" : 2,
      "name" : "Butler MG",
      "referenceId" : "RGD:A441967"
    }, {
      "firstName" : "M D",
      "lastName" : "Sanders",
      "authorRank" : 3,
      "name" : "Sanders MD",
      "referenceId" : "RGD:A599075"
    }, {
      "firstName" : "I D",
      "lastName" : "Feurer",
      "authorRank" : 4,
      "name" : "Feurer ID",
      "referenceId" : "RGD:A599076"
    }, {
      "firstName" : "T",
      "lastName" : "Thompson",
      "authorRank" : 5,
      "name" : "Thompson T",
      "referenceId" : "RGD:A599077"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119264"
    } ]
  }, {
    "primaryId" : "PMID:10349618",
    "title" : "The role of the brachyury gene in heart development and left-right specification in the mouse.",
    "datePublished" : "1998-09-01T00:00:00.000-05:00",
    "citation" : "King T, etal., Mech Dev 1998 Dec;79(1-2):29-37.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-06T11:16:04.000-05:00",
    "volume" : "79",
    "pages" : "29-37",
    "abstract" : "The midline has a theoretical role in the development of left-right asymmetry, and this is supported by both genetic analyses and experimental manipulation of midline structures in vertebrates. The mouse brachyury (T) gene encodes a transcription factor which is expressed in the developing notochord and is required for its development. T/T mice lack a mature notochord and have a dorsalised neural tube. We have examined the hearts of T/T mice and have found consistent morphological abnormalities, resulting in ventrally displaced ventricular loops, and a 50% incidence of inverted heart situs. Three TGF-beta related genes, lefty-1, lefty-2 and nodal, are expressed asymmetrically in mouse embryos, and are implicated in the development of situs. We find that nodal, which is normally expressed around the node and in left lateral plate mesoderm in early somite embryos, is completely absent at this stage in T/T embryos. In contrast, lefty-1 and lefty-2, which are normally expressed in the left half of prospective floorplate and left lateral plate mesoderm, respectively, are both expressed in T/T embryos only in a broad patch of ventral cells in, and just rostral to, the node region. These results implicate the node as a source of instructive signals driving expression of nodal and lefty-2 in the left lateral plate mesoderm, and being required for normal looping and situs of the heart.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "King",
      "authorRank" : 1,
      "name" : "King T",
      "referenceId" : "RGD:A55735"
    }, {
      "firstName" : "RS",
      "lastName" : "Beddington",
      "authorRank" : 2,
      "name" : "Beddington RS",
      "referenceId" : "RGD:A37185"
    }, {
      "firstName" : "NA",
      "lastName" : "Brown",
      "authorRank" : 3,
      "name" : "Brown NA",
      "referenceId" : "RGD:A39593"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549647"
    } ]
  }, {
    "primaryId" : "PMID:10349636",
    "title" : "High-efficiency full-length cDNA cloning.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Carninci P and Hayashizaki Y, Methods Enzymol 1999;303:19-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-25T11:24:37.000-06:00",
    "volume" : "303",
    "pages" : "19-44",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Carninci",
      "authorRank" : 1,
      "name" : "Carninci P",
      "referenceId" : "RGD:A299650"
    }, {
      "firstName" : "Y",
      "lastName" : "Hayashizaki",
      "authorRank" : 2,
      "name" : "Hayashizaki Y",
      "referenceId" : "RGD:A299782"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:729356"
    } ]
  }, {
    "primaryId" : "PMID:10349840",
    "title" : "Prostate apoptosis response-4 production in synaptic compartments following apoptotic and excitotoxic insults: evidence for a pivotal role in mitochondrial dysfunction and neuronal degeneration.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Duan W, etal., J Neurochem. 1999 Jun;72(6):2312-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-03-19T14:50:49.000-05:00",
    "volume" : "72",
    "pages" : "2312-22",
    "abstract" : "Synapses are often located at great distances from the cell body and so must be capable of transducing signals into both local and distant responses. Although progress has been made in understanding biochemical cascades involved in neuronal death during development of the nervous system and in various neurodegenerative disorders, it is not known whether such cascades function locally in synaptic compartments. Prostate apoptosis response-4 (Par-4) is a leucine zipper and death domain-containing protein that plays a role in neuronal apoptosis. We now report  that Par-4 levels are rapidly increased in cortical synaptosomes and in dendrites of hippocampal neurons in culture and in vivo, following exposure to apoptotic or excitotoxic insults. Par-4 expression is regulated at the translational level within synaptic compartments. Par-4 antisense treatment suppressed mitochondrial  dysfunction and caspase activation in synaptosomes and prevented death of cultured hippocampal neurons following exposure to excitotoxic and apoptotic insults. Local translational regulation of death-related proteins in synaptic compartments may play a role in programmed cell death, adaptive remodeling of synapses, and neurodegenerative disorders.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Duan",
      "authorRank" : 1,
      "name" : "Duan W",
      "referenceId" : "RGD:A34546"
    }, {
      "firstName" : "VM",
      "lastName" : "Rangnekar",
      "authorRank" : 2,
      "name" : "Rangnekar VM",
      "referenceId" : "RGD:A6280"
    }, {
      "firstName" : "MP",
      "lastName" : "Mattson",
      "authorRank" : 3,
      "name" : "Mattson MP",
      "referenceId" : "RGD:A8873"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9835366"
    } ]
  }, {
    "primaryId" : "PMID:10350070",
    "title" : "A novel 45 kDa secretory protein from rat olfactory epithelium: primary structure and localisation.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Merkulova MI, etal., FEBS Lett 1999 Apr 30;450(1-2):126-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:26.000-05:00",
    "volume" : "450",
    "pages" : "126-30",
    "abstract" : "cDNA clones encoding the 45 kDa protein were isolated from a rat olfactory epithelium cDNA library and their inserts were sequenced. The reconstructed protein sequence comprises 400 amino acids with a calculated molecular mass of 46,026 Da. A homology was revealed between the amino acid sequence of the 45 kDa protein and the proteins involved in the transfer of hydrophobic ligands. Using in situ hybridisation, the 45 kDa protein mRNA expression was detected in the layer of supportive cells of olfactory epithelium, apical region of trachea, surface layer of the ciliated bronchial epithelium in lung and in skin epidermis.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MI",
      "lastName" : "Merkulova",
      "authorRank" : 1,
      "name" : "Merkulova MI",
      "referenceId" : "RGD:A9460"
    }, {
      "firstName" : "SG",
      "lastName" : "Andreeva",
      "authorRank" : 2,
      "name" : "Andreeva SG",
      "referenceId" : "RGD:A9459"
    }, {
      "firstName" : "TM",
      "lastName" : "Shuvaeva",
      "authorRank" : 3,
      "name" : "Shuvaeva TM",
      "referenceId" : "RGD:A9461"
    }, {
      "firstName" : "SV",
      "lastName" : "Novoselov",
      "authorRank" : 4,
      "name" : "Novoselov SV",
      "referenceId" : "RGD:A8984"
    }, {
      "firstName" : "IV",
      "lastName" : "Peshenko",
      "authorRank" : 5,
      "name" : "Peshenko IV",
      "referenceId" : "RGD:A9463"
    }, {
      "firstName" : "MF",
      "lastName" : "Bystrova",
      "authorRank" : 6,
      "name" : "Bystrova MF",
      "referenceId" : "RGD:A16764"
    }, {
      "firstName" : "VI",
      "lastName" : "Novoselov",
      "authorRank" : 7,
      "name" : "Novoselov VI",
      "referenceId" : "RGD:A9462"
    }, {
      "firstName" : "EE",
      "lastName" : "Fesenko",
      "authorRank" : 8,
      "name" : "Fesenko EE",
      "referenceId" : "RGD:A9464"
    }, {
      "firstName" : "VM",
      "lastName" : "Lipkin",
      "authorRank" : 9,
      "name" : "Lipkin VM",
      "referenceId" : "RGD:A9465"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632225"
    } ]
  }, {
    "primaryId" : "PMID:10350213",
    "title" : "Rac-GTPase, osteoclast cytoskeleton and bone resorption.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Razzouk S, etal., Eur J Cell Biol. 1999 Apr;78(4):249-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-01T13:50:49.000-06:00",
    "volume" : "78",
    "pages" : "249-55",
    "abstract" : "The members of the Rho-GTPase subfamily, Rac1 and Rac2, are intimately involved in the organization of the cytoskeleton, and the p21-activated kinases or PAKs are targets of these proteins. Rac1 and Rac2 are also essential components of NADPH oxidase, the enzyme responsible for generating free radicals. The cytoskeleton modulates the adhesion of osteoclasts to bone and its subsequent resorption. These cells contain NADPH diaphorase activity, and free radicals influence bone resorption. The influence of Rac1, Rac2 and PAK1 on the cytoskeleton, resorbing activity and NADPH diaphorase activity of disaggregated rat osteoclasts was investigated by permeabilisation with saponin and introducing specific anti-Rac1, anti-Rac2 or anti-PAK1 antibodies. Rhodamine-phalloidin stain was used to identify actin in osteoclasts cultured on plastic slides, and the bone-slice method was used to measure resorption. Saponin permeabilisation did not affect the cytoskeletal organization or bone resorption. Anti-Rac antibodies caused dose- and time-dependent cytoskeletal changes. The osteoclasts rounded up and developed retraction fibers; actin rings were disrupted and large actin dots were seen at the periphery of the cells. Osteoclast resorptive activity was depressed after incubation with the antibodies. The total area resorbed by treated cells and the mean pit area were smaller than those of controls. Anti-PAK1 antibody caused similar changes. None of the antibodies altered the NADPH diaphorase activity. Thus, Rac-GTPases are present in rat osteoclasts and are involved in the organization of the actin cytoskeleton and in resorptive activity. These effects may be mediated by PAK1 kinase, but do not influence osteoclast NADPH diaphorase activity.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Razzouk",
      "authorRank" : 1,
      "name" : "Razzouk S",
      "referenceId" : "RGD:A65545"
    }, {
      "firstName" : "M",
      "lastName" : "Lieberherr",
      "authorRank" : 2,
      "name" : "Lieberherr M",
      "referenceId" : "RGD:A73679"
    }, {
      "firstName" : "G",
      "lastName" : "Cournot",
      "authorRank" : 3,
      "name" : "Cournot G",
      "referenceId" : "RGD:A73680"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599401"
    } ]
  }, {
    "primaryId" : "PMID:10350214",
    "title" : "Serum albumin as a potential carrier for the apocrine secretion of proteins in the rat coagulating gland.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Wilhelm B, etal., Eur J Cell Biol. 1999 Apr;78(4):256-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-23T15:04:54.000-05:00",
    "volume" : "78",
    "pages" : "256-64",
    "abstract" : "A protein of 66k was purified to homogeneity from the total secretion of rat coagulating gland. Its close structural relationship to serum albumin was demonstrated by N-terminal amino acid sequence analysis, proteolytic fingerprinting and Western blotting studies using polyclonal antibodies raised against the 66k protein and rat serum albumin. Immunofluorescence staining showed that the 66k protein was localised in the cytoplasm of coagulating gland epithelial cells from which it is released via apocrine blebs. Performing immunoelectron microscopy, the 66k protein was by no means detectable in the endoplasmic reticulum and the Golgi apparatus. Reverse transcription-PCR, Northern blotting studies and in situ hybridisation experiments demonstrated that mRNA of albumin is not expressed by coagulating gland epithelial cells. Therefore, intravascular albumin should be transferred into the epithelial cells of the rat coagulating gland followed by secretion via aposomes. Furthermore, overlay blots proved that the 66k protein binds to the apocrine proteins carbonic anhydrase II and secretory transglutaminase and vice versa. In contrast, no binding was evident to the merocrine 115k protein and to cytoplasmic resident proteins e.g. lactate dehydrogenase. These findings point to the assumption that serum albumin taken up from extracellular sources could function as a selective carrier for cytoplasmic proteins destined for apocrine secretion.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Wilhelm",
      "authorRank" : 1,
      "name" : "Wilhelm B",
      "referenceId" : "RGD:A49809"
    }, {
      "firstName" : "A",
      "lastName" : "Meinhardt",
      "authorRank" : 2,
      "name" : "Meinhardt A",
      "referenceId" : "RGD:A32007"
    }, {
      "firstName" : "H",
      "lastName" : "Renneberg",
      "authorRank" : 3,
      "name" : "Renneberg H",
      "referenceId" : "RGD:A27314"
    }, {
      "firstName" : "D",
      "lastName" : "Linder",
      "authorRank" : 4,
      "name" : "Linder D",
      "referenceId" : "RGD:A49813"
    }, {
      "firstName" : "HJ",
      "lastName" : "Gabius",
      "authorRank" : 5,
      "name" : "Gabius HJ",
      "referenceId" : "RGD:A35649"
    }, {
      "firstName" : "G",
      "lastName" : "Aumuller",
      "authorRank" : 6,
      "name" : "Aumuller G",
      "referenceId" : "RGD:A25988"
    }, {
      "firstName" : "J",
      "lastName" : "Seitz",
      "authorRank" : 7,
      "name" : "Seitz J",
      "referenceId" : "RGD:A49814"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600714"
    } ]
  }, {
    "primaryId" : "PMID:10350562",
    "title" : "Fibroblast growth factor-8 protects cultured rat hippocampal neurons from oxidative insult.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Mark RJ, etal., Brain Res 1999 May 29;830(1):88-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-22T17:17:29.000-05:00",
    "volume" : "830",
    "pages" : "88-93",
    "abstract" : "Basic fibroblast growth factor (bFGF) has been reported to have neuroprotective properties following excitotoxic, metabolic, and oxidative insults. We report here that another FGF family member, FGF-8 is able to protect rat hippocampal cultures from oxidative stress. The b isoform of FGF-8 protected hippocampal cultures from hydrogen peroxide with an EC50 of approximately 25 ng/ml. In a time course study, using pre-, co-, post-treatment paradigms, we report that bFGF and FGF-8b were neuroprotective when added as a pre-treatment, co-treatment, and even at 2 h post-insult. Using neuronal enriched cultures, we demonstrate that bFGF and FGF-8b neuroprotection partially results from a direct action of the growth factors on neurons. The direct action on neurons may work in concert with normal and FGF-stimulated glial secretion products to give the full FGF protective effect. FGF-8b showed maximal protection at 50 ng/ml, whereas bFGF showed maximal protection at 10 ng/ml. Despite requiring higher concentrations to elicit protection, FGF-8b is able to attain levels of protection equivalent to that of bFGF (attenuation of 75-80% of hydrogen peroxide induced death). We also report that bFGF and FGF-8b are able to protect the human neuroblastoma cell line, SK-N-MC, from peroxide-induced LDH release by 50%. From these studies, we conclude that FGF-8b is another member of the FGF family which may show in vivo efficacy for the treatment of oxidative insults, such as stroke.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RJ",
      "lastName" : "Mark",
      "authorRank" : 1,
      "name" : "Mark RJ",
      "referenceId" : "RGD:A25852"
    }, {
      "firstName" : "KS",
      "lastName" : "Fuson",
      "authorRank" : 2,
      "name" : "Fuson KS",
      "referenceId" : "RGD:A25853"
    }, {
      "firstName" : "K",
      "lastName" : "Keane-Lazar",
      "authorRank" : 3,
      "name" : "Keane-Lazar K",
      "referenceId" : "RGD:A25854"
    }, {
      "firstName" : "PC",
      "lastName" : "May",
      "authorRank" : 4,
      "name" : "May PC",
      "referenceId" : "RGD:A25855"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:708333"
    } ]
  }, {
    "primaryId" : "PMID:10350607",
    "title" : "Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Fujimoto K, etal., Biochim Biophys Acta. 1999 May 18;1431(2):306-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:46:39.000-05:00",
    "volume" : "1431",
    "pages" : "306-14",
    "abstract" : "The active site of sepiapterin reductase (SPR), which is a member of the NADP(H)-preferring short-chain dehydrogenase/reductase (SDR) family and acts as the terminal enzyme in the biosynthetic pathway of tetrahydrobiopterin cofactor (BH4), was investigated by truncation and site-directed mutagenesis. The truncation mutants showed that N-terminal and C-terminal residues contribute to bind coenzyme and substrate, respectively. The mutant rSPRA29V showed decreased activity; however, the A-X-L-L-S sequence, which has been reported as a putative  pterin binding site, was estimated to preferably work as a component in the region for binding coenzyme rather than substrate. Site-directed mutants of rSPRS158D, rSPRY171V, and rSPRK175I showed low, but significant, activity having  similar Km values and kcat/Km values less than 25%, for both sepiapterin and NADPH. Both amino acids Tyr-171 and Ser-158 are located within a similar distance to the carbonyl group of the substrate in the crystal structure of mouse SPR, and the double point mutant rSPRY171V+S158D was indicated to be inactive. These results showed that Ser-158, Tyr-171, and Lys-175 contributed to the catalytic activity of SPR, and both Tyr-171 and Ser-158 are simultaneously necessary on proton transfer to the carbonyl functional groups of substrate.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Fujimoto",
      "authorRank" : 1,
      "name" : "Fujimoto K",
      "referenceId" : "RGD:A5368"
    }, {
      "firstName" : "H",
      "lastName" : "Ichinose",
      "authorRank" : 2,
      "name" : "Ichinose H",
      "referenceId" : "RGD:A11697"
    }, {
      "firstName" : "T",
      "lastName" : "Nagatsu",
      "authorRank" : 3,
      "name" : "Nagatsu T",
      "referenceId" : "RGD:A11696"
    }, {
      "firstName" : "T",
      "lastName" : "Nonaka",
      "authorRank" : 4,
      "name" : "Nonaka",
      "referenceId" : "RGD:A187403"
    }, {
      "firstName" : "Y",
      "lastName" : "Mitsui",
      "authorRank" : 5,
      "name" : "Mitsui Y",
      "referenceId" : "RGD:A29517"
    }, {
      "firstName" : "S",
      "lastName" : "Katoh",
      "authorRank" : 6,
      "name" : "Katoh S",
      "referenceId" : "RGD:A30702"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554741"
    } ]
  }, {
    "primaryId" : "PMID:10350608",
    "title" : "Membrane topography of the renal phosphate carrier NaPi-2: limited proteolysis studies.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Paquin J, etal., Biochim Biophys Acta. 1999 May 18;1431(2):315-28.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-10T16:22:03.000-05:00",
    "volume" : "1431",
    "pages" : "315-28",
    "abstract" : "The rat sodium/phosphate cotransporter NaPi-2 is a 70 kDa polypeptide (p70) for which eight transmembrane segments have been predicted. We have shown that p70 exists predominantly as p45 and p40 fragments which are linked by disulfide bonds. In this work, the p40 fragment, corresponding to the C-terminus of NaPi-2, was purified from renal brush-border membranes using non-reducing and then reducing column electrophoresis followed by enzymatic deglycosylation and SDS-PAGE. The N-terminal sequence obtained for this fragment, VEAIG, indicates that the formation of p45 and p40 arises from the cleavage of p70 between arginine-319 and valine-320. In order to determine the membrane topography of NaPi-2, brush-border membrane vesicles were digested with various proteases and the transporter-derived proteolytic peptides were subsequently identified by Western blotting using N- and C-terminal-directed antibodies. Our results lead us to propose an alternative topographical model in which p45 and p40 possess three  transmembrane domains each and indicate that the processing site of p70 for the generation of p45 and p40 is localized in a large protein core facing the extracellular milieu. This localization of the cleavage site indicated that NaPi-2 could either be processed intracellularly by vesicular proteases or extracellularly by secretory proteases or by brush-border membrane ectoenzymes.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Paquin",
      "authorRank" : 1,
      "name" : "Paquin J",
      "referenceId" : "RGD:A104442"
    }, {
      "firstName" : "E",
      "lastName" : "Vincent",
      "authorRank" : 2,
      "name" : "Vincent",
      "referenceId" : "RGD:A169615"
    }, {
      "firstName" : "A",
      "lastName" : "Dugre",
      "authorRank" : 3,
      "name" : "Dugre",
      "referenceId" : "RGD:A169616"
    }, {
      "firstName" : "Y",
      "lastName" : "Xiao",
      "authorRank" : 4,
      "name" : "Xiao Y",
      "referenceId" : "RGD:A11215"
    }, {
      "firstName" : "CJ",
      "lastName" : "Boyer",
      "authorRank" : 5,
      "name" : "Boyer",
      "referenceId" : "RGD:A169614"
    }, {
      "firstName" : "R",
      "lastName" : "Beliveau",
      "authorRank" : 6,
      "name" : "Beliveau R",
      "referenceId" : "RGD:A69499"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7243176"
    } ]
  }, {
    "primaryId" : "PMID:10350619",
    "title" : "Characterisation of several Hsp70 interacting proteins from mammalian organelles.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Naylor DJ, etal., Biochim Biophys Acta 1999 May 18;1431(2):443-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:11:49.000-05:00",
    "volume" : "1431",
    "pages" : "443-50",
    "abstract" : "Since both the spectrum and characteristics of in vivo substrates with affinity for Hsp70 members are largely unknown, we have investigated the range and type of mammalian organellar proteins which selectively interact with immobilised Escherichia coli Hsp70 (DnaK). Amongst a subset of organellar proteins selectively retained on DnaK, the major constituents represent unstable proteins and subunits of oligomeric proteins. The interactions with DnaK were diminished in the presence of mt-Hsp70 and BiP, while the complexes formed with DnaK were dissociated in the presence of K+ and GrpE-like co-chaperones, suggesting that these organellar proteins constitute general Hsp70 substrates. Protein sequence analysis identified the major DnaK interacting constituents as the mitochondrial transcription factor A, the alpha- (but not the beta-) subunit of succinyl CoA synthetase, mitochondrial 2,4-dienoyl CoA reductase, endoplasmic reticulum cyclophilin-B, peroxisomal multifunctional enzyme and a previously undescribed peroxisomal protein suspected to represent an isoform of 2,4-dienoyl CoA reductase. The selective retention of these fully synthesised proteins on Hsp70 most likely reflects the function of this molecular chaperone in protein biogenesis, but additionally, could extend the known functions of Hsp70 to include modulating the activities of certain proteins or enzymes which are important in cellular homeostasis.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Naylor",
      "authorRank" : 1,
      "name" : "Naylor DJ",
      "referenceId" : "RGD:A9638"
    }, {
      "firstName" : "NJ",
      "lastName" : "Hoogenraad",
      "authorRank" : 2,
      "name" : "Hoogenraad NJ",
      "referenceId" : "RGD:A9639"
    }, {
      "firstName" : "PB",
      "lastName" : "Hoj",
      "authorRank" : 3,
      "name" : "Hoj PB",
      "referenceId" : "RGD:A9640"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70655"
    } ]
  }, {
    "primaryId" : "PMID:10350628",
    "title" : "Cloning and preliminary characterization of a 121 kDa protein with multiple predicted C2 domains.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Morris NJ, etal., Biochim Biophys Acta 1999 May 18;1431(2):525-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:05.000-06:00",
    "volume" : "1431",
    "pages" : "525-30",
    "abstract" : "In the course of characterizing proteins present in a preparation of vesicles from rat adipocytes containing glucose transporters, we examined a protein that migrated at 115 kDa upon SDS gel electrophoresis (designated vp115). Sequences of tryptic peptides were obtained, and from this information the cDNA for rat vp115 was cloned. The cDNA encodes an open reading frame for a protein of 121 kDa. Computer-aided sequence analysis predicted that vp115 has a potential membrane-inserted or membrane-spanning domain toward its amino terminus, followed by five C2 domains. Immunoblotting revealed that vp115 was not actually a component of the glucose transporter-containing vesicles, was most abundant in the plasma membranes and high density microsome fractions of rat adipocytes, and was expressed in all the major rat tissues.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NJ",
      "lastName" : "Morris",
      "authorRank" : 1,
      "name" : "Morris NJ",
      "referenceId" : "RGD:A34385"
    }, {
      "firstName" : "SA",
      "lastName" : "Ross",
      "authorRank" : 2,
      "name" : "Ross SA",
      "referenceId" : "RGD:A124064"
    }, {
      "firstName" : "JM",
      "lastName" : "Neveu",
      "authorRank" : 3,
      "name" : "Neveu JM",
      "referenceId" : "RGD:A7530"
    }, {
      "firstName" : "WS",
      "lastName" : "Lane",
      "authorRank" : 4,
      "name" : "Lane WS",
      "referenceId" : "RGD:A104579"
    }, {
      "firstName" : "GE",
      "lastName" : "Lienhard",
      "authorRank" : 5,
      "name" : "Lienhard GE",
      "referenceId" : "RGD:A105126"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69883"
    } ]
  }, {
    "primaryId" : "PMID:10350638",
    "title" : "Genomic organization and regulatory elements of the rat latexin gene, which is expressed in a cell type-specific manner in both central and peripheral nervous systems.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Miyasaka N, etal., Brain Res Mol Brain Res 1999 May 21;69(1):62-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:16.000-05:00",
    "volume" : "69",
    "pages" : "62-72",
    "abstract" : "Latexin, a carboxypeptidase A inhibitor, is expressed in a cell type-specific manner in both central and peripheral nervous systems in the rat. In the neocortex, a specific subpopulation of neurons in layers V and VI expresses latexin. In the primary sensory ganglia, the expression is restricted to smaller diameter neurons. As a first step to clarify regulatory mechanisms underlying cell type-specific expression of latexin, we have determined the organization of the rat latexin gene and analyzed its regulatory elements. The latexin gene spans approximately 5.8 kb, and consists of six exons and five introns. Three transcription initiation sites were mapped. The upstream region lacks typical TATA or CAAT boxes but has several GC-rich sites. To assess promoter activity, the luciferase reporter gene fused to the 5'-flanking region (6.4 kb) of the latexin gene was transiently transfected into several cell lines. Luciferase activity was 2-8 times higher in latexin-expressing cells (PC12) than non-expressing cells (NS20 and L6). Deletion analysis with PC12 cells revealed that a core promoter is located between nucleotide positions -261 and -201 relative to the A of the initiation codon. Nerve growth factor (NGF)-responsive element(s) is located between positions -518 and -262, in which AP-1, AP-2 and NF-kappaB binding sites are found. Furthermore, we demonstrate that a 1.3 kb genomic fragment containing the first intron has transcriptional enhancing activity in PC12 cells. These results suggest that up and downstream regulatory elements are involved in the control of cell type-specific expression of latexin.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Miyasaka",
      "authorRank" : 1,
      "name" : "Miyasaka N",
      "referenceId" : "RGD:A20176"
    }, {
      "firstName" : "Y",
      "lastName" : "Hatanaka",
      "authorRank" : 2,
      "name" : "Hatanaka Y",
      "referenceId" : "RGD:A4978"
    }, {
      "firstName" : "M",
      "lastName" : "Jin",
      "authorRank" : 3,
      "name" : "Jin M",
      "referenceId" : "RGD:A20359"
    }, {
      "firstName" : "Y",
      "lastName" : "Arimatsu",
      "authorRank" : 4,
      "name" : "Arimatsu Y",
      "referenceId" : "RGD:A4984"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633266"
    } ]
  }, {
    "primaryId" : "PMID:10350639",
    "title" : "Molecular cloning and characterization of two putative G protein-coupled receptors which are highly expressed in the central nervous system.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Leng N, etal., Brain Res Mol Brain Res 1999 May 21;69(1):73-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:06:26.000-05:00",
    "volume" : "69",
    "pages" : "73-83",
    "abstract" : "We have cloned from a rat hypothalamic cDNA library two closely related G protein-coupled receptors (GPCRs) which we have designated GPCR/CNS1 and GPCR/CNS2. The peptide sequences of these two G protein-coupled receptors shared 42% identity with each other and were next most closely related to the endothelin receptors and the bombesin-like peptide receptors (approximately 25% identity). Northern blot analysis showed that both GPCR/CNS1 and GPCR/CNS2 were very highly expressed in rat brain. In situ hybridization of rat brain demonstrated broad distribution of both receptors throughout the central nervous system. GPCR/CNS1 appeared to be expressed primarily in glial cells of the fiber tracts, while GPCR/CNS2 was expressed primarily in cells of the gray matter. The different distribution patterns of these two receptors in rat brain suggests distinct functional roles for each receptor in the central nervous system. Expression of these two receptors in Xenopus oocytes showed no response to any known endothelin and bombesin-like peptides. Therefore, the endogenous ligands and physiological significance of GPCR/CNS1 and GPCR/CNS2 remain to be elucidated, but may be related to the endothelins or bombesins. The very abundant expression in brain by these two receptors, however, suggests that they play important roles in the central nervous system.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Leng",
      "authorRank" : 1,
      "name" : "Leng N",
      "referenceId" : "RGD:A19061"
    }, {
      "firstName" : "G",
      "lastName" : "Gu",
      "authorRank" : 2,
      "name" : "Gu G",
      "referenceId" : "RGD:A19062"
    }, {
      "firstName" : "RB",
      "lastName" : "Simerly",
      "authorRank" : 3,
      "name" : "Simerly RB",
      "referenceId" : "RGD:A7538"
    }, {
      "firstName" : "ER",
      "lastName" : "Spindel",
      "authorRank" : 4,
      "name" : "Spindel ER",
      "referenceId" : "RGD:A19063"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632894"
    } ]
  }, {
    "primaryId" : "PMID:10350641",
    "title" : "Identification of a novel gene, OASIS, which encodes for a putative CREB/ATF family transcription factor in the long-term cultured astrocytes and gliotic tissue.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Honma Y, etal., Brain Res Mol Brain Res 1999 May 21;69(1):93-103.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-07T12:39:12.000-06:00",
    "volume" : "69",
    "pages" : "93-103",
    "abstract" : "Gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system (CNS). To study the mechanisms underlying gliosis, we performed differential display screening for genes specifically induced in long-term cultured astrocytes used as an in vitro gliosis model. We identified and characterized a gene (named OASIS, for old astrocyte specifically-induced substance) expressed in long-term cultured mouse astrocytes, or 'old astrocytes (OA)'. The OASIS gene encoded a putative transcription factor belonging to the cyclic AMP responsive element binding protein/activating transcription factor (CREB/ATF) gene family, with homology to box B-binding factor-2 (BBF-2), a Drosophila transcription factor. Its expression was developmentally regulated; OASIS mRNA was primarily expressed in the salivary gland and cartilage in the mouse embryo and it was transiently upregulated in the brain during postnatal two weeks. The expression became weaker in the adult brain. We also demonstrated that an expression of the OASIS mRNA was induced in response to the cryo-injury of the mouse cerebral cortex. The distribution pattern of the OASIS-positive cells in the injured cortex was very similar to that of the glial fibrillary acidic protein (GFAP)-positive cells. These results suggest that OASIS protein may play a role in gliotic events.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Honma",
      "authorRank" : 1,
      "name" : "Honma Y",
      "referenceId" : "RGD:A56801"
    }, {
      "firstName" : "K",
      "lastName" : "Kanazawa",
      "authorRank" : 2,
      "name" : "Kanazawa K",
      "referenceId" : "RGD:A56802"
    }, {
      "firstName" : "T",
      "lastName" : "Mori",
      "authorRank" : 3,
      "name" : "Mori T",
      "referenceId" : "RGD:A151972"
    }, {
      "firstName" : "Y",
      "lastName" : "Tanno",
      "authorRank" : 4,
      "name" : "Tanno Y",
      "referenceId" : "RGD:A56804"
    }, {
      "firstName" : "M",
      "lastName" : "Tojo",
      "authorRank" : 5,
      "name" : "Tojo M",
      "referenceId" : "RGD:A56805"
    }, {
      "firstName" : "H",
      "lastName" : "Kiyosawa",
      "authorRank" : 6,
      "name" : "Kiyosawa H",
      "referenceId" : "RGD:A162383"
    }, {
      "firstName" : "J",
      "lastName" : "Takeda",
      "authorRank" : 7,
      "name" : "Takeda J",
      "referenceId" : "RGD:A13883"
    }, {
      "firstName" : "T",
      "lastName" : "Nikaido",
      "authorRank" : 8,
      "name" : "Nikaido T",
      "referenceId" : "RGD:A35970"
    }, {
      "firstName" : "T",
      "lastName" : "Tsukamoto",
      "authorRank" : 9,
      "name" : "Tsukamoto T",
      "referenceId" : "RGD:A161483"
    }, {
      "firstName" : "S",
      "lastName" : "Yokoya",
      "authorRank" : 10,
      "name" : "Yokoya S",
      "referenceId" : "RGD:A56807"
    }, {
      "firstName" : "A",
      "lastName" : "Wanaka",
      "authorRank" : 11,
      "name" : "Wanaka A",
      "referenceId" : "RGD:A8705"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556605"
    } ]
  }, {
    "primaryId" : "PMID:10350643",
    "title" : "Expression of preprogalanin mRNA following acute and chronic restraint stress in brains of normotensive and hypertensive rats.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Sweerts BW, etal., Brain Res Mol Brain Res. 1999 May 21;69(1):113-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-05-09T13:10:12.000-05:00",
    "volume" : "69",
    "pages" : "113-23",
    "abstract" : "Exposure to stress is known to induce widespread changes in the central nervous system (CNS) involving multiple neuropeptides. The neuropeptide galanin has been implicated in the central response to different stressors; however, the role of galanin in the response to restraint stress has not been reported. Therefore, this study utilised in situ hybridisation histochemistry to observe the effects of acute and chronic restraint stress on preprogalanin (preproGAL) mRNA expression in the CNS of normotensive (Wistar Kyoto; WKY) and Spontaneously Hypertensive (SHR) rats. Rats were exposed to 1 h of restraint for 0 (control), 1, 3, 5, or 10 consecutive days, and central preproGAL mRNA expression following these restraint periods was compared between strains. Significant differences in the basal expression of preproGAL mRNA were detected, with expression decreased by approximately 50% in the supraoptic nucleus (SON; P<0. 01) and increased by approximately 100% in the rostral ventrolateral medulla (RVLM; P<0.05) of SHR when compared to WKY. Following acute restraint (1 session), preproGAL mRNA expression was significantly increased by approximately 135% in the central nucleus of the amygdala (CeA; P<0.05) in WKY. In SHR, significant increases of up to 300% were observed in the CeA (P<0.01) and SON (P<0.05) following chronic restraint (up to 10 days). In addition, expression of preproGAL mRNA was significantly decreased in the locus coeruleus (LC) of SHR following acute restraint (1 session) (P<0.05). These results provide the first evidence that both acute (LC) and chronic (CeA, SON) restraint stress is associated with alterations in preproGAL mRNA expression. As such, the present study provides further evidence linking neurons containing galanin with the central response to restraint stress.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BW",
      "lastName" : "Sweerts",
      "authorRank" : 1,
      "name" : "Sweerts BW",
      "referenceId" : "RGD:A82499"
    }, {
      "firstName" : "B",
      "lastName" : "Jarrott",
      "authorRank" : 2,
      "name" : "Jarrott B",
      "referenceId" : "RGD:A82500"
    }, {
      "firstName" : "AJ",
      "lastName" : "Lawrence",
      "authorRank" : 3,
      "name" : "Lawrence AJ",
      "referenceId" : "RGD:A82501"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1624336"
    } ]
  }, {
    "primaryId" : "PMID:10352094",
    "title" : "Developmental regulation of nitric oxide synthase expression in rat skeletal bone.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Hukkanen MV, etal., J Bone Miner Res. 1999 Jun;14(6):868-77.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-08T11:09:53.000-06:00",
    "volume" : "14",
    "pages" : "868-77",
    "abstract" : "Nitric oxide (NO) has been implicated in bone growth and remodeling by studies showing that inhibition of NO-synthase (NOS) activity retards normal gain in bone mineral density both during skeletal development and after sexual maturity. In the present study, we aimed to assess the level of expression and cellular localization of the three NOS isoforms during skeletal bone development from neonatal to sexual maturity in female Wistar rats. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the presence of NOS1 (neuronal), NOS2 (inducible), and NOS3 (endothelial) transcripts in femoral bone  from neonatal, 4-, 8-, and 12-week-old rats. RT-PCR amplified NOS1, NOS2, and NOS3 transcripts of 472-, 807-, and 289-bp, respectively. There were no detectable differences in the levels of NOS1 mRNA between the groups; however, NOS2 mRNA was more abundant in the neonatal group compared with 4-, 8-, and 12-week groups. Expression of NOS1 protein could not be detected in bones by either Western blotting or immunocytochemistry in any of the age groups investigated. Western blots for NOS2 revealed expression in the neonatal group only and it was not detected in any of the older age groups. Immunostaining for NOS2 was also most evident in the neonatal group and was localized specifically to trabecular osteoblasts and osteoclasts. In all age groups studied, NOS3 mRNA and protein were found in bone-resorbing osteoclasts, cuboidal active osteoblasts, and osteocytes. Semiquantitative RT-PCR provided evidence of down-regulation of NOS3 transcripts during the skeletal development. This was confirmed using in situ hybridization, which showed higher expression in neonatal and 4-week groups than in other groups. Western blots and counting the ratio of trabecular osteoblasts that were NOS3 immunoreactive showed parallel down-regulation of NOS3 protein during skeletal development. Taken together, these data show that there is regulation of NOS2 and in particular NOS3 expression during skeletal development and this may be significant to trabecular  bone growth and remodeling.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MV",
      "lastName" : "Hukkanen",
      "authorRank" : 1,
      "name" : "Hukkanen",
      "referenceId" : "RGD:A177667"
    }, {
      "firstName" : "LA",
      "lastName" : "Platts",
      "authorRank" : 2,
      "name" : "Platts",
      "referenceId" : "RGD:A177668"
    }, {
      "firstName" : "I",
      "lastName" : "Fernandez De Marticorena",
      "authorRank" : 3,
      "name" : "Fernandez De Marticorena",
      "referenceId" : "RGD:A177669"
    }, {
      "firstName" : "M",
      "lastName" : "O'Shaughnessy",
      "authorRank" : 4,
      "name" : "O'Shaughnessy",
      "referenceId" : "RGD:A177670"
    }, {
      "firstName" : "I",
      "lastName" : "MacIntyre",
      "authorRank" : 5,
      "name" : "MacIntyre I",
      "referenceId" : "RGD:A36644"
    }, {
      "firstName" : "JM",
      "lastName" : "Polak",
      "authorRank" : 6,
      "name" : "Polak",
      "referenceId" : "RGD:A177671"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7794707"
    } ]
  }, {
    "primaryId" : "PMID:10352164",
    "title" : "A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ibdah JA, etal., N Engl J Med. 1999 Jun 3;340(22):1723-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:48:19.000-05:00",
    "volume" : "340",
    "pages" : "1723-31",
    "abstract" : "BACKGROUND: Acute fatty liver of pregnancy and the HELLP syndrome (hemolysis, elevated liver-enzyme levels, and a low platelet count) are serious hepatic disorders that may occur during pregnancy in women whose fetuses are later found  to have a deficiency of long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase.  This enzyme resides in the mitochondrial trifunctional protein, which also contains the active site of long-chain 2,3-enoyl-CoA hydratase and long-chain 3-ketoacyl-CoA thiolase. We undertook this study to determine the relation between mutations in the trifunctional protein in infants with defects in fatty-acid oxidation and acute liver disease during pregnancy in their mothers. METHODS: In 24 children with 3-hydroxyacyl-CoA dehydrogenase deficiency, we used  DNA amplification and nucleotide-sequence analyses to identify mutations in the alpha subunit of the trifunctional protein. We then correlated the results with the presence of liver disease during pregnancy in the mothers. RESULTS: Nineteen  children had a deficiency only of long-chain 3-hydroxyacyl-CoA dehydrogenase and  presented with hypoketotic hypoglycemia and fatty liver. In eight children, we identified a homozygous mutation in which glutamic acid at residue 474 was changed to glutamine. Eleven other children were compound heterozygotes, with this mutation in one allele of the alpha-subunit gene and a different mutation in the other allele. While carrying fetuses with the Glu474Gln mutation, 79 percent  of the heterozygous mothers had fatty liver of pregnancy or the HELLP syndrome. Five other children, who presented with neonatal dilated cardiomyopathy or progressive neuromyopathy, had complete deficiency of the trifunctional protein (loss of activity of all three enzymes). None had the Glu474Gln mutation, and none of their mothers had liver disease during pregnancy. CONCLUSIONS: Women with acute liver disease during pregnancy may have a Glu474Gln mutation in long-chain  hydroxyacyl-CoA dehydrogenase. Their infants are at risk for hypoketotic hypoglycemia and fatty liver.",
    "issueName" : "22",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Ibdah",
      "authorRank" : 1,
      "name" : "Ibdah JA",
      "referenceId" : "RGD:A123147"
    }, {
      "firstName" : "MJ",
      "lastName" : "Bennett",
      "authorRank" : 2,
      "name" : "Bennett MJ",
      "referenceId" : "RGD:A37422"
    }, {
      "firstName" : "P",
      "lastName" : "Rinaldo",
      "authorRank" : 3,
      "name" : "Rinaldo P",
      "referenceId" : "RGD:A78454"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhao",
      "authorRank" : 4,
      "name" : "Zhao",
      "referenceId" : "RGD:A415939"
    }, {
      "firstName" : "B",
      "lastName" : "Gibson",
      "authorRank" : 5,
      "name" : "Gibson B",
      "referenceId" : "RGD:A75441"
    }, {
      "firstName" : "HF",
      "lastName" : "Sims",
      "authorRank" : 6,
      "name" : "Sims HF",
      "referenceId" : "RGD:A29320"
    }, {
      "firstName" : "AW",
      "lastName" : "Strauss",
      "authorRank" : 7,
      "name" : "Strauss",
      "referenceId" : "RGD:A412707"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062760"
    } ]
  }, {
    "primaryId" : "PMID:10352942",
    "title" : "Is the perinatal lethal form of Gaucher disease more common than classic type 2 Gaucher disease?",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Stone DL, etal., Eur J Hum Genet. 1999 May-Jun;7(4):505-9. doi: 10.1038/sj.ejhg.5200315.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:45:43.000-05:00",
    "volume" : "7",
    "pages" : "505-9",
    "abstract" : "In recent years there has been increased recognition of a severe perinatal lethal form of Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase. We previously reported a case of severe type 2 Gaucher disease which was seen in a medical center in Rotterdam and now present three new cases from two other families seen at the same center. Mutational analyses of these cases revealed two novel mutations, H311R and V398F, located in exons 8 and 9, respectively. The identification of four cases of lethal type 2 Gaucher disease in a single center seems to be a function of increased awareness of this phenotype, rather than of geographic clustering. The actual incidence of lethal type 2 Gaucher disease may be underestimated, as many cases may have been misclassified as collodion babies or hydrops of unknown cause.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D L",
      "lastName" : "Stone",
      "authorRank" : 1,
      "name" : "Stone DL",
      "referenceId" : "RGD:A564539"
    }, {
      "firstName" : "O P",
      "lastName" : "van Diggelen",
      "authorRank" : 2,
      "name" : "van Diggelen OP",
      "referenceId" : "RGD:A584037"
    }, {
      "firstName" : "J B",
      "lastName" : "de Klerk",
      "authorRank" : 3,
      "name" : "de Klerk JB",
      "referenceId" : "RGD:A584038"
    }, {
      "firstName" : "J L",
      "lastName" : "Gaillard",
      "authorRank" : 4,
      "name" : "Gaillard JL",
      "referenceId" : "RGD:A584039"
    }, {
      "firstName" : "M F",
      "lastName" : "Niermeijer",
      "authorRank" : 5,
      "name" : "Niermeijer MF",
      "referenceId" : "RGD:A439648"
    }, {
      "firstName" : "R",
      "lastName" : "Willemsen",
      "authorRank" : 6,
      "name" : "Willemsen R",
      "referenceId" : "RGD:A13940"
    }, {
      "firstName" : "N",
      "lastName" : "Tayebi",
      "authorRank" : 7,
      "name" : "Tayebi N",
      "referenceId" : "RGD:A564540"
    }, {
      "firstName" : "E",
      "lastName" : "Sidransky",
      "authorRank" : 8,
      "name" : "Sidransky E",
      "referenceId" : "RGD:A145807"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598116913"
    } ]
  }, {
    "primaryId" : "PMID:10353249",
    "title" : "Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Ona VO, etal., Nature 1999 May 20;399(6733):263-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T12:03:06.000-06:00",
    "volume" : "399",
    "pages" : "263-7",
    "abstract" : "Huntington's disease is an autosomal-dominant progressive neurodegenerative disorder resulting in specific neuronal loss and dysfunction in the striatum and cortex. The disease is universally fatal, with a mean survival following onset of 15-20 years and, at present, there is no effective treatment. The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M(r) 350K). The length of the CAG/polyglutamine repeat is inversely correlated with the age of disease onset. The molecular pathways mediating the neuropathology of Huntington's disease are poorly understood. Transgenic mice expressing exon 1 of the human huntingtin gene with an expanded CAG/polyglutamine repeat develop a progressive syndrome with many of the characteristics of human Huntington's disease. Here we demonstrate evidence of caspase-1 activation in the brains of mice and humans with the disease. In this transgenic mouse model of Huntington's disease, expression of a dominant-negative caspase-1 mutant extends survival and delays the appearance of neuronal inclusions, neurotransmitter receptor alterations and onset of symptoms, indicating that caspase-1 is important in the pathogenesis of the disease. In addition, we demonstrate that intracerebroventricular administration of a caspase inhibitor delays disease progression and mortality in the mouse model of Huntington's disease.",
    "issueName" : "6733",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "VO",
      "lastName" : "Ona",
      "authorRank" : 1,
      "name" : "Ona VO",
      "referenceId" : "RGD:A36691"
    }, {
      "firstName" : "M",
      "lastName" : "Li",
      "authorRank" : 2,
      "name" : "Li M",
      "referenceId" : "RGD:A5679"
    }, {
      "firstName" : "JP",
      "lastName" : "Vonsattel",
      "authorRank" : 3,
      "name" : "Vonsattel JP",
      "referenceId" : "RGD:A36692"
    }, {
      "firstName" : "LJ",
      "lastName" : "Andrews",
      "authorRank" : 4,
      "name" : "Andrews LJ",
      "referenceId" : "RGD:A36693"
    }, {
      "firstName" : "SQ",
      "lastName" : "Khan",
      "authorRank" : 5,
      "name" : "Khan SQ",
      "referenceId" : "RGD:A36694"
    }, {
      "firstName" : "WM",
      "lastName" : "Chung",
      "authorRank" : 6,
      "name" : "Chung WM",
      "referenceId" : "RGD:A36695"
    }, {
      "firstName" : "AS",
      "lastName" : "Frey",
      "authorRank" : 7,
      "name" : "Frey AS",
      "referenceId" : "RGD:A36696"
    }, {
      "firstName" : "AS",
      "lastName" : "Menon",
      "authorRank" : 8,
      "name" : "Menon AS",
      "referenceId" : "RGD:A36697"
    }, {
      "firstName" : "XJ",
      "lastName" : "Li",
      "authorRank" : 9,
      "name" : "Li XJ",
      "referenceId" : "RGD:A154516"
    }, {
      "firstName" : "PE",
      "lastName" : "Stieg",
      "authorRank" : 10,
      "name" : "Stieg PE",
      "referenceId" : "RGD:A36699"
    }, {
      "firstName" : "J",
      "lastName" : "Yuan",
      "authorRank" : 11,
      "name" : "Yuan J",
      "referenceId" : "RGD:A36700"
    }, {
      "firstName" : "JB",
      "lastName" : "Penney",
      "authorRank" : 12,
      "name" : "Penney JB",
      "referenceId" : "RGD:A36701"
    }, {
      "firstName" : "AB",
      "lastName" : "Young",
      "authorRank" : 13,
      "name" : "Young AB",
      "referenceId" : "RGD:A36702"
    }, {
      "firstName" : "JH",
      "lastName" : "Cha",
      "authorRank" : 14,
      "name" : "Cha JH",
      "referenceId" : "RGD:A34501"
    }, {
      "firstName" : "RM",
      "lastName" : "Friedlander",
      "authorRank" : 15,
      "name" : "Friedlander RM",
      "referenceId" : "RGD:A36703"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734691"
    } ]
  }, {
    "primaryId" : "PMID:10353322",
    "title" : "Comparison of urinary excretion of albumin and alpha-1-antitrypsin in patients with arterial hypertension.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Lisowska-Myjak B, etal., Scand J Clin Lab Invest. 1999 Apr;59(2):93-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-12-05T13:35:56.000-06:00",
    "volume" : "59",
    "pages" : "93-7",
    "abstract" : "The aim of the presented pilot study was to compare urinary excretion of two plasma proteins similar in molecular mass and isoelectric point: albumin and alpha-1-antitrypsin (AAT) in patients with different forms of arterial hypertension and in healthy subjects. The 24-h urinary excretion of albumin and AAT were assessed in 52 patients, 29 with essential hypertension and 23 with secondary hypertension, caused by renovascular hypertension, adrenal phaeochromocytoma and obturative sleep apnoea syndrome. The concentrations of albumin and AAT were determined by rocket immunodiffusion. An increase of mean albumin and AAT urinary excretion was demonstrated, as compared to the control group, both in the patients with essential hypertension and with secondary hypertension. In 93.2% of the healthy subjects no AAT presence in urine was detected. No correlation was found between the excretion of albumin and AAT with urine.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Lisowska-Myjak",
      "authorRank" : 1,
      "name" : "Lisowska-Myjak B",
      "referenceId" : "RGD:A89534"
    }, {
      "firstName" : "J",
      "lastName" : "Pachecka",
      "authorRank" : 2,
      "name" : "Pachecka J",
      "referenceId" : "RGD:A89535"
    }, {
      "firstName" : "P",
      "lastName" : "Witak",
      "authorRank" : 3,
      "name" : "Witak P",
      "referenceId" : "RGD:A89536"
    }, {
      "firstName" : "S",
      "lastName" : "Radowicki",
      "authorRank" : 4,
      "name" : "Radowicki S",
      "referenceId" : "RGD:A89537"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1643147"
    } ]
  }, {
    "primaryId" : "PMID:10353334",
    "title" : "Hyperammonemia: regulation of argininosuccinate synthetase and argininosuccinate lyase genes in aggregating cell cultures of fetal rat brain.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Braissant O, etal., Neurosci Lett. 1999 May 7;266(2):89-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-25T12:49:06.000-06:00",
    "volume" : "266",
    "pages" : "89-92",
    "abstract" : "Hyperammonemia in the brain leads to poorly understood alterations of nitric oxide (NO) synthesis. Arginine, the substrate of nitric oxide synthases, might be recycled from the citrulline produced with NO by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL). The regulation of AS and AL genes during hyperammonemia is unknown in the brain. We used brain cell aggregates cultured from dissociated telencephalic cortex of rat embryos to analyze the regulation of AS and AL genes in hyperammonemia. Using RNase protection assay and non-radioactive in situ hybridization on aggregate cryosections, we show that both AS and AL genes are induced in astrocytes but not in neurons of aggregates exposed to 5 mM NH4Cl. Our work suggests that the hyperammonemic brain might increase its recycling of citrulline to arginine.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Braissant",
      "authorRank" : 1,
      "name" : "Braissant O",
      "referenceId" : "RGD:A21731"
    }, {
      "firstName" : "P",
      "lastName" : "Honegger",
      "authorRank" : 2,
      "name" : "Honegger P",
      "referenceId" : "RGD:A17752"
    }, {
      "firstName" : "M",
      "lastName" : "Loup",
      "authorRank" : 3,
      "name" : "Loup M",
      "referenceId" : "RGD:A73156"
    }, {
      "firstName" : "K",
      "lastName" : "Iwase",
      "authorRank" : 4,
      "name" : "Iwase K",
      "referenceId" : "RGD:A73157"
    }, {
      "firstName" : "M",
      "lastName" : "Takiguchi",
      "authorRank" : 5,
      "name" : "Takiguchi M",
      "referenceId" : "RGD:A16197"
    }, {
      "firstName" : "C",
      "lastName" : "Bachmann",
      "authorRank" : 6,
      "name" : "Bachmann C",
      "referenceId" : "RGD:A73158"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599267"
    } ]
  }, {
    "primaryId" : "PMID:10353541",
    "title" : "Hepatic gene expression and cytokine responses to sterile inflammation: comparison with cecal ligation and puncture sepsis in the rat.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Bazel S, etal., Shock. 1999 May;11(5):347-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-30T15:37:04.000-05:00",
    "volume" : "11",
    "pages" : "347-55",
    "abstract" : "Inflammatory stimulation of hepatic acute phase protein expression is, in part, modulated by tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-beta), and IL-6. These cytokines also may mediate some aspects of the persistent inflammation and metabolic dysregulation of sepsis. Cecal ligation and puncture (CLP) sepsis in male Sprague-Dawley rats inappropriately decreases hepatocellular transcription of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), carnitine palmitoyltransferase II (CPTII), acetyl CoA acyltransferase (ACA), and ornithine transcarbamylase (OTC). We hypothesize that 1) transcriptional reprogramming does not occur after simple inflammation induced by subcutaneous turpentine injection, 2) the pattern of acute phase gene expression after CLP differs from that following turpentine injection, and 3) the different responses reflect differences in the intrahepatic activity of TNFalpha/IL-1beta or IL-6. Gene expression, transcription factor activity, and cytokine abundance were determined after either a subcutaneous injection of turpentine or CLP. After turpentine injection, PEPCK, G6Pase, CPTII, ACA, and OTC expression were unchanged, different from previously reported data following CLP. Both turpentine injection and CLP increased expression of TNFalpha/IL-1beta-regulated alpha1-acid glycoprotein, and IL-6-regulated alpha2-macroglobulin and decreased expression of transthyretin (a negative acute phase protein). However, the magnitude and temporal pattern of expression differed. Turpentine injection increased the activity of the TNFalpha/IL-1beta-linked transcription factor NF-kappaB and the intrahepatic abundance of TNFalpha in a manner similar to that observed after CLP but only slightly altered the activity of the IL-6-linked transcription factor Stat-3 and intrahepatic IL-6 abundance. This differed significantly from observations after CLP. We conclude that CLP-induced alterations in hepatic gene expression may reflect differences in IL-6 activity.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Bazel",
      "authorRank" : 1,
      "name" : "Bazel S",
      "referenceId" : "RGD:A128481"
    }, {
      "firstName" : "KM",
      "lastName" : "Andrejko",
      "authorRank" : 2,
      "name" : "Andrejko KM",
      "referenceId" : "RGD:A70551"
    }, {
      "firstName" : "J",
      "lastName" : "Chen",
      "authorRank" : 3,
      "name" : "Chen J",
      "referenceId" : "RGD:A161502"
    }, {
      "firstName" : "CS",
      "lastName" : "Deutschman",
      "authorRank" : 4,
      "name" : "Deutschman CS",
      "referenceId" : "RGD:A70553"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4144069"
    } ]
  }, {
    "primaryId" : "PMID:10353610",
    "title" : "Mutation of the 9q34 gene TSC1 in sporadic bladder cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hornigold N, etal., Oncogene. 1999 Apr 22;18(16):2657-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:42:41.000-05:00",
    "volume" : "18",
    "pages" : "2657-61",
    "abstract" : "Deletions involving chromosome 9 occur in more than 50% of human bladder cancers  of all grades and stages. Most involve loss of the whole chromosome or of an entire chromosome arm but some small deletions are found which can be used to define critical regions which may contain tumour suppressor genes. We have localized such a critical region of deletion at 9q34 between the markers D9S149 and D9S66, an interval which contains the Tuberous Sclerosis gene TSC1. Single strand conformation polymorphism (SSCP) and sequence analysis of TSC1 in bladder  tumours and cell lines with 9q34 loss of heterozygosity (LOH) has identified five mutations in retained TSC1 alleles. Our results support the hypothesis that TSC1  can act as a bladder tumour suppressor gene.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Hornigold",
      "authorRank" : 1,
      "name" : "Hornigold",
      "referenceId" : "RGD:A251360"
    }, {
      "firstName" : "J",
      "lastName" : "Devlin",
      "authorRank" : 2,
      "name" : "Devlin",
      "referenceId" : "RGD:A251361"
    }, {
      "firstName" : "AM",
      "lastName" : "Davies",
      "authorRank" : 3,
      "name" : "Davies AM",
      "referenceId" : "RGD:A16309"
    }, {
      "firstName" : "JS",
      "lastName" : "Aveyard",
      "authorRank" : 4,
      "name" : "Aveyard",
      "referenceId" : "RGD:A251362"
    }, {
      "firstName" : "T",
      "lastName" : "Habuchi",
      "authorRank" : 5,
      "name" : "Habuchi T",
      "referenceId" : "RGD:A38157"
    }, {
      "firstName" : "MA",
      "lastName" : "Knowles",
      "authorRank" : 6,
      "name" : "Knowles MA",
      "referenceId" : "RGD:A45001"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062495"
    } ]
  }, {
    "primaryId" : "PMID:10353622",
    "title" : "In vitro and in vivo alterations of enzymatic glycosylation in diabetes.",
    "datePublished" : "1000-01-01T00:00:00.000-06:00",
    "citation" : "Rellier N, etal., Life Sci. 1999;64(17):1571-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-01-15T16:59:24.000-06:00",
    "volume" : "64",
    "pages" : "1571-83",
    "abstract" : "Carbohydrate composition changes of glycoconjugates constituting the glycocalix of microvascular cells could be involved in the alterations of cell-cell interactions observed in diabetic retinopathy. In this field, we have recently reported that advanced glycation end products (AGEs) modify galactose, fucose and sialic acid contents of specific cellular glycoproteins. To better understand the mechanisms involved in glycoprotein modifications in diabetes, we now investigate whether glucose and AGEs could affect the activities of enzymes involved in galactose, fucose and sialic acid metabolism : glycosyltransferases (synthesis) and glycosidases (catabolism). For this, bovine retinal endothelial cells (BREC) and pericytes (BRP) were cultured in the presence of high glucose concentration or AGEs, and cell glycosidase and glycosyltransferase activities were measured. The same enzymatic activities were studied in the whole retina from streptozotocin-treated rats. The results show that high glucose concentration did not affect glycosidases and glycosyltransferases neither in BRP nor in BREC except for galactosyltransferase activities in BREC. Concerning BRP, only galactosyltransferase activities were altered by AGEs. In contrast, in BREC, AGEs increased beta-D galactosidase, alpha-L fucosidase and neuraminidase activities (+37%, +56%, 36% respectively) whereas galactosyltransferase, fucosyltransferase and sialyltransferase activities were decreased (-11%, -24% and -23% respectively). In the retina from diabetic rats, beta-D galactosidase, alpha-L fucosidase and neuraminidase activities increased (+70%, +57%, +78% respectively) whereas fucosyl and sialyltransferase decreased (-7% and -15% respectively). The possible consequence of these enzymatic activity changes could be a defect in the carbohydrate content of some glycoproteins that might participate in the endothelial cell dysfunctions in diabetic microangiopathy.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Rellier",
      "authorRank" : 1,
      "name" : "Rellier N",
      "referenceId" : "RGD:A117905"
    }, {
      "firstName" : "D",
      "lastName" : "Ruggiero-Lopez",
      "authorRank" : 2,
      "name" : "Ruggiero-Lopez D",
      "referenceId" : "RGD:A117906"
    }, {
      "firstName" : "M",
      "lastName" : "Lecomte",
      "authorRank" : 3,
      "name" : "Lecomte M",
      "referenceId" : "RGD:A117907"
    }, {
      "firstName" : "M",
      "lastName" : "Lagarde",
      "authorRank" : 4,
      "name" : "Lagarde M",
      "referenceId" : "RGD:A112360"
    }, {
      "firstName" : "N",
      "lastName" : "Wiernsperger",
      "authorRank" : 5,
      "name" : "Wiernsperger N",
      "referenceId" : "RGD:A117908"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2315932"
    } ]
  }, {
    "primaryId" : "PMID:10353629",
    "title" : "Increased nitric oxide synthase expression in aorta of cirrhotic rats.",
    "datePublished" : "1000-05-01T00:00:00.000-06:00",
    "citation" : "Liu H, etal., Life Sci. 1999;64(19):1753-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-05-28T08:34:45.000-05:00",
    "volume" : "64",
    "pages" : "1753-9",
    "abstract" : "The characteristic cardiovascular changes in liver cirrhosis are vasodilatation and increased cardiac output. Augmented activity of the vasorelaxant factor, nitric oxide (NO), stimulated by cytokines, have been suggested to play a role in the pathogenesis, but previous studies show conflicting results. We therefore aimed to evaluate the entire pathway from cytokines to the final metabolites, nitrate/nitrite. The levels of serum Tumor Necrosis Factor-alpha (TNFalpha) and nitrate/nitrite (NOx) were measured, and aorta content of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein were determined by reverse-transcription polymerase chain reaction and Western blotting in rats with cirrhosis due to chronic bile duct ligation and sham-operated controls. Compared to control rats, serum TNFalpha levels were significantly elevated in cirrhotic rats (48.4+/-21.1 vs 16.8+/-9.0 pg/ml, p<0.01); iNOS mRNA was detectable whereas it was absent in controls, and eNOS mRNA levels was significantly higher in aortae of cirrhotic rats. Aortic eNOS protein content was significantly higher in cirrhotic rats, but iNOS protein was undetectable by Western blotting in both groups. Serum NOx concentrations in the cirrhotic group were significantly higher than those in controls (3.5+/-1.0 vs 2.3+/-0.5 microM, p<0.01). These results suggest that NO activity in cirrhosis is increased, and is predominantly due to eNOS since the detectable iNOS mRNA does not seem to be expressed as protein. The increased NOS activity in the arterial system may play a role in the systemic hemodynamic changes occurring in cirrhosis.",
    "issueName" : "19",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu H",
      "referenceId" : "RGD:A10359"
    }, {
      "firstName" : "D",
      "lastName" : "Song",
      "authorRank" : 2,
      "name" : "Song D",
      "referenceId" : "RGD:A123978"
    }, {
      "firstName" : "SS",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee SS",
      "referenceId" : "RGD:A4920"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2325278"
    } ]
  }, {
    "primaryId" : "PMID:10353719",
    "title" : "Stable expression of a recombinant sodium-dependent, pyrimidine-selective nucleoside transporter (CNT1) in a transport-deficient mouse leukemia cell line.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Crawford CR, etal., Biochem Cell Biol. 1998;76(5):843-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-04-06T10:16:36.000-05:00",
    "volume" : "76",
    "pages" : "843-51",
    "abstract" : "Previous studies of nucleoside transport in mammalian cells have identified two types of activities: the equilibrative nucleoside transporters and concentrative, Na+-nucleoside cotransporters. Characterization of the concentrative nucleoside transporters has been hampered by the presence in most cells and tissues of multiple transporters with overlapping permeant specificities. With the recent cloning of cDNAs encoding rat and human members of the concentrative nucleoside transporter (CNT) family, it is now possible to study the concentrative transporters in isolation by use of functional expression systems. We report here the isolation of a nucleoside transport-deficient subline of L1210 mouse leukemia (L1210/DNC3) that is a suitable recipient for stable expression of cloned nucleoside transporter cDNAs. We have used L1210/DNC3 as the recipient in gene transfer studies to develop a stable cell line (L1210/DU5) that produces the recombinant concentrative nucleoside transporter with selectivity for pyrimidine nucleosides (CNT1) that was initially identified in rat intestine (Q.Q. Huang, S.Y. Yao, M.W. Ritzel, A.R.P. Paterson, C.E. Cass, and J.D. Young. 1994. J. Biol. Chem. 269: 17,757-17,760). L1210/DU5 was used to examine the permeant selectivity of recombinant rat CNT1 by comparing a series of nucleoside analogs with respect to (i) inhibition of inward fluxes of [3H]thymidine, (ii) initial rates of transport of 3H-analog, and (iii) cytotoxicity to L1210/DU5 versus the parental transport-deficient cell line. By all three criteria, recombinant CNT1 transported 5-fluoro-2'-deoxyuridine and 5-fluorouridine well and cytosine arabinoside poorly. Although some purine nucleosides (2'-deoxyadenosinedeoxyadeno-2'-deoxyadenosine, 7-deazaadenosine) were potent inhibitors of CNT1, they were poor permeants when uptake was measured directly by analysis of isotopic fluxes or indirectly by comparison of cytotoxicity ratios. We conclude that comparison of analog cytotoxicity to L1210/DU5 versus L1210/DNC3 is a reliable indirect predictor of transportability, suggesting that cytotoxicity assays with a panel of such cell lines, each with a different recombinant nucleoside transporter, would be a valuable tool in the development of antiviral and antitumor nucleoside analogs.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CR",
      "lastName" : "Crawford",
      "authorRank" : 1,
      "name" : "Crawford CR",
      "referenceId" : "RGD:A121450"
    }, {
      "firstName" : "CE",
      "lastName" : "Cass",
      "authorRank" : 2,
      "name" : "Cass CE",
      "referenceId" : "RGD:A121451"
    }, {
      "firstName" : "JD",
      "lastName" : "Young",
      "authorRank" : 3,
      "name" : "Young JD",
      "referenceId" : "RGD:A121452"
    }, {
      "firstName" : "JA",
      "lastName" : "Belt",
      "authorRank" : 4,
      "name" : "Belt JA",
      "referenceId" : "RGD:A121453"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317447"
    } ]
  }, {
    "primaryId" : "PMID:10353780",
    "title" : "Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wang ZJ, etal., J Med Genet. 1999 May;36(5):365-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:46:47.000-05:00",
    "volume" : "36",
    "pages" : "365-8",
    "abstract" : "Germline mutations of the LKB1 (STK11) serine/threonine kinase gene (chromosome 19p13.3) cause Peutz-Jeghers syndrome, which is characterised by hamartomas of the gastrointestinal tract and typical pigmentation. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general  population. Here, we report the results of a screen for germline LKB1 mutations by DNA sequencing in 12 Peutz-Jeghers patients (three sporadic and nine familial  cases). Mutations were found in seven (58%) cases, in exons 1, 2, 4, 6, and 9. Five of these mutations, two of which are identical, are predicted to lead to a truncated protein (three frameshifts, two nonsense changes). A further mutation is an in frame deletion of 6 bp, resulting in a deletion of lysine and asparagine; the second of these amino acids is conserved between species. The seventh mutation is a missense change in exon 2, converting lysine to arginine, affecting non-conserved amino acids and of uncertain functional significance. Despite the fact that Peutz-Jeghers syndrome is usually an early onset disease with characteristic clinical features, predictive and diagnostic testing for LKB1 mutations will be useful for selected patients in both familial and non-familial  contexts.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ZJ",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang ZJ",
      "referenceId" : "RGD:A74004"
    }, {
      "firstName" : "M",
      "lastName" : "Churchman",
      "authorRank" : 2,
      "name" : "Churchman M",
      "referenceId" : "RGD:A122287"
    }, {
      "firstName" : "E",
      "lastName" : "Avizienyte",
      "authorRank" : 3,
      "name" : "Avizienyte",
      "referenceId" : "RGD:A248482"
    }, {
      "firstName" : "C",
      "lastName" : "McKeown",
      "authorRank" : 4,
      "name" : "McKeown C",
      "referenceId" : "RGD:A75078"
    }, {
      "firstName" : "S",
      "lastName" : "Davies",
      "authorRank" : 5,
      "name" : "Davies S",
      "referenceId" : "RGD:A108617"
    }, {
      "firstName" : "DG",
      "lastName" : "Evans",
      "authorRank" : 6,
      "name" : "Evans DG",
      "referenceId" : "RGD:A37085"
    }, {
      "firstName" : "A",
      "lastName" : "Ferguson",
      "authorRank" : 7,
      "name" : "Ferguson",
      "referenceId" : "RGD:A269518"
    }, {
      "firstName" : "I",
      "lastName" : "Ellis",
      "authorRank" : 8,
      "name" : "Ellis I",
      "referenceId" : "RGD:A62076"
    }, {
      "firstName" : "WH",
      "lastName" : "Xu",
      "authorRank" : 9,
      "name" : "Xu WH",
      "referenceId" : "RGD:A83463"
    }, {
      "firstName" : "ZY",
      "lastName" : "Yan",
      "authorRank" : 10,
      "name" : "Yan",
      "referenceId" : "RGD:A269519"
    }, {
      "firstName" : "LA",
      "lastName" : "Aaltonen",
      "authorRank" : 11,
      "name" : "Aaltonen LA",
      "referenceId" : "RGD:A36425"
    }, {
      "firstName" : "IP",
      "lastName" : "Tomlinson",
      "authorRank" : 12,
      "name" : "Tomlinson IP",
      "referenceId" : "RGD:A36426"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067905"
    } ]
  }, {
    "primaryId" : "PMID:10353784",
    "title" : "Connexin26 deafness in several interconnected families.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wilcox SA, etal., J Med Genet. 1999 May;36(5):383-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:30:53.000-05:00",
    "volume" : "36",
    "pages" : "383-5",
    "abstract" : "Mutations in the connexin26 gene are the basis of much autosomal recessive sensorineural deafness. There is a high frequency of mutant alleles, largely accounted for by one common mutation, 35delG. We have studied a group of families, who had been brought together through marriages between Deaf persons, in which there are more than 30 Deaf people in four generations. We show that many of the several cases of deafness are the result of 35delG homozygosity or 35delG/Q57X compound heterozygosity at the connexin26 locus. A considerable range of audiographic phenotypes was observed. The combined effects of a high population frequency of mutant alleles, and of positive assortative marriage among the Deaf, led to an infrequently observed recessive pedigree pattern.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SA",
      "lastName" : "Wilcox",
      "authorRank" : 1,
      "name" : "Wilcox",
      "referenceId" : "RGD:A277429"
    }, {
      "firstName" : "AH",
      "lastName" : "Osborn",
      "authorRank" : 2,
      "name" : "Osborn",
      "referenceId" : "RGD:A274257"
    }, {
      "firstName" : "DR",
      "lastName" : "Allen-Powell",
      "authorRank" : 3,
      "name" : "Allen-Powell",
      "referenceId" : "RGD:A277430"
    }, {
      "firstName" : "MA",
      "lastName" : "Maw",
      "authorRank" : 4,
      "name" : "Maw",
      "referenceId" : "RGD:A277428"
    }, {
      "firstName" : "HH",
      "lastName" : "Dahl",
      "authorRank" : 5,
      "name" : "Dahl HH",
      "referenceId" : "RGD:A21975"
    }, {
      "firstName" : "RJ",
      "lastName" : "Gardner",
      "authorRank" : 6,
      "name" : "Gardner RJ",
      "referenceId" : "RGD:A80901"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072391"
    } ]
  }, {
    "primaryId" : "PMID:10353879",
    "title" : "Immunologic parameters as predictive factors of cytomegalovirus disease in renal  allograft recipients.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Nordoy I, etal., J Infect Dis. 1999 Jul;180(1):195-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-03-15T16:29:06.000-05:00",
    "volume" : "180",
    "pages" : "195-8",
    "abstract" : "Cytomegalovirus (CMV) disease is a major problem in renal transplant recipients,  but few predictive markers of the disease are known. Several immunologic parameters of potential relevance for the defense against CMV were measured after renal transplantation in 25 patients before any manifestations of CMV infection occurred. In 10 patients who later developed CMV disease, plasma levels of interleukin-8 were significantly higher, whereas the levels of macrophage inflammatory protein-1alpha (MIP-1alpha) were significantly lower than in 15 patients who did not develop CMV disease. Also, lower numbers of CD4+ and CD8+ lymphocytes were observed in patients who later had CMV disease. These findings were independent of previous rejection therapy and were particularly pronounced in patients with primary CMV infection. Interleukin-8 and MIP-1alpha may be predictive markers of CMV disease and could be of potential use in selecting patients for prophylactic treatment.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Nordoy",
      "authorRank" : 1,
      "name" : "Nordoy",
      "referenceId" : "RGD:A168293"
    }, {
      "firstName" : "F",
      "lastName" : "Muller",
      "authorRank" : 2,
      "name" : "Muller F",
      "referenceId" : "RGD:A9848"
    }, {
      "firstName" : "KP",
      "lastName" : "Nordal",
      "authorRank" : 3,
      "name" : "Nordal",
      "referenceId" : "RGD:A168294"
    }, {
      "firstName" : "H",
      "lastName" : "Rollag",
      "authorRank" : 4,
      "name" : "Rollag",
      "referenceId" : "RGD:A168295"
    }, {
      "firstName" : "E",
      "lastName" : "Lien",
      "authorRank" : 5,
      "name" : "Lien E",
      "referenceId" : "RGD:A100776"
    }, {
      "firstName" : "P",
      "lastName" : "Aukrust",
      "authorRank" : 6,
      "name" : "Aukrust P",
      "referenceId" : "RGD:A64531"
    }, {
      "firstName" : "SS",
      "lastName" : "Froland",
      "authorRank" : 7,
      "name" : "Froland SS",
      "referenceId" : "RGD:A64528"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7241836"
    } ]
  }, {
    "primaryId" : "PMID:10354207",
    "title" : "Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kalsi KK, etal., Eur J Clin Invest. 1999 Jun;29(6):469-77. doi: 10.1046/j.1365-2362.1999.00468.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-04-04T17:02:18.000-05:00",
    "volume" : "29",
    "pages" : "469-77",
    "abstract" : "<br><b>BACKGROUND: </b>Impaired energy metabolism in the failing human heart could be an important mechanism of functional deterioration. The purpose of this study was to assess the changes of myocardial energy metabolism in the human heart at end-stage heart failure.<br><b>MATERIALS AND METHODS: </b>The left ventricular myocardium of patients undergoing heart transplantation due to dilated (DCM, n = 14) or hypertrophic cardiomyopathy (HCM, n = 5) and non-diseased donor heart samples (n = 4) were analysed for citrate synthase (CS), enzymes of the glycolytic pathway as well as concentrations of phosphocreatine (PCr), creatine (Cr), adenine and guanine nucleotides.<br><b>RESULTS: </b>Total creatine levels (phosphocreatine + creatine) were significantly decreased (P < 0.05) in both groups of diseased hearts (3.87 +/- 0.57 in DCM, 5.09 +/- 1.23 in HCM compared with control 10. 7 +/- 3.5 micromol g-1 wet weight). There was a trend for higher guanine nucleotide content in failing hearts, but no significant differences were observed in total adenine nucleotides and total NAD content. CS was markedly reduced (P < 0.05) in both groups of diseased hearts: in the DCM to 13.8 +/- 1.3 micromol min-1 g-1 wet weight, and in HCM to 11.9 +/- 2.4 compared with the control 29.2 +/- 2.2. Glycolytic enzymes were decreased compared with the control, and this decrease was greater in DCM than in HCM. Echocardiographic indices of contractility were considerably better in hypertrophic cardiomyopathy.<br><b>CONCLUSION: </b>Despite the different mechanisms of cardiac failure and the differences in contractility of the heart we have observed, metabolic changes are very similar in hypertrophic and dilated cardiomyopathy. Depletion of the creatine pool suggests an alteration in the intracellular energy reserves and transfer, whereas the decrease in citrate synthase activity suggests reduced oxidative capacity in both dilated and hypertrophic cardiomyopathy.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K K",
      "lastName" : "Kalsi",
      "authorRank" : 1,
      "name" : "Kalsi KK",
      "referenceId" : "RGD:A526222"
    }, {
      "firstName" : "R T",
      "lastName" : "Smolenski",
      "authorRank" : 2,
      "name" : "Smolenski RT",
      "referenceId" : "RGD:A449390"
    }, {
      "firstName" : "R D",
      "lastName" : "Pritchard",
      "authorRank" : 3,
      "name" : "Pritchard RD",
      "referenceId" : "RGD:A526223"
    }, {
      "firstName" : "A",
      "lastName" : "Khaghani",
      "authorRank" : 4,
      "name" : "Khaghani A",
      "referenceId" : "RGD:A132645"
    }, {
      "firstName" : "A M",
      "lastName" : "Seymour",
      "authorRank" : 5,
      "name" : "Seymour AM",
      "referenceId" : "RGD:A526224"
    }, {
      "firstName" : "M H",
      "lastName" : "Yacoub",
      "authorRank" : 6,
      "name" : "Yacoub MH",
      "referenceId" : "RGD:A526225"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:243048483"
    } ]
  }, {
    "primaryId" : "PMID:10354514",
    "title" : "Identification of a novel substitution in the constant region of a gene coding for an amyloidogenic kappa1 light chain.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wally J, etal., Biochim Biophys Acta. 1999 May 31;1454(1):49-56.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:55:24.000-05:00",
    "volume" : "1454",
    "pages" : "49-56",
    "abstract" : "Current concepts regarding the association between immunoglobulin (Ig) light chain structure and AL amyloidosis (AL) emphasize Ig variable region amino acid substitutions because the majority of light chain amyloid fibrils that have been  sequenced contain amino termini of the variable region with only small amounts of the constant region. In this report, we describe a patient with rapidly progressive AL whose amyloid deposits contained primarily monoclonal kappa light  chain constant region fragments. We sequenced and analyzed this AL protein, determining that it was an O18-O8 kappa1 variant and that the constant region possessed an unusual Ser-->Asn substitution at position 177. Using pre-mortem bone marrow cells, we cloned and sequenced the cDNA for this AL protein (HCAK1) and, using DNA from post-mortem somatic tissue, we cloned and sequenced the patient's kappa germline O18-O8 donor and kappa constant region (Ckappa) gene segments. The cDNA that coded for HCAK1 contained a variable region that was derived from O18-O8, showing 96.1% homology to germline, and a Ckappa that had a  nucleotide substitution (AGC to AAC), resulting in the 177Ser-->Asn replacement.  Two Ckappa genes were cloned from somatic tissue DNA, one identical to a known Ckappa sequence and another containing this substitution which likely is a new Ckappa allotype. Our findings indicate that further investigation is warranted into the contributions genetic polymorphisms and light chain constant regions may make to amyloidogenesis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Wally",
      "authorRank" : 1,
      "name" : "Wally",
      "referenceId" : "RGD:A238452"
    }, {
      "firstName" : "G",
      "lastName" : "Kica",
      "authorRank" : 2,
      "name" : "Kica",
      "referenceId" : "RGD:A238453"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhang",
      "authorRank" : 3,
      "name" : "Zhang Y",
      "referenceId" : "RGD:A5934"
    }, {
      "firstName" : "T",
      "lastName" : "Ericsson",
      "authorRank" : 4,
      "name" : "Ericsson",
      "referenceId" : "RGD:A238454"
    }, {
      "firstName" : "LH",
      "lastName" : "Connors",
      "authorRank" : 5,
      "name" : "Connors",
      "referenceId" : "RGD:A233432"
    }, {
      "firstName" : "MD",
      "lastName" : "Benson",
      "authorRank" : 6,
      "name" : "Benson MD",
      "referenceId" : "RGD:A58856"
    }, {
      "firstName" : "JJ",
      "lastName" : "Liepnieks",
      "authorRank" : 7,
      "name" : "Liepnieks JJ",
      "referenceId" : "RGD:A141702"
    }, {
      "firstName" : "J",
      "lastName" : "Murray",
      "authorRank" : 8,
      "name" : "Murray J",
      "referenceId" : "RGD:A78800"
    }, {
      "firstName" : "M",
      "lastName" : "Skinner",
      "authorRank" : 9,
      "name" : "Skinner M",
      "referenceId" : "RGD:A135952"
    }, {
      "firstName" : "RL",
      "lastName" : "Comenzo",
      "authorRank" : 10,
      "name" : "Comenzo",
      "referenceId" : "RGD:A238455"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11057585"
    } ]
  }, {
    "primaryId" : "PMID:10355968",
    "title" : "Expression pattern of a newly recognized protein, LECT2, in hepatocellular carcinoma and its premalignant lesion.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Uchida T, etal., Pathol Int. 1999 Feb;49(2):147-51. doi: 10.1046/j.1440-1827.1999.00836.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-08-17T16:15:57.000-05:00",
    "volume" : "49",
    "pages" : "147-51",
    "abstract" : "Leukocyte cell-derived chemotoxin 2 (LECT2) is a recently isolated protein and has been shown to be synthesized by human hepatocytes. All hepatocytes show diffuse immunostaining for LECT2 within the cytoplasm. In the present study, an attempt was made to clarify the expression pattern of LECT2 in nine cases of low-grade malignant hepatocellular carcinoma (LGM-HCC) and five cases of advanced HCC and 19 cases of premalignant lesion, termed atypical hyperplasia (AH), using the indirect immunoperoxidase technique. Variable spotty to coarsely diffuse staining in the majority of cells, a mixture of positively staining and negatively staining areas, and essentially negative staining was observed within the cellular cytoplasm of AH, LGM-HCC and advanced HCC, respectively. The expression of LECT2 became weaker with the progression of multistep hepatocarcinogenesis. The data clearly demonstrate that LECT2 becomes essentially negative in full-blown HCC cells and that the histological distinction between AH and LGM-HCC is valid. It also seems likely that LECT2 is related to hepatocyte growth.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Uchida",
      "authorRank" : 1,
      "name" : "Uchida T",
      "referenceId" : "RGD:A139576"
    }, {
      "firstName" : "H",
      "lastName" : "Nagai",
      "authorRank" : 2,
      "name" : "Nagai H",
      "referenceId" : "RGD:A38153"
    }, {
      "firstName" : "K",
      "lastName" : "Gotoh",
      "authorRank" : 3,
      "name" : "Gotoh K",
      "referenceId" : "RGD:A50096"
    }, {
      "firstName" : "H",
      "lastName" : "Kanagawa",
      "authorRank" : 4,
      "name" : "Kanagawa H",
      "referenceId" : "RGD:A519692"
    }, {
      "firstName" : "H",
      "lastName" : "Kouyama",
      "authorRank" : 5,
      "name" : "Kouyama H",
      "referenceId" : "RGD:A519693"
    }, {
      "firstName" : "T",
      "lastName" : "Kawanishi",
      "authorRank" : 6,
      "name" : "Kawanishi T",
      "referenceId" : "RGD:A115269"
    }, {
      "firstName" : "S",
      "lastName" : "Mima",
      "authorRank" : 7,
      "name" : "Mima S",
      "referenceId" : "RGD:A519694"
    }, {
      "firstName" : "S",
      "lastName" : "Yamagoe",
      "authorRank" : 8,
      "name" : "Yamagoe S",
      "referenceId" : "RGD:A519695"
    }, {
      "firstName" : "K",
      "lastName" : "Suzuki",
      "authorRank" : 9,
      "name" : "Suzuki K",
      "referenceId" : "RGD:A159682"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:153323339"
    } ]
  }, {
    "primaryId" : "PMID:10356136",
    "title" : "Infantile encephalopathy associated with the MELAS A3243G mutation.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Sue CM, etal., J Pediatr. 1999 Jun;134(6):696-700.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-12T20:10:49.000-05:00",
    "volume" : "134",
    "pages" : "696-700",
    "abstract" : "MELAS syndrome is typically characterized by normal early development and childhood-onset recurrent neurologic deficits (stroke-like episodes), seizures, short stature, lactic acidosis, and ragged red fibers on muscle biopsy specimens. It is usually, but not invariably, associated with the A3243G point mutation in the mitochondrial DNA tRNALeu(UUR) gene. We report 3 unrelated children with the  A3243G mutation who presented with severe psychomotor delay in early infancy. One patient's clinical picture was more consistent with Leigh syndrome, with apneic episodes, ataxia, and bilateral striatal lesions on brain magnetic resonance imaging (MRI). The second patient had generalized seizures refractory to treatment and bilateral occipital lesions on brain MRI. The third child had atypical retinal pigmentary changes, seizures, areflexia, and cerebral atrophy on brain MRI. All patients had several atypical features in addition to early onset: absence of an acute or focal neurologic deficit, variable serum and cerebrospinal fluid lactate levels, lack of ragged red fibers in muscle biopsy specimens. The proportion of mutant mtDNA in available tissues was relatively low (range, 5% to  51% in muscle; 4% to 39% in blood). These observations further extend the phenotypic expression of the A3243G \"MELAS\" mutation. Our findings confirm previous observations that there is poor correlation between abundance of mutant  mtDNA in peripheral tissues and neurologic phenotype. This suggests that other factors contribute to the phenotypic expression of this mutation.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CM",
      "lastName" : "Sue",
      "authorRank" : 1,
      "name" : "Sue CM",
      "referenceId" : "RGD:A64194"
    }, {
      "firstName" : "C",
      "lastName" : "Bruno",
      "authorRank" : 2,
      "name" : "Bruno C",
      "referenceId" : "RGD:A63343"
    }, {
      "firstName" : "AL",
      "lastName" : "Andreu",
      "authorRank" : 3,
      "name" : "Andreu",
      "referenceId" : "RGD:A252346"
    }, {
      "firstName" : "A",
      "lastName" : "Cargan",
      "authorRank" : 4,
      "name" : "Cargan",
      "referenceId" : "RGD:A395928"
    }, {
      "firstName" : "JR",
      "lastName" : "Mendell",
      "authorRank" : 5,
      "name" : "Mendell JR",
      "referenceId" : "RGD:A37816"
    }, {
      "firstName" : "CY",
      "lastName" : "Tsao",
      "authorRank" : 6,
      "name" : "Tsao",
      "referenceId" : "RGD:A395929"
    }, {
      "firstName" : "M",
      "lastName" : "Luquette",
      "authorRank" : 7,
      "name" : "Luquette",
      "referenceId" : "RGD:A395930"
    }, {
      "firstName" : "J",
      "lastName" : "Paolicchi",
      "authorRank" : 8,
      "name" : "Paolicchi",
      "referenceId" : "RGD:A395931"
    }, {
      "firstName" : "S",
      "lastName" : "Shanske",
      "authorRank" : 9,
      "name" : "Shanske S",
      "referenceId" : "RGD:A53211"
    }, {
      "firstName" : "S",
      "lastName" : "DiMauro",
      "authorRank" : 10,
      "name" : "DiMauro S",
      "referenceId" : "RGD:A53213"
    }, {
      "firstName" : "DC",
      "lastName" : "De Vivo",
      "authorRank" : 11,
      "name" : "De Vivo DC",
      "referenceId" : "RGD:A82156"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11553119"
    } ]
  }, {
    "primaryId" : "PMID:10356329",
    "title" : "Engineered mutants in the switch II loop of Ran define the contribution made by key residues to the interaction with nuclear transport factor 2 (NTF2) and the role of this interaction in nuclear protein import.",
    "datePublished" : "1999-06-11T00:00:00.000-05:00",
    "citation" : "Kent HM, etal., J Mol Biol. 1999 Jun 11;289(3):565-77.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-07-05T00:02:16.000-05:00",
    "volume" : "289",
    "pages" : "565-77",
    "abstract" : "Nuclear protein import requires a precisely choreographed series of interactions between nuclear pore components and soluble factors such as importin-beta, Ran, and nuclear transport factor 2 (NTF2). We used the crystal structure of the GDPRan-NTF2 complex to design mutants in the switch II loop of Ran to probe the contribution of Lys71, Phe72 and Arg76 to this interaction. X-ray crystallography showed that the F72Y, F72W and R76E mutations did not introduce major structural changes into the mutant Ran. The GDP-bound form of the switch II mutants showed no detectable binding to NTF2, providing direct evidence that salt bridges involving Lys71 and Arg76 and burying Phe72 are all crucial for the interaction between Ran and NTF2. Nuclear protein accumulation in digitonin-permeabilzed cells was impaired with Ran mutants deficient in NTF2 binding, confirming that the NTF2-Ran interaction is required for efficient transport. We used mutants of the yeast Ran homologue Gsp1p to investigate the effect of the F72Y and R76E mutations in vivo. Although neither mutant was viable when integrated into the genome as a single copy, yeast mildly overexpressing the Gsp1p mutant corresponding Ran F72Y on a centromeric plasmid were viable, confirming that this mutant retained the essential properties of wild-type Ran. However, yeast expressing the Gsp1p mutant corresponding to R76E to comparable levels were not viable, although strains overexpressing the mutant to higher levels using an episomal 2micrometers plasmid were viable, indicating that the R76E mutation may also have interfered with other interactions made by Gsp1p.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H M",
      "lastName" : "Kent",
      "authorRank" : 1,
      "name" : "Kent HM",
      "referenceId" : "RGD:A446667"
    }, {
      "firstName" : "M S",
      "lastName" : "Moore",
      "authorRank" : 2,
      "name" : "Moore MS",
      "referenceId" : "RGD:A446668"
    }, {
      "firstName" : "B B",
      "lastName" : "Quimby",
      "authorRank" : 3,
      "name" : "Quimby BB",
      "referenceId" : "RGD:A446669"
    }, {
      "firstName" : "A M",
      "lastName" : "Baker",
      "authorRank" : 4,
      "name" : "Baker AM",
      "referenceId" : "RGD:A446670"
    }, {
      "firstName" : "A J",
      "lastName" : "McCoy",
      "authorRank" : 5,
      "name" : "McCoy AJ",
      "referenceId" : "RGD:A446671"
    }, {
      "firstName" : "G A",
      "lastName" : "Murphy",
      "authorRank" : 6,
      "name" : "Murphy GA",
      "referenceId" : "RGD:A446672"
    }, {
      "firstName" : "A H",
      "lastName" : "Corbett",
      "authorRank" : 7,
      "name" : "Corbett AH",
      "referenceId" : "RGD:A446673"
    }, {
      "firstName" : "M",
      "lastName" : "Stewart",
      "authorRank" : 8,
      "name" : "Stewart M",
      "referenceId" : "RGD:A45122"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12911013"
    } ]
  }, {
    "primaryId" : "PMID:10356629",
    "title" : "Glucocorticoid receptors in anorexia nervosa and Cushing's disease.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Invitti C, etal., Biol Psychiatry. 1999 Jun 1;45(11):1467-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-11-16T17:26:09.000-06:00",
    "volume" : "45",
    "pages" : "1467-71",
    "abstract" : "BACKGROUND: Patients with anorexia nervosa do not display cushingoid features in  spite of elevated cortisol plasma levels. Whether a cortisol resistance or a reduced availability of the metabolic substrates necessary to develop the effect  of glucocorticoids is responsible for this has not been established. METHODS: Twenty-two patients with severe restrictive anorexia nervosa, 10 patients with active Cushing's disease, and 24 healthy volunteers without psychiatric disorders or mood alterations were investigated. Glucocorticoid receptor characteristics were examined on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which represents  an index of DNA synthesis. RESULTS: The number of glucocorticoid receptors on mononuclear leukocytes (MNL) was comparable in patients with anorexia nervosa, patients with active Cushing's disease, and normal subjects (binding capacity 3.3 +/- 0.23 vs. 3.7 +/- 0.30 and 3.5 +/- 0.20 fmol/10(6) cells). Conversely, glucocorticoid receptor affinity was significantly decreased in anorexia nervosa  as well as in Cushing's patients compared to control subjects (dissociation constant 4.0 +/- 0.31 and 4.1 +/- 0.34 vs. 2.9 +/- 0.29 nmol/L, p < .001) and inversely correlated with the levels of urinary free cortisol in both groups of patients. Basal [3H]thymidine incorporation in MNL was significantly reduced in anorexia nervosa as well as in Cushing's patients compared to control subjects (p < .001) and was diminished by dexamethasone to an extent similar to control subjects in patients with anorexia nervosa, but significantly (p < .001) less in  those with Cushing's disease. In patients with anorexia nervosa, the incorporation of [3H]thymidine into the MNL was inversely correlated with urinary free cortisol levels. CONCLUSIONS: These data indicate that the lack of cushingoid features in patients with anorexia nervosa is not ascribable to a reduced sensitivity to glucocorticoids but is more likely due to the paucity of metabolic substrates.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Invitti",
      "authorRank" : 1,
      "name" : "Invitti C",
      "referenceId" : "RGD:A85005"
    }, {
      "firstName" : "G",
      "lastName" : "Redaelli",
      "authorRank" : 2,
      "name" : "Redaelli G",
      "referenceId" : "RGD:A159721"
    }, {
      "firstName" : "G",
      "lastName" : "Baldi",
      "authorRank" : 3,
      "name" : "Baldi G",
      "referenceId" : "RGD:A159722"
    }, {
      "firstName" : "F",
      "lastName" : "Cavagnini",
      "authorRank" : 4,
      "name" : "Cavagnini F",
      "referenceId" : "RGD:A85004"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7174723"
    } ]
  }, {
    "primaryId" : "PMID:103573",
    "title" : "k Chain variable regions from three galactan binding myeloma proteins.",
    "datePublished" : "1978-06-01T00:00:00.000-05:00",
    "citation" : "Rao DN, etal., Biochemistry. 1978 Dec 12;17(25):5555-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:36:05.000-05:00",
    "volume" : "17",
    "pages" : "5555-9",
    "abstract" : "A series of seven BALB/c myeloma proteins has been identified with binding specificity for antigens containing beta(1 leads to 6)-D-galactopyranosyl moieties. We have determined the primary amino acid sequence of the first 108 residues from the light chains of three of these proteins. The framework portions of the variable regions of these three light chains are identical with residue 100 at which position three different amino acids are found in the three chains.  An additional interchange was found at position 106 in one of the proteins. Based on recent DNA sequence studies suggesting that the variable region ends at residue 97, these substitutions indicate the possible existance of multiple genes coding for the region beginning at residue 98 and continuing toward the carboxy terminus. A single amino acid interchange was observed in complementarity determining regions occurring in L3. This substitution (Ile-Trp) would require changes in all three codon bases to produce the respective amino acids if one were derived from the other. Two of these chains are thus indistinguishable for their first 100 amino acids and are the first pair of k chains to exhibit complete identity over their variable regions.",
    "issueName" : "25",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DN",
      "lastName" : "Rao",
      "authorRank" : 1,
      "name" : "Rao",
      "referenceId" : "RGD:A211284"
    }, {
      "firstName" : "S",
      "lastName" : "Rudikoff",
      "authorRank" : 2,
      "name" : "Rudikoff S",
      "referenceId" : "RGD:A57057"
    }, {
      "firstName" : "M",
      "lastName" : "Potter",
      "authorRank" : 3,
      "name" : "Potter",
      "referenceId" : "RGD:A229260"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340645"
    } ]
  }, {
    "primaryId" : "PMID:10357812",
    "title" : "Recruitment of an alternatively spliced form of synaptojanin 2 to mitochondria by the interaction with the PDZ domain of a mitochondrial outer membrane protein.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Nemoto Y and De Camilli P, EMBO J 1999 Jun 1;18(11):2991-3006.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-11-26T12:12:49.000-06:00",
    "volume" : "18",
    "pages" : "2991-3006",
    "abstract" : "Synaptojanin 1 is an inositol 5'-phosphatase highly enriched in nerve terminals with a putative role in recycling of synaptic vesicles. We have previously described synaptojanin 2, which is more broadly expressed as multiple alternatively spliced forms. Here we have identified and characterized a novel mitochondrial outer membrane protein, OMP25, with a single PDZ domain that specifically binds to a unique motif in the C-terminus of synaptojanin 2A. This motif is encoded by the exon sequence specific to synaptojanin 2A. OMP25 mRNA is widely expressed in rat tissues. OMP25 is localized to the mitochondrial outer membrane via the C-terminal transmembrane region, with the PDZ domain facing the cytoplasm. Overexpression of OMP25 results in perinuclear clustering of mitochondria in transfected cells. This effect is mimicked by enforced expression of synaptojanin 2A on the mitochondrial outer membrane, but not by the synaptojanin 2A mutants lacking the inositol 5'-phosphatase domain. Our findings provide evidence that OMP25 mediates recruitment of synaptojanin 2A to mitochondria and that modulation of inositol phospholipids by synaptojanin 2A may play a role in maintenance of the intracellular distribution of mitochondria.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Nemoto",
      "authorRank" : 1,
      "name" : "Nemoto Y",
      "referenceId" : "RGD:A6107"
    }, {
      "firstName" : "P",
      "lastName" : "De Camilli",
      "authorRank" : 2,
      "name" : "De Camilli P",
      "referenceId" : "RGD:A6113"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69391"
    } ]
  }, {
    "primaryId" : "PMID:10357815",
    "title" : "Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Park J, etal., EMBO J. 1999 Jun 1;18(11):3024-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-10-15T11:45:29.000-05:00",
    "volume" : "18",
    "pages" : "3024-33",
    "abstract" : "Serum and glucocorticoid-inducible kinase (SGK) is a novel member of the serine/threonine protein kinase family that is transcriptionally regulated. In this study, we have investigated the regulatory mechanisms that control SGK activity. We have established a peptide kinase assay for SGK and present evidence demonstrating that SGK is a component of the phosphoinositide 3 (PI 3)-kinase signaling pathway. Treatment of human embryo kidney 293 cells with insulin, IGF-1 or pervanadate induced a 3- to 12-fold activation of ectopically expressed SGK. Activation was completely abolished by pretreatment of cells with the PI 3-kinase inhibitor, LY294002. Treatment of activated SGK with protein phosphatase 2A in vitro led to kinase inactivation. Consistent with the similarity of SGK to other second-messenger regulated kinases, mutation of putative phosphorylation sites at Thr256 and Ser422 inhibited SGK activation. Cotransfection of PDK1 with SGK caused a 6-fold activation of SGK activity, whereas kinase-dead PDK1 caused no activation. GST-pulldown assays revealed a direct interaction between PDK1 and the catalytic domain of SGK. Treatment of rat mammary tumor cells with serum caused hyperphosphorylation of endogenous SGK, and promoted translocation to the nucleus. Both hyperphosphorylation and nuclear translocation could be inhibited by wortmannin, but not by rapamycin.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Park",
      "authorRank" : 1,
      "name" : "Park J",
      "referenceId" : "RGD:A10241"
    }, {
      "firstName" : "ML",
      "lastName" : "Leong",
      "authorRank" : 2,
      "name" : "Leong ML",
      "referenceId" : "RGD:A88986"
    }, {
      "firstName" : "P",
      "lastName" : "Buse",
      "authorRank" : 3,
      "name" : "Buse P",
      "referenceId" : "RGD:A88987"
    }, {
      "firstName" : "AC",
      "lastName" : "Maiyar",
      "authorRank" : 4,
      "name" : "Maiyar AC",
      "referenceId" : "RGD:A7973"
    }, {
      "firstName" : "GL",
      "lastName" : "Firestone",
      "authorRank" : 5,
      "name" : "Firestone GL",
      "referenceId" : "RGD:A7974"
    }, {
      "firstName" : "BA",
      "lastName" : "Hemmings",
      "authorRank" : 6,
      "name" : "Hemmings BA",
      "referenceId" : "RGD:A58402"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642777"
    } ]
  }, {
    "primaryId" : "PMID:10357839",
    "title" : "Atypical expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in subcutaneous adipose tissue of male rats.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Thumelin S, etal., J Lipid Res. 1999 Jun;40(6):1071-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-24T16:55:11.000-05:00",
    "volume" : "40",
    "pages" : "1071-7",
    "abstract" : "The mRNAs encoding mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mtHMG-CoA synthase), the rate limiting enzyme in ketone body production, are highly expressed in subcutaneous (SC) and, to a lesser extent, in peri-epididymal (PE) rat adipose tissues. This atypical mtHMG-CoA synthase gene expression is dependent on the age (from 9 weeks of age) and sex (higher in male than in female) of the rats. In contrast, the expression of mtHMG-CoA synthase in SC adipose deposit is independent of the nutritional state (fed versus starved) or of the thermic environment (24 degrees C versus 4 degrees C). The expression of mtHMG-CoA synthase is suppressed in SC fat pads of castrated male rats whereas treatment of castrated rats with testosterone restores a normal level of expression. Moreover, testosterone injection induces the expression mtHMG-CoA synthase in SC adipose tissue of age-matched females. The presence of the mtHMG-CoA synthase immunoreactive protein confers to mitochondria isolated from SC adipose deposits, the capacity to produce ketone bodies at a rate similar to that found in liver mitochondria (SC = 13.7 +/- 0.7, liver = 16.4 +/- 1.4 nmol/min/mg prot). mtHMG-CoA synthase is expressed in the stromal vascular fraction (SVF) whatever the adipose deposit considered. While acetyl-CoA carboxylase (ACC) is only expressed in mature adipocytes, the other lipogenic enzymes, fatty acid synthase (FAS) and citrate cleavage enzyme (CCE), are expressed both in SVF cells and mature adipocytes. The expression of lipogenic enzyme genes is markedly reduced in adipocytes but not in SVF cells isolated from 48-h starved male rats. When SVF is subfractionated, mtHMG-CoA synthase mRNAs are mainly recovered in two fractions containing poorly digested structures such as microcapillaries whereas the lowest expression is found in the pre-adipocyte fraction. Interestingly, FAS and CCE mRNAs co-segregate with mtHMG-CoA synthase mRNA. The possible physiological relevance of such atypical expression of mtHMG-CoA synthase is discussed.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Thumelin",
      "authorRank" : 1,
      "name" : "Thumelin S",
      "referenceId" : "RGD:A125429"
    }, {
      "firstName" : "C",
      "lastName" : "Kohl",
      "authorRank" : 2,
      "name" : "Kohl C",
      "referenceId" : "RGD:A13709"
    }, {
      "firstName" : "J",
      "lastName" : "Girard",
      "authorRank" : 3,
      "name" : "Girard J",
      "referenceId" : "RGD:A125435"
    }, {
      "firstName" : "JP",
      "lastName" : "Pegorier",
      "authorRank" : 4,
      "name" : "Pegorier JP",
      "referenceId" : "RGD:A13712"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2326128"
    } ]
  }, {
    "primaryId" : "PMID:10357843",
    "title" : "Evidence for a third genetic locus causing familial hypercholesterolemia. A non-LDLR, non-APOB kindred.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Haddad L, etal., J Lipid Res. 1999 Jun;40(6):1113-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:55:39.000-05:00",
    "volume" : "40",
    "pages" : "1113-22",
    "abstract" : "Monogenically inherited hypercholesterolemia is most commonly caused by mutations at the low density lipoprotein receptor (LDLR) locus causing familial hypercholesterolemia (FH) or at the apolipoprotein B (APOB) locus causing the disorder familial defective apoB (FDB). Probands from 47 kindreds with a strict clinical diagnosis of FH were selected from the Cardiovascular Genetics Research Lipid Clinic, Utah, for molecular genetic analysis. Using a combination of single-strand conformation polymorphism (SSCP) and direct sequencing, 12 different LDLR gene mutations were found in 16 of the probands. Three of the probands were carriers of the APOB R3500Q mutation. In five of the remaining 28 pedigrees where no mutation had been detected, samples from enough relatives were available to examine co-segregation with the LDLR region using the microsatellite marker D19S221, which is within 1 Mb centromeric of the LDLR locus, and D19S394, sited within 150 kb telomeric of the LDLR locus. In four of the families there was strong evidence for co-segregation between the LDLR locus and the phenotype of hypercholesterolemia, but in one large family with 18 living affected members and clear-cut bimodal hypercholesterolemia, there were numerous exclusions of co-segregation. Using length polymorphic markers within and outside the APOB gene, linkage of phenotype in this family to the APOB region was similarly excluded. In this large family, the degree of hypercholesterolemia, prevalence of tendon xanthomata, and occurrence of early coronary disease were indistinguishable from the other families studied. In summary, the data provide unequivocal evidence that a third locus can be etiological for monogenic familial hypercholesterolemia and should be reinvigorating to research in this field.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Haddad",
      "authorRank" : 1,
      "name" : "Haddad L",
      "referenceId" : "RGD:A597320"
    }, {
      "firstName" : "I N",
      "lastName" : "Day",
      "authorRank" : 2,
      "name" : "Day IN",
      "referenceId" : "RGD:A597321"
    }, {
      "firstName" : "S",
      "lastName" : "Hunt",
      "authorRank" : 3,
      "name" : "Hunt S",
      "referenceId" : "RGD:A86384"
    }, {
      "firstName" : "R R",
      "lastName" : "Williams",
      "authorRank" : 4,
      "name" : "Williams RR",
      "referenceId" : "RGD:A597322"
    }, {
      "firstName" : "S E",
      "lastName" : "Humphries",
      "authorRank" : 5,
      "name" : "Humphries SE",
      "referenceId" : "RGD:A584297"
    }, {
      "firstName" : "P N",
      "lastName" : "Hopkins",
      "authorRank" : 6,
      "name" : "Hopkins PN",
      "referenceId" : "RGD:A597323"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118965"
    } ]
  }, {
    "primaryId" : "PMID:10357884",
    "title" : "A diabetogenic gene prevents T cells from receiving costimulatory signals.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Moore JK, etal., Cell Immunol. 1999 May 25;194(1):90-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-02-26T09:39:19.000-06:00",
    "volume" : "194",
    "pages" : "90-7",
    "abstract" : "T cell fate following antigen encounter is determined by several intracellular signals generated by the interaction of the T cell with an antigen-presenting cell. In the periphery activation requires T cell receptor signaling (signal one) in combination with costimulatory signals (signal two), usually provided through the cognate interaction of CD28 and B7 molecules. Provision of signal one alone to purified murine peripheral T cells in vitro induces apoptosis or anergy rather than promoting activation. These T cells can be rescued from apoptosis if they are provided with costimulation supplied, for example, by engaging the CD28 co-receptor with an anti-CD28 monoclonal antibody or by adding an exogenous source of interleukin-2. However, a majority of peripheral T cells from autoimmune, diabetes-prone Biobreeding (BB) rats exhibited different responses to these stimuli. T cells from these rats could not be rescued from apoptosis by costimulation. This was not due to the inability of BB-DP T cells to upregulate CD28 and the IL-2 receptor in response to TCR crosslinking. The failure of these costimulatory interactions to rescue BB-DP T cells segregated with the diabetes-susceptibility gene iddm1. Iddm1 in the rat causes peripheral T cell lymphopenia, which is associated with a dramatically shortened peripheral T cell life span. Our results indicate that a diabetogenic gene may contribute to autoimmunity by negating costimulatory signals important for the survival of long-lived peripheral T cells.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JK",
      "lastName" : "Moore",
      "authorRank" : 1,
      "name" : "Moore JK",
      "referenceId" : "RGD:A37858"
    }, {
      "firstName" : "DP",
      "lastName" : "Gold",
      "authorRank" : 2,
      "name" : "Gold DP",
      "referenceId" : "RGD:A104032"
    }, {
      "firstName" : "SC",
      "lastName" : "Dreskin",
      "authorRank" : 3,
      "name" : "Dreskin SC",
      "referenceId" : "RGD:A104033"
    }, {
      "firstName" : "A",
      "lastName" : "Lernmark",
      "authorRank" : 4,
      "name" : "Lernmark A",
      "referenceId" : "RGD:A163556"
    }, {
      "firstName" : "D",
      "lastName" : "Bellgrau",
      "authorRank" : 5,
      "name" : "Bellgrau D",
      "referenceId" : "RGD:A104020"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303777"
    } ]
  }, {
    "primaryId" : "PMID:10357921",
    "title" : "Analysis of the Fas system and Bcl-2 in rat liver allograft rejection.",
    "datePublished" : "1999-06-15T00:00:00.000-05:00",
    "citation" : "Hiroyasu S, etal., J Surg Res. 1999 Jun 15;84(2):204-11. doi: 10.1006/jsre.1999.5644.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-08-12T10:35:12.000-05:00",
    "volume" : "84",
    "pages" : "204-11",
    "abstract" : "<br><b>BACKGROUND: </b>Apoptosis is involved in the mechanism of cell death observed in liver allograft rejection. The liver cells are sensitive to Fas-mediated apoptosis; however, little is known about the involvement of the Fas system in liver allograft rejection. We used rat models to investigate the expression of Fas/Fas ligand and apoptosis-related proteins during liver allograft rejection.<br><b>MATERIALS AND METHODS: </b>DA rats to Lewis, and Lewis to Lewis orthotopic liver transplantation were performed; liver samples were collected on days 1, 3, 5, 7, and 9 postoperatively (each n = 3). Apoptosis was monitored by TUNEL and electron microscopy. The expression of Fas, FasL, bcl-2, and bax was examined at the mRNA level and by means of immunohistochemistry.<br><b>RESULTS: </b>The TUNEL index in the allografts and isografts on day 7 was 20.1 +/- 1.5 and 7.7 +/- 2.6/1000 cells, respectively. Fas and bax mRNA were constitutively expressed in both of the groups. The expression of Fas ligand mRNA in the allografts which rose on day 5 was 10 times stronger compared to that in the isografts. On the other hand, bcl-2 mRNA was generally expressed in the isografts while it decreased in the allografts. The immunohistochemical analysis also showed an increased reactivity of Fas ligand on day 5 in the allograft, which was observed both in parenchymal and nonparenchymal cells.<br><b>CONCLUSIONS: </b>These results strongly suggest that Fas/Fas ligand interaction mediates the liver injury during allograft rejection. In addition, other regulatory factors of apoptosis, such as bcl-2, might also be involved in this pathogenesis.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Hiroyasu",
      "authorRank" : 1,
      "name" : "Hiroyasu S",
      "referenceId" : "RGD:A472517"
    }, {
      "firstName" : "M",
      "lastName" : "Shiraishi",
      "authorRank" : 2,
      "name" : "Shiraishi M",
      "referenceId" : "RGD:A74907"
    }, {
      "firstName" : "T",
      "lastName" : "Koji",
      "authorRank" : 3,
      "name" : "Koji T",
      "referenceId" : "RGD:A33729"
    }, {
      "firstName" : "T",
      "lastName" : "Mamadi",
      "authorRank" : 4,
      "name" : "Mamadi T",
      "referenceId" : "RGD:A472520"
    }, {
      "firstName" : "H",
      "lastName" : "Sugawa",
      "authorRank" : 5,
      "name" : "Sugawa H",
      "referenceId" : "RGD:A472539"
    }, {
      "firstName" : "Y",
      "lastName" : "Muto",
      "authorRank" : 6,
      "name" : "Muto Y",
      "referenceId" : "RGD:A17509"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14700698"
    } ]
  }, {
    "primaryId" : "PMID:10358008",
    "title" : "Targeted disruption of the beta2 adrenergic receptor gene.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Chruscinski AJ, etal., J Biol Chem. 1999 Jun 11;274(24):16694-700.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-01-26T11:21:36.000-06:00",
    "volume" : "274",
    "pages" : "16694-700",
    "abstract" : "beta-Adrenergic receptors (beta-ARs) are members of the superfamily of G-protein-coupled receptors that mediate the effects of catecholamines in the sympathetic nervous system. Three distinct beta-AR subtypes have been identified (beta1-AR, beta2-AR, and beta3-AR). In order to define further the role of the different beta-AR subtypes, we have used gene targeting to inactivate selectively the beta2-AR gene in mice. Based on intercrosses of heterozygous knockout (beta2-AR +/-) mice, there is no prenatal lethality associated with this mutation. Adult knockout mice (beta2-AR -/-) appear grossly normal and are fertile. Their resting heart rate and blood pressure are normal, and they have a normal chronotropic response to the beta-AR agonist isoproterenol. The hypotensive response to isoproterenol, however, is significantly blunted compared with wild type mice. Despite this defect in vasodilation, beta2-AR -/- mice can still exercise normally and actually have a greater total exercise capacity than wild type mice. At comparable workloads, beta2-AR -/- mice had a lower respiratory exchange ratio than wild type mice suggesting a difference in energy metabolism. beta2-AR -/- mice become hypertensive during exercise and exhibit a greater hypertensive response to epinephrine compared with wild type mice. In summary, the primary physiologic consequences of the beta2-AR gene disruption are observed only during the stress of exercise and are the result of alterations in both vascular tone and energy metabolism.",
    "issueName" : "24",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AJ",
      "lastName" : "Chruscinski",
      "authorRank" : 1,
      "name" : "Chruscinski AJ",
      "referenceId" : "RGD:A58071"
    }, {
      "firstName" : "DK",
      "lastName" : "Rohrer",
      "authorRank" : 2,
      "name" : "Rohrer DK",
      "referenceId" : "RGD:A58051"
    }, {
      "firstName" : "E",
      "lastName" : "Schauble",
      "authorRank" : 3,
      "name" : "Schauble E",
      "referenceId" : "RGD:A58072"
    }, {
      "firstName" : "KH",
      "lastName" : "Desai",
      "authorRank" : 4,
      "name" : "Desai KH",
      "referenceId" : "RGD:A58073"
    }, {
      "firstName" : "D",
      "lastName" : "Bernstein",
      "authorRank" : 5,
      "name" : "Bernstein D",
      "referenceId" : "RGD:A58032"
    }, {
      "firstName" : "BK",
      "lastName" : "Kobilka",
      "authorRank" : 6,
      "name" : "Kobilka BK",
      "referenceId" : "RGD:A39435"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1559321"
    } ]
  }, {
    "primaryId" : "PMID:10358009",
    "title" : "Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Rohrer DK, etal., J Biol Chem. 1999 Jun 11;274(24):16701-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-01-25T12:47:03.000-06:00",
    "volume" : "274",
    "pages" : "16701-8",
    "abstract" : "The activation state of beta-adrenergic receptors (beta-ARs) in vivo is an important determinant of hemodynamic status, cardiac performance, and metabolic rate. In order to achieve homeostasis in vivo, the cellular signals generated by beta-AR activation are integrated with signals from a number of other distinct receptors and signaling pathways. We have utilized genetic knockout models to test directly the role of beta1- and/or beta2-AR expression on these homeostatic control mechanisms. Despite total absence of beta1- and beta2-ARs, the predominant cardiovascular beta-adrenergic subtypes, basal heart rate, blood pressure, and metabolic rate do not differ from wild type controls. However, stimulation of beta-AR function by beta-AR agonists or exercise reveals significant impairments in chronotropic range, vascular reactivity, and metabolic rate. Surprisingly, the blunted chronotropic and metabolic response to exercise seen in beta1/beta2-AR double knockouts fails to impact maximal exercise capacity. Integrating the results from single beta1- and beta2-AR knockouts as well as the beta1-/beta2-AR double knock-out suggest that in the mouse, beta-AR stimulation of cardiac inotropy and chronotropy is mediated almost exclusively by the beta1-AR, whereas vascular relaxation and metabolic rate are controlled by all three beta-ARs (beta1-, beta2-, and beta3-AR). Compensatory alterations in cardiac muscarinic receptor density and vascular beta3-AR responsiveness are also observed in beta1-/beta2-AR double knockouts. In addition to its ability to define beta-AR subtype-specific functions, this genetic approach is also useful in identifying adaptive alterations that serve to maintain critical physiological setpoints such as heart rate, blood pressure, and metabolic rate when cellular signaling mechanisms are perturbed.",
    "issueName" : "24",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DK",
      "lastName" : "Rohrer",
      "authorRank" : 1,
      "name" : "Rohrer DK",
      "referenceId" : "RGD:A58051"
    }, {
      "firstName" : "A",
      "lastName" : "Chruscinski",
      "authorRank" : 2,
      "name" : "Chruscinski A",
      "referenceId" : "RGD:A58031"
    }, {
      "firstName" : "EH",
      "lastName" : "Schauble",
      "authorRank" : 3,
      "name" : "Schauble EH",
      "referenceId" : "RGD:A58052"
    }, {
      "firstName" : "D",
      "lastName" : "Bernstein",
      "authorRank" : 4,
      "name" : "Bernstein D",
      "referenceId" : "RGD:A58032"
    }, {
      "firstName" : "BK",
      "lastName" : "Kobilka",
      "authorRank" : 5,
      "name" : "Kobilka BK",
      "referenceId" : "RGD:A39435"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1559316"
    } ]
  }, {
    "primaryId" : "PMID:10358057",
    "title" : "Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Daviet L, etal., J Biol Chem 1999 Jun 11;274(24):17058-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-31T15:18:28.000-05:00",
    "volume" : "274",
    "pages" : "17058-62",
    "abstract" : "The carboxyl-terminal cytoplasmic domain of the angiotensin II type 1 (AT1) receptor has recently been shown to interact with several classes of cytoplasmic proteins that regulate different aspects of AT1 receptor physiology. Employing yeast two-hybrid screening of a mouse kidney cDNA library with the carboxyl-terminal cytoplasmic domain of the murine AT1a receptor as a bait, we have isolated a novel protein with a predicted molecular mass of 18 kDa, which we have named ATRAP (for AT1 receptor-associated protein). ATRAP interacts specifically with the carboxyl-terminal domain of the AT1a receptor but not with those of angiotensin II type 2 (AT2), m3 muscarinic acetylcholine, bradykinin B2, endothelin B, and beta2-adrenergic receptors. The mRNA of ATRAP was abundantly expressed in kidney, heart, and testis but was poorly expressed in lung, liver, spleen, and brain. The ATRAP-AT1a receptor association was confirmed by affinity chromatography, by specific co-immunoprecipitation of the two proteins, and by fluorescence microscopy, showing co-localization of these proteins in intact cells. Overexpression of ATRAP in COS-7 cells caused a marked inhibition of AT1a receptor-mediated activation of phospholipase C without affecting m3 receptor-mediated activation. In conclusion, we have isolated a novel protein that interacts specifically with the carboxyl-terminal cytoplasmic domain of the AT1a receptor and affects AT1a receptor signaling.",
    "issueName" : "24",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Daviet",
      "authorRank" : 1,
      "name" : "Daviet L",
      "referenceId" : "RGD:A39201"
    }, {
      "firstName" : "JY",
      "lastName" : "Lehtonen",
      "authorRank" : 2,
      "name" : "Lehtonen JY",
      "referenceId" : "RGD:A55114"
    }, {
      "firstName" : "K",
      "lastName" : "Tamura",
      "authorRank" : 3,
      "name" : "Tamura K",
      "referenceId" : "RGD:A4675"
    }, {
      "firstName" : "DP",
      "lastName" : "Griese",
      "authorRank" : 4,
      "name" : "Griese DP",
      "referenceId" : "RGD:A55115"
    }, {
      "firstName" : "M",
      "lastName" : "Horiuchi",
      "authorRank" : 5,
      "name" : "Horiuchi M",
      "referenceId" : "RGD:A17967"
    }, {
      "firstName" : "VJ",
      "lastName" : "Dzau",
      "authorRank" : 6,
      "name" : "Dzau VJ",
      "referenceId" : "RGD:A118092"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549469"
    } ]
  }, {
    "primaryId" : "PMID:10358066",
    "title" : "Cloning and expression of a novel galactoside beta1, 3-glucuronyltransferase involved in the biosynthesis of HNK-1 epitope.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Shimoda Y, etal., J Biol Chem 1999 Jun 11;274(24):17115-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:24.000-05:00",
    "volume" : "274",
    "pages" : "17115-22",
    "abstract" : "We isolated a cDNA encoding a novel glucuronyltransferase, designated GlcAT-D, involved in the biosynthesis of the HNK-1 carbohydrate epitope from rat embryo cDNA by the degenerate polymerase chain reaction method. The new cDNA sequence revealed an open reading frame coding for a protein of 324 amino acids with type II transmembrane protein topology. The amino acid sequence of GlcAT-D displayed 50.0% identity to rat GlcAT-P, which is involved in the biosynthesis of the HNK-1 epitope on glycoproteins. Expression of GlcAT-D in COS-7 cells resulted in the formation of the HNK-1 epitope on the cell surface. The enzyme expressed in COS-7 cells transferred a glucuronic acid (GlcA) not only to asialo-orosomucoid, a glycoprotein bearing terminal N-acetyllactosamine structure, but also to paragloboside (lacto-N-neotetraosylceramide), a precursor of the HNK-1 epitope on glycolipids. Furthermore, substrate specificity analysis using a soluble chimeric form of GlcAT-D revealed that GlcAT-D transfers a GlcA not only to Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc-pyridylamine++ + but also to Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc-pyridylamine++ +. Enzymatic hydrolysis and Smith degradation of the reaction product indicated that GlcAT-D transfers a GlcA through a beta1,3-linkage to a terminal galactose. The GlcAT-D transcripts were detected in embryonic, postnatal, and adult rat brain. In situ hybridization analysis revealed that the expression pattern of GlcAT-D transcript in embryo is similar to that of GlcAT-P, but distinct expression of GlcAT-D was observed in the embryonic pallidum and retina. Regions that expressed GlcAT-D and/or GlcAT-P were always HNK-1-positive, indicating that both GlcATs are involved in the synthesis of the HNK-1 epitope in vivo.",
    "issueName" : "24",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Shimoda",
      "authorRank" : 1,
      "name" : "Shimoda Y",
      "referenceId" : "RGD:A16779"
    }, {
      "firstName" : "Y",
      "lastName" : "Tajima",
      "authorRank" : 2,
      "name" : "Tajima Y",
      "referenceId" : "RGD:A16780"
    }, {
      "firstName" : "T",
      "lastName" : "Nagase",
      "authorRank" : 3,
      "name" : "Nagase T",
      "referenceId" : "RGD:A118939"
    }, {
      "firstName" : "K",
      "lastName" : "Harii",
      "authorRank" : 4,
      "name" : "Harii K",
      "referenceId" : "RGD:A16782"
    }, {
      "firstName" : "N",
      "lastName" : "Osumi",
      "authorRank" : 5,
      "name" : "Osumi N",
      "referenceId" : "RGD:A16783"
    }, {
      "firstName" : "Y",
      "lastName" : "Sanai",
      "authorRank" : 6,
      "name" : "Sanai Y",
      "referenceId" : "RGD:A16784"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632231"
    } ]
  }, {
    "primaryId" : "PMID:10358187",
    "title" : "Antibody prevents virus reactivation within the central nervous system.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Lin MT, etal., J Immunol. 1999 Jun 15;162(12):7358-68.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:34:59.000-05:00",
    "volume" : "162",
    "pages" : "7358-68",
    "abstract" : "The neurotropic JHM strain of mouse hepatitis virus (JHMV) produces an acute CNS  infection characterized by encephalomyelitis and demyelination. The immune response cannot completely eliminate virus, resulting in persistence associated with chronic ongoing CNS demyelination. The contribution of humoral immunity to viral clearance and persistent infection was investigated in mice homozygous for  disruption of the Ig mu gene (IgM-/-). Acute disease developed with equal kinetics and severity in IgM-/- and syngeneic C57BL/6 (wt) mice. However, clinical disease progressed in IgM-/- mice, while wt mice recovered. Viral clearance during acute infection was similar in both groups, supporting a primary role of cell-mediated immunity in viral clearance. In contrast to wt mice, in which infectious virus was reduced to below detection following acute infection,  increasing infectious virus was recovered from the CNS of the IgM-/- mice following initial clearance. No evidence was obtained for selection of variant viruses nor was there an apparent loss of cell-mediated immunity in the absence of Ab. Passive transfer of anti-JHMV Ab following initial clearance prevented reactivation of infectious virus within the CNS of IgM-/- mice. These data demonstrate the clearance of infectious virus during acute disease by cell-mediated immunity. However, immunologic control is not maintained in the absence of anti-viral Ab, resulting in recrudescence of infectious virus. These data suggest that humoral immunity plays no role in controlling virus during acute infection, but plays an important role in establishing and maintaining CNS  viral persistence.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MT",
      "lastName" : "Lin",
      "authorRank" : 1,
      "name" : "Lin MT",
      "referenceId" : "RGD:A87493"
    }, {
      "firstName" : "DR",
      "lastName" : "Hinton",
      "authorRank" : 2,
      "name" : "Hinton DR",
      "referenceId" : "RGD:A158148"
    }, {
      "firstName" : "NW",
      "lastName" : "Marten",
      "authorRank" : 3,
      "name" : "Marten NW",
      "referenceId" : "RGD:A86829"
    }, {
      "firstName" : "CC",
      "lastName" : "Bergmann",
      "authorRank" : 4,
      "name" : "Bergmann CC",
      "referenceId" : "RGD:A158150"
    }, {
      "firstName" : "SA",
      "lastName" : "Stohlman",
      "authorRank" : 5,
      "name" : "Stohlman SA",
      "referenceId" : "RGD:A158147"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340580"
    } ]
  }, {
    "primaryId" : "PMID:10358201",
    "title" : "Rhinovirus regulation of IL-1 receptor antagonist in vivo and in vitro: a potential mechanism of symptom resolution.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Yoon HJ, etal., J Immunol. 1999 Jun 15;162(12):7461-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-16T13:20:24.000-05:00",
    "volume" : "162",
    "pages" : "7461-9",
    "abstract" : "Rhinovirus (RV) upper respiratory tract infections are prototypic transient inflammatory responses. To address the mechanism of disease resolution in these infections, we determined if RV stimulated the production of the IL-1 receptor antagonist (IL-1ra) in vivo and in vitro. In contrast to IL-1alpha and IL-1beta, immunoreactive IL-1ra was readily detected in the nasal washings of normal human volunteers. Symptomatic RV infection caused a small increase in IL-1alpha, a modest increase in IL-1beta, and an impressive increase in IL-1ra. Maximal induction of IL-1alpha and IL-1beta was transiently noted 48 h after RV infection. In contrast, maximal induction of IL-1ra was prolonged appearing 48-72 h after RV infection. These time points corresponded to the periods of peak symptomatology and the onset of symptom resolution, respectively. Western analysis of nasal washings demonstrated that RV stimulated the accumulation of intracellular IL-1ra type I in all and secreted IL-1ra in a subset of volunteers. Unstimulated normal respiratory epithelial cells contained intracellular IL-1ra type I mRNA and protein. RV infection increased the intracellular levels and extracellular transport of this IL-1ra moiety without causing significant changes in the levels of IL-1ra mRNA. IL-1ra may play an important role in the resolution of RV respiratory infections. RV stimulates epithelial cell IL-1ra elaboration, at least in part, via a novel translational and/or posttranslational mechanism.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HJ",
      "lastName" : "Yoon",
      "authorRank" : 1,
      "name" : "Yoon HJ",
      "referenceId" : "RGD:A70852"
    }, {
      "firstName" : "Z",
      "lastName" : "Zhu",
      "authorRank" : 2,
      "name" : "Zhu Z",
      "referenceId" : "RGD:A7842"
    }, {
      "firstName" : "JR",
      "lastName" : "Gwaltney JM",
      "authorRank" : 3,
      "name" : "Gwaltney JM JR",
      "referenceId" : "RGD:A127469"
    }, {
      "firstName" : "JA",
      "lastName" : "Elias",
      "authorRank" : 4,
      "name" : "Elias JA",
      "referenceId" : "RGD:A127470"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4143183"
    } ]
  }, {
    "primaryId" : "PMID:10358204",
    "title" : "The role of an epithelial neutrophil-activating peptide-78-like protein in rat adjuvant-induced arthritis.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Halloran MM, etal., J Immunol. 1999 Jun 15;162(12):7492-500.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-07-18T17:30:05.000-05:00",
    "volume" : "162",
    "pages" : "7492-500",
    "abstract" : "The chemokine, epithelial neutrophil-activating peptide-78 (ENA-78), is a potent neutrophil chemotaxin whose expression is increased in inflamed synovial tissue and fluid in human rheumatoid arthritis compared with osteoarthritis. Since ENA-78 has been implicated in the pathogenesis of RA, we examined the expression of an ENA-78-like protein during the development of rat adjuvant-induced arthritis (AIA). Using an ELISA assay, we found increased levels of antigenic ENA-78-like protein in the sera of AIA animals compared with control normal animals by day 7 postadjuvant injection. ENA-78-like protein levels continued to increase as AIA developed. ENA-78-like protein levels in joint homogenates were increased in AIA animals later in the development of the disease, by day 18 during maximal arthritis, compared with control animals. Expression of ENA-78-like protein in both the AIA serum and joint correlated with the progression of inflammation of the joints. Anti-human ENA-78 administered before disease onset modified the severity of AIA, while administration of anti-ENA-78 after clinical onset of AIA did not modify the disease. These data support a role for an ENA-78-like protein as an important chemokine in the progression and maintenance of AIA.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Halloran",
      "authorRank" : 1,
      "name" : "Halloran MM",
      "referenceId" : "RGD:A91129"
    }, {
      "firstName" : "JM",
      "lastName" : "Woods",
      "authorRank" : 2,
      "name" : "Woods JM",
      "referenceId" : "RGD:A60788"
    }, {
      "firstName" : "RM",
      "lastName" : "Strieter",
      "authorRank" : 3,
      "name" : "Strieter RM",
      "referenceId" : "RGD:A49755"
    }, {
      "firstName" : "Z",
      "lastName" : "Szekanecz",
      "authorRank" : 4,
      "name" : "Szekanecz Z",
      "referenceId" : "RGD:A91130"
    }, {
      "firstName" : "MV",
      "lastName" : "Volin",
      "authorRank" : 5,
      "name" : "Volin MV",
      "referenceId" : "RGD:A104176"
    }, {
      "firstName" : "S",
      "lastName" : "Hosaka",
      "authorRank" : 6,
      "name" : "Hosaka S",
      "referenceId" : "RGD:A141598"
    }, {
      "firstName" : "3RD",
      "lastName" : "Haines GK",
      "authorRank" : 7,
      "name" : "Haines GK 3RD",
      "referenceId" : "RGD:A120966"
    }, {
      "firstName" : "SL",
      "lastName" : "Kunkel",
      "authorRank" : 8,
      "name" : "Kunkel SL",
      "referenceId" : "RGD:A69785"
    }, {
      "firstName" : "MD",
      "lastName" : "Burdick",
      "authorRank" : 9,
      "name" : "Burdick MD",
      "referenceId" : "RGD:A49748"
    }, {
      "firstName" : "A",
      "lastName" : "Walz",
      "authorRank" : 10,
      "name" : "Walz A",
      "referenceId" : "RGD:A127504"
    }, {
      "firstName" : "AE",
      "lastName" : "Koch",
      "authorRank" : 11,
      "name" : "Koch AE",
      "referenceId" : "RGD:A60793"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5135272"
    } ]
  }, {
    "primaryId" : "PMID:10359313",
    "title" : "Bacterial conjunctivitis in Muc1 null mice.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Kardon R, etal., Invest Ophthalmol Vis Sci. 1999 Jun;40(7):1328-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-09-23T18:04:28.000-05:00",
    "volume" : "40",
    "pages" : "1328-35",
    "abstract" : "PURPOSE: In contrast to wild-type mice, genetically engineered Mucin1 (Muc1) null animals display a marked propensity for development of blepharitis and conjunctivitis. Molecular approaches confirmed the presence of Muc1 mRNA and protein in the conjunctival tissue of wild-type mice and identified the bacterial species in Muc1 null symptomatic mice. METHODS: Muc1 null animals housed in a conventional facility were examined for visually apparent inflammation of the eye and surrounding tissue. Blood taken from overtly affected animals was assayed for antibodies to common murine viral agents. Swabs of infected eyes and whole eye preparations were used to detect and speciate bacterial pathogens. Frozen sections of whole eye, lid margin, and Harderian gland were immunostained with antibodies to Muc1 and cytokeratin 14, both epithelial cell markers. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were performed on RNA isolated from conjunctiva and Harderian gland of wild-type mice  to compare relative levels of transcript. RESULTS: Student's unpaired t-test performed on the eye inflammation frequency of Muc1 null mice confirmed a statistical significance (P < 0.01) when compared to wild-type background animals housed in the same room. Analysis of blood samples from affected Muc1 null animals detected no common murine viral pathogens. Bacterial analysis of conjunctival swabs and whole eye preparations demonstrated the presence of coagulase-negative Staphylococcus, Streptococcus type alpha, and Corynebacterium  group G2. Muc1 antibody staining of wild-type sections revealed the presence of Muc1 on conjunctival goblet and non-goblet cells and on the epithelium of the Harderian gland. Serial sections stained with cytokeratin 14 antibody confirmed the epithelial nature of cells expressing the Muc1 protein. RNA from conjunctiva  and Harderian gland subjected to RT-PCR and northern blot analysis showed an abundance of Muc1 transcript in these tissues. CONCLUSIONS: Muc1 mRNA and protein are present in murine conjunctival and Harderian gland epithelia. Animals lacking Muc1 mRNA and protein are predisposed to developing eye inflammation when compared to wild-type animals with an intact Muc1 gene. Muc1 appears to play a critical protective role at the ocular surface, presumably by acting as a barrier to infection by certain bacterial strains.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Kardon",
      "authorRank" : 1,
      "name" : "Kardon",
      "referenceId" : "RGD:A173200"
    }, {
      "firstName" : "RE",
      "lastName" : "Price",
      "authorRank" : 2,
      "name" : "Price RE",
      "referenceId" : "RGD:A117628"
    }, {
      "firstName" : "J",
      "lastName" : "Julian",
      "authorRank" : 3,
      "name" : "Julian J",
      "referenceId" : "RGD:A20850"
    }, {
      "firstName" : "E",
      "lastName" : "Lagow",
      "authorRank" : 4,
      "name" : "Lagow",
      "referenceId" : "RGD:A173201"
    }, {
      "firstName" : "SC",
      "lastName" : "Tseng",
      "authorRank" : 5,
      "name" : "Tseng",
      "referenceId" : "RGD:A173202"
    }, {
      "firstName" : "SJ",
      "lastName" : "Gendler",
      "authorRank" : 6,
      "name" : "Gendler SJ",
      "referenceId" : "RGD:A123848"
    }, {
      "firstName" : "DD",
      "lastName" : "Carson",
      "authorRank" : 7,
      "name" : "Carson DD",
      "referenceId" : "RGD:A20851"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7349379"
    } ]
  }, {
    "primaryId" : "PMID:10359324",
    "title" : "Expression of cell adhesion molecules on limbal and neovascular endothelium in corneal inflammatory neovascularization.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Zhu SN and Dana MR, Invest Ophthalmol Vis Sci. 1999 Jun;40(7):1427-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-04-07T11:53:45.000-05:00",
    "volume" : "40",
    "pages" : "1427-34",
    "abstract" : "PURPOSE: To investigate the expression of cell-adhesion molecules on corneolimbal and neovascular endothelium and the associated leukocyte infiltration in an experimental model of inflammatory corneal neovascularization (NV). METHODS: Corneal NV was induced in BALB/c mice by placement of nylon sutures. Interleukin-1 receptor antagonist (IL-1ra) was used topically to determine whether suppression of IL-1 could affect adhesion molecule expression and leukocytic infiltration. At set time points, corneal samples were analyzed immunohistochemically for expression of P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, and platelet- endothelial adhesion molecule (PECAM)-1. Leukocytic infiltration at different time points was quantified histologically. In companion experiments mice deficient in ICAM-1 were investigated to determine the functional relevance of this molecule in corneal leukocyte infiltration. RESULTS: Significant enhanced expression of ICAM-1 was detected on the corneolimbal vascular endothelium as early as 8 hours and on the newly formed corneal NV by day 3, and treatment with  IL-1ra led to significant suppression of this expression. IL-1ra-induced suppression of ICAM-1 expression was accompanied by a profound decrease in corneal leukocytic infiltration by 44.6% at day 1 (P < 0.003), 71.8% at day 3 (P  < 0.001), 60.1% at day 7 (P < 0.001), and 63.8% at day 14 (P < 0.001), compared with control corneas. Similarly, in ICAM-1 knockout mice, the corneal leukocytic  infiltration was 50.3%, 52.9%, and 36.4%, compared with wild-type control animals on day 1 (P < 0.001), day 7 (P < 0.005), and day 14 (P < 0.001), respectively. Expression of PECAM-1 was constitutively present on perilimbal vascular endothelium and had no response to IL-1ra treatment. No significant expression of P-selectin, E-selectin, or VCAM-1 was detected in this experimental model. CONCLUSIONS: These results suggest that leukocytic infiltration in this model of  inflammatory corneal NV is closely associated with ICAM-1 expression, and that topical IL-1ra displays corneal anti-inflammatory effects, largely by suppressing ICAM-1 expression on vascular endothelial cells.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SN",
      "lastName" : "Zhu",
      "authorRank" : 1,
      "name" : "Zhu SN",
      "referenceId" : "RGD:A42488"
    }, {
      "firstName" : "MR",
      "lastName" : "Dana",
      "authorRank" : 2,
      "name" : "Dana",
      "referenceId" : "RGD:A182219"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8549790"
    } ]
  }, {
    "primaryId" : "PMID:10359334",
    "title" : "Inhibitory effect of TNP-470 on experimental choroidal neovascularization in a rat model.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Ishida K, etal., Invest Ophthalmol Vis Sci. 1999 Jun;40(7):1512-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-15T14:47:13.000-05:00",
    "volume" : "40",
    "pages" : "1512-9",
    "abstract" : "PURPOSE: To determine whether an angiogenic inhibitor, TNP- 470 (TNP), an analogue of fumagillin, inhibits choroidal neovascularization (CNV) induced by diode laser photocoagulation in a rat experimental model. METHODS: Fundus laser photocoagulation was performed on Brown Norway rats to induce CNV. In the treatment group, TNP was administered intraperitoneally at the time of laser photocoagulation and on day 7 (50 mg/kg at each time). The incidence of CNV formation was evaluated by fluorescein angiography. The retina was collected from the rats on days 1, 3, 7, and 14 after laser photocoagulation, and semiquantitative polymerase chain reaction (PCR) analyses for the expression of mRNA of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were carried out. Localization of bFGF mRNA was studied by in situ  reverse transcription-PCR (RT-PCR). The numbers of positively labeled cells for bFGF mRNA were compared between the TNP treatment and control groups. RESULTS: The incidence of CNV formation was 22.7% in the TNP-treated rats and that in the  control rats was 61.4% (P < 0.001). The semiquantitative PCR analyses showed that bFGF mRNA was upregulated on days 3 and 7 in the control rats, but no significant changes were found in TNP-treated rats. There was no detectable difference in VEGF gene expression between the control and TNP-treated rats. bFGF mRNA was detected by in situ RT-PCR in the regenerated retinal pigment epithelial cells and cells of the outer and inner nuclear layers of the control rats. The number of positive cells for bFGF mRNA in the TNP treatment group was significantly smaller than that of the control group (P < 0.05) on days 3 and 14. CONCLUSIONS:  TNP- 470 treatment reduced the incidence of laser-induced CNV formation in this experimental model. The expression of bFGF associated with CNV formation was also significantly reduced by the TNP treatment.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Ishida",
      "authorRank" : 1,
      "name" : "Ishida K",
      "referenceId" : "RGD:A31827"
    }, {
      "firstName" : "N",
      "lastName" : "Yoshimura",
      "authorRank" : 2,
      "name" : "Yoshimura N",
      "referenceId" : "RGD:A18622"
    }, {
      "firstName" : "M",
      "lastName" : "Mandai",
      "authorRank" : 3,
      "name" : "Mandai M",
      "referenceId" : "RGD:A96548"
    }, {
      "firstName" : "Y",
      "lastName" : "Honda",
      "authorRank" : 4,
      "name" : "Honda Y",
      "referenceId" : "RGD:A14462"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8655568"
    } ]
  }, {
    "primaryId" : "PMID:10359335",
    "title" : "Differential distribution of dystrophins in rat retina.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Claudepierre T, etal., Invest Ophthalmol Vis Sci 1999 Jun;40(7):1520-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-25T07:49:28.000-05:00",
    "volume" : "40",
    "pages" : "1520-9",
    "abstract" : "PURPOSE: Duchenne muscular dystrophy is frequently associated with a reduced amplitude of b-wave under scotopic conditions in the electroretinogram. This suggests that the dystrophin gene-encoded proteins play a role in retinal neurotransmission. The abnormal neurotransmission has been attributed to altered expressions of C-terminal products of the dystrophin gene in the outer plexiform layer, where photoreceptor cells form synapses with secondary neurons. The present study was undertaken to determine the cellular distribution of each member of the dystrophin superfamily in rat retina. METHODS: Examined in the study were the developmental pattern of dystrophins in rat retinae that exhibit inherited progressive photoreceptor degeneration; dystrophins messengers expression in the outer and the inner retina of normal rats, prepared by mechanical fractionation through the outer plexiform layer; and immunolocalization of dystrophin proteins and utrophin in normal and degenerated adult rat retinae, with several antibodies prepared against specific regions of the dystrophin superfamily. RESULTS: The results showed that Dp260 is exclusively localized in photoreceptor cells; Dp140 seems to be present in perivascular astrocytes; the exon 78 spliced isoform of Dp71 and the unspliced form are located in Muller glial cells and in perivascular astrocytes, respectively. Muller glial cells also contain utrophin. CONCLUSIONS: Although the role of these membrane cytoskeletal proteins remains to be elucidated in retina, the results support the hypothesis that b-wave reduction may be caused by molecular anomalies of C-terminal products of the dystrophin gene expressed in both neuron and glial cells.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Claudepierre",
      "authorRank" : 1,
      "name" : "Claudepierre T",
      "referenceId" : "RGD:A45102"
    }, {
      "firstName" : "F",
      "lastName" : "Rodius",
      "authorRank" : 2,
      "name" : "Rodius F",
      "referenceId" : "RGD:A45103"
    }, {
      "firstName" : "M",
      "lastName" : "Frasson",
      "authorRank" : 3,
      "name" : "Frasson M",
      "referenceId" : "RGD:A45104"
    }, {
      "firstName" : "V",
      "lastName" : "Fontaine",
      "authorRank" : 4,
      "name" : "Fontaine V",
      "referenceId" : "RGD:A45105"
    }, {
      "firstName" : "S",
      "lastName" : "Picaud",
      "authorRank" : 5,
      "name" : "Picaud S",
      "referenceId" : "RGD:A45106"
    }, {
      "firstName" : "H",
      "lastName" : "Dreyfus",
      "authorRank" : 6,
      "name" : "Dreyfus H",
      "referenceId" : "RGD:A45107"
    }, {
      "firstName" : "D",
      "lastName" : "Mornet",
      "authorRank" : 7,
      "name" : "Mornet D",
      "referenceId" : "RGD:A45108"
    }, {
      "firstName" : "A",
      "lastName" : "Rendon",
      "authorRank" : 8,
      "name" : "Rendon A",
      "referenceId" : "RGD:A45109"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300412"
    } ]
  }, {
    "primaryId" : "PMID:10359560",
    "title" : "Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Geraci MW, etal., J Clin Invest 1999 Jun;103(11):1509-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:54:40.000-06:00",
    "volume" : "103",
    "pages" : "1509-15",
    "abstract" : "Prostacyclin synthase (PGIS) is the final committed enzyme in the metabolic pathway leading to prostacyclin (PGI2) production. Patients with severe pulmonary hypertension have a PGIS deficiency of their precapillary vessels, but the importance of this deficiency for lung vascular remodeling remains unclear. We hypothesized that selective pulmonary overexpression of PGIS may prevent the development of pulmonary hypertension. To study this hypothesis, transgenic mice were created with selective pulmonary PGIS overexpression using a construct of the 3.7-kb human surfactant protein-C (SP-C) promoter and the rat PGIS cDNA. Transgenic mice (Tg+) and nontransgenic littermates (Tg-) were subjected to a simulated altitude of 17,000 ft for 5 weeks, and right ventricular systolic pressure (RVSP) was measured. Histology was performed on the lungs. The Tg+ mice produced 2-fold more pulmonary 6-keto prostaglandin F1alpha (PGF1alpha) levels than did Tg- mice. After exposure to chronic hypobaric hypoxia, Tg+ mice have lower RVSP than do Tg- mice. Histologic examination of the lungs revealed nearly normal arteriolar vessels in the Tg+ mice in comparison with vessel wall hypertrophy in the Tg- mice. These studies demonstrate that Tg+ mice were protected from the development of pulmonary hypertension after exposure to chronic hypobaric hypoxia. We conclude that PGIS plays a major role in modifying the pulmonary vascular response to chronic hypoxia. This has important implications for the pathogenesis and treatment of severe pulmonary hypertension.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MW",
      "lastName" : "Geraci",
      "authorRank" : 1,
      "name" : "Geraci MW",
      "referenceId" : "RGD:A27183"
    }, {
      "firstName" : "B",
      "lastName" : "Gao",
      "authorRank" : 2,
      "name" : "Gao B",
      "referenceId" : "RGD:A27184"
    }, {
      "firstName" : "DC",
      "lastName" : "Shepherd",
      "authorRank" : 3,
      "name" : "Shepherd DC",
      "referenceId" : "RGD:A27185"
    }, {
      "firstName" : "MD",
      "lastName" : "Moore",
      "authorRank" : 4,
      "name" : "Moore MD",
      "referenceId" : "RGD:A27186"
    }, {
      "firstName" : "JY",
      "lastName" : "Westcott",
      "authorRank" : 5,
      "name" : "Westcott JY",
      "referenceId" : "RGD:A27187"
    }, {
      "firstName" : "KA",
      "lastName" : "Fagan",
      "authorRank" : 6,
      "name" : "Fagan KA",
      "referenceId" : "RGD:A27188"
    }, {
      "firstName" : "LA",
      "lastName" : "Alger",
      "authorRank" : 7,
      "name" : "Alger LA",
      "referenceId" : "RGD:A27189"
    }, {
      "firstName" : "RM",
      "lastName" : "Tuder",
      "authorRank" : 8,
      "name" : "Tuder RM",
      "referenceId" : "RGD:A27190"
    }, {
      "firstName" : "NF",
      "lastName" : "Voelkel",
      "authorRank" : 9,
      "name" : "Voelkel NF",
      "referenceId" : "RGD:A8426"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727270"
    } ]
  }, {
    "primaryId" : "PMID:10359588",
    "title" : "Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT/enhancer binding protein epsilon.",
    "datePublished" : "1999-06-07T00:00:00.000-05:00",
    "citation" : "Lekstrom-Himes JA, etal., J Exp Med. 1999 Jun 7;189(11):1847-52. doi: 10.1084/jem.189.11.1847.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:27:27.000-05:00",
    "volume" : "189",
    "pages" : "1847-52",
    "abstract" : "Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. CCAAT/enhancer binding protein (C/EBP)epsilon, a member of the leucine zipper family of transcription factors, is expressed primarily in myeloid cells, and its knockout mouse model possesses distinctive defects, including a lack of neutrophil secondary granule proteins. Sequence analysis of the genomic DNA of a patient with SGD revealed a five-basepair deletion in the second exon of the C/EBPepsilon locus. The predicted frame shift results in a truncation of the 32-kD major C/EBPepsilon isoform, with loss of the dimerization domain, DNA binding region, and transcriptional activity. The multiple functional defects observed in these early neutrophil progenitor cells, a consequence of C/EBPepsilon deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBPepsilon for the promyelocyte-myelocyte transition in myeloid differentiation.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J A",
      "lastName" : "Lekstrom-Himes",
      "authorRank" : 1,
      "name" : "Lekstrom-Himes JA",
      "referenceId" : "RGD:A592357"
    }, {
      "firstName" : "S E",
      "lastName" : "Dorman",
      "authorRank" : 2,
      "name" : "Dorman SE",
      "referenceId" : "RGD:A592358"
    }, {
      "firstName" : "P",
      "lastName" : "Kopar",
      "authorRank" : 3,
      "name" : "Kopar P",
      "referenceId" : "RGD:A592359"
    }, {
      "firstName" : "S M",
      "lastName" : "Holland",
      "authorRank" : 4,
      "name" : "Holland SM",
      "referenceId" : "RGD:A592181"
    }, {
      "firstName" : "J I",
      "lastName" : "Gallin",
      "authorRank" : 5,
      "name" : "Gallin JI",
      "referenceId" : "RGD:A592360"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118132"
    } ]
  }, {
    "primaryId" : "PMID:10359651",
    "title" : "Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters.",
    "datePublished" : "1999-06-15T00:00:00.000-05:00",
    "citation" : "Jasinska R, etal., Biochem J. 1999 Jun 15;340 ( Pt 3):677-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-12-20T13:04:10.000-06:00",
    "volume" : "340 ( Pt 3)",
    "pages" : "677-86",
    "abstract" : "Lipid phosphate phosphohydrolase (LPP)-1 cDNA was cloned from a rat liver cDNA library. It codes for a 32-kDa protein that shares 87 and 82% amino acid sequence identities with putative products of murine and human LPP-1 cDNAs, respectively. Membrane fractions of rat2 fibroblasts that stably expressed mouse or rat LPP-1 exhibited 3.1-3. 6-fold higher specific activities for phosphatidate dephosphorylation compared with vector controls. Increases in the dephosphorylation of lysophosphatidate, ceramide 1-phosphate, sphingosine 1-phosphate and diacylglycerol pyrophosphate were similar to those for phosphatidate. Rat2 fibroblasts expressing mouse LPP-1 cDNA showed 1.6-2.3-fold increases in the hydrolysis of exogenous lysophosphatidate, phosphatidate and ceramide 1-phosphate compared with vector control cells. Recombinant LPP-1 was located partially in plasma membranes with its C-terminus on the cytosolic surface. Lysophosphatidate dephosphorylation was inhibited by extracellular Ca2+ and this inhibition was diminished by extracellular Mg2+. Changing intracellular Ca2+ concentrations did not alter exogenous lysophosphatidate dephosphorylation significantly. Permeabilized fibroblasts showed relatively little latency for the dephosphorylation of exogenous lysophosphatidate. LPP-1 expression decreased the activation of mitogen-activated protein kinase and DNA synthesis by exogenous lysophosphatidate. The product of LPP-1 cDNA is concluded to act partly to degrade exogenous lysophosphatidate and thereby regulate its effects on cell signalling.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Jasinska",
      "authorRank" : 1,
      "name" : "Jasinska R",
      "referenceId" : "RGD:A477770"
    }, {
      "firstName" : "Q X",
      "lastName" : "Zhang",
      "authorRank" : 2,
      "name" : "Zhang QX",
      "referenceId" : "RGD:A471351"
    }, {
      "firstName" : "C",
      "lastName" : "Pilquil",
      "authorRank" : 3,
      "name" : "Pilquil C",
      "referenceId" : "RGD:A477771"
    }, {
      "firstName" : "I",
      "lastName" : "Singh",
      "authorRank" : 4,
      "name" : "Singh I",
      "referenceId" : "RGD:A41044"
    }, {
      "firstName" : "J",
      "lastName" : "Xu",
      "authorRank" : 5,
      "name" : "Xu J",
      "referenceId" : "RGD:A162581"
    }, {
      "firstName" : "J",
      "lastName" : "Dewald",
      "authorRank" : 6,
      "name" : "Dewald J",
      "referenceId" : "RGD:A477766"
    }, {
      "firstName" : "D A",
      "lastName" : "Dillon",
      "authorRank" : 7,
      "name" : "Dillon DA",
      "referenceId" : "RGD:A477772"
    }, {
      "firstName" : "L G",
      "lastName" : "Berthiaume",
      "authorRank" : 8,
      "name" : "Berthiaume LG",
      "referenceId" : "RGD:A477773"
    }, {
      "firstName" : "G M",
      "lastName" : "Carman",
      "authorRank" : 9,
      "name" : "Carman GM",
      "referenceId" : "RGD:A477774"
    }, {
      "firstName" : "D W",
      "lastName" : "Waggoner",
      "authorRank" : 10,
      "name" : "Waggoner DW",
      "referenceId" : "RGD:A477764"
    }, {
      "firstName" : "D N",
      "lastName" : "Brindley",
      "authorRank" : 11,
      "name" : "Brindley DN",
      "referenceId" : "RGD:A477767"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:15090857"
    } ]
  }, {
    "primaryId" : "PMID:10359787",
    "title" : "Rapid and reversible relocalization of heat shock factor 1 within seconds to nuclear stress granules.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Jolly C, etal., Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6769-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-11-09T20:11:30.000-06:00",
    "volume" : "96",
    "pages" : "6769-74",
    "abstract" : "Heat shock factor 1 (HSF1) is essential for the stress-induced expression of heat shock genes. On exposure to heat shock, HSF1 localizes within seconds to discrete nuclear granules. On recovery from heat shock, HSF1 rapidly dissipates from these stress granules to a diffuse nucleoplasmic distribution, typical of unstressed cells. Subsequent reexposure to heat shock results in the rapid relocalization of HSF1 to the same stress granules with identical kinetics. Although the appearance of HSF1 stress granules corresponds to the hyperphosphorylated, trimeric DNA-binding state of HSF1 and correlates temporally with the inducible transcription of heat shock genes, they are also present in heat-shocked mitotic  cells that are devoid of transcription. This finding suggests a role for HSF1 stress granules as a nuclear compartment for the temporal regulation and spatial  organization of HSF1 activity and reveals new features of the dynamics of nuclear organization.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Jolly",
      "authorRank" : 1,
      "name" : "Jolly",
      "referenceId" : "RGD:A408370"
    }, {
      "firstName" : "Y",
      "lastName" : "Usson",
      "authorRank" : 2,
      "name" : "Usson Y",
      "referenceId" : "RGD:A82738"
    }, {
      "firstName" : "RI",
      "lastName" : "Morimoto",
      "authorRank" : 3,
      "name" : "Morimoto",
      "referenceId" : "RGD:A205362"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11561113"
    } ]
  }, {
    "primaryId" : "PMID:10359808",
    "title" : "Matrix metalloproteinase deficiencies affect contact hypersensitivity: stromelysin-1 deficiency prevents the response and gelatinase B deficiency prolongs the response.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Wang M, etal., Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6885-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-07-09T15:49:22.000-05:00",
    "volume" : "96",
    "pages" : "6885-9",
    "abstract" : "Matrix metalloproteinases (MMPs) are expressed by T cells and macrophages, but there is a paucity of evidence for their role in immune responses. We have studied mice with deficiencies of stromelysin-1 (MMP-3) or gelatinase B (MMP-9) in a dinitrofluorobenzene (DNFB)-induced model of contact hypersensitivity (CHS). Stromelysin-1-deficient mice showed a markedly impaired CHS response to topical DNFB, although they responded normally to cutaneously applied phenol, an acute irritant. Lymphocytes from lymph nodes of DNFB-sensitized stromelysin-1-deficient mice did not proliferate in response to specific soluble antigen dinitrobenzenesulfonic acid, but did proliferate identically to lymph node lymphocytes from wild-type mice when presented with the mitogen Con A. An intradermal injection of stromelysin-1 immediately before DNFB sensitization rescued the impaired CHS response to DNFB in stromelysin-1-deficient mice. Unlike stromelysin-1-deficient mice, gelatinase B-deficient mice exhibited a CHS response comparable to wild-type controls at 1 day postchallenge, but the response persisted beyond 7 days in contrast to the complete resolution observed  in wild-type mice by 7 days. However, gelatinase B-deficient mice had a normal rate of resolution of acute inflammation elicited by cutaneous phenol. Gelatinase B-deficient mice failed to show IL-10 production at the site of CHS, an essential feature of resolution in control mice. These results indicate that stromelysin-1  and gelatinase B serve important functions in CHS. Stromelysin-1 is required for  initiation of the response, whereas gelatinase B plays a critical role in its resolution.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang M",
      "referenceId" : "RGD:A9187"
    }, {
      "firstName" : "X",
      "lastName" : "Qin",
      "authorRank" : 2,
      "name" : "Qin X",
      "referenceId" : "RGD:A48018"
    }, {
      "firstName" : "JS",
      "lastName" : "Mudgett",
      "authorRank" : 3,
      "name" : "Mudgett",
      "referenceId" : "RGD:A190971"
    }, {
      "firstName" : "TA",
      "lastName" : "Ferguson",
      "authorRank" : 4,
      "name" : "Ferguson",
      "referenceId" : "RGD:A174262"
    }, {
      "firstName" : "RM",
      "lastName" : "Senior",
      "authorRank" : 5,
      "name" : "Senior",
      "referenceId" : "RGD:A180140"
    }, {
      "firstName" : "HG",
      "lastName" : "Welgus",
      "authorRank" : 6,
      "name" : "Welgus",
      "referenceId" : "RGD:A180200"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8693317"
    } ]
  }, {
    "primaryId" : "PMID:10360172",
    "title" : "Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "James PF, etal., Mol Cell 1999 May;3(5):555-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:43:48.000-06:00",
    "volume" : "3",
    "pages" : "555-63",
    "abstract" : "It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous alpha 2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous alpha 1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the alpha 2 isoform with ouabain increases the contractility of heterozygous alpha 1 hearts. These results definitively illustrate a specific role for the alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PF",
      "lastName" : "James",
      "authorRank" : 1,
      "name" : "James PF",
      "referenceId" : "RGD:A29375"
    }, {
      "firstName" : "IL",
      "lastName" : "Grupp",
      "authorRank" : 2,
      "name" : "Grupp IL",
      "referenceId" : "RGD:A36189"
    }, {
      "firstName" : "G",
      "lastName" : "Grupp",
      "authorRank" : 3,
      "name" : "Grupp G",
      "referenceId" : "RGD:A36190"
    }, {
      "firstName" : "AL",
      "lastName" : "Woo",
      "authorRank" : 4,
      "name" : "Woo AL",
      "referenceId" : "RGD:A29374"
    }, {
      "firstName" : "GR",
      "lastName" : "Askew",
      "authorRank" : 5,
      "name" : "Askew GR",
      "referenceId" : "RGD:A36191"
    }, {
      "firstName" : "ML",
      "lastName" : "Croyle",
      "authorRank" : 6,
      "name" : "Croyle ML",
      "referenceId" : "RGD:A32650"
    }, {
      "firstName" : "RA",
      "lastName" : "Walsh",
      "authorRank" : 7,
      "name" : "Walsh RA",
      "referenceId" : "RGD:A36192"
    }, {
      "firstName" : "JB",
      "lastName" : "Lingrel",
      "authorRank" : 8,
      "name" : "Lingrel JB",
      "referenceId" : "RGD:A80284"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734617"
    } ]
  }, {
    "primaryId" : "PMID:10360224",
    "title" : "Proteases and protease inhibitors in taurocholate-induced acute pancreatitis in rats.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kruse P, etal., Int J Pancreatol. 1999 Apr;25(2):113-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-11T14:08:36.000-05:00",
    "volume" : "25",
    "pages" : "113-21",
    "abstract" : "CONCLUSION: Taurocholate-induced acute pancreatitis (AP) in the rat mimics early  necrotizing human pancreatitis. Protease activation and protease inhibitor consumption occur consistent with a two-stage development, and contact-phase activation is a possible primary event in this model. BACKGROUND: Proteases and protease inhibitors have been indicated to play an important role in both human and experimental acute pancreatitis, although little is known about them in rats. METHODS: Three percent sodium taurocholate was infused into the bilio-pancreatic  duct to induce AP, and over 0-72 h we measured lipase, amylase, albumin, prekallikrein, factor X, alpha-1-macroglobulin, alpha-2-antiplasmin, antithrombin III, alpha-1-protease inhibitor, and C1-esterase inhibitor (all in plasma) and histologic and macroscopic findings. RESULTS: A severe necrotizing, nonlethal, AP was induced with an early increase in plasma lipase and alpha-amylase activity levels and peritoneal exudate followed by a return to near control levels after 72 h. Histologic score and pancreatic wet weight ratio increased initially and remained high during the observation period. The protease inhibitors C1-esterase  inhibitor, alpha-2-antiplasmin, and antithrombin III decreased early, within 0-6  h, whereafter levels normalized. The protease inhibitors alpha-1-macroglobulin and alpha-1-protease inhibitor later gradually decreased over the 72 h.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Kruse",
      "authorRank" : 1,
      "name" : "Kruse P",
      "referenceId" : "RGD:A84308"
    }, {
      "firstName" : "E",
      "lastName" : "Hage",
      "authorRank" : 2,
      "name" : "Hage E",
      "referenceId" : "RGD:A17933"
    }, {
      "firstName" : "A",
      "lastName" : "Lasson",
      "authorRank" : 3,
      "name" : "Lasson A",
      "referenceId" : "RGD:A84309"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8661651"
    } ]
  }, {
    "primaryId" : "PMID:10360396",
    "title" : "Fabry disease: comparison of enzymatic, linkage, and mutation analysis for carrier detection in a family with a novel mutation (30delG).",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ashton-Prolla P, etal., Am J Med Genet. 1999 Jun 11;84(5):420-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:13:33.000-05:00",
    "volume" : "84",
    "pages" : "420-4",
    "abstract" : "Fabry disease (FD) is an X-linked recessive disorder caused by the deficient activity of the lysosomal enzyme alpha-galactosidase A (alpha-Gal A). Affected males are reliably diagnosed by demonstration of deficient alpha-Gal A activity in plasma or leukocytes. However, identification of female carriers is problematic due to Lyonization, requiring mutation identification and/or linkage  studies for accurate carrier detection. Here, we describe a large Brazilian kindred with Fabry disease that permitted comparison of biochemical and molecular diagnostic techniques. Initially, the plasma alpha-Gal A activities were determined in at-risk affected males and potential female carriers; affected males were readily diagnosed, while the females had variable results. To detect carrier females, haplotype analysis using 10 polymorphic markers adjacent to the  gene was performed. Subsequently, solid-phase direct sequencing of the alpha-Gal  A gene demonstrated a novel single base deletion in exon 1 (30delG). Discrepancies were observed between the enzymatic and molecular diagnoses in two  at-risk females. These findings emphasize the need for precise heterozygote diagnosis by mutation and/or haplotype analyses in all families with Fabry disease.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Ashton-Prolla",
      "authorRank" : 1,
      "name" : "Ashton-Prolla",
      "referenceId" : "RGD:A260042"
    }, {
      "firstName" : "GA",
      "lastName" : "Ashley",
      "authorRank" : 2,
      "name" : "Ashley",
      "referenceId" : "RGD:A256476"
    }, {
      "firstName" : "R",
      "lastName" : "Giugliani",
      "authorRank" : 3,
      "name" : "Giugliani R",
      "referenceId" : "RGD:A145289"
    }, {
      "firstName" : "RF",
      "lastName" : "Pires",
      "authorRank" : 4,
      "name" : "Pires",
      "referenceId" : "RGD:A281168"
    }, {
      "firstName" : "RJ",
      "lastName" : "Desnick",
      "authorRank" : 5,
      "name" : "Desnick RJ",
      "referenceId" : "RGD:A15118"
    }, {
      "firstName" : "CM",
      "lastName" : "Eng",
      "authorRank" : 6,
      "name" : "Eng CM",
      "referenceId" : "RGD:A80664"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072070"
    } ]
  }, {
    "primaryId" : "PMID:10360666",
    "title" : "Propylnitrosourea-induced T-lymphomas in LEXF RI strains of rats: genetic analysis.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Lu LM, etal., Br J Cancer 1999 May;80(5-6):855-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-07-30T15:34:41.000-05:00",
    "volume" : "80",
    "pages" : "855-61",
    "abstract" : "Oral administration of propylnitrosourea (PNU) in drinking water induces high incidence of lympho-haemopoietic malignancies in rats. Previously we reported that F344 strain rats were highly susceptible to T-lymphomas, and LE/Stm rats, to erythro- or myeloid leukaemias. For analysis of the genetic factors determining types of diseases, we have established LEXF recombinant inbred strains of rats comprising 23 substrains, each derived from intercross between F344 and LE/Stm rats. Rats of 23 LEXF substrains were given PNU, and the development of tumours was observed. The overall incidence of haemopoietic tumours ranged from 100% to 66.7%, and the fractions of T-lymphomas, from 100% to 4%, showing a continuous spectrum. Based on the genetic profile published as a strain distribution pattern table for the LEXF, we screened the potential quantitative trait loci involved in determination of the types of disease and length of the latency period. Statistical calculation was performed using the Map Manager QT software developed by Manly. Four loci, on chromosome 4, 7, 10 and 18, were suggested to associate with the T-lymphoma susceptibility and three loci, on chromosome 1, 5 and 16, with the length of the latency period. These putative loci were further examined in backcross (F344 x LE)F1 x LE. Among seven loci suggested by the recombinant inbred study, three loci, on chromosome 5, 7 and 10, were significantly associated with T-lymphomas and another locus on chromosome 1, just weakly. These observations indicate that PNU-induced lymphomagenesis is a multifactorial genetic process involving a number of loci linked with susceptibility and resistance.",
    "issueName" : "5-6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LM",
      "lastName" : "Lu",
      "authorRank" : 1,
      "name" : "Lu LM",
      "referenceId" : "RGD:A10764"
    }, {
      "firstName" : "H",
      "lastName" : "Shisa",
      "authorRank" : 2,
      "name" : "Shisa H",
      "referenceId" : "RGD:A97213"
    }, {
      "firstName" : "J",
      "lastName" : "Tanuma",
      "authorRank" : 3,
      "name" : "Tanuma J",
      "referenceId" : "RGD:A97212"
    }, {
      "firstName" : "H",
      "lastName" : "Hiai",
      "authorRank" : 4,
      "name" : "Hiai H",
      "referenceId" : "RGD:A7203"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619600"
    } ]
  }, {
    "primaryId" : "PMID:10360777",
    "title" : "Ataxia with isolated vitamin E deficiency: a Japanese family carrying a novel mutation in the alpha-tocopherol transfer protein gene.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hoshino M, etal., Ann Neurol. 1999 Jun;45(6):809-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:45:21.000-05:00",
    "volume" : "45",
    "pages" : "809-12",
    "abstract" : "We report a Japanese family with ataxia with isolated vitamin E deficiency (AVED). Gene analysis revealed a single nucleotide substitution of T to C at nucleotide position 2 in the alpha-tocopherol transfer protein gene (TTPA). This  substitution abolishes the start codon. The proband and his affected sister were  homozygous for this mutation, and their serum alpha-tocopherol concentrations were remarkably reduced. Relations between the mutations and clinical features are discussed.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Hoshino",
      "authorRank" : 1,
      "name" : "Hoshino M",
      "referenceId" : "RGD:A57077"
    }, {
      "firstName" : "N",
      "lastName" : "Masuda",
      "authorRank" : 2,
      "name" : "Masuda",
      "referenceId" : "RGD:A324586"
    }, {
      "firstName" : "Y",
      "lastName" : "Ito",
      "authorRank" : 3,
      "name" : "Ito Y",
      "referenceId" : "RGD:A13854"
    }, {
      "firstName" : "M",
      "lastName" : "Murata",
      "authorRank" : 4,
      "name" : "Murata",
      "referenceId" : "RGD:A405408"
    }, {
      "firstName" : "J",
      "lastName" : "Goto",
      "authorRank" : 5,
      "name" : "Goto J",
      "referenceId" : "RGD:A38915"
    }, {
      "firstName" : "M",
      "lastName" : "Sakurai",
      "authorRank" : 6,
      "name" : "Sakurai M",
      "referenceId" : "RGD:A53113"
    }, {
      "firstName" : "I",
      "lastName" : "Kanazawa",
      "authorRank" : 7,
      "name" : "Kanazawa",
      "referenceId" : "RGD:A394117"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067871"
    } ]
  }, {
    "primaryId" : "PMID:10361244",
    "title" : "HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID).",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "De La Concha EG, etal., Clin Exp Immunol. 1999 Jun;116(3):516-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-08-25T15:45:14.000-05:00",
    "volume" : "116",
    "pages" : "516-20",
    "abstract" : "Most cases of CVID occur sporadically, but familial cases do also occur and 15% of the patients with the disease have first degree relatives with IgA deficiency (IgAD). Our purpose was to study CVID association with HLA class II alleles and to ascertain whether this disease shares a common genetic background with IgAD in our population. Patients with CVID (n = 42), were typed using gene amplification and sequence-specific oligonucleotide probing for HLA-DRB1, DRB3, DQA1 and DQB1 loci and their typing compared with that of 96 IgAD and 334 healthy controls. We observed a positive association between non-Asp residues at position 57 of the HLA-DQbeta chain and CVID, although much weaker than in IgAD. Further, we found an association between CVID and homozygosity for genes encoding HLA class II molecules, especially HLA-DQ, not seen in IgAD. The data support the hypothesis that a restricted diversity of HLA class II molecules may contribute to susceptibility to CVID.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EG",
      "lastName" : "De la Concha",
      "authorRank" : 1,
      "name" : "De la Concha EG",
      "referenceId" : "RGD:A106637"
    }, {
      "firstName" : "M",
      "lastName" : "Fernandez-Arquero",
      "authorRank" : 2,
      "name" : "Fernandez-Arquero M",
      "referenceId" : "RGD:A106636"
    }, {
      "firstName" : "A",
      "lastName" : "Martinez",
      "authorRank" : 3,
      "name" : "Martinez A",
      "referenceId" : "RGD:A13346"
    }, {
      "firstName" : "F",
      "lastName" : "Vidal",
      "authorRank" : 4,
      "name" : "Vidal F",
      "referenceId" : "RGD:A76119"
    }, {
      "firstName" : "P",
      "lastName" : "Vigil",
      "authorRank" : 5,
      "name" : "Vigil P",
      "referenceId" : "RGD:A143845"
    }, {
      "firstName" : "L",
      "lastName" : "Conejero",
      "authorRank" : 6,
      "name" : "Conejero L",
      "referenceId" : "RGD:A143846"
    }, {
      "firstName" : "MC",
      "lastName" : "Garcia-Rodriguez",
      "authorRank" : 7,
      "name" : "Garcia-Rodriguez MC",
      "referenceId" : "RGD:A143847"
    }, {
      "firstName" : "G",
      "lastName" : "Fontan",
      "authorRank" : 8,
      "name" : "Fontan G",
      "referenceId" : "RGD:A77573"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5147864"
    } ]
  }, {
    "primaryId" : "PMID:10362251",
    "title" : "Isolation and characterization of mammalian homologues of Caenorhabditis elegans lin-7: localization at cell-cell junctions.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Irie M, etal., Oncogene 1999 May 6;18(18):2811-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:50.000-05:00",
    "volume" : "18",
    "pages" : "2811-7",
    "abstract" : "In Caenorhabditis elegans, the vulval induction is mediated by the let-23 receptor tyrosine kinase (RTK)/ Ras signaling pathway. The precise localization of the let-23 RTK at the epithelial junctions is essential for the vulval induction, and requires three genes including lin-2, -7, and -10. The mammalian homologue of lin-2 has been identified as a protein interacting with a neuronal adhesion molecule, neurexin, and named CASK. CASK has recently been reported to interact with syndecans and an actin-binding protein, band 4.1, at epithelial and synaptic junctions, and to play central roles in the formation of cell-cell junctions. The product of C. elegans lin-7 directly interacts with let-23 RTK and localize it at epithelial junctions. Here, we report three rat homologues of lin-7 ubiquitously expressed in various tissues. These homologues are accumulated at the junctional complex region in cultured Madin-Darby canine kidney cells, and are also localized at the synaptic junctions in neurons. The mammalian homologues of lin-7 may be implicated in the formation of cell-cell junctions.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Irie",
      "authorRank" : 1,
      "name" : "Irie M",
      "referenceId" : "RGD:A4764"
    }, {
      "firstName" : "Y",
      "lastName" : "Hata",
      "authorRank" : 2,
      "name" : "Hata Y",
      "referenceId" : "RGD:A122620"
    }, {
      "firstName" : "M",
      "lastName" : "Deguchi",
      "authorRank" : 3,
      "name" : "Deguchi M",
      "referenceId" : "RGD:A16949"
    }, {
      "firstName" : "N",
      "lastName" : "Ide",
      "authorRank" : 4,
      "name" : "Ide N",
      "referenceId" : "RGD:A15957"
    }, {
      "firstName" : "K",
      "lastName" : "Hirao",
      "authorRank" : 5,
      "name" : "Hirao K",
      "referenceId" : "RGD:A4762"
    }, {
      "firstName" : "I",
      "lastName" : "Yao",
      "authorRank" : 6,
      "name" : "Yao I",
      "referenceId" : "RGD:A8910"
    }, {
      "firstName" : "H",
      "lastName" : "Nishioka",
      "authorRank" : 7,
      "name" : "Nishioka H",
      "referenceId" : "RGD:A12325"
    }, {
      "firstName" : "Y",
      "lastName" : "Takai",
      "authorRank" : 8,
      "name" : "Takai Y",
      "referenceId" : "RGD:A151861"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633233"
    } ]
  }, {
    "primaryId" : "PMID:10362258",
    "title" : "Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation.",
    "datePublished" : "1999-05-06T00:00:00.000-05:00",
    "citation" : "Billon N, etal., Oncogene. 1999 May 6;18(18):2872-82. doi: 10.1038/sj.onc.1202712.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-02-03T06:06:57.000-06:00",
    "volume" : "18",
    "pages" : "2872-82",
    "abstract" : "Addition of nerve growth factor (NGF) to PC12 cells promotes neuronal differentiation while inhibiting cell proliferation. In order to understand how NGF exerts its antimitogenic effect during differentiation, we have studied the mechanism by which this factor activates the promoter of the CDK inhibitor p21W4F1/CIP1. The minimal region of the p21 promoter required for the NGF-induction was mapped to a contiguous stretch of 10 bp located 83 bases upstream of the transcription initiation site. This GC-rich region was shown to interact specifically with the transcription factor Sp1 and the related protein Sp3, in either exponentially-growing or NGF-treated PC12 cells. The addition of NGF resulted in an accumulation of the transcriptional co-activator p300 in complexes associated with the NGF-responsive region. Transcriptional activity of Sp1, Sp3 and p300 was specifically induced by NGF in a Gal4-fusion assay, indicating that induction of p21 during neuronal differentiation may involve regulation of the activity of these factors by NGF. Furthermore, p300 was able to act as a co-activator for Sp1-mediated transcriptional activation in PC12 cells, suggesting that p300 and Sp1 may cooperate in activating p21 transcription during the withdrawal of neuronal precursors from the cell cycle. This hypothesis is supported by experiments showing that p300 and Sp1 form complexes in PC12 cells.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Billon",
      "authorRank" : 1,
      "name" : "Billon N",
      "referenceId" : "RGD:A93611"
    }, {
      "firstName" : "D",
      "lastName" : "Carlisi",
      "authorRank" : 2,
      "name" : "Carlisi D",
      "referenceId" : "RGD:A455300"
    }, {
      "firstName" : "M B",
      "lastName" : "Datto",
      "authorRank" : 3,
      "name" : "Datto MB",
      "referenceId" : "RGD:A455301"
    }, {
      "firstName" : "L A",
      "lastName" : "van Grunsven",
      "authorRank" : 4,
      "name" : "van Grunsven LA",
      "referenceId" : "RGD:A455302"
    }, {
      "firstName" : "A",
      "lastName" : "Watt",
      "authorRank" : 5,
      "name" : "Watt A",
      "referenceId" : "RGD:A44335"
    }, {
      "firstName" : "X F",
      "lastName" : "Wang",
      "authorRank" : 6,
      "name" : "Wang XF",
      "referenceId" : "RGD:A455303"
    }, {
      "firstName" : "B B",
      "lastName" : "Rudkin",
      "authorRank" : 7,
      "name" : "Rudkin BB",
      "referenceId" : "RGD:A455304"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13506263"
    } ]
  }, {
    "primaryId" : "PMID:10362365",
    "title" : "Mutations in the RAD54 recombination gene in primary cancers.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Matsuda M, etal., Oncogene. 1999 Jun 3;18(22):3427-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-13T16:26:47.000-06:00",
    "volume" : "18",
    "pages" : "3427-30",
    "abstract" : "Association of a recombinational repair protein RAD51 with tumor suppressors BRCA1 and BRCA2 suggests that defects in homologous recombination are responsible for tumor formation. Also recent findings that a protein associated with the MRE11/RAD50 repair complex is mutated in Nijmegen breakage syndrome characterized by increased cancer incidence and ionizing radiation sensitivity strongly support this idea. However, the direct roles of BRCA proteins and the protein responsible for NBS in recombinational repair are not clear though they are associated with the recombinational repair complexes. Since RAD51 forms a complex with other members of the RAD52 epistasis group and with BRCA proteins, it is reasonable to ask if alterations of members of the RAD52 epistasis group lead to tumor development. Here we describe missense mutations at functional regions of RAD54 and the absence of the wild-type RAD54 expression resulting from aberrant splicing in primary cancers. Since RAD54 is a recombinational protein associated with RAD51, this is the first genetic evidence that cancer arises from a defect in repair processes involving homologous recombination.",
    "issueName" : "22",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Matsuda",
      "authorRank" : 1,
      "name" : "Matsuda M",
      "referenceId" : "RGD:A17185"
    }, {
      "firstName" : "K",
      "lastName" : "Miyagawa",
      "authorRank" : 2,
      "name" : "Miyagawa K",
      "referenceId" : "RGD:A25798"
    }, {
      "firstName" : "M",
      "lastName" : "Takahashi",
      "authorRank" : 3,
      "name" : "Takahashi M",
      "referenceId" : "RGD:A4629"
    }, {
      "firstName" : "T",
      "lastName" : "Fukuda",
      "authorRank" : 4,
      "name" : "Fukuda T",
      "referenceId" : "RGD:A9510"
    }, {
      "firstName" : "T",
      "lastName" : "Kataoka",
      "authorRank" : 5,
      "name" : "Kataoka T",
      "referenceId" : "RGD:A75016"
    }, {
      "firstName" : "T",
      "lastName" : "Asahara",
      "authorRank" : 6,
      "name" : "Asahara T",
      "referenceId" : "RGD:A33759"
    }, {
      "firstName" : "H",
      "lastName" : "Inui",
      "authorRank" : 7,
      "name" : "Inui H",
      "referenceId" : "RGD:A30277"
    }, {
      "firstName" : "M",
      "lastName" : "Watatani",
      "authorRank" : 8,
      "name" : "Watatani M",
      "referenceId" : "RGD:A75017"
    }, {
      "firstName" : "M",
      "lastName" : "Yasutomi",
      "authorRank" : 9,
      "name" : "Yasutomi M",
      "referenceId" : "RGD:A75018"
    }, {
      "firstName" : "N",
      "lastName" : "Kamada",
      "authorRank" : 10,
      "name" : "Kamada N",
      "referenceId" : "RGD:A38067"
    }, {
      "firstName" : "K",
      "lastName" : "Dohi",
      "authorRank" : 11,
      "name" : "Dohi K",
      "referenceId" : "RGD:A42135"
    }, {
      "firstName" : "K",
      "lastName" : "Kamiya",
      "authorRank" : 12,
      "name" : "Kamiya K",
      "referenceId" : "RGD:A67265"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599748"
    } ]
  }, {
    "primaryId" : "PMID:103625",
    "title" : "Complete sequence of constant and 3' noncoding regions of an immunoglobulin mRNA  using the dideoxynucleotide method of RNA sequencing.",
    "datePublished" : "1978-04-01T00:00:00.000-06:00",
    "citation" : "Hamlyn PH, etal., Cell. 1978 Nov;15(3):1067-75.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T15:12:09.000-05:00",
    "volume" : "15",
    "pages" : "1067-75",
    "abstract" : "Three synthetic oligonucleotides were prepared to be complementary to known regions of the mouse immunoglublin light chain mRNA, and their ability to prime the transcription of complementary DNA (cDNA) was studied. The sequence of the cDNA was determined by adapting for mRNA the DNA sequencing method of Sanger, Nicklen and Coulson (1977) which uses 2'3' dideoxy ribonucleotides. A continuous  sequence of 532 nucleotides was obtained, 321 corresponding to the whole of the constant region of the mRNA and the remaining 211 being the complete 3' noncoding region of the mRNA. The termination codon U-A-G occurs at the expected position in the mRNA corresponding to the triplet following the C terminal cystine. The nucleotide sequence is partially corroborated by the sequence of fragments obtained previously from 32P-mRNA fingerprints and endonuclease IV digests of 32P-cDNA, and is in agreement with the amino acid sequence of the constant region, except for a rearrangement of four amino acids (between amino acid positions 163 and 166). A revision of the amino acid sequence confirms the nucleic acid sequence.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PH",
      "lastName" : "Hamlyn",
      "authorRank" : 1,
      "name" : "Hamlyn",
      "referenceId" : "RGD:A231519"
    }, {
      "firstName" : "GG",
      "lastName" : "Browniee",
      "authorRank" : 2,
      "name" : "Browniee",
      "referenceId" : "RGD:A241214"
    }, {
      "firstName" : "CC",
      "lastName" : "Cheng",
      "authorRank" : 3,
      "name" : "Cheng",
      "referenceId" : "RGD:A188809"
    }, {
      "firstName" : "MJ",
      "lastName" : "Gait",
      "authorRank" : 4,
      "name" : "Gait",
      "referenceId" : "RGD:A231520"
    }, {
      "firstName" : "C",
      "lastName" : "Milstein",
      "authorRank" : 5,
      "name" : "Milstein",
      "referenceId" : "RGD:A220593"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11058325"
    } ]
  }, {
    "primaryId" : "PMID:10362553",
    "title" : "Analysis of the roles of the head domains of type IV rat neuronal intermediate filament proteins in filament assembly using domain-swapped chimeric proteins.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Ching GY and Liem RK, J Cell Sci. 1999 Jul;112 ( Pt 13):2233-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-02-16T13:13:18.000-06:00",
    "volume" : "112 ( Pt 13)",
    "pages" : "2233-40",
    "abstract" : "Type IV neuronal intermediate filament proteins consist of alpha-internexin, which can self-assemble into filaments and the neurofilament triplet proteins, which are obligate heteropolymers, at least in rodents. These IF proteins therefore provide good systems for elucidating the mechanism of intermediate filament assembly. To analyze the roles of the head domains of these proteins in  contributing to their differential assembly properties, we generated chimeric proteins by swapping the head domains between rat alpha-internexin and either rat NF-L or NF-M and examined their assembly properties in transfected cells that lack their own cytoplasmic intermediate filament network. Lalphaalpha and Malphaalpha, the chimeric proteins generated by replacing the head domain of alpha-internexin with those of NF-L and NF-M, respectively, were unable to self-assemble into filaments. In contrast, alphaLL, a chimeric NF-L protein generated by replacing the head domain of NF-L with that of alpha-internexin, was able to self-assemble into filaments, whereas MLL, a chimeric NF-L protein containing the NF-M head domain, was unable to do so. These results demonstrate that the alpha-internexin head domain is essential for alpha-internexin's ability to self-assemble. While coassembly of Lalphaalpha with NF-M and coassembly of Malphaalpha with NF-L resulted in formation of filaments, coassembly of Lalphaalpha with NF-L and coassembly of Malphaalpha with NF-M yielded punctate patterns. These coassembly results show that heteropolymeric filament formation requires that one partner has the NF-L head domain and the other partner has the  NF-M head domain. Thus, the head domains of rat NF-L and NF-M play important roles in determining the obligate heteropolymeric nature of filament formation. The data obtained from these self-assembly and coassembly studies provide some new insights into the mechanism of intermediate filament assembly.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GY",
      "lastName" : "Ching",
      "authorRank" : 1,
      "name" : "Ching GY",
      "referenceId" : "RGD:A7448"
    }, {
      "firstName" : "RK",
      "lastName" : "Liem",
      "authorRank" : 2,
      "name" : "Liem RK",
      "referenceId" : "RGD:A7449"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9698446"
    } ]
  }, {
    "primaryId" : "PMID:10362555",
    "title" : "Sequential recruitment of NPC proteins to the nuclear periphery at the end of mitosis.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Bodoor K, etal., J Cell Sci. 1999 Jul;112 ( Pt 13):2253-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-10-01T15:40:14.000-05:00",
    "volume" : "112 ( Pt 13)",
    "pages" : "2253-64",
    "abstract" : "Nuclear pore complexes (NPCs) are extremely elaborate structures that mediate the bidirectional movement of macromolecules between the nucleus and cytoplasm. With  a mass of about 125 MDa, NPCs are thought to be composed of 50 or more distinct protein subunits, each present in multiple copies. During mitosis in higher cells the nuclear envelope is disassembled and its components, including NPC subunits,  are dispersed throughout the mitotic cytoplasm. At the end of mitosis, all of these components are reutilized. Using both conventional and digital confocal immunofluorescence microscopy we have been able to define a time course of post-mitotic assembly for a group of NPC components (CAN/Nup214, Nup153, POM121,  p62 and Tpr) relative to the integral nuclear membrane protein LAP2 and the NPC membrane glycoprotein gp210. Nup153, a component of the nuclear basket, associates with chromatin towards the end of anaphase, in parallel with the inner nuclear membrane protein, LAP2. However, immunogold labeling suggests that the initial Nup153 chromatin association is membrane-independent. Assembly of the remaining proteins follows that of the nuclear membranes and occurs in the sequence POM121, p62, CAN/Nup214 and gp210/Tpr. Since p62 remains as a complex with three other NPC proteins (p58, 54, 45) during mitosis and CAN/Nup214 maintains a similar interaction with its partner, Nup84, the relative timing of assembly of these additional four proteins may also be inferred. These observations suggest that there is a sequential association of NPC proteins with  chromosomes during nuclear envelope reformation and the recruitment of at least eight of these precedes that of gp210. These findings support a model in which it is POM121 rather than gp210 that defines initial membrane-associated NPC assembly intermediates.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Bodoor",
      "authorRank" : 1,
      "name" : "Bodoor K",
      "referenceId" : "RGD:A21441"
    }, {
      "firstName" : "S",
      "lastName" : "Shaikh",
      "authorRank" : 2,
      "name" : "Shaikh S",
      "referenceId" : "RGD:A43942"
    }, {
      "firstName" : "D",
      "lastName" : "Salina",
      "authorRank" : 3,
      "name" : "Salina",
      "referenceId" : "RGD:A206548"
    }, {
      "firstName" : "WH",
      "lastName" : "Raharjo",
      "authorRank" : 4,
      "name" : "Raharjo",
      "referenceId" : "RGD:A206549"
    }, {
      "firstName" : "R",
      "lastName" : "Bastos",
      "authorRank" : 5,
      "name" : "Bastos R",
      "referenceId" : "RGD:A21438"
    }, {
      "firstName" : "M",
      "lastName" : "Lohka",
      "authorRank" : 6,
      "name" : "Lohka",
      "referenceId" : "RGD:A206550"
    }, {
      "firstName" : "B",
      "lastName" : "Burke",
      "authorRank" : 7,
      "name" : "Burke B",
      "referenceId" : "RGD:A21442"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10401210"
    } ]
  }, {
    "primaryId" : "PMID:10362617",
    "title" : "Effect of GIP and GLP-1 antagonists on insulin release in the rat.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Tseng CC, etal., Am J Physiol. 1999 Jun;276(6 Pt 1):E1049-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:36:16.000-05:00",
    "volume" : "276",
    "pages" : "E1049-54",
    "abstract" : "Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are potent insulinotropic peptides released from the small intestine. To  examine their relative contribution to postprandial insulin release, a specific GIP antagonist (ANTGIP) and a GLP-1 antagonist, exendin-(9-39)-NH2, were infused  into rats after an intragastric glucose meal. In control rats, plasma glucose and insulin levels rose gradually during the first 20 min and then decreased. Exendin-(9-39)-NH2 administration inhibited postprandial insulin secretion by 32% at 20 min and concomitantly increased plasma glucose concentrations. In contrast, ANTGIP treatment not only induced a 54% decrease in insulin secretion but also a  15% reduction in plasma glucose levels 20 min after the glucose meal. In vivo studies in rats demonstrated that glucose uptake in the upper small intestine was significantly inhibited by the ANTGIP, an effect that might account for the decrease in plasma glucose levels observed in ANTGIP-treated rats. When the two antagonists were administered to rats concomitantly, no potentiating effect on either insulin release or plasma glucose concentration was detected. Glucose meal-stimulated GLP-1 release was not affected by ANTGIP administration, whereas  postprandial glucagon levels were diminished in rats receiving exendin-(9-39)-NH2. The results of these studies suggest that GIP and GLP-1 may share a common mechanism in stimulating pancreatic insulin release. Furthermore,  the GIP receptor appears to play a role in facilitating glucose uptake in the small intestine.",
    "issueName" : "6 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CC",
      "lastName" : "Tseng",
      "authorRank" : 1,
      "name" : "Tseng CC",
      "referenceId" : "RGD:A19034"
    }, {
      "firstName" : "XY",
      "lastName" : "Zhang",
      "authorRank" : 2,
      "name" : "Zhang XY",
      "referenceId" : "RGD:A51898"
    }, {
      "firstName" : "MM",
      "lastName" : "Wolfe",
      "authorRank" : 3,
      "name" : "Wolfe MM",
      "referenceId" : "RGD:A19038"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553736"
    } ]
  }, {
    "primaryId" : "PMID:10362649",
    "title" : "Rat intestinal alpha1-antitrypsin secretion is regulated by triacylglycerol feeding.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Xie QM, etal., Am J Physiol. 1999 Jun;276(6 Pt 1):G1452-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-15T18:16:25.000-05:00",
    "volume" : "276",
    "pages" : "G1452-60",
    "abstract" : "alpha1-Antitrypsin (AAT) is secreted by the enterocyte, but its regulation of expression, intramucosal distribution, and functional status are unclear. After corn oil gavage (plus Pluronic L-81 to block chylomicron release), rat intestine was examined for mRNA encoding AAT, immunoreactivity by light and electron microscopy, and protein content by Western blot. Species-specific antisera used were raised against both AAT and surfactant-like particle (SLP), a membrane secreted by the enterocyte in response to fat feeding. Purified luminal SLP was fractionated by Bio-Gel P-200 chromatography to assess its interaction with AAT. Triacylglycerol feeding maximally increased mucosal mRNA-encoding AAT and AAT intracellular protein content by 3 and 5 h, respectively. Immunocytochemistry revealed predominance of AAT in basolateral spaces around enterocytes and Pluronic-blocked extracellular accumulation of AAT, patterns nearly identical to those of secreted SLP. About 10% of AAT was reversibly associated with SLP. Luminal AAT was smaller (51 kDa) than mature AAT (55 kDa) and did not form a complex with pancreatic elastase. When the common bile duct was tied, excluding pancreatic proteases from the lumen, mature AAT that was cleaved by pancreatic elastase was secreted. The luminal secretion of AAT and its reversible association with SLP suggest an intracellular association and a possible role for AAT during lipid digestion and absorption.",
    "issueName" : "6 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "QM",
      "lastName" : "Xie",
      "authorRank" : 1,
      "name" : "Xie QM",
      "referenceId" : "RGD:A94824"
    }, {
      "firstName" : "JS",
      "lastName" : "Shao",
      "authorRank" : 2,
      "name" : "Shao JS",
      "referenceId" : "RGD:A23586"
    }, {
      "firstName" : "DH",
      "lastName" : "Alpers",
      "authorRank" : 3,
      "name" : "Alpers DH",
      "referenceId" : "RGD:A117166"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292229"
    } ]
  }, {
    "primaryId" : "PMID:10362653",
    "title" : "MRP3, a new ATP-binding cassette protein localized to the canalicular domain of the hepatocyte.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Ortiz DF, etal., Am J Physiol. 1999 Jun;276(6 Pt 1):G1493-500.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:37:02.000-05:00",
    "volume" : "276",
    "pages" : "G1493-500",
    "abstract" : "Bile secretion in liver is driven in large part by ATP-binding cassette (ABC)-type proteins that reside in the canalicular membrane and effect ATP-dependent transport of bile acids, phospholipids, and non-bile acid organic anions. Canalicular ABC-type proteins can be classified into two subfamilies based on membrane topology and sequence identity: MDR1, MDR3, and SPGP resemble the multidrug resistance (MDR) P-glycoprotein, whereas MRP2 is similar in structure and sequence to the multidrug resistance protein MRP1 and transports similar substrates. We now report the isolation of the rMRP3 gene from rat liver, which codes for a protein 1522 amino acids in length that exhibits extensive sequence similarity with MRP1 and MRP2. Northern blot analyses indicate that rMRP3 is expressed in lung and intestine of Sprague-Dawley rats as well as in liver of Eisai hyperbilirubinemic rats and TR- mutant rats, which are deficient in MRP2 expression. rMRP3 expression is also transiently induced in liver shortly after birth and during obstructive cholestasis. Antibodies raised against MRP3 recognize a polypeptide of 190-200 kDa, which is reduced in size to 155-165 kDa after treatment with endoglycosidases. Immunoblot analysis and immunoconfocal microscopy indicate that rMRP3 is present in the canalicular membrane, suggesting that it may play a role in bile formation.",
    "issueName" : "6 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DF",
      "lastName" : "Ortiz",
      "authorRank" : 1,
      "name" : "Ortiz",
      "referenceId" : "RGD:A184950"
    }, {
      "firstName" : "S",
      "lastName" : "Li",
      "authorRank" : 2,
      "name" : "Li S",
      "referenceId" : "RGD:A12216"
    }, {
      "firstName" : "R",
      "lastName" : "Iyer",
      "authorRank" : 3,
      "name" : "Iyer R",
      "referenceId" : "RGD:A36111"
    }, {
      "firstName" : "X",
      "lastName" : "Zhang",
      "authorRank" : 4,
      "name" : "Zhang X",
      "referenceId" : "RGD:A6544"
    }, {
      "firstName" : "P",
      "lastName" : "Novikoff",
      "authorRank" : 5,
      "name" : "Novikoff",
      "referenceId" : "RGD:A184951"
    }, {
      "firstName" : "IM",
      "lastName" : "Arias",
      "authorRank" : 6,
      "name" : "Arias",
      "referenceId" : "RGD:A184952"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553810"
    } ]
  }, {
    "primaryId" : "PMID:10362728",
    "title" : "A novel developmentally regulated gene in lung mesenchyme: homology to a tumor-derived trypsin inhibitor.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kaplan F, etal., Am J Physiol 1999 Jun;276(6 Pt 1):L1027-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:56.000-05:00",
    "volume" : "276",
    "pages" : "L1027-36",
    "abstract" : "We used differential display-PCR (DD-PCR) to identify glucocorticoid-inducible genes that regulate lung development in late gestation. DD-PCR, a method to screen for differentially expressed genes, is based on a comparison of mRNAs isolated from a subset of two or more cell populations by analysis of RT-PCR products on DNA-sequencing gels. We isolated cDNA probes representing mRNAs expressed in primary cultures of rat lung fibroblasts, but not in epithelial cells, on fetal day 20. A day 20 glucocorticoid-treated fibroblast cDNA library was screened with a single probe to isolate the 3.1-kb cDNA late-gestation lung 1 (LGL1; GenBank accession no. AF109674) encoding a deduced polypeptide of 188 amino acids. Northern analysis confirmed that LGL1 is expressed in human, rat, and mouse fetal lungs, induced by glucocorticoid, developmentally regulated in fibroblasts but not detectable in epithelium. In situ hybridization confirmed LGL1 expression in the mesenchyme, but not in the epithelium, of fetal rat lung, kidney, and gut. The predicted LGL1 gene product (lgl1) showed 81% homology to P25TI, a polypeptide trypsin inhibitor recently identified in human glioblastoma and neuroblastoma cells but not detected in normal human tissues. Both lgl1 and P25TI belong to the CRISP family of cysteine-rich extracellular proteins. Trypsin is produced by both normal bronchial epithelial and lung adenocarcinoma cells. Although additional studies will be necessary to clearly establish a functional role for lgl1, we propose that lgl1 has a role in normal lung development that is likely to be via regulation of extracellular matrix degradation.",
    "issueName" : "6 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Kaplan",
      "authorRank" : 1,
      "name" : "Kaplan F",
      "referenceId" : "RGD:A19937"
    }, {
      "firstName" : "P",
      "lastName" : "Ledoux",
      "authorRank" : 2,
      "name" : "Ledoux P",
      "referenceId" : "RGD:A20469"
    }, {
      "firstName" : "FQ",
      "lastName" : "Kassamali",
      "authorRank" : 3,
      "name" : "Kassamali FQ",
      "referenceId" : "RGD:A20470"
    }, {
      "firstName" : "S",
      "lastName" : "Gagnon",
      "authorRank" : 4,
      "name" : "Gagnon S",
      "referenceId" : "RGD:A19934"
    }, {
      "firstName" : "M",
      "lastName" : "Post",
      "authorRank" : 5,
      "name" : "Post M",
      "referenceId" : "RGD:A8217"
    }, {
      "firstName" : "D",
      "lastName" : "Koehler",
      "authorRank" : 6,
      "name" : "Koehler D",
      "referenceId" : "RGD:A19936"
    }, {
      "firstName" : "J",
      "lastName" : "Deimling",
      "authorRank" : 7,
      "name" : "Deimling J",
      "referenceId" : "RGD:A20471"
    }, {
      "firstName" : "NB",
      "lastName" : "Sweezey",
      "authorRank" : 8,
      "name" : "Sweezey NB",
      "referenceId" : "RGD:A19933"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633294"
    } ]
  }, {
    "primaryId" : "PMID:10362749",
    "title" : "Kinetic profile of the rat CYP4A isoforms: arachidonic acid metabolism and isoform-specific inhibitors.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Nguyen X, etal., Am J Physiol. 1999 Jun;276(6 Pt 2):R1691-700.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-02-12T12:44:45.000-06:00",
    "volume" : "276",
    "pages" : "R1691-700",
    "abstract" : "20-Hydroxyeicosatetraenoic acid (HETE), the cytochrome P-450 (CYP) 4A omega-hydroxylation product of arachidonic acid, has potent biological effects on renal tubular and vascular functions and on the control of arterial pressure. We have expressed high levels of the rat CYP4A1, -4A2, -4A3, and -4A8 cDNAs, using baculovirus and Sf 9 insect cells. Arachidonic acid omega- and omega-1-hydroxylations were catalyzed by three of the CYP4A isoforms; the highest catalytic efficiency of 947 nM-1. min-1 for CYP4A1 was followed by 72 and 22 nM-1. min-1 for CYP4A2 and CYP4A3, respectively. CYP4A2 and CYP4A3 exhibited an additional arachidonate 11,12-epoxidation activity, whereas CYP4A1 operated solely as an omega-hydroxylase. CYP4A8 did not catalyze arachidonic or linoleic acid but did have a detectable lauric acid omega-hydroxylation activity. The inhibitory activity of various acetylenic and olefinic fatty acid analogs revealed differences and indicated isoform-specific inhibition. These studies suggest that CYP4A1, despite its low expression in extrahepatic tissues, may constitute the major source of 20-HETE synthesis. Moreover, the ability of CYP4A2 and -4A3 to catalyze the formation of two opposing biologically active metabolites, 20-HETE and 11, 12-epoxyeicosatrienoic acid, may be of great significance to the regulation of vascular tone.",
    "issueName" : "6 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Nguyen",
      "authorRank" : 1,
      "name" : "Nguyen X",
      "referenceId" : "RGD:A103538"
    }, {
      "firstName" : "MH",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang MH",
      "referenceId" : "RGD:A13162"
    }, {
      "firstName" : "KM",
      "lastName" : "Reddy",
      "authorRank" : 3,
      "name" : "Reddy KM",
      "referenceId" : "RGD:A103539"
    }, {
      "firstName" : "JR",
      "lastName" : "Falck",
      "authorRank" : 4,
      "name" : "Falck JR",
      "referenceId" : "RGD:A13843"
    }, {
      "firstName" : "ML",
      "lastName" : "Schwartzman",
      "authorRank" : 5,
      "name" : "Schwartzman ML",
      "referenceId" : "RGD:A70021"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303410"
    } ]
  }, {
    "primaryId" : "PMID:10362788",
    "title" : "Activating c-kit gene mutations in human germ cell tumors.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Tian Q, etal., Am J Pathol. 1999 Jun;154(6):1643-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-11T18:02:20.000-05:00",
    "volume" : "154",
    "pages" : "1643-7",
    "abstract" : "The c-kit gene encodes a tyrosine kinase receptor (KIT) that is required in normal spermatogenesis and is expressed in seminomas and dysgerminomas, a subset of human germ cell tumors (GCTs). To determine whether activating mutations of the c-kit gene occur in GCTs, primary tissue samples of 33 testicular and ovarian tumors were examined for mutations in the juxtamembrane and phosphotransferase domains by polymerase chain reaction amplification and DNA sequencing. A novel missense mutation (D816H) was found in the phosphotransferase domain in tumors of seminoma/dysgerminoma differentiation. The c-kit alleles in nonneoplastic tissues from these patients were wild type, suggesting that the mutant alleles were acquired and selected for during malignant transformation. In cell transfection experiments, the D816H mutant protein was a constitutively activated kinase and was constitutively phosphorylated on tyrosine residues. This is the first description of an activating c-kit mutation in GCTs and is evidence that the KIT signal transduction pathway is important in the pathogenesis of neoplasms with seminoma differentiation.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Tian",
      "authorRank" : 1,
      "name" : "Tian Q",
      "referenceId" : "RGD:A66421"
    }, {
      "firstName" : "JR",
      "lastName" : "Frierson HF",
      "authorRank" : 2,
      "name" : "Frierson HF JR",
      "referenceId" : "RGD:A94758"
    }, {
      "firstName" : "GW",
      "lastName" : "Krystal",
      "authorRank" : 3,
      "name" : "Krystal GW",
      "referenceId" : "RGD:A94759"
    }, {
      "firstName" : "CA",
      "lastName" : "Moskaluk",
      "authorRank" : 4,
      "name" : "Moskaluk CA",
      "referenceId" : "RGD:A35514"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292181"
    } ]
  }, {
    "primaryId" : "PMID:10362791",
    "title" : "Frequent loss of KAI1 expression in squamous and lymphoid neoplasms. An immunohistochemical study of archival tissues.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Geradts J, etal., Am J Pathol 1999 Jun;154(6):1665-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-02-20T15:37:44.000-06:00",
    "volume" : "154",
    "pages" : "1665-71",
    "abstract" : "The metastasis suppressor gene KAI1 was identified by its ability to inhibit the formation of pulmonary metastases in experimental models for prostatic carcinoma. Down-regulation of this gene may be correlated with the invasive phenotype in melanomas and colon and bladder carcinomas and with the metastatic phenotype in carcinomas of the lung, breast, prostate, and pancreas. The goal of our study was to establish an immunohistochemical method to detect KAI1 expression in archival tissues. Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls, we observed strong membrane staining in lymphoid follicular centers and squamous epithelia. We then demonstrated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions. All eight reactive lymph nodes were KAI1 positive. In contrast, three of 13 follicular small cleaved and five of 13 diffuse large cell lymphomas were KAI1 negative. Seventy-nine percent (37 of 47) of invasive squamous cell carcinomas from the lung (n = 15), head and neck (n = 18), and cervix (n = 14) showed extensive KAI1 down-regulation. Loss of KAI1 expression was also found in a subset of 10 high-grade cervical dysplasias. Our data show that (i) immunohistochemistry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and high-grade lymphomas; and (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an important role of the gene in the suppression of invasion in these malignancies.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Geradts",
      "authorRank" : 1,
      "name" : "Geradts J",
      "referenceId" : "RGD:A8495"
    }, {
      "firstName" : "R",
      "lastName" : "Maynard",
      "authorRank" : 2,
      "name" : "Maynard R",
      "referenceId" : "RGD:A8496"
    }, {
      "firstName" : "MJ",
      "lastName" : "Birrer",
      "authorRank" : 3,
      "name" : "Birrer MJ",
      "referenceId" : "RGD:A8497"
    }, {
      "firstName" : "D",
      "lastName" : "Hendricks",
      "authorRank" : 4,
      "name" : "Hendricks D",
      "referenceId" : "RGD:A8498"
    }, {
      "firstName" : "SL",
      "lastName" : "Abbondanzo",
      "authorRank" : 5,
      "name" : "Abbondanzo SL",
      "referenceId" : "RGD:A8499"
    }, {
      "firstName" : "KM",
      "lastName" : "Fong",
      "authorRank" : 6,
      "name" : "Fong KM",
      "referenceId" : "RGD:A8500"
    }, {
      "firstName" : "JC",
      "lastName" : "Barrett",
      "authorRank" : 7,
      "name" : "Barrett JC",
      "referenceId" : "RGD:A6240"
    }, {
      "firstName" : "DP",
      "lastName" : "Lombardi",
      "authorRank" : 8,
      "name" : "Lombardi DP",
      "referenceId" : "RGD:A8501"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70284"
    } ]
  }, {
    "primaryId" : "PMID:10362802",
    "title" : "Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Nupponen NN, etal., Am J Pathol. 1999 Jun;154(6):1777-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-02-18T16:23:58.000-06:00",
    "volume" : "154",
    "pages" : "1777-83",
    "abstract" : "Amplification at the long arm of chromosome 8 occurs in a large fraction of breast and prostate cancers. To clone the target genes for this amplification, we used suppression subtraction hybridization to identify overexpressed genes in the breast cancer cell line SK-Br-3, which harbors amplification at 8q (8q21 and 8q23-q24). A differentially expressed gene identified by SSH, the p40 subunit of eukaryotic translation initiation factor 3 (eIF3), was localized to 8q23 and found to be highly amplified and overexpressed in the breast and prostate cancer cell lines studied. High-level amplification of eIF3-p40 was found in 30% of hormone-refractory prostate tumors and in 18% of untreated primary breast tumors. In the vast majority of the cases, p40 and c-myc were amplified with equal copy numbers. Tumors with higher copy numbers of p40 than c-myc were also found. Expression of p40 mRNA was analyzed with in situ hybridization. The amplification of eIF3-p40 gene was associated with overexpression of its mRNA, as expected for a functional target gene of the amplification. These results imply that genomic aberrations of translation initiation factors, such as eIF3-p40, may contribute to the pathogenesis of breast and prostate cancer.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NN",
      "lastName" : "Nupponen",
      "authorRank" : 1,
      "name" : "Nupponen NN",
      "referenceId" : "RGD:A92030"
    }, {
      "firstName" : "K",
      "lastName" : "Porkka",
      "authorRank" : 2,
      "name" : "Porkka K",
      "referenceId" : "RGD:A89151"
    }, {
      "firstName" : "L",
      "lastName" : "Kakkola",
      "authorRank" : 3,
      "name" : "Kakkola L",
      "referenceId" : "RGD:A92031"
    }, {
      "firstName" : "M",
      "lastName" : "Tanner",
      "authorRank" : 4,
      "name" : "Tanner M",
      "referenceId" : "RGD:A92032"
    }, {
      "firstName" : "K",
      "lastName" : "Persson",
      "authorRank" : 5,
      "name" : "Persson K",
      "referenceId" : "RGD:A92033"
    }, {
      "firstName" : "A",
      "lastName" : "Borg",
      "authorRank" : 6,
      "name" : "Borg A",
      "referenceId" : "RGD:A36538"
    }, {
      "firstName" : "J",
      "lastName" : "Isola",
      "authorRank" : 7,
      "name" : "Isola J",
      "referenceId" : "RGD:A92034"
    }, {
      "firstName" : "T",
      "lastName" : "Visakorpi",
      "authorRank" : 8,
      "name" : "Visakorpi T",
      "referenceId" : "RGD:A92024"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289902"
    } ]
  }, {
    "primaryId" : "PMID:103630",
    "title" : "Sequences of mouse immunoglobulin light chain genes before and after somatic changes.",
    "datePublished" : "1978-06-01T00:00:00.000-05:00",
    "citation" : "Bernard O, etal., Cell. 1978 Dec;15(4):1133-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:38:25.000-05:00",
    "volume" : "15",
    "pages" : "1133-44",
    "abstract" : "We have determined the nucleotide sequences of the germ line gene as well as a corresponding somatically mutated and rearranged gene coding for a mouse immunoglobulin lambdaI type light chain. These sequencing studies were carried out on three Eco RI-DNA fragments which had been cloned from BALB/c mouse embryos or a lambdaI chainsecreting myeloma, H2020. The embryonic DNA clone Ig 99lambda contains two protein-encoding segments, one for the majority of the hydrophobic leader (L) and the other for the rest of the leader and the variable (V) region of the lambda0 chain (Cohn et al., 1974); these segments are separated by a 93 base pair (bp) intervening sequence (I-small). The coding of the V region ends with His at residue 97. The second embryonic DNA clone Ig 25lambda includes a 39  bp DNA segment (J) coding for the rest of the conventionally defined V region (that is, up to residue 110), and also contains the sequence coding for the constant (C) region approximately 1250 untranslated bp (I-large) away from the J  sequence. The J sequence is directly linked with the V-coding sequence in the myeloma DNA clone, Ig 303lambda, which has the various DNA segments arranged in the following order: 5' untranslated region, L, l-small, V linked with J, l-large, C, 3' untranslated sequence. The lg 303lambda V DNA sequence codes for the V region synthesized by the H2020 myeloma and is different from the lg 99lambda V DNA sequence by only two bases. No silent base change was observed between the two DNA clones for the entire sequence spanning the 5' untranslated regions and the V-coding segments. These results confirm the previously drawn conclusion that an active complete lambdaI gene arises by somatic recombination that takes place at the ends of the V-coding DNA segment and the J sequence. No sequence homology was observed at or near the sites of the recombination.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Bernard",
      "authorRank" : 1,
      "name" : "Bernard O",
      "referenceId" : "RGD:A44665"
    }, {
      "firstName" : "N",
      "lastName" : "Hozumi",
      "authorRank" : 2,
      "name" : "Hozumi N",
      "referenceId" : "RGD:A43068"
    }, {
      "firstName" : "S",
      "lastName" : "Tonegawa",
      "authorRank" : 3,
      "name" : "Tonegawa S",
      "referenceId" : "RGD:A36666"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340775"
    } ]
  }, {
    "primaryId" : "PMID:103631",
    "title" : "The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells.",
    "datePublished" : "1978-04-01T00:00:00.000-06:00",
    "citation" : "Schibler U, etal., Cell. 1978 Dec;15(4):1495-509.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T15:11:52.000-05:00",
    "volume" : "15",
    "pages" : "1495-509",
    "abstract" : "The nuclear precursors of the immunoglobulin messenger RNAs of MPC-11 cells were  characterized with respect to size, amount per cell and extent of polyadenylation. These cells produce three Ig mRNAs: a 1.8 kb component coding for a gamma2b heavy chain (H mRNA), a 1.2 kb mRNA coding for a k light chain (L mRNA) and a 0.8 kb mRNA coding for the constant region portion of the k light chain (Lf mRNA). To identify the pre-mRNAs without ambiguity, we constructed recombinant DNA plasmids containing H and L cDNA sequences, and used the cloned cDNAs as hybridization probes for analysis of steady state nuclear RNA and in DNA excess hybridization experiments with pulse-labeled nuclear RNA. The nuclear molecules containing Ig sequences consist of an 11 kb component (H1), which we believe to be the primary transcript of the H gene, 5.3 kb (L1), and 3.3 kb (L2)  components, which seem to be primary transcripts of the L and L1 genes, components corresponding to mature size H, L and Lf mRNAs, and several intermediate-sized components which include the processing derivatives. The precursor role of these nuclear molecules was established by studies of their labeling kinetics and by appropriate pulse-chase experiments. All the pre-mRNA species including H1, L1 and L2 contain poly(A), thus suggesting that polyadenylation is an early event in the processing of these mRNAs. The MPC-11 cell contains about 30,000 and 40,000 cytoplasmic H and L mRNA molecules, respectively, which must be produced within one cell generation (approximately 24 hr). In comparison, the nucleus contains about 100-150 molecules of total pre-mRNA and only about 10-15 molecules of presumptive primary transcripts for each of these Ig species. These values indicate very rapid transcription rates (greater than 20 transcripts per min) and exceptionally fast processing rates (approximately 0.5 min for the primary transcripts and approximately 5 min for overall nuclear processing) for the Ig mRNAs. Thus rapid transcription and processing, together with high cytoplasmic stability, account for the high abundance of Ig mRNAs in the myeloma cell.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "U",
      "lastName" : "Schibler",
      "authorRank" : 1,
      "name" : "Schibler",
      "referenceId" : "RGD:A377553"
    }, {
      "firstName" : "KB",
      "lastName" : "Marcu",
      "authorRank" : 2,
      "name" : "Marcu",
      "referenceId" : "RGD:A241148"
    }, {
      "firstName" : "RP",
      "lastName" : "Perry",
      "authorRank" : 3,
      "name" : "Perry",
      "referenceId" : "RGD:A233013"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11058300"
    } ]
  }, {
    "primaryId" : "PMID:10363126",
    "title" : "Linkage disequilibrium at the cystathionine beta synthase (CBS) locus and the association between genetic variation at the CBS locus and plasma levels of homocysteine. The Ears II Group. European Atherosclerosis Research Study.",
    "datePublished" : "1998-06-01T00:00:00.000-05:00",
    "citation" : "De Stefano V, etal., Ann Hum Genet. 1998 Nov;62(Pt 6):481-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T20:28:15.000-05:00",
    "volume" : "62",
    "pages" : "481-90",
    "abstract" : "Cystathionine beta synthase (CBS) is a key enzyme in homocysteine metabolism. We  have examined four apparently non-functional polymorphisms in the CBS gene and have determined their frequency, degree of linkage disequilibrium and association with plasma homocysteine levels. The polymorphisms are a 68 bp insertion in exon  8, C699T in exon 8, C1080T in exon 11 and C1985T in the 3' untranslated region. 785 individuals participating in the European Atherosclerosis Research Study II (EARSII), from 11 countries across Europe were genotyped for these polymorphisms. The 68bp insertion had the highest frequency in the UK and in the Middle region,  with a lower frequency in the Baltic and the South (p = 0.01), and the exon 11 polymorphism had the highest frequencies of the rare allele in the Baltic (p < 0.05). There was a high degree of linkage disequilibrium between the polymorphisms (p < 0.001 overall), except between C699T and the C1985T, with three common haplotypes accounting for nearly 80% of chromosomes. Examination of  the association between these polymorphisms and plasma homocysteine levels revealed that the carriers of the rare alleles of the C699T, C1080T and C1985T polymorphisms had lower plasma homocysteine concentrations than those homozygous  for the common alleles, although these differences were not statistically significant. The thermolabile valine variant caused by a substitution of a C for  a T at nucleotide 677 in the methylenetetrahydrofolate reductase (MTHFR) has previously been shown to have profound effects on plasma levels of homocysteine in this sample, but the homocysteine-raising effect associated with this thermolabile variant was not seen in carriers of the 68 bp insertion, with this interaction being statistically significant (p < 0.001). These data demonstrate that variation in the CBS gene as detected with these four polymorphisms, had no  statistically significant effect on plasma homocysteine levels in these healthy young men. However, the presence of the 68 bp insertion, which is found in approximately 7.5% of individuals in the populations of Europe sampled, abolishes the raising effect of thermolabile MTHFR Val/Val genotype, and may be of importance in the situation of high homocysteine.",
    "issueName" : "Pt 6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "De Stefano",
      "authorRank" : 1,
      "name" : "De Stefano",
      "referenceId" : "RGD:A232057"
    }, {
      "firstName" : "V",
      "lastName" : "Dekou",
      "authorRank" : 2,
      "name" : "Dekou",
      "referenceId" : "RGD:A317757"
    }, {
      "firstName" : "V",
      "lastName" : "Nicaud",
      "authorRank" : 3,
      "name" : "Nicaud V",
      "referenceId" : "RGD:A38081"
    }, {
      "firstName" : "JF",
      "lastName" : "Chasse",
      "authorRank" : 4,
      "name" : "Chasse",
      "referenceId" : "RGD:A322916"
    }, {
      "firstName" : "J",
      "lastName" : "London",
      "authorRank" : 5,
      "name" : "London",
      "referenceId" : "RGD:A188067"
    }, {
      "firstName" : "D",
      "lastName" : "Stansbie",
      "authorRank" : 6,
      "name" : "Stansbie",
      "referenceId" : "RGD:A317758"
    }, {
      "firstName" : "SE",
      "lastName" : "Humphries",
      "authorRank" : 7,
      "name" : "Humphries SE",
      "referenceId" : "RGD:A58860"
    }, {
      "firstName" : "V",
      "lastName" : "Gudnason",
      "authorRank" : 8,
      "name" : "Gudnason V",
      "referenceId" : "RGD:A40091"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11099010"
    } ]
  }, {
    "primaryId" : "PMID:10363127",
    "title" : "Comprehensive mutation analysis of TSC1 using two-dimensional DNA electrophoresis with DGGE.",
    "datePublished" : "1998-04-01T00:00:00.000-06:00",
    "citation" : "Dabora SL, etal., Ann Hum Genet. 1998 Nov;62(Pt 6):491-504.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:37:33.000-05:00",
    "volume" : "62",
    "pages" : "491-504",
    "abstract" : "Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised  by the development of benign tumors in multiple organs often causing serious neurologic impairment. To develop a reliable genetic test for TSC, two-dimensional electrophoresis with denaturing gradient gel electrophoresis (2D  DGGE) has been developed to detect mutations in TSC1. The 23 exons of TSC1 were amplified using two rounds of PCR. In the first round, all coding regions of TSC1 were amplified in four fragments ranging in size from 7.4 kb to 9.9 kb. In the second round, 32 fragments representing 23 exons were amplified using primers designed to avoid overlapping fragments and with a GC clamp on one end to optimise melting characteristics. These exon fragments were then separated by size in the first dimension using a polyacrylamide gel, and by melting characteristics in the second dimension using a urea/formamide gradient to yield  32 distinct bands. If a mutation is present, four bands instead of one, are typically observed. During the development of this assay, we analysed 63 patient  samples with known TSC1 mutations from prior studies. These 63 patients had 68 known mutations or polymorphisms. With DGGE, all 68 of these were identified (45  point mutations, 3 small insertions, 20 small deletions) and an additional 27 single base variants were discovered. To evaluate the assay, we analysed 19 of these samples in a blinded study. In the blinded analysis, 19/20 (95%) known mutations or polymorphisms were detected. The single missed mutation in the blinded analysis could be identified in retrospect and the assay was modified accordingly. During this study, we identified 2 new mutations (exon 8 and exon 15), a new polymorphism (intron 4), and the first variant identified in a non-coding exon (exon 2).",
    "issueName" : "Pt 6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SL",
      "lastName" : "Dabora",
      "authorRank" : 1,
      "name" : "Dabora",
      "referenceId" : "RGD:A250228"
    }, {
      "firstName" : "I",
      "lastName" : "Sigalas",
      "authorRank" : 2,
      "name" : "Sigalas",
      "referenceId" : "RGD:A250229"
    }, {
      "firstName" : "F",
      "lastName" : "Hall",
      "authorRank" : 3,
      "name" : "Hall",
      "referenceId" : "RGD:A250230"
    }, {
      "firstName" : "C",
      "lastName" : "Eng",
      "authorRank" : 4,
      "name" : "Eng",
      "referenceId" : "RGD:A405865"
    }, {
      "firstName" : "J",
      "lastName" : "Vijg",
      "authorRank" : 5,
      "name" : "Vijg J",
      "referenceId" : "RGD:A55184"
    }, {
      "firstName" : "DJ",
      "lastName" : "Kwiatkowski",
      "authorRank" : 6,
      "name" : "Kwiatkowski DJ",
      "referenceId" : "RGD:A11930"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062216"
    } ]
  }, {
    "primaryId" : "PMID:10363580",
    "title" : "Increased choline kinase activity and elevated phosphocholine levels in human colon cancer.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Nakagami K, etal., Jpn J Cancer Res. 1999 Apr;90(4):419-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-10-13T13:22:59.000-05:00",
    "volume" : "90",
    "pages" : "419-24",
    "abstract" : "Nuclear magnetic resonance spectroscopy has detected elevated phosphocholine levels in human tumor tissues and cells, and in cells that were transformed with  the activated Ha-ras gene and stimulated in vitro with growth-promoting factors such as platelet-derived growth factor, epidermal growth factor, and phorbol ester. However, the mechanism of the elevation and the function of the increased  phosphocholine levels have not been clearly demonstrated. We studied phosphocholine levels enzymatically and analyzed the activity of choline kinase,  which catalyzes the phosphorylation of choline to produce phosphocholine, in human colon cancer and adenoma. Both choline kinase activity and phosphocholine levels were increased in colon cancer and adenoma tissue. The activation of choline kinase and the increased levels of choline kinase alpha were partly responsible for the elevated phosphocholine levels. This study suggests that choline kinase might play a role in growth promotion or signal transduction in carcinogenesis.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Nakagami",
      "authorRank" : 1,
      "name" : "Nakagami",
      "referenceId" : "RGD:A206932"
    }, {
      "firstName" : "T",
      "lastName" : "Uchida",
      "authorRank" : 2,
      "name" : "Uchida",
      "referenceId" : "RGD:A413544"
    }, {
      "firstName" : "S",
      "lastName" : "Ohwada",
      "authorRank" : 3,
      "name" : "Ohwada",
      "referenceId" : "RGD:A206934"
    }, {
      "firstName" : "Y",
      "lastName" : "Koibuchi",
      "authorRank" : 4,
      "name" : "Koibuchi",
      "referenceId" : "RGD:A206935"
    }, {
      "firstName" : "Y",
      "lastName" : "Suda",
      "authorRank" : 5,
      "name" : "Suda Y",
      "referenceId" : "RGD:A56021"
    }, {
      "firstName" : "T",
      "lastName" : "Sekine",
      "authorRank" : 6,
      "name" : "Sekine T",
      "referenceId" : "RGD:A4123"
    }, {
      "firstName" : "Y",
      "lastName" : "Morishita",
      "authorRank" : 7,
      "name" : "Morishita Y",
      "referenceId" : "RGD:A42933"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10401945"
    } ]
  }, {
    "primaryId" : "PMID:10363598",
    "title" : "In vivo migration of lymphocytes in chronically rejecting rat kidney allografts.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Muller V, etal., Transpl Int. 1999;12(2):145-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-05T15:44:49.000-06:00",
    "volume" : "12",
    "pages" : "145-51",
    "abstract" : "Histological analyses have identified lymphocytes and macrophages as the predominant leukocyte populations that infiltrate organs undergoing chronic rejection. In order to define the time frame of this infiltration, we investigated the in vivo migration pattern of lymphocytes in a well-established rat model of chronic kidney allograft rejection. F344 kidneys were orthotopically transplanted into bilaterally nephrectomized Lewis rats. Recipients were treated with cyclosporin A (1.5 mg/kg/per day) for the first 10 days. After anti-CD18 or vehicle pretreatment, peripheral blood lymphocytes obtained from naive Lewis rats and labeled with 3H-uridine were injected into transplanted rats 12 and 16 weeks after transplantation. Organs were harvested 4, 8, and 12 h thereafter. After 12 weeks, proteinuria developed, accompanied by all signs of chronic rejection including glomerular sclerosis. Labeled lymphocytes rapidly infiltrated grafted kidneys 4 h after injection. Even more lymphocytes had accumulated in the grafts 12 h after injection. After 16 weeks, few lymphocytes had emigrated into the graft at 4 h, while infiltration was most pronounced by 12 h. Pretreatment with anti-CD18 inhibited the influx of lymphocytes. There was no difference between the patterns of lymphocytes derived from naive and transplanted rats. Our results emphasize the importance of endothelial cells in chronically rejecting kidneys for the control of leukocyte influx. Beta2-integrins may play a central role in determining the transendothelial migration during this process.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Muller",
      "authorRank" : 1,
      "name" : "Muller V",
      "referenceId" : "RGD:A76656"
    }, {
      "firstName" : "P",
      "lastName" : "Hamar",
      "authorRank" : 2,
      "name" : "Hamar P",
      "referenceId" : "RGD:A76657"
    }, {
      "firstName" : "A",
      "lastName" : "Szabo",
      "authorRank" : 3,
      "name" : "Szabo A",
      "referenceId" : "RGD:A63065"
    }, {
      "firstName" : "M",
      "lastName" : "Vogelsang",
      "authorRank" : 4,
      "name" : "Vogelsang M",
      "referenceId" : "RGD:A76658"
    }, {
      "firstName" : "T",
      "lastName" : "Philipp",
      "authorRank" : 5,
      "name" : "Philipp T",
      "referenceId" : "RGD:A76659"
    }, {
      "firstName" : "U",
      "lastName" : "Heemann",
      "authorRank" : 6,
      "name" : "Heemann U",
      "referenceId" : "RGD:A76660"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600231"
    } ]
  }, {
    "primaryId" : "PMID:10363827",
    "title" : "Regulation of the LIM-type homeobox gene islet-1 during neuronal regeneration.",
    "datePublished" : "1000-06-01T00:00:00.000-06:00",
    "citation" : "Hol EM, etal., Neuroscience. 1999;88(3):917-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-06-25T18:44:41.000-05:00",
    "volume" : "88",
    "pages" : "917-25",
    "abstract" : "Peripheral nerve lesion leads to prominent changes in gene expression in the injured neurons, a process co-ordinated by transcription factors. During development the transcription factor islet-1 plays an important role in differentiation and axogenesis. In axotomized adult neurons a process of axonal regrowth and re-establishment of the neuronal function has to be activated. Thus, we studied changes in the expression of islet-1 after axotomy, under the assumption that frequently developmentally regulated factors are reactivated during neuronal regeneration. We investigated the regulation of islet-1 expression with (i) semi-quantitative reverse transcription polymerase chain reaction and (ii) confocal microscopy in combination with quantitative image analysis. Islet-1 expression was suprisingly down-regulated in motoneurons and sensory neurons of adult rats after axotomy. A maximal reduction in the expression level was reached between day 3 and 7 after nerve lesion, a period of extensive axonal sprouting. Islet-1 expression attained control level at day 42 after lesion, a time-point at which target reinnervation takes place. The decreased expression of islet-1 during axonal regeneration is in contrast to the high levels of islet-1 expression during axogenesis in the developing nervous system. Thus, the proposed role of islet-1 in axonal target finding during axogenesis could not be confirmed in the adult rat. The observed down-regulation of islet-1 rather suggests that the activation of downstream genes important for the embryonic pattern of axonal path finding is suppressed. Moreover, in the adult nervous system islet-1 might be one of the transcription factors regulating the expression of proteins significant for the physiological intact neuronal phenotype.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EM",
      "lastName" : "Hol",
      "authorRank" : 1,
      "name" : "Hol EM",
      "referenceId" : "RGD:A108660"
    }, {
      "firstName" : "FW",
      "lastName" : "Schwaiger",
      "authorRank" : 2,
      "name" : "Schwaiger FW",
      "referenceId" : "RGD:A24197"
    }, {
      "firstName" : "A",
      "lastName" : "Werner",
      "authorRank" : 3,
      "name" : "Werner A",
      "referenceId" : "RGD:A34593"
    }, {
      "firstName" : "A",
      "lastName" : "Schmitt",
      "authorRank" : 4,
      "name" : "Schmitt A",
      "referenceId" : "RGD:A33881"
    }, {
      "firstName" : "G",
      "lastName" : "Raivich",
      "authorRank" : 5,
      "name" : "Raivich G",
      "referenceId" : "RGD:A108661"
    }, {
      "firstName" : "GW",
      "lastName" : "Kreutzberg",
      "authorRank" : 6,
      "name" : "Kreutzberg GW",
      "referenceId" : "RGD:A45506"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311122"
    } ]
  }, {
    "primaryId" : "PMID:10363932",
    "title" : "CBP associates with the p42/p44 MAPK enzymes and is phosphorylated following NGF treatment.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Liu YZ, etal., Neuroreport. 1999 Apr 26;10(6):1239-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-08-03T12:52:07.000-05:00",
    "volume" : "10",
    "pages" : "1239-43",
    "abstract" : "The ability of the CBP (CREB binding protein) coactivator to stimulate transcription has previously been shown to be stimulated by treatment of neuronal cells with nerve growth factor (NGF). This effect is dependent upon activation of the p42/p44 MAPK (mitogen activated protein kinase) pathway. Here we show that both CBP and the related p300 protein directly associate with the p42/p44 MAPK enzymes both prior to and following their activation by NGF and that CBP is phosphorylated following NGF treatment. These results indicate that phosphorylation of CBP itself by the p42/p44 MAPK pathway is likely to be critical for its role in NGF-mediated stimulation of gene expression.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YZ",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu YZ",
      "referenceId" : "RGD:A39858"
    }, {
      "firstName" : "NS",
      "lastName" : "Thomas",
      "authorRank" : 2,
      "name" : "Thomas NS",
      "referenceId" : "RGD:A50459"
    }, {
      "firstName" : "DS",
      "lastName" : "Latchman",
      "authorRank" : 3,
      "name" : "Latchman DS",
      "referenceId" : "RGD:A12520"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2312282"
    } ]
  }, {
    "primaryId" : "PMID:10363999",
    "title" : "Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Brodin G, etal., Cancer Res. 1999 Jun 1;59(11):2731-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-12-16T13:32:08.000-06:00",
    "volume" : "59",
    "pages" : "2731-8",
    "abstract" : "Transforming growth factor (TGF)-beta1 is induced in the prostate after castration and has been implicated in apoptosis of epithelial cells during involution. TGF-beta1-mediated receptor activation induces phosphorylation of Smad2 and Smad3, which form complexes with Smad4, that translocate to the nucleus to regulate transcription of target genes. Smad6 and Smad7 antagonize the action of signal-transducing Smads. We have examined the immunohistochemical expression of different Smad molecules in the epithelium of rat ventral prostate before and after castration, in androgen-sensitive Dunning R3327 PAP prostatic tumor cells from untreated and castrated rats, and after treatment with estrogen. In the ventral prostate, a significant increase of phosphorylated Smad2 (P-Smad2) was observed after castration. In prostatic tumor cells we observed an increased expression of Smad2 and P-Smad2 after treatment. The levels of Smad3 and, in particular, Smad4 were enhanced in the normal ventral prostate, as well as in the tumors after castration. Interestingly, Smad6 and Smad7 expression was also up-regulated in cells with increased Smad2 activation. The staining for Smad2, P-Smad2, Smad3, Smad4, and Smad7 was nuclear in some cells and was present in areas with a large number of apoptotic cells identified by various morphological criteria, formation of apoptotic bodies and, in adjacent sections, by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Our results suggest that the signal transduction pathway for TGF-beta, leading to apoptosis, is activated in the normal prostate after castration and in the tumor model after castration, without or with estrogen treatment.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Brodin",
      "authorRank" : 1,
      "name" : "Brodin G",
      "referenceId" : "RGD:A116343"
    }, {
      "firstName" : "P",
      "lastName" : "Ten Dijke",
      "authorRank" : 2,
      "name" : "Ten Dijke P",
      "referenceId" : "RGD:A15560"
    }, {
      "firstName" : "K",
      "lastName" : "Funa",
      "authorRank" : 3,
      "name" : "Funa K",
      "referenceId" : "RGD:A27686"
    }, {
      "firstName" : "CH",
      "lastName" : "Heldin",
      "authorRank" : 4,
      "name" : "Heldin CH",
      "referenceId" : "RGD:A54894"
    }, {
      "firstName" : "M",
      "lastName" : "Landstrom",
      "authorRank" : 5,
      "name" : "Landstrom M",
      "referenceId" : "RGD:A81635"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2315072"
    } ]
  }, {
    "primaryId" : "PMID:10364159",
    "title" : "Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Gingras AC, etal., Genes Dev. 1999 Jun 1;13(11):1422-37.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:18:15.000-05:00",
    "volume" : "13",
    "pages" : "1422-37",
    "abstract" : "The multisubunit eukaryotic translation initiation factor (eIF) 4F recruits 40S ribosomal subunits to the 5' end of mRNA. The eIF4F subunit eIF4E interacts directly with the mRNA 5' cap structure. Assembly of the eIF4F complex is inhibited by a family of repressor polypeptides, the eIF4E-binding proteins (4E-BPs). Binding of the 4E-BPs to eIF4E is regulated by phosphorylation: Hypophosphorylated 4E-BP isoforms interact strongly with eIF4E, whereas hyperphosphorylated isoforms do not. 4E-BP1 is hypophosphorylated in quiescent cells, but is hyperphosphorylated on multiple sites following exposure to a variety of extracellular stimuli. The PI3-kinase/Akt pathway and the kinase FRAP/mTOR signal to 4E-BP1. FRAP/mTOR has been reported to phosphorylate 4E-BP1 directly in vitro. However, it is not known if FRAP/mTOR is responsible for the phosphorylation of all 4E-BP1 sites, nor which sites must be phosphorylated to release 4E-BP1 from eIF4E. To address these questions, a recombinant FRAP/mTOR protein and a FRAP/mTOR immunoprecipitate were utilized in in vitro kinase assays to phosphorylate 4E-BP1. Phosphopeptide mapping of the in vitro-labeled protein yielded two 4E-BP1 phosphopeptides that comigrated with phosphopeptides produced  in vivo. Mass spectrometry analysis indicated that these peptides contain phosphorylated Thr-37 and Thr-46. Thr-37 and Thr-46 are efficiently phosphorylated in vitro by FRAP/mTOR when 4E-BP1 is bound to eIF4E. However, phosphorylation at these sites was not associated with a loss of eIF4E binding. Phosphorylated Thr-37 and Thr-46 are detected in all phosphorylated in vivo 4E-BP1 isoforms, including those that interact with eIF4E. Finally, mutational analysis demonstrated that phosphorylation of Thr-37/Thr-46 is required for subsequent phosphorylation of several carboxy-terminal serum-sensitive sites. Taken together, our results suggest that 4E-BP1 phosphorylation by FRAP/mTOR on Thr-37 and Thr-46 is a priming event for subsequent phosphorylation of the carboxy-terminal serum-sensitive sites.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AC",
      "lastName" : "Gingras",
      "authorRank" : 1,
      "name" : "Gingras",
      "referenceId" : "RGD:A185076"
    }, {
      "firstName" : "SP",
      "lastName" : "Gygi",
      "authorRank" : 2,
      "name" : "Gygi SP",
      "referenceId" : "RGD:A50094"
    }, {
      "firstName" : "B",
      "lastName" : "Raught",
      "authorRank" : 3,
      "name" : "Raught B",
      "referenceId" : "RGD:A34600"
    }, {
      "firstName" : "RD",
      "lastName" : "Polakiewicz",
      "authorRank" : 4,
      "name" : "Polakiewicz RD",
      "referenceId" : "RGD:A89274"
    }, {
      "firstName" : "RT",
      "lastName" : "Abraham",
      "authorRank" : 5,
      "name" : "Abraham RT",
      "referenceId" : "RGD:A4819"
    }, {
      "firstName" : "MF",
      "lastName" : "Hoekstra",
      "authorRank" : 6,
      "name" : "Hoekstra",
      "referenceId" : "RGD:A205655"
    }, {
      "firstName" : "R",
      "lastName" : "Aebersold",
      "authorRank" : 7,
      "name" : "Aebersold",
      "referenceId" : "RGD:A361324"
    }, {
      "firstName" : "N",
      "lastName" : "Sonenberg",
      "authorRank" : 8,
      "name" : "Sonenberg N",
      "referenceId" : "RGD:A13932"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041044"
    } ]
  }, {
    "primaryId" : "PMID:10364211",
    "title" : "Molecular cloning and functional characterization of brefeldin A-ADP-ribosylated substrate. A novel protein involved in the maintenance of the Golgi structure.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Spano S, etal., J Biol Chem 1999 Jun 18;274(25):17705-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:04.000-06:00",
    "volume" : "274",
    "pages" : "17705-10",
    "abstract" : "Brefeldin A (BFA) is a fungal metabolite that disassembles the Golgi apparatus into tubular networks and causes the dissociation of coatomer proteins from Golgi membranes. We have previously shown that an additional effect of BFA is to stimulate the ADP-ribosylation of two cytosolic proteins of 38 and 50 kDa (brefeldin A-ADP-riboslyated substrate (BARS)) and that this effect greatly facilitates the Golgi-disassembling activity of the toxin. In this study, BARS has been purified from rat brain cytosol and microsequenced, and the BARS cDNA has been cloned. BARS shares high homology with two known proteins, C-terminal-binding protein 1 (CtBP1) and CtBP2. It is therefore a third member of the CtBP family. The role of BARS in Golgi disassembly by BFA was verified in permeabilized cells. In the presence of dialyzed cytosol that had been previously depleted of BARS or treated with an anti-BARS antibody, BFA potently disassembled the Golgi. However, in cytosol complemented with purified BARS, or even in control cytosols containing physiological levels of BARS, the action of BFA on Golgi disassembly was strongly inhibited. These results suggest that BARS exerts a negative control on Golgi tubulation, with important consequences for the structure and function of the Golgi complex.",
    "issueName" : "25",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Spano",
      "authorRank" : 1,
      "name" : "Spano S",
      "referenceId" : "RGD:A7285"
    }, {
      "firstName" : "MG",
      "lastName" : "Silletta",
      "authorRank" : 2,
      "name" : "Silletta MG",
      "referenceId" : "RGD:A7286"
    }, {
      "firstName" : "A",
      "lastName" : "Colanzi",
      "authorRank" : 3,
      "name" : "Colanzi A",
      "referenceId" : "RGD:A7287"
    }, {
      "firstName" : "S",
      "lastName" : "Alberti",
      "authorRank" : 4,
      "name" : "Alberti S",
      "referenceId" : "RGD:A7288"
    }, {
      "firstName" : "G",
      "lastName" : "Fiucci",
      "authorRank" : 5,
      "name" : "Fiucci G",
      "referenceId" : "RGD:A7289"
    }, {
      "firstName" : "C",
      "lastName" : "Valente",
      "authorRank" : 6,
      "name" : "Valente C",
      "referenceId" : "RGD:A7290"
    }, {
      "firstName" : "A",
      "lastName" : "Fusella",
      "authorRank" : 7,
      "name" : "Fusella A",
      "referenceId" : "RGD:A7291"
    }, {
      "firstName" : "M",
      "lastName" : "Salmona",
      "authorRank" : 8,
      "name" : "Salmona M",
      "referenceId" : "RGD:A7292"
    }, {
      "firstName" : "A",
      "lastName" : "Mironov",
      "authorRank" : 9,
      "name" : "Mironov A",
      "referenceId" : "RGD:A7293"
    }, {
      "firstName" : "A",
      "lastName" : "Luini",
      "authorRank" : 10,
      "name" : "Luini A",
      "referenceId" : "RGD:A7294"
    }, {
      "firstName" : "D",
      "lastName" : "Corda",
      "authorRank" : 11,
      "name" : "Corda D",
      "referenceId" : "RGD:A7295"
    }, {
      "firstName" : "S",
      "lastName" : "Spanfo",
      "authorRank" : 12,
      "name" : "Spanfo S",
      "referenceId" : "RGD:A7296"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69822"
    } ]
  }, {
    "primaryId" : "PMID:10364234",
    "title" : "Mammalian homologues of the Drosophila slit protein are ligands of the heparan sulfate proteoglycan glypican-1 in brain.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Liang Y, etal., J Biol Chem 1999 Jun 18;274(25):17885-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:54.000-05:00",
    "volume" : "274",
    "pages" : "17885-92",
    "abstract" : "Using an affinity matrix in which a recombinant glypican-Fc fusion protein expressed in 293 cells was coupled to protein A-Sepharose, we have isolated from rat brain at least two proteins that were detected by SDS-polyacrylamide gel electrophoresis as a single 200-kDa silver-stained band, from which 16 partial peptide sequences were obtained by nano-electrospray tandem mass spectrometry. Mouse expressed sequence tags containing two of these peptides were employed for oligonucleotide design and synthesis of probes by polymerase chain reaction and enabled us to isolate from a rat brain cDNA library a 4.1-kilobase clone that encoded two of our peptide sequences and represented the N-terminal portion of a protein containing a signal peptide and three leucine-rich repeats. Comparisons with recently published sequences also showed that our peptides were derived from proteins that are members of the Slit/MEGF protein family, which share a number of structural features such as N-terminal leucine-rich repeats and C-terminal epidermal growth factor-like motifs, and in Drosophila Slit is necessary for the development of midline glia and commissural axon pathways. All of the five known rat and human Slit proteins contain 1523-1534 amino acids, and our peptide sequences correspond best to those present in human Slit-1 and Slit-2. Binding of these ligands to the glypican-Fc fusion protein requires the presence of the heparan sulfate chains, but the interaction appears to be relatively specific for glypican-1 insofar as no other identified heparin-binding proteins were isolated using our affinity matrix. Northern analysis demonstrated the presence of two mRNA species of 8. 6 and 7.5 kilobase pairs using probes based on both N- and C-terminal sequences, and in situ hybridization histochemistry showed that these glypican-1 ligands are synthesized by neurons, such as hippocampal pyramidal cells and cerebellar granule cells, where we have previously also demonstrated glypican-1 mRNA and immunoreactivity. Our results therefore indicate that Slit family proteins are functional ligands of glypican-1 in nervous tissue and suggest that their interactions may be critical for certain stages of central nervous system histogenesis.",
    "issueName" : "25",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Liang",
      "authorRank" : 1,
      "name" : "Liang Y",
      "referenceId" : "RGD:A162007"
    }, {
      "firstName" : "RS",
      "lastName" : "Annan",
      "authorRank" : 2,
      "name" : "Annan RS",
      "referenceId" : "RGD:A5757"
    }, {
      "firstName" : "SA",
      "lastName" : "Carr",
      "authorRank" : 3,
      "name" : "Carr SA",
      "referenceId" : "RGD:A5758"
    }, {
      "firstName" : "S",
      "lastName" : "Popp",
      "authorRank" : 4,
      "name" : "Popp S",
      "referenceId" : "RGD:A5759"
    }, {
      "firstName" : "M",
      "lastName" : "Mevissen",
      "authorRank" : 5,
      "name" : "Mevissen M",
      "referenceId" : "RGD:A5760"
    }, {
      "firstName" : "RK",
      "lastName" : "Margolis",
      "authorRank" : 6,
      "name" : "Margolis RK",
      "referenceId" : "RGD:A34074"
    }, {
      "firstName" : "RU",
      "lastName" : "Margolis",
      "authorRank" : 7,
      "name" : "Margolis RU",
      "referenceId" : "RGD:A52376"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68764"
    } ]
  }, {
    "primaryId" : "PMID:10364312",
    "title" : "gamma delta+ T cells regulate major histocompatibility complex class II(IA and IE)-dependent susceptibility to coxsackievirus B3-induced autoimmune myocarditis.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Huber SA, etal., J Virol. 1999 Jul;73(7):5630-6. doi: 10.1128/JVI.73.7.5630-5636.1999.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-06-30T09:53:06.000-05:00",
    "volume" : "73",
    "pages" : "5630-6",
    "abstract" : "Coxsackievirus B3 (CVB3) infection induces myocardial inflammation and myocyte necrosis in some, but not all, strains of mice. C57BL/6 mice, which inherently lack major histocompatibility complex (MHC) class II IE antigen, develop minimal cardiac lesions despite high levels of virus in the heart. The present experiments evaluate the relative roles of class II IA and IE expression on myocarditis susceptibility in four transgenic C57BL/6 mouse strains differing in MHC class II antigen expression. Animals lacking MHC class II IE antigen (C57BL/6 [IA+ IE-] and ABo [IA- IE-]) developed minimal cardiac lesions subsequent to infection despite high concentrations of virus in the heart. In contrast, strains expressing IE (ABo Ealpha [IA- IE+] and Bl.Tg.Ealpha [IA+ IE+]) had substantial cardiac injury. Myocarditis susceptibility correlated to a Th1 (gamma interferon-positive) cell response in the spleen, while disease resistance correlated to a preferential Th2 (interleukin-4-positive) phenotype. Vgamma/Vdelta analysis indicates that distinct subpopulations of gamma delta+ T cells are activated after CVB3 infection of C57BL/6 and Bl.Tg.Ealpha mice. Depletion of gamma delta+ T cells abrogated myocarditis susceptibility in IE+ animals and resulted in a Th1-->Th2 phenotype shift. These studies indicate that the MHC class II antigen haplotype controls myocarditis susceptibility, that this control is most likely mediated through the type of gamma delta T cells activated during CVB3 infection, and finally that different subpopulations of gamma delta+ T cells may either promote or inhibit Th1 cell responses.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S A",
      "lastName" : "Huber",
      "authorRank" : 1,
      "name" : "Huber SA",
      "referenceId" : "RGD:A501816"
    }, {
      "firstName" : "J E",
      "lastName" : "Stone",
      "authorRank" : 2,
      "name" : "Stone JE",
      "referenceId" : "RGD:A501817"
    }, {
      "firstName" : "D H",
      "lastName" : "Wagner",
      "authorRank" : 3,
      "name" : "Wagner DH",
      "referenceId" : "RGD:A501818"
    }, {
      "firstName" : "J",
      "lastName" : "Kupperman",
      "authorRank" : 4,
      "name" : "Kupperman J",
      "referenceId" : "RGD:A501819"
    }, {
      "firstName" : "L",
      "lastName" : "Pfeiffer",
      "authorRank" : 5,
      "name" : "Pfeiffer L",
      "referenceId" : "RGD:A501820"
    }, {
      "firstName" : "C",
      "lastName" : "David",
      "authorRank" : 6,
      "name" : "David C",
      "referenceId" : "RGD:A6562"
    }, {
      "firstName" : "R L",
      "lastName" : "O'Brien",
      "authorRank" : 7,
      "name" : "O'Brien RL",
      "referenceId" : "RGD:A501821"
    }, {
      "firstName" : "G S",
      "lastName" : "Davis",
      "authorRank" : 8,
      "name" : "Davis GS",
      "referenceId" : "RGD:A501822"
    }, {
      "firstName" : "M K",
      "lastName" : "Newell",
      "authorRank" : 9,
      "name" : "Newell MK",
      "referenceId" : "RGD:A501823"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:127285795"
    } ]
  }, {
    "primaryId" : "PMID:10364516",
    "title" : "X-linked dyskeratosis congenita is predominantly caused by missense mutations in  the DKC1 gene.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Knight SW, etal., Am J Hum Genet. 1999 Jul;65(1):50-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-27T12:57:13.000-06:00",
    "volume" : "65",
    "pages" : "50-8",
    "abstract" : "Dyskeratosis congenita is a rare inherited bone marrow-failure syndrome characterized by abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. More than 80% of patients develop bone-marrow failure, and this is the major cause of premature death. The X-linked form of the disease (MIM 305000) has been shown to be caused by mutations in the DKC1 gene. The gene encodes a 514-amino-acid protein, dyskerin, that is homologous to Saccharomyces cerevisiae  Cbf5p and rat Nap57 proteins. By analogy to the homologues in other species, dyskerin is predicted to be a nucleolar protein with a role in both the biogenesis of ribosomes and, in particular, the pseudouridylation of rRNA precursors. We have determined the genomic structure of the DKC1 gene; it consists of 15 exons spanning a region of 15 kb. This has enabled us to screen for mutations in the genomic DNA, by using SSCP analysis. Mutations were detected in 21 of 37 additional families with dyskeratosis congenita that were analyzed. These mutations consisted of 11 different single-nucleotide substitutions, which  resulted in 10 missense mutations and 1 putative splicing mutation within an intron. The missense change A353V was observed in 10 different families and was shown to be a recurring de novo event. Two polymorphisms were also detected, one  of which resulted in the insertion of an additional lysine in the carboxy-terminal polylysine domain. It is apparent that X-linked dyskeratosis congenita is predominantly caused by missense mutations; the precise effect on the function of dyskerin remains to be determined.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SW",
      "lastName" : "Knight",
      "authorRank" : 1,
      "name" : "Knight SW",
      "referenceId" : "RGD:A37907"
    }, {
      "firstName" : "NS",
      "lastName" : "Heiss",
      "authorRank" : 2,
      "name" : "Heiss NS",
      "referenceId" : "RGD:A37906"
    }, {
      "firstName" : "TJ",
      "lastName" : "Vulliamy",
      "authorRank" : 3,
      "name" : "Vulliamy TJ",
      "referenceId" : "RGD:A37908"
    }, {
      "firstName" : "S",
      "lastName" : "Greschner",
      "authorRank" : 4,
      "name" : "Greschner",
      "referenceId" : "RGD:A211078"
    }, {
      "firstName" : "G",
      "lastName" : "Stavrides",
      "authorRank" : 5,
      "name" : "Stavrides",
      "referenceId" : "RGD:A211079"
    }, {
      "firstName" : "GS",
      "lastName" : "Pai",
      "authorRank" : 6,
      "name" : "Pai",
      "referenceId" : "RGD:A211080"
    }, {
      "firstName" : "G",
      "lastName" : "Lestringant",
      "authorRank" : 7,
      "name" : "Lestringant",
      "referenceId" : "RGD:A211081"
    }, {
      "firstName" : "N",
      "lastName" : "Varma",
      "authorRank" : 8,
      "name" : "Varma",
      "referenceId" : "RGD:A211082"
    }, {
      "firstName" : "PJ",
      "lastName" : "Mason",
      "authorRank" : 9,
      "name" : "Mason PJ",
      "referenceId" : "RGD:A9818"
    }, {
      "firstName" : "I",
      "lastName" : "Dokal",
      "authorRank" : 10,
      "name" : "Dokal I",
      "referenceId" : "RGD:A37910"
    }, {
      "firstName" : "A",
      "lastName" : "Poustka",
      "authorRank" : 11,
      "name" : "Poustka A",
      "referenceId" : "RGD:A7556"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10755414"
    } ]
  }, {
    "primaryId" : "PMID:10364519",
    "title" : "Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Chen B, etal., Am J Hum Genet. 1999 Jul;65(1):77-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-10T11:19:58.000-06:00",
    "volume" : "65",
    "pages" : "77-87",
    "abstract" : "Deficiency of the GM2 activator protein, encoded by GM2A, results in the rare AB-variant form of GM2 gangliosidosis. Four mutations have been identified, but the human gene structure has been only partially characterized. We report a new patient from a Laotian deme whose cells are deficient in both GM2-activator mRNA and protein. However, reverse transcription (RT)-PCR detected some normal-sized cDNA and a smaller cDNA species, which was not seen in the RT-PCR products from normal controls. Sequencing revealed that, although the patient's normal-sized cDNA contained a single nonsense mutation in exon 2, his smaller cDNA was the result of an in-frame deletion of exon 2. Long PCR was used to amplify introns 1 and 2 from patient and normal genomic DNA, and no differences in size, in 5' and 3' end sequences, or in restriction-mapping patterns were observed. From these data we developed a set of four PCR primers that can be used to identify GM2A mutations. We use this procedure to demonstrate that the patient is likely homozygous for the nonsense mutation. Other reports have associated nonsense mutations with dramatically reduced levels of mRNA and with an increased level of skipping of the exon containing the mutation, thus reestablishing an open reading frame. However, a recent article has concluded that, in some cases, the latter observation is caused by an artifact of RT-PCR. In support of this conclusion, we demonstrate that, if the competing, normal-sized cDNA is removed from the initial RT-PCR products, from both patient and normal cells, by an exon 2-specific restriction digest; a second round of PCR produces similar amounts of exon 2-deleted cDNA.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Chen",
      "authorRank" : 1,
      "name" : "Chen B",
      "referenceId" : "RGD:A5012"
    }, {
      "firstName" : "B",
      "lastName" : "Rigat",
      "authorRank" : 2,
      "name" : "Rigat B",
      "referenceId" : "RGD:A39176"
    }, {
      "firstName" : "C",
      "lastName" : "Curry",
      "authorRank" : 3,
      "name" : "Curry C",
      "referenceId" : "RGD:A72090"
    }, {
      "firstName" : "DJ",
      "lastName" : "Mahuran",
      "authorRank" : 4,
      "name" : "Mahuran DJ",
      "referenceId" : "RGD:A4916"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598993"
    } ]
  }, {
    "primaryId" : "PMID:10364520",
    "title" : "MEFV-Gene analysis in armenian patients with Familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Cazeneuve C, etal., Am J Hum Genet. 1999 Jul;65(1):88-97.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:02:09.000-05:00",
    "volume" : "65",
    "pages" : "88-97",
    "abstract" : "Familial Mediterranean fever (FMF) is a recessively inherited disorder that is common in patients of Armenian ancestry. To date, its diagnosis, which can be made only retrospectively, is one of exclusion, based entirely on nonspecific clinical signs that result from serosal inflammation and that may lead to unnecessary surgery. Renal amyloidosis, prevented by colchicine, is the most severe complication of FMF, a disorder associated with mutations in the MEFV gene. To evaluate the diagnostic and prognostic value of MEFV-gene analysis, we investigated 90 Armenian FMF patients from 77 unrelated families that were not selected through genetic-linkage analysis. Eight mutations, one of which (R408Q)  is new, were found to account for 93% of the 163 independent FMF alleles, with both FMF alleles identified in 89% of the patients. In several instances, family  studies provided molecular evidence for pseudodominant transmission and incomplete penetrance of the disease phenotype. The M694V homozygous genotype was found to be associated with a higher prevalence of renal amyloidosis and arthritis, compared with other genotypes (P=.0002 and P=.006, respectively). The  demonstration of both the diagnostic and prognostic value of MEFV analysis and particular modes of inheritance should lead to new ways for management of FMF-including genetic counseling and therapeutic decisions in affected families.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Cazeneuve",
      "authorRank" : 1,
      "name" : "Cazeneuve C",
      "referenceId" : "RGD:A126503"
    }, {
      "firstName" : "T",
      "lastName" : "Sarkisian",
      "authorRank" : 2,
      "name" : "Sarkisian",
      "referenceId" : "RGD:A259413"
    }, {
      "firstName" : "C",
      "lastName" : "Pecheux",
      "authorRank" : 3,
      "name" : "Pecheux C",
      "referenceId" : "RGD:A81932"
    }, {
      "firstName" : "M",
      "lastName" : "Dervichian",
      "authorRank" : 4,
      "name" : "Dervichian",
      "referenceId" : "RGD:A261669"
    }, {
      "firstName" : "B",
      "lastName" : "Nedelec",
      "authorRank" : 5,
      "name" : "Nedelec B",
      "referenceId" : "RGD:A10111"
    }, {
      "firstName" : "P",
      "lastName" : "Reinert",
      "authorRank" : 6,
      "name" : "Reinert",
      "referenceId" : "RGD:A255137"
    }, {
      "firstName" : "A",
      "lastName" : "Ayvazyan",
      "authorRank" : 7,
      "name" : "Ayvazyan",
      "referenceId" : "RGD:A261670"
    }, {
      "firstName" : "JC",
      "lastName" : "Kouyoumdjian",
      "authorRank" : 8,
      "name" : "Kouyoumdjian",
      "referenceId" : "RGD:A259412"
    }, {
      "firstName" : "H",
      "lastName" : "Ajrapetyan",
      "authorRank" : 9,
      "name" : "Ajrapetyan",
      "referenceId" : "RGD:A259405"
    }, {
      "firstName" : "M",
      "lastName" : "Delpech",
      "authorRank" : 10,
      "name" : "Delpech M",
      "referenceId" : "RGD:A10114"
    }, {
      "firstName" : "M",
      "lastName" : "Goossens",
      "authorRank" : 11,
      "name" : "Goossens",
      "referenceId" : "RGD:A414424"
    }, {
      "firstName" : "C",
      "lastName" : "Dode",
      "authorRank" : 12,
      "name" : "Dode C",
      "referenceId" : "RGD:A81930"
    }, {
      "firstName" : "G",
      "lastName" : "Grateau",
      "authorRank" : 13,
      "name" : "Grateau G",
      "referenceId" : "RGD:A81937"
    }, {
      "firstName" : "S",
      "lastName" : "Amselem",
      "authorRank" : 14,
      "name" : "Amselem S",
      "referenceId" : "RGD:A57194"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065360"
    } ]
  }, {
    "primaryId" : "PMID:10364529",
    "title" : "Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Chapman K, etal., Am J Hum Genet 1999 Jul;65(1):167-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-04-13T15:20:29.000-05:00",
    "volume" : "65",
    "pages" : "167-74",
    "abstract" : "We present a two-stage genomewide scan for osteoarthritis-susceptibility loci, using 481 families that each contain at least one affected sibling pair. The first stage, with 272 microsatellite markers and 297 families, involved a sparse map covering 23 chromosomes at intervals of approximately 15 cM. Sixteen markers that showed evidence of linkage at nominal P</=.05 were then taken through to the second stage, with an additional 184 families. This second stage confirmed evidence of linkage for markers on chromosome 11q. Additional markers from this region were then typed to create a denser map. We obtained a maximum single-point LOD score, at D11S901, of 2.40 (P=.0004) and a maximum multipoint-LOD score of 3.15, between markers D11S1358 and D11S35. A subset of 196 of the 481 families, comprising affected female sibling pairs, generated a corrected LOD score of 2.54 (P=.0003) for marker D11S901, with evidence for linkage extending 12 cM proximal to this marker. When we stratified for affected male sibling pairs there was no evidence of linkage to chromosome 11. Our data suggest that a female-specific susceptibility gene for idiopathic osteoarthritis is located on chromosome 11q.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Chapman",
      "authorRank" : 1,
      "name" : "Chapman K",
      "referenceId" : "RGD:A34805"
    }, {
      "firstName" : "Z",
      "lastName" : "Mustafa",
      "authorRank" : 2,
      "name" : "Mustafa Z",
      "referenceId" : "RGD:A35557"
    }, {
      "firstName" : "C",
      "lastName" : "Irven",
      "authorRank" : 3,
      "name" : "Irven C",
      "referenceId" : "RGD:A35558"
    }, {
      "firstName" : "AJ",
      "lastName" : "Carr",
      "authorRank" : 4,
      "name" : "Carr AJ",
      "referenceId" : "RGD:A35559"
    }, {
      "firstName" : "K",
      "lastName" : "Clipsham",
      "authorRank" : 5,
      "name" : "Clipsham K",
      "referenceId" : "RGD:A35560"
    }, {
      "firstName" : "A",
      "lastName" : "Smith",
      "authorRank" : 6,
      "name" : "Smith A",
      "referenceId" : "RGD:A381294"
    }, {
      "firstName" : "J",
      "lastName" : "Chitnavis",
      "authorRank" : 7,
      "name" : "Chitnavis J",
      "referenceId" : "RGD:A35561"
    }, {
      "firstName" : "JS",
      "lastName" : "Sinsheimer",
      "authorRank" : 8,
      "name" : "Sinsheimer JS",
      "referenceId" : "RGD:A35565"
    }, {
      "firstName" : "VA",
      "lastName" : "Bloomfield",
      "authorRank" : 9,
      "name" : "Bloomfield VA",
      "referenceId" : "RGD:A35562"
    }, {
      "firstName" : "M",
      "lastName" : "McCartney",
      "authorRank" : 10,
      "name" : "McCartney M",
      "referenceId" : "RGD:A35563"
    }, {
      "firstName" : "O",
      "lastName" : "Cox",
      "authorRank" : 11,
      "name" : "Cox O",
      "referenceId" : "RGD:A35564"
    }, {
      "firstName" : "LR",
      "lastName" : "Cardon",
      "authorRank" : 12,
      "name" : "Cardon LR",
      "referenceId" : "RGD:A40014"
    }, {
      "firstName" : "B",
      "lastName" : "Sykes",
      "authorRank" : 13,
      "name" : "Sykes B",
      "referenceId" : "RGD:A35566"
    }, {
      "firstName" : "J",
      "lastName" : "Loughlin",
      "authorRank" : 14,
      "name" : "Loughlin J",
      "referenceId" : "RGD:A35556"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1285222"
    } ]
  }, {
    "primaryId" : "PMID:10364562",
    "title" : "Strain differences in neointimal hyperplasia in the rat.",
    "datePublished" : "1999-06-11T00:00:00.000-05:00",
    "citation" : "Assadnia S, etal., Circ Res. 1999 Jun 11;84(11):1252-7. doi: 10.1161/01.res.84.11.1252.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-10-05T21:13:05.000-05:00",
    "volume" : "84",
    "pages" : "1252-7",
    "abstract" : "We performed an initial screen of 11 rat strains by use of a standard balloon injury to the left iliac artery to observe whether genetically determined differences existed in the development of neointimal hyperplasia. Neointimal hyperplasia was assayed 8 weeks after the vascular injury on coded microscopic sections. Statistically significant differences in the percentages of the vascular wall cross-sectional areas composed of intima (percentage intima) secondary to neointimal hyperplasia were noted among the different rat strains (P<0.02), with the Brown-Norway (BN), Dark Agouti, and Milan normotensive strain rats having the highest and the spontaneously hypertensive rats (SHR) having the lowest percentages of intima. In a separate experiment, F1 hybrids of SHRxBN strains and parental BN and SHR underwent the vascular injury, and the parental strains again showed a statistically significant difference from one another in the mean percentage of intima (P<0. 0001). The F1 hybrids showed an average percentage of intima intermediate between those of the parental strains. The average lumen size of the injured BN vessels were significantly smaller than that of the noninjured control vessels (P=0.044), but this significance disappeared when the circular areas of these vessels were calculated without taking neointimal growth into consideration (P=0.649). These results provide the groundwork for a genetic linkage analysis to identify the genes that influence the development of neointimal hyperplasia after vascular injury.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Assadnia",
      "authorRank" : 1,
      "name" : "Assadnia S",
      "referenceId" : "RGD:A347"
    }, {
      "firstName" : "J P",
      "lastName" : "Rapp",
      "authorRank" : 2,
      "name" : "Rapp JP",
      "referenceId" : "RGD:A488748"
    }, {
      "firstName" : "A L",
      "lastName" : "Nestor",
      "authorRank" : 3,
      "name" : "Nestor AL",
      "referenceId" : "RGD:A488749"
    }, {
      "firstName" : "T",
      "lastName" : "Pringle",
      "authorRank" : 4,
      "name" : "Pringle T",
      "referenceId" : "RGD:A119996"
    }, {
      "firstName" : "G J",
      "lastName" : "Cerilli",
      "authorRank" : 5,
      "name" : "Cerilli GJ",
      "referenceId" : "RGD:A488750"
    }, {
      "firstName" : "W T",
      "lastName" : "Gunning",
      "authorRank" : 6,
      "name" : "Gunning WT",
      "referenceId" : "RGD:A488751"
    }, {
      "firstName" : "T H",
      "lastName" : "Webb",
      "authorRank" : 7,
      "name" : "Webb TH",
      "referenceId" : "RGD:A488752"
    }, {
      "firstName" : "M",
      "lastName" : "Kligman",
      "authorRank" : 8,
      "name" : "Kligman M",
      "referenceId" : "RGD:A488753"
    }, {
      "firstName" : "D C",
      "lastName" : "Allison",
      "authorRank" : 9,
      "name" : "Allison DC",
      "referenceId" : "RGD:A488754"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:39456133"
    } ]
  }, {
    "primaryId" : "PMID:10364683",
    "title" : "A novel G to A substitution at nucleotide 1734 of the FBN1 gene predicting a C534Y mutation responsible for marfan syndrome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kilpatrick MW, etal., Hum Hered. 1999 Jun;49(3):176-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:51:57.000-05:00",
    "volume" : "49",
    "pages" : "176-7",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MW",
      "lastName" : "Kilpatrick",
      "authorRank" : 1,
      "name" : "Kilpatrick MW",
      "referenceId" : "RGD:A78134"
    }, {
      "firstName" : "P",
      "lastName" : "Lembessis",
      "authorRank" : 2,
      "name" : "Lembessis P",
      "referenceId" : "RGD:A102512"
    }, {
      "firstName" : "E",
      "lastName" : "Rose",
      "authorRank" : 3,
      "name" : "Rose",
      "referenceId" : "RGD:A280068"
    }, {
      "firstName" : "P",
      "lastName" : "Tsipouras",
      "authorRank" : 4,
      "name" : "Tsipouras P",
      "referenceId" : "RGD:A56701"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071649"
    } ]
  }, {
    "primaryId" : "PMID:10365252",
    "title" : "Effect of alpha lipoic acid amide on hexachlorobenzene porphyria.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Vilas GL, etal., Biochem Mol Biol Int. 1999 May;47(5):815-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-10-22T17:05:29.000-05:00",
    "volume" : "47",
    "pages" : "815-23",
    "abstract" : "The aim of this work is to study the effect of thioctamide--the commercial form of alpha lipoic acid amide--on the porphyrinogenic action of hexachlorobenzene (HCB). For this purpose, porphyria was induced in rats by chronic HCB treatment, with or without simultaneous thioctamide administration. Two different groups of rats were used as reference: one treated with vehicle (control) and the other treated with thioctamide (TO). Urine delta aminolevulic acid, porphobilinogen, and porphyrin excretions were lower in the HCB + TO treated group than in the HCB group, and the same happened with liver uroporphyrin accumulation. On the other hand, the second stage of uroporphyrinogen-decarboxylase activity was significantly higher in the HCB + TO group than in the HCB group. delta aminolevulic acid synthase activity was higher in the HCB group. Hepatic thiobarbituric acid reactive substances were lower in HCB + TO group than in HCB group. Thus, we might suggest that TO would decrease HCB effects by means of its free radical scavenging ability, and by having a direct effect on uroporphyrinogen-decarboxylase activity.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GL",
      "lastName" : "Vilas",
      "authorRank" : 1,
      "name" : "Vilas GL",
      "referenceId" : "RGD:A129524"
    }, {
      "firstName" : "C",
      "lastName" : "Aldonatti",
      "authorRank" : 2,
      "name" : "Aldonatti C",
      "referenceId" : "RGD:A128858"
    }, {
      "firstName" : "LC",
      "lastName" : "San Martin de Viale",
      "authorRank" : 3,
      "name" : "San Martin de Viale LC",
      "referenceId" : "RGD:A80225"
    }, {
      "firstName" : "MC",
      "lastName" : "Rios de Molina",
      "authorRank" : 4,
      "name" : "Rios de Molina MC",
      "referenceId" : "RGD:A128856"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4145076"
    } ]
  }, {
    "primaryId" : "PMID:10365842",
    "title" : "Small bowel ischaemia-reperfusion increases plasma concentrations of oxidised proteins in rats.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Abu-Zidan FM, etal., Eur J Surg. 1999 Apr;165(4):383-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-05-19T08:58:59.000-05:00",
    "volume" : "165",
    "pages" : "383-9",
    "abstract" : "OBJECTIVES: To find out whether plasma concentrations of protein carbonyl (a specific marker of oxidative damage of proteins) are increased during intestinal  ischaemia-reperfusion and whether they are correlated with von Willebrand's factor (vWF, a marker of endothelial injury) or myeloperoxidase (a marker of neutrophil activation). DESIGN: Randomised experimental study. SETTING: University department of surgery, New Zealand. ANIMALS: Thirty anaesthetised adult Wistar rats. INTERVENTIONS: The sham operated group (n = 10) had laparotomy and isolation of the superior mesenteric artery without clamping. The ischaemia-reperfusion group (IR, n = 10) had the superior mesenteric artery clamped for 1 hour and reperfusion for 15 minutes. The control group (n = 10) had direct puncture of the heart to sample blood. MAIN OUTCOME MEASURES: Plasma concentrations of protein carbonyl, vWF, and myeloperoxidase. RESULTS: Plasma protein carbonyl concentrations were significantly higher in the IR group than in the sham group (p < 0.02, Mann-Whitney test, median (range) 0.187 (0.141-0.242) compared with 0.144 (0.121-0.185) nmol/mg) and in the control group (p < 0.01, Mann-Whitney test, median (range) 0.187 (0.141-0.242) compared with 0.136 (0.108-0.175) nmol/mg). There was a significant correlation between protein carbonyl and vWF concentrations (r = 0.54, F = 10.9, p < 0.003, linear regression) but not with those of myeloperoxidase. CONCLUSION: Intestinal ischaemia-reperfusion caused an increase in the plasma protein carbonyl concentration, which is possibly produced by endothelial cells.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FM",
      "lastName" : "Abu-Zidan",
      "authorRank" : 1,
      "name" : "Abu-Zidan",
      "referenceId" : "RGD:A305530"
    }, {
      "firstName" : "CC",
      "lastName" : "Winterbourn",
      "authorRank" : 2,
      "name" : "Winterbourn",
      "referenceId" : "RGD:A247990"
    }, {
      "firstName" : "MJ",
      "lastName" : "Bonham",
      "authorRank" : 3,
      "name" : "Bonham",
      "referenceId" : "RGD:A305531"
    }, {
      "firstName" : "MO",
      "lastName" : "Simovic",
      "authorRank" : 4,
      "name" : "Simovic",
      "referenceId" : "RGD:A305532"
    }, {
      "firstName" : "H",
      "lastName" : "Buss",
      "authorRank" : 5,
      "name" : "Buss",
      "referenceId" : "RGD:A305533"
    }, {
      "firstName" : "JA",
      "lastName" : "Windsor",
      "authorRank" : 6,
      "name" : "Windsor",
      "referenceId" : "RGD:A305534"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11080742"
    } ]
  }, {
    "primaryId" : "PMID:10366024",
    "title" : "Differential expression of bcl-w and bcl-x messenger RNA in the developing and adult rat nervous system.",
    "datePublished" : "2002-08-01T00:00:00.000-05:00",
    "citation" : "Hamner S, etal., Neuroscience 1999;91(2):673-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-21T16:24:15.000-05:00",
    "volume" : "91",
    "pages" : "673-84",
    "abstract" : "The bcl-2 family of proteins comprises both anti-apoptotic and pro-apoptotic members, which play a pivotal role in regulating cell death. Bcl-w is a recently identified member of this family, which was shown to inhibit apoptosis in haemopoietic cell lines. However, the function and expression patterns of bcl-w in the nervous system have so far not been described. We have cloned complementary DNA corresponding to rat bcl-w and analysed the expression of bcl-w messenger RNA during rat brain development, using RNA blotting and in situ hybridization techniques. We also compared the expression patterns of bcl-w with those of bcl-xL. During brain development, the levels of bcl-w messenger RNA were found to increase, with highest expression located to specific regions of the mature brain, such as hippocampus, cerebellum, piriform cortex and locus coeruleus. Bcl-w messenger RNA was expressed by neurons, as shown with double labeling with neuronal markers. In contrast to bcl-w, bcl-xL messenger RNA expression levels were highest during early development, particularly in cortex, hippocampus, thalamus, spinal cord and dorsal root ganglia. During postnatal development the expression of bcl-xL messenger RNA decreased and were only detected at low levels in the adult nervous system. As shown earlier for bcl-2, the expression of bcl-w and bcl-x messenger RNA in cultured cerebellar granule cells was not altered by the deprivation of neurotrophic factors. The present results suggest that bcl-w may play an important role in the mature nervous system.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Hamner",
      "authorRank" : 1,
      "name" : "Hamner S",
      "referenceId" : "RGD:A12028"
    }, {
      "firstName" : "Y",
      "lastName" : "Skoglosa",
      "authorRank" : 2,
      "name" : "Skoglosa Y",
      "referenceId" : "RGD:A16103"
    }, {
      "firstName" : "D",
      "lastName" : "Lindholm",
      "authorRank" : 3,
      "name" : "Lindholm D",
      "referenceId" : "RGD:A12033"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632002"
    } ]
  }, {
    "primaryId" : "PMID:10366449",
    "title" : "Identification of a human homolog of the Drosophila rotated abdomen gene (POMT1) encoding a putative protein O-mannosyl-transferase, and assignment to human chromosome 9q34.1.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Jurado LA, etal., Genomics 1999 Jun 1;58(2):171-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-11T09:25:05.000-05:00",
    "volume" : "58",
    "pages" : "171-80",
    "abstract" : "We have isolated a human gene homologous to Drosophila melanogaster rotated abdomen, rt, a poorly viable recessive mutation causing a clockwise twisted abdomen in affected flies due to defects in embryonic muscle development. The human gene, like rt, encodes a protein with high homology to the yeast mannosyl-transferases (Pmts) and has been named POMT1. POMT1 is expressed as a 3.1-kb transcript in all tissues tested, with highest levels in testis and fetal brain. Alternative splicing of several exons in all tissues predicts the generation of several protein isoforms. The most common mRNA variant encodes a 725-aa protein with 40% identity and 62.5% similarity to rt, as well as 30.5% identity and 54% similarity to yeast Pmts. Computer prediction of protein sorting suggests that the POMT1 product could be an integral protein of the endoplasmic reticulum membrane. Given the strong conservation of protein motifs between POMT1 and the yeast Pmts, POMT1 may function as a mannosyl-transferase involved in O-mannosylation of proteins, being the first of such a class found in mammals. The POMT1 locus has been assigned to human chromosome 9q34.1 by somatic cell hybrids, radiation hybrids, and linkage analysis. On the basis of the rt phenotype, POMT1 could be a candidate for uncharacterized genetic disorders of the muscular system, such as some forms of congenital muscular dystrophy or congenital myopathy.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LA",
      "lastName" : "Jurado",
      "authorRank" : 1,
      "name" : "Jurado LA",
      "referenceId" : "RGD:A52373"
    }, {
      "firstName" : "A",
      "lastName" : "Coloma",
      "authorRank" : 2,
      "name" : "Coloma A",
      "referenceId" : "RGD:A52374"
    }, {
      "firstName" : "J",
      "lastName" : "Cruces",
      "authorRank" : 3,
      "name" : "Cruces J",
      "referenceId" : "RGD:A35397"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358414"
    } ]
  }, {
    "primaryId" : "PMID:10366565",
    "title" : "The role of gamma interferon in immune resistance to vaginal infection by herpes  simplex virus type 2 in mice.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Parr MB and Parr EL, Virology. 1999 Jun 5;258(2):282-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-05T09:39:38.000-06:00",
    "volume" : "258",
    "pages" : "282-94",
    "abstract" : "We investigated the role of interferon gamma (IFN-gamma) in a mouse model of immunity to vaginal infection by herpes simplex virus type 2 (HSV-2). Within 8 h  after immune mice were challenged intravaginally with HSV-2, IFN-gamma concentrations in vaginal secretions reached levels that can be antiviral in vitro. This rapid synthesis of IFN-gamma occurred in immune-challenged mice but not in nonimmune-challenged mice, indicating that it required memory T cells. Immunostaining and in situ hybridization revealed that the IFN-gamma was synthesized by cells whose morphological appearance suggested that they were lymphocytes and macrophage-like cells in the mucosa. The presence of IFN-gamma in vaginal secretions was correlated with upregulation of MHC class II antigens in the epithelium and with vigorous (30-fold) recruitment of T and B lymphocytes into the vagina. In vivo administration of anti-IFN-gamma to immune mice 17 h before virus challenge blocked the subsequent appearance of IFN-gamma in vaginal  secretions, blocked upregulation of class II antigens, blocked adherence of T cells to endothelium and their recruitment into the vagina, and markedly reduced  immunity against reinfection of the vaginal epithelium.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MB",
      "lastName" : "Parr",
      "authorRank" : 1,
      "name" : "Parr",
      "referenceId" : "RGD:A179037"
    }, {
      "firstName" : "EL",
      "lastName" : "Parr",
      "authorRank" : 2,
      "name" : "Parr",
      "referenceId" : "RGD:A179038"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8158034"
    } ]
  }, {
    "primaryId" : "PMID:10366592",
    "title" : "Isolation, cloning, and localization of rat PV-1, a novel endothelial caveolar protein.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Stan RV, etal., J Cell Biol 1999 Jun 14;145(6):1189-98.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:52.000-05:00",
    "volume" : "145",
    "pages" : "1189-98",
    "abstract" : "By using an immunoisolation procedure (Stan, R.-V., W.G. Roberts, K. Ihida, D. Predescu, L. Saucan, L. Ghitescu, and G.E. Palade. 1997. Mol. Biol. Cell. 8:595-605) developed in our laboratory, we have isolated a caveolar subfraction from rat lung endothelium and we have partially characterized the proteins of this subfraction which include an apparently caveolae-specific glycoprotein we propose to call PV-1 (formerly known as gp68). The isolation and partial sequencing of PV-1, combined with the cloning of the full length PV-1 cDNA led to the following conclusions: (a) PV-1 is a novel single span type II integral membrane protein (438 amino acids long) which forms homodimers in situ; (b) the transmembrane domain of PV-1 is near the NH2 terminus defining a short cytoplasmic endodomain and a large COOH-terminal ectodomain exposed to the blood plasma; (c) PV-1 is N-glycosylated and its glycan antennae bear terminal nonreducing galactosyl residues in alpha1-3 linkage. PV-1 is expressed mostly in the lung but both the messenger RNA and the protein can be detected at lower levels also in kidney, spleen, liver, heart, muscle, and brain. No signal could be detected in testis and two lower molecular weight forms were detected in brain. Immunocytochemical studies carried out by immunodiffusion on rat lung with an anti-PV-1 polyclonal antibody directed against a COOH-terminal epitope reveal a specific localization of PV-1 to the stomatal diaphragms of rat lung endothelial caveolae and confirm the extracellular orientation of the PV-1 COOH terminus.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RV",
      "lastName" : "Stan",
      "authorRank" : 1,
      "name" : "Stan RV",
      "referenceId" : "RGD:A21991"
    }, {
      "firstName" : "L",
      "lastName" : "Ghitescu",
      "authorRank" : 2,
      "name" : "Ghitescu L",
      "referenceId" : "RGD:A21995"
    }, {
      "firstName" : "BS",
      "lastName" : "Jacobson",
      "authorRank" : 3,
      "name" : "Jacobson BS",
      "referenceId" : "RGD:A21996"
    }, {
      "firstName" : "GE",
      "lastName" : "Palade",
      "authorRank" : 4,
      "name" : "Palade GE",
      "referenceId" : "RGD:A21993"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633737"
    } ]
  }, {
    "primaryId" : "PMID:10366629",
    "title" : "Ephrin-A binding and EphA receptor expression delineate the matrix compartment of the striatum.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Janis LS, etal., J Neurosci. 1999 Jun 15;19(12):4962-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-11-12T13:02:11.000-06:00",
    "volume" : "19",
    "pages" : "4962-71",
    "abstract" : "The striatum integrates limbic and neocortical inputs to regulate sensorimotor and psychomotor behaviors. This function is dependent on the segregation of striatal projection neurons into anatomical and functional components, such as the striosome and matrix compartments. In the present study the association of ephrin-A cell surface ligands and EphA receptor tyrosine kinases (RTKs) with the organization of these compartments was determined in postnatal rats. Ephrin-A1 and ephrin-A4 selectively bind to EphA receptors on neurons restricted to the matrix compartment. Binding is absent from the striosomes, which were identified by mu-opioid receptor immunostaining. In contrast, ephrin-A2, ephrin-A3, and ephrin-A5 exhibit a different mosaic binding pattern that appears to define a subset of matrix neurons. In situ hybridization for EphA RTKs reveals that the two different ligand binding patterns strictly match the mRNA expression patterns of EphA4 and EphA7. Ligand-receptor binding assays indicate that ephrin-A1 and ephrin-A4 selectively bind EphA4 but not EphA7 in the lysates of striatal tissue. Conversely, ephrin-A2, ephrin-A3, and ephrin-A5 bind EphA7 but not EphA4. These observations implicate selective interactions between ephrin-A molecules and EphA RTKs as potential mechanisms for regulating the compartmental organization of the striatum.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LS",
      "lastName" : "Janis",
      "authorRank" : 1,
      "name" : "Janis LS",
      "referenceId" : "RGD:A101763"
    }, {
      "firstName" : "RM",
      "lastName" : "Cassidy",
      "authorRank" : 2,
      "name" : "Cassidy RM",
      "referenceId" : "RGD:A101764"
    }, {
      "firstName" : "LF",
      "lastName" : "Kromer",
      "authorRank" : 3,
      "name" : "Kromer LF",
      "referenceId" : "RGD:A101765"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301959"
    } ]
  }, {
    "primaryId" : "PMID:10366634",
    "title" : "Modulation of learning and anxiety by corticotropin-releasing factor (CRF) and stress: differential roles of CRF receptors 1 and 2.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Radulovic J, etal., J Neurosci. 1999 Jun 15;19(12):5016-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-10-05T10:14:05.000-05:00",
    "volume" : "19",
    "pages" : "5016-25",
    "abstract" : "The differential modulation of learning and anxiety by corticotropin-releasing factor (CRF) through CRF receptor subtypes 1 (CRFR1) and 2 (CRFR2) is demonstrated. As learning paradigm, context- and tone-dependent fear conditioning of the mouse was used. Injection of CRF into the dorsal hippocampus before training enhanced learning through CRFR1 as demonstrated by the finding that this effect was prevented by the local injection of the unselective CRFR antagonist astressin, but not by the CRFR2-specific antagonist antisauvagine-30 (anti-Svg-30). In contrast, injection of CRF into the lateral intermediate septum impaired learning through CRFR2, as demonstrated by the ability of antisauvagine-30 to block this effect. When antisauvagine-30 was injected alone into the lateral intermediate septum, learning was enhanced. Such tonic control of learning was not observed when astressin or antisauvagine-30 was injected into the dorsal hippocampus. Injection of CRF after the training into the dorsal hippocampus and the lateral intermediate septum also enhanced and impaired learning, respectively. Thus, it was indicated that CRF acted on memory consolidation. It was concluded that the observed effects reflected changes of associative learning and not arousal, attention, or motivation. Although a dose of 20 pmol human/rat CRF was sufficient to affect learning significantly, a fivefold higher dose was required to induce anxiety by injection into the septum. Immobilization for 1 hr generated a stress response that included the induction of anxiety through septal CRFR2 and the subsequent enhancement of learning through hippocampal CRFR1. The involvement of either receptor subtype was demonstrated by region-specific injections of astressin and antisauvagine-30.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Radulovic",
      "authorRank" : 1,
      "name" : "Radulovic J",
      "referenceId" : "RGD:A37480"
    }, {
      "firstName" : "A",
      "lastName" : "Ruhmann",
      "authorRank" : 2,
      "name" : "Ruhmann A",
      "referenceId" : "RGD:A145377"
    }, {
      "firstName" : "T",
      "lastName" : "Liepold",
      "authorRank" : 3,
      "name" : "Liepold T",
      "referenceId" : "RGD:A145378"
    }, {
      "firstName" : "J",
      "lastName" : "Spiess",
      "authorRank" : 4,
      "name" : "Spiess J",
      "referenceId" : "RGD:A12305"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5508167"
    } ]
  }, {
    "primaryId" : "PMID:10366647",
    "title" : "Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kerr BJ, etal., J Neurosci. 1999 Jun 15;19(12):5138-48.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-30T13:05:53.000-05:00",
    "volume" : "19",
    "pages" : "5138-48",
    "abstract" : "Central sensitization, the hyperexcitability of spinal processing that often accompanies peripheral injury, is a major component of many persistent pain states. Here we report that the neurotrophin, brain-derived neurotrophic factor (BDNF), is a modulator of excitability within the spinal cord and contributes to  the mechanism of central sensitization. BDNF, localized in primary sensory neuron cell bodies and central terminals, potentiates nociceptive spinal reflex responses in an in vitro spinal cord preparation and induces c-fos expression in  dorsal horn neurons. NMDA receptor-mediated responses, known as a major contributor to central sensitization, were significantly enhanced by exogenous BDNF. Systemic NGF treatment, a procedure that mimics peripheral inflammatory states, raises BDNF levels in sensory neurons and increases nociceptive spinal reflex excitability. This increased central excitability is reduced by trkB-IgG,  a BDNF \"antagonist.\" We also show directly that inflammatory pain-related behavior depends on BDNF release in vivo. Thus behavioral nociceptive responses induced by intraplantar formalin and by intraplantar carageenan are significantly attenuated by trkB-IgG. Hence BDNF is appropriately localized and regulated in inflammatory states and is sufficient and necessary for the expression of central sensitization in the spinal cord. We propose that BDNF may function as a modulator of central sensitization in pathological states, and our results suggest that pharmacological antagonism of BDNF may prove an effective and novel  analgesic strategy for the treatment of persistent inflammatory pain states.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BJ",
      "lastName" : "Kerr",
      "authorRank" : 1,
      "name" : "Kerr BJ",
      "referenceId" : "RGD:A153787"
    }, {
      "firstName" : "EJ",
      "lastName" : "Bradbury",
      "authorRank" : 2,
      "name" : "Bradbury",
      "referenceId" : "RGD:A188774"
    }, {
      "firstName" : "DL",
      "lastName" : "Bennett",
      "authorRank" : 3,
      "name" : "Bennett",
      "referenceId" : "RGD:A188775"
    }, {
      "firstName" : "PM",
      "lastName" : "Trivedi",
      "authorRank" : 4,
      "name" : "Trivedi",
      "referenceId" : "RGD:A188776"
    }, {
      "firstName" : "P",
      "lastName" : "Dassan",
      "authorRank" : 5,
      "name" : "Dassan",
      "referenceId" : "RGD:A188777"
    }, {
      "firstName" : "J",
      "lastName" : "French",
      "authorRank" : 6,
      "name" : "French",
      "referenceId" : "RGD:A188778"
    }, {
      "firstName" : "DB",
      "lastName" : "Shelton",
      "authorRank" : 7,
      "name" : "Shelton",
      "referenceId" : "RGD:A188779"
    }, {
      "firstName" : "SB",
      "lastName" : "McMahon",
      "authorRank" : 8,
      "name" : "McMahon SB",
      "referenceId" : "RGD:A87071"
    }, {
      "firstName" : "SW",
      "lastName" : "Thompson",
      "authorRank" : 9,
      "name" : "Thompson SW",
      "referenceId" : "RGD:A87072"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8657096"
    } ]
  }, {
    "primaryId" : "PMID:10366653",
    "title" : "Oscillation and light induction of timeless mRNA in the mammalian circadian clock.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Tischkau SA, etal., J Neurosci 1999 Jun 15;19(12):RC15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T10:07:31.000-05:00",
    "volume" : "19",
    "pages" : "RC15",
    "abstract" : "Circadian rhythms in Drosophila melanogaster depend on a molecular feedback loop generated by oscillating products of the period (per) and timeless (tim) genes. In mammals, three per homologs are cyclically expressed in the suprachiasmatic nucleus (SCN), site of the circadian clock, and two of these, mPer1 and mPer2, are induced in response to light. Although this light response distinguishes the mammalian clock from its Drosophila counterpart, overall regulation, including homologous transcriptional activators, appears to be similar. Thus, the basic mechanisms used to generate circadian timing have been conserved. However, contrary to expectations, the recently isolated mammalian tim homolog was reported not to cycle. In this study, we examined mRNA levels of the same tim homolog using a different probe. We observed a significant (approximately threefold) diurnal variation in mTim expression within mouse SCN using two independent methods. Peak levels were evident at the day-to-night transition in light-entrained animals, and the oscillation persisted on the second day in constant conditions. Furthermore, light pulses known to induce phase delays caused significant elevation in mTim mRNA. In contrast, phase-advancing light pulses did not affect mTim levels. The mTim expression profile and the response to nocturnal light are similar to mPer2 and are delayed compared with mPer1. We conclude that temporal ordering of mTim and mPer2 parallels that of their fly homologs. We predict that mTIM may be the preferred functional partner for mPER2 and that expression of mTim and mPer2 may, in fact, be driven by mPER1.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SA",
      "lastName" : "Tischkau",
      "authorRank" : 1,
      "name" : "Tischkau SA",
      "referenceId" : "RGD:A21767"
    }, {
      "firstName" : "JA",
      "lastName" : "Barnes",
      "authorRank" : 2,
      "name" : "Barnes JA",
      "referenceId" : "RGD:A35569"
    }, {
      "firstName" : "FJ",
      "lastName" : "Lin",
      "authorRank" : 3,
      "name" : "Lin FJ",
      "referenceId" : "RGD:A35572"
    }, {
      "firstName" : "EM",
      "lastName" : "Myers",
      "authorRank" : 4,
      "name" : "Myers EM",
      "referenceId" : "RGD:A35573"
    }, {
      "firstName" : "JW",
      "lastName" : "Barnes",
      "authorRank" : 5,
      "name" : "Barnes JW",
      "referenceId" : "RGD:A35568"
    }, {
      "firstName" : "EL",
      "lastName" : "Meyer-Bernstein",
      "authorRank" : 6,
      "name" : "Meyer-Bernstein EL",
      "referenceId" : "RGD:A35574"
    }, {
      "firstName" : "WJ",
      "lastName" : "Hurst",
      "authorRank" : 7,
      "name" : "Hurst WJ",
      "referenceId" : "RGD:A10381"
    }, {
      "firstName" : "PW",
      "lastName" : "Burgoon",
      "authorRank" : 8,
      "name" : "Burgoon PW",
      "referenceId" : "RGD:A35570"
    }, {
      "firstName" : "D",
      "lastName" : "Chen",
      "authorRank" : 9,
      "name" : "Chen D",
      "referenceId" : "RGD:A5571"
    }, {
      "firstName" : "A",
      "lastName" : "Sehgal",
      "authorRank" : 10,
      "name" : "Sehgal A",
      "referenceId" : "RGD:A35575"
    }, {
      "firstName" : "MU",
      "lastName" : "Gillette",
      "authorRank" : 11,
      "name" : "Gillette MU",
      "referenceId" : "RGD:A10383"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734504"
    } ]
  }, {
    "primaryId" : "PMID:10366717",
    "title" : "Identification of a 24 kDa intrinsic membrane protein from mammalian peroxisomes.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Reguenga C, etal., Biochim Biophys Acta. 1999 Jun 9;1445(3):337-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:44:10.000-05:00",
    "volume" : "1445",
    "pages" : "337-41",
    "abstract" : "A 24 kDa protein from rat liver peroxisomal membrane was isolated and subjected to Edman degradation. Using the N-terminal sequence of this polypeptide we have identified several rat and human expressed sequence tags in the GenBank Database. The complete sequence of a human cDNA clone was determined. The open reading frame encodes an extremely basic protein 212 amino acid residues long. A high similarity between this mammalian protein and hypothetical proteins from Caenorhabditis elegans and Neurospora crassa was found. Hydropathy analysis reveals the existence of two putative membrane-spanning domains in conserved regions of the three homologous proteins.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Reguenga",
      "authorRank" : 1,
      "name" : "Reguenga C",
      "referenceId" : "RGD:A84007"
    }, {
      "firstName" : "ME",
      "lastName" : "Oliveira",
      "authorRank" : 2,
      "name" : "Oliveira ME",
      "referenceId" : "RGD:A84008"
    }, {
      "firstName" : "AM",
      "lastName" : "Gouveia",
      "authorRank" : 3,
      "name" : "Gouveia AM",
      "referenceId" : "RGD:A84009"
    }, {
      "firstName" : "C",
      "lastName" : "Eckerskorn",
      "authorRank" : 4,
      "name" : "Eckerskorn",
      "referenceId" : "RGD:A186735"
    }, {
      "firstName" : "C",
      "lastName" : "Sa-Miranda",
      "authorRank" : 5,
      "name" : "Sa-Miranda C",
      "referenceId" : "RGD:A84010"
    }, {
      "firstName" : "JE",
      "lastName" : "Azevedo",
      "authorRank" : 6,
      "name" : "Azevedo JE",
      "referenceId" : "RGD:A84011"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554507"
    } ]
  }, {
    "primaryId" : "PMID:10366722",
    "title" : "cDNA and structural organization of the gene Pole1 for the mouse DNA polymerase epsilon catalytic subunit.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Huang D, etal., Biochim Biophys Acta 1999 Jun 9;1445(3):363-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-02-25T10:59:17.000-06:00",
    "volume" : "1445",
    "pages" : "363-71",
    "abstract" : "The cDNA and the gene for the mouse DNA polymerase epsilon catalytic subunit were cloned. The deduced protein sequence shows remarkable evolutionary conservation in DNA polymerase epsilon family. However, several conserved elements involved in template-primer binding differ from those of other class B polymerases. This is likely to reflect a distinctive function of the enzyme. The gene that was assigned to chromosome 5 region E3-E5, consists of 49 exons and has a non-conforming splice site in the junction of exon and intron 13. A CpG island covers the promoter region which contains several putative consensus elements critical for S phase upregulated and serum responsive promoters.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Huang",
      "authorRank" : 1,
      "name" : "Huang D",
      "referenceId" : "RGD:A23973"
    }, {
      "firstName" : "R",
      "lastName" : "Knuuti",
      "authorRank" : 2,
      "name" : "Knuuti R",
      "referenceId" : "RGD:A50916"
    }, {
      "firstName" : "H",
      "lastName" : "Palosaari",
      "authorRank" : 3,
      "name" : "Palosaari H",
      "referenceId" : "RGD:A50917"
    }, {
      "firstName" : "H",
      "lastName" : "Pospiech",
      "authorRank" : 4,
      "name" : "Pospiech H",
      "referenceId" : "RGD:A50918"
    }, {
      "firstName" : "JE",
      "lastName" : "Syvaoja",
      "authorRank" : 5,
      "name" : "Syvaoja JE",
      "referenceId" : "RGD:A50919"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1334510"
    } ]
  }, {
    "primaryId" : "PMID:10366744",
    "title" : "Co-expression of c-Jun and ATF-2 characterizes the surviving retinal ganglion cells which maintain axonal connections after partial optic nerve injury.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Kreutz MR, etal., Brain Res Mol Brain Res. 1999 Jun 8;69(2):232-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-07-13T17:21:55.000-05:00",
    "volume" : "69",
    "pages" : "232-41",
    "abstract" : "The expression of c-fos, c-jun, jun-b, jun-d, srf and pc4 mRNA was examined after partial optic nerve crush in the adult rat retina by in situ hybridization. Optic nerve injury led exclusively to the upregulation of c-jun, with cellular label indicative for c-jun mRNA in the retinal ganglion cell layer after two days, three days and one week post-injury. This expression pattern was in accordance with the appearance of c-Jun immunoreactivity in retinal flat mounts. Injection of an antisense but not a missense oligonucleotide against c-jun after partial crush resulted in a reduced number of connected retinal ganglion cells (RGCs) as  shown by retrograde labeling. Prelabeling of RGCs with fluorogold before optic nerve section and subsequent antisense targeting against c-jun, however, led to a slightly higher number of surviving but axotomized RGCs. C-Jun antibody staining  of retinal whole mounts pre- or postlabeled after crush by intracollicular administration of fluorogold showed strong c-Jun immunoreactivity in connected RGCs and also in a population of disconnected RGCs. Double labeling with an antibody directed against the transcription factor ATF-2 revealed strong co-expression of c-Jun and ATF-2 in connected RGCs but not in axotomized cells. Taken together these data indicate that both RGCs in continuity and those in discontinuity with the superior colliculus respond both equally to the noxious stimulus with c-Jun expression. Moreover, the co-expression of c-Jun with high levels of ATF-2 appears to be essential for either the continuity or survival of  RGCs which remain connected with their target. In disconnected RGCs, however, low levels of ATF-2 and the co-expression of c-Jun may be related to cell death.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MR",
      "lastName" : "Kreutz",
      "authorRank" : 1,
      "name" : "Kreutz MR",
      "referenceId" : "RGD:A13765"
    }, {
      "firstName" : "A",
      "lastName" : "Bien",
      "authorRank" : 2,
      "name" : "Bien",
      "referenceId" : "RGD:A204408"
    }, {
      "firstName" : "CK",
      "lastName" : "Vorwerk",
      "authorRank" : 3,
      "name" : "Vorwerk",
      "referenceId" : "RGD:A204409"
    }, {
      "firstName" : "TM",
      "lastName" : "Bockers",
      "authorRank" : 4,
      "name" : "Bockers TM",
      "referenceId" : "RGD:A11518"
    }, {
      "firstName" : "CI",
      "lastName" : "Seidenbecher",
      "authorRank" : 5,
      "name" : "Seidenbecher CI",
      "referenceId" : "RGD:A17386"
    }, {
      "firstName" : "W",
      "lastName" : "Tischmeyer",
      "authorRank" : 6,
      "name" : "Tischmeyer W",
      "referenceId" : "RGD:A93615"
    }, {
      "firstName" : "BA",
      "lastName" : "Sabel",
      "authorRank" : 7,
      "name" : "Sabel BA",
      "referenceId" : "RGD:A17388"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10047417"
    } ]
  }, {
    "primaryId" : "PMID:10367071",
    "title" : "[Congenital long QT syndrome. The value of genetics in prognostic evaluation].",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Denjoy I, etal., Arch Mal Coeur Vaiss. 1999 May;92(5):557-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:11:01.000-05:00",
    "volume" : "92",
    "pages" : "557-63",
    "abstract" : "The congenital long QT syndrome (QTL) is a heterogenic clinical and genetic entity characterised by prolongation of the QT interval which may be complicated  by syncope and sudden death. Four genes have been identified for the cardiac potassium (KCNQ1, HERG and KCNE1) and sodium (SCN5A). The aim of this study was to assess the prognosis of the disease by the site of mutation identified on the  morbid gene. Thirty-two genotyped families participated to this study. Each subject gave a clinical history, an ECG and a search for genetic mutation. Eighteen mutations in the transmembrane domains of KCNQ1 were identified in 25 families and 2 mutations in the C-terminal part were found in 4 families. The phenotype was less severe in C-terminal part mutations: less syncopes and sudden  deaths (22 vs 55%, p < 0.001) and a shorter QTc (458 +/- 31 ms vs 479 +/- 31 ms,  p = 0.0003). Three mutations were detected in the C-terminal part of HERG in 3 different families. Their phenotype was less severe with syncoped related to hypokalemia. The authors also report the case of a family in which two subjects who were the most severely affected had two mutations, one in HERG and the other  in KCNQ1. This study confirms the value of a genetic research in assessing the severity of the congenital long QT syndrome.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Denjoy",
      "authorRank" : 1,
      "name" : "Denjoy",
      "referenceId" : "RGD:A172939"
    }, {
      "firstName" : "JM",
      "lastName" : "Lupoglazoff",
      "authorRank" : 2,
      "name" : "Lupoglazoff",
      "referenceId" : "RGD:A253157"
    }, {
      "firstName" : "C",
      "lastName" : "Donger",
      "authorRank" : 3,
      "name" : "Donger",
      "referenceId" : "RGD:A260376"
    }, {
      "firstName" : "M",
      "lastName" : "Berthet",
      "authorRank" : 4,
      "name" : "Berthet",
      "referenceId" : "RGD:A250666"
    }, {
      "firstName" : "P",
      "lastName" : "Richard",
      "authorRank" : 5,
      "name" : "Richard P",
      "referenceId" : "RGD:A53382"
    }, {
      "firstName" : "N",
      "lastName" : "Neyroud",
      "authorRank" : 6,
      "name" : "Neyroud N",
      "referenceId" : "RGD:A62822"
    }, {
      "firstName" : "E",
      "lastName" : "Villain",
      "authorRank" : 7,
      "name" : "Villain",
      "referenceId" : "RGD:A256043"
    }, {
      "firstName" : "V",
      "lastName" : "Lucet",
      "authorRank" : 8,
      "name" : "Lucet",
      "referenceId" : "RGD:A172941"
    }, {
      "firstName" : "P",
      "lastName" : "Coumel",
      "authorRank" : 9,
      "name" : "Coumel",
      "referenceId" : "RGD:A253160"
    }, {
      "firstName" : "P",
      "lastName" : "Guicheney",
      "authorRank" : 10,
      "name" : "Guicheney P",
      "referenceId" : "RGD:A37505"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065638"
    } ]
  }, {
    "primaryId" : "PMID:10367906",
    "title" : "Increased junctional diversity in fetal B cells results in a loss of protective anti-phosphorylcholine antibodies in adult mice.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Benedict CL and Kearney JF, Immunity. 1999 May;10(5):607-17.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:42:28.000-05:00",
    "volume" : "10",
    "pages" : "607-17",
    "abstract" : "Fetal Igs are less diverse than adult Igs, largely because of the lack of N addition in the absence of Tdt. To test whether the absence of Tdt is essential,  we generated Tg mice that express Tdt and add N regions in fetal B cells. When challenged as adults with PC-containing Streptococcus pneumoniae, these mice fail to make the hallmark T15 anti-PC Ab encoded by canonical rearrangements of Ig H and L chain genes. The anti-PC Abs from these mice are altered by premature N addition and do not protect against death from virulent pneumococcal infection. These results show that maintenance of lower Ig diversity in early life is essential for the acquisition of a complete functional adult repertoire.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CL",
      "lastName" : "Benedict",
      "authorRank" : 1,
      "name" : "Benedict",
      "referenceId" : "RGD:A332120"
    }, {
      "firstName" : "JF",
      "lastName" : "Kearney",
      "authorRank" : 2,
      "name" : "Kearney JF",
      "referenceId" : "RGD:A82466"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340919"
    } ]
  }, {
    "primaryId" : "PMID:10369164",
    "title" : "A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and subcortical band heterotopia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kato M, etal., Hum Genet. 1999 Apr;104(4):341-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-05-18T16:49:42.000-05:00",
    "volume" : "104",
    "pages" : "341-4",
    "abstract" : "The doublecortin (DCX) gene was recently found to be involved in patients with X-linked lissencephaly and subcortical band heterotopia or double cortex syndrome. We have studied the coding regions of the DCX gene in 11 Japanese patients with cortical dysplasia and have identified three different mutations (R186C in exon 3, R272X and R303X in exon 5) in four sporadic female cases. R272X, which has been detected in two unrelated cases, is a novel mutation. Although the number of cases studied remains limited, exon 5 may be a common mutational site in Japanese patients in contrast to many previous reports concerning exons 2 and 3.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kato",
      "authorRank" : 1,
      "name" : "Kato M",
      "referenceId" : "RGD:A17842"
    }, {
      "firstName" : "T",
      "lastName" : "Kimura",
      "authorRank" : 2,
      "name" : "Kimura T",
      "referenceId" : "RGD:A6130"
    }, {
      "firstName" : "C",
      "lastName" : "Lin",
      "authorRank" : 3,
      "name" : "Lin C",
      "referenceId" : "RGD:A162012"
    }, {
      "firstName" : "A",
      "lastName" : "Ito",
      "authorRank" : 4,
      "name" : "Ito A",
      "referenceId" : "RGD:A151341"
    }, {
      "firstName" : "S",
      "lastName" : "Kodama",
      "authorRank" : 5,
      "name" : "Kodama S",
      "referenceId" : "RGD:A36150"
    }, {
      "firstName" : "T",
      "lastName" : "Morikawa",
      "authorRank" : 6,
      "name" : "Morikawa T",
      "referenceId" : "RGD:A46459"
    }, {
      "firstName" : "T",
      "lastName" : "Soga",
      "authorRank" : 7,
      "name" : "Soga T",
      "referenceId" : "RGD:A18082"
    }, {
      "firstName" : "K",
      "lastName" : "Hayasaka",
      "authorRank" : 8,
      "name" : "Hayasaka K",
      "referenceId" : "RGD:A52908"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12904717"
    } ]
  }, {
    "primaryId" : "PMID:10369222",
    "title" : "Differential, regional, and cellular expression of the stathmin family transcripts in the adult rat brain.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ozon S, etal., J Neurosci Res 1999 Jun 1;56(5):553-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-03-14T15:31:53.000-06:00",
    "volume" : "56",
    "pages" : "553-64",
    "abstract" : "Stathmin is a ubiquitous cytosolic phosphoprotein, preferentially expressed in the nervous system, and previously described as a relay integrating diverse intracellular signaling pathways. Stathmin is the generic element of a mammalian protein family including SCG10, SCLIP, and RB3 with its splice variants RB3' and RB3\". In contrast with stathmin, SCG10, SCLIP, and RB3/RB3'/RB3\" are exclusively expressed in the nervous system, stathmin and SCG10 being mostly expressed during cell proliferation and differentiation, and SCLIP and RB3 rather in mature neural cells. To further understand their specific roles in the CNS, we compared the localization of the stathmin, SCG10, SCLIP, and RB3 transcripts in adult rat brain. Northern blot analysis as well as in situ hybridization experiments showed that all stathmin-related mRNAs are expressed in a wide range of adult rat brain areas. At a regional level, SCG10 and SCLIP appear generally distributed similarly except in a few areas. The pattern of expression of the RB3 transcript is very different from that of the three other members of the stathmin family. Furthermore, unlike SCG10 and SCLIP, which were detected only in neurons, but like stathmin, RB3 was detected in neurons and also in glial cells of the white matter. Altogether, our results suggest distinct roles for each member of the stathmin-related phosphoprotein family, in regard to their specific regional and cellular localization in the rat brain.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Ozon",
      "authorRank" : 1,
      "name" : "Ozon S",
      "referenceId" : "RGD:A6223"
    }, {
      "firstName" : "S",
      "lastName" : "El Mestikawy",
      "authorRank" : 2,
      "name" : "El Mestikawy S",
      "referenceId" : "RGD:A1268"
    }, {
      "firstName" : "A",
      "lastName" : "Sobel",
      "authorRank" : 3,
      "name" : "Sobel A",
      "referenceId" : "RGD:A41696"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61521"
    } ]
  }, {
    "primaryId" : "PMID:10369247",
    "title" : "A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Achermann JC, etal., Nat Genet. 1999 Jun;22(2):125-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-07T20:16:14.000-06:00",
    "volume" : "22",
    "pages" : "125-6",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JC",
      "lastName" : "Achermann",
      "authorRank" : 1,
      "name" : "Achermann JC",
      "referenceId" : "RGD:A71995"
    }, {
      "firstName" : "M",
      "lastName" : "Ito",
      "authorRank" : 2,
      "name" : "Ito M",
      "referenceId" : "RGD:A5288"
    }, {
      "firstName" : "M",
      "lastName" : "Ito",
      "authorRank" : 3,
      "name" : "Ito M",
      "referenceId" : "RGD:A5288"
    }, {
      "firstName" : "PC",
      "lastName" : "Hindmarsh",
      "authorRank" : 4,
      "name" : "Hindmarsh PC",
      "referenceId" : "RGD:A80920"
    }, {
      "firstName" : "JL",
      "lastName" : "Jameson",
      "authorRank" : 5,
      "name" : "Jameson JL",
      "referenceId" : "RGD:A47682"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568420"
    } ]
  }, {
    "primaryId" : "PMID:10369255",
    "title" : "A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Knight JC, etal., Nat Genet. 1999 Jun;22(2):145-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-05-14T19:32:20.000-05:00",
    "volume" : "22",
    "pages" : "145-50",
    "abstract" : "Genetic variation in cytokine promoter regions is postulated to influence susceptibility to infection, but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown. Through systematic DNA footprinting of the TNF (encoding tumour necrosis factor, TNF) promoter region, we have identified a single nucleotide polymorphism (SNP) that causes the helix-turn-helix transcription factor OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in human monocytes. The OCT-1-binding genotype, found in approximately 5% of Africans, is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations, after correction for other known TNF polymorphisms and linked HLA alleles.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JC",
      "lastName" : "Knight",
      "authorRank" : 1,
      "name" : "Knight JC",
      "referenceId" : "RGD:A82753"
    }, {
      "firstName" : "I",
      "lastName" : "Udalova",
      "authorRank" : 2,
      "name" : "Udalova I",
      "referenceId" : "RGD:A82754"
    }, {
      "firstName" : "AV",
      "lastName" : "Hill",
      "authorRank" : 3,
      "name" : "Hill AV",
      "referenceId" : "RGD:A82755"
    }, {
      "firstName" : "BM",
      "lastName" : "Greenwood",
      "authorRank" : 4,
      "name" : "Greenwood BM",
      "referenceId" : "RGD:A55913"
    }, {
      "firstName" : "N",
      "lastName" : "Peshu",
      "authorRank" : 5,
      "name" : "Peshu N",
      "referenceId" : "RGD:A82756"
    }, {
      "firstName" : "K",
      "lastName" : "Marsh",
      "authorRank" : 6,
      "name" : "Marsh K",
      "referenceId" : "RGD:A82757"
    }, {
      "firstName" : "D",
      "lastName" : "Kwiatkowski",
      "authorRank" : 7,
      "name" : "Kwiatkowski D",
      "referenceId" : "RGD:A82758"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1624967"
    } ]
  }, {
    "primaryId" : "PMID:10369256",
    "title" : "Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Camacho JA, etal., Nat Genet. 1999 Jun;22(2):151-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-22T12:37:01.000-06:00",
    "volume" : "22",
    "pages" : "151-8",
    "abstract" : "Neurospora crassa ARG13 and Saccharomyces cerevisiae ARG11 encode mitochondrial carrier family (MCF) proteins that transport ornithine across the mitochondrial inner membrane. We used their sequences to identify EST candidates that partially encode orthologous mammalian transporters. We thereby identified such a gene (ORNT1) that maps to 13q14 and whose expression, similar to that of other urea cycle (UC) components, was high in liver and varied with changes in dietary protein. ORNT1 expression restores ornithine metabolism in fibroblasts from patients with hyperammonaemia-hyperornithinaemia-homocitrullinuria (HHH) syndrome. In a survey of 11 HHH probands, we identified 3 ORNT1 mutant alleles that account for 21 of 22 possible mutant ORNT1 genes in our patients: F188delta, which is common in French-Canadian HHH patients and encodes an unstable protein; E180K, which encodes a stable, properly targeted protein that is inactive; and a 13q14 microdeletion. Our results show that ORNT1 encodes the mitochondrial ornithine transporter involved in UC function and is defective in HHH syndrome.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Camacho",
      "authorRank" : 1,
      "name" : "Camacho JA",
      "referenceId" : "RGD:A73041"
    }, {
      "firstName" : "C",
      "lastName" : "Obie",
      "authorRank" : 2,
      "name" : "Obie C",
      "referenceId" : "RGD:A44695"
    }, {
      "firstName" : "B",
      "lastName" : "Biery",
      "authorRank" : 3,
      "name" : "Biery B",
      "referenceId" : "RGD:A73042"
    }, {
      "firstName" : "BK",
      "lastName" : "Goodman",
      "authorRank" : 4,
      "name" : "Goodman BK",
      "referenceId" : "RGD:A73043"
    }, {
      "firstName" : "CA",
      "lastName" : "Hu",
      "authorRank" : 5,
      "name" : "Hu CA",
      "referenceId" : "RGD:A73044"
    }, {
      "firstName" : "S",
      "lastName" : "Almashanu",
      "authorRank" : 6,
      "name" : "Almashanu S",
      "referenceId" : "RGD:A73045"
    }, {
      "firstName" : "G",
      "lastName" : "Steel",
      "authorRank" : 7,
      "name" : "Steel G",
      "referenceId" : "RGD:A73046"
    }, {
      "firstName" : "R",
      "lastName" : "Casey",
      "authorRank" : 8,
      "name" : "Casey R",
      "referenceId" : "RGD:A73047"
    }, {
      "firstName" : "M",
      "lastName" : "Lambert",
      "authorRank" : 9,
      "name" : "Lambert M",
      "referenceId" : "RGD:A17778"
    }, {
      "firstName" : "GA",
      "lastName" : "Mitchell",
      "authorRank" : 10,
      "name" : "Mitchell GA",
      "referenceId" : "RGD:A73048"
    }, {
      "firstName" : "D",
      "lastName" : "Valle",
      "authorRank" : 11,
      "name" : "Valle D",
      "referenceId" : "RGD:A6039"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599239"
    } ]
  }, {
    "primaryId" : "PMID:10369257",
    "title" : "The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Kobayashi K, etal., Nat Genet. 1999 Jun;22(2):159-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-22T12:47:35.000-06:00",
    "volume" : "22",
    "pages" : "159-63",
    "abstract" : "Citrullinaemia (CTLN) is an autosomal recessive disease caused by deficiency of argininosuccinate synthetase (ASS). Adult-onset type II citrullinaemia (CTLN2) is characterized by a liver-specific ASS deficiency with no abnormalities in hepatic ASS mRNA or the gene ASS (refs 1-17). CTLN2 patients (1/100,000 in Japan) suffer from a disturbance of consciousness and coma, and most die with cerebral edema within a few years of onset. CTLN2 differs from classical citrullinaemia (CTLN1, OMIM 215700) in that CTLN1 is neonatal or infantile in onset, with ASS enzyme defects (in all tissues) arising due to mutations in ASS on chromosome 9q34 (refs 18-21). We collected 118 CTLN2 families, and localized the CTLN2 locus to chromosome 7q21.3 by homozygosity mapping analysis of individuals from 18 consanguineous unions. Using positional cloning we identified a novel gene, SLC25A13, and found five different DNA sequence alterations that account for mutations in all consanguineous patients examined. SLC25A13 encodes a 3.4-kb transcript expressed most abundantly in liver. The protein encoded by SLC25A13, named citrin, is bipartite in structure, containing a mitochondrial carrier motif and four EF-hand domains, suggesting it is a calcium-dependent mitochondrial solute transporter with a role in urea cycle function.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Kobayashi",
      "authorRank" : 1,
      "name" : "Kobayashi K",
      "referenceId" : "RGD:A314641"
    }, {
      "firstName" : "DS",
      "lastName" : "Sinasac",
      "authorRank" : 2,
      "name" : "Sinasac DS",
      "referenceId" : "RGD:A73053"
    }, {
      "firstName" : "M",
      "lastName" : "Iijima",
      "authorRank" : 3,
      "name" : "Iijima M",
      "referenceId" : "RGD:A36141"
    }, {
      "firstName" : "AP",
      "lastName" : "Boright",
      "authorRank" : 4,
      "name" : "Boright AP",
      "referenceId" : "RGD:A73054"
    }, {
      "firstName" : "L",
      "lastName" : "Begum",
      "authorRank" : 5,
      "name" : "Begum L",
      "referenceId" : "RGD:A36163"
    }, {
      "firstName" : "JR",
      "lastName" : "Lee",
      "authorRank" : 6,
      "name" : "Lee JR",
      "referenceId" : "RGD:A42972"
    }, {
      "firstName" : "T",
      "lastName" : "Yasuda",
      "authorRank" : 7,
      "name" : "Yasuda T",
      "referenceId" : "RGD:A20775"
    }, {
      "firstName" : "S",
      "lastName" : "Ikeda",
      "authorRank" : 8,
      "name" : "Ikeda S",
      "referenceId" : "RGD:A5605"
    }, {
      "firstName" : "R",
      "lastName" : "Hirano",
      "authorRank" : 9,
      "name" : "Hirano R",
      "referenceId" : "RGD:A73055"
    }, {
      "firstName" : "H",
      "lastName" : "Terazono",
      "authorRank" : 10,
      "name" : "Terazono H",
      "referenceId" : "RGD:A73056"
    }, {
      "firstName" : "MA",
      "lastName" : "Crackower",
      "authorRank" : 11,
      "name" : "Crackower MA",
      "referenceId" : "RGD:A14624"
    }, {
      "firstName" : "I",
      "lastName" : "Kondo",
      "authorRank" : 12,
      "name" : "Kondo I",
      "referenceId" : "RGD:A72596"
    }, {
      "firstName" : "LC",
      "lastName" : "Tsui",
      "authorRank" : 13,
      "name" : "Tsui LC",
      "referenceId" : "RGD:A22700"
    }, {
      "firstName" : "SW",
      "lastName" : "Scherer",
      "authorRank" : 14,
      "name" : "Scherer SW",
      "referenceId" : "RGD:A37723"
    }, {
      "firstName" : "T",
      "lastName" : "Saheki",
      "authorRank" : 15,
      "name" : "Saheki T",
      "referenceId" : "RGD:A7026"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599241"
    } ]
  }, {
    "primaryId" : "PMID:10369259",
    "title" : "Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Drazen JM, etal., Nat Genet 1999 Jun;22(2):168-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:42:22.000-06:00",
    "volume" : "22",
    "pages" : "168-70",
    "abstract" : "Clinically similar asthma patients may develop airway obstruction by different mechanisms. Asthma treatments that specifically interfere with the 5-lipoxygenase (ALOX5) pathway provide a method to identify those patients in whom the products of the ALOX5 pathway (that is, the leukotrienes) contribute to the expression of the asthma phenotype. Failure of an asthma patient to respond to treatment with ALOX5-pathway modifiers indicates that leukotrienes are not critical to the expression of the asthmatic phenotype in that patient. We previously defined a family of DNA sequence variants in the core promoter of the gene ALOX5 (on chromosome 10q11.2) associated with diminished promoter-reporter activity in tissue culture. Because expression of ALOX5 is in part transcriptionally regulated, we reasoned that patients with these sequence variants may have diminished gene transcription, and therefore decreased ALOX5 product production and a diminished clinical response to treatment with a drug targeting this pathway. Such an effect indicates an interaction between gene promoter sequence variants and drug-treatment responses, that is, a pharmacogenetic effect of a promoter sequence on treatment responses.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Drazen",
      "authorRank" : 1,
      "name" : "Drazen JM",
      "referenceId" : "RGD:A35843"
    }, {
      "firstName" : "CN",
      "lastName" : "Yandava",
      "authorRank" : 2,
      "name" : "Yandava CN",
      "referenceId" : "RGD:A35844"
    }, {
      "firstName" : "L",
      "lastName" : "Dube",
      "authorRank" : 3,
      "name" : "Dube L",
      "referenceId" : "RGD:A35845"
    }, {
      "firstName" : "N",
      "lastName" : "Szczerback",
      "authorRank" : 4,
      "name" : "Szczerback N",
      "referenceId" : "RGD:A35846"
    }, {
      "firstName" : "R",
      "lastName" : "Hippensteel",
      "authorRank" : 5,
      "name" : "Hippensteel R",
      "referenceId" : "RGD:A35847"
    }, {
      "firstName" : "A",
      "lastName" : "Pillari",
      "authorRank" : 6,
      "name" : "Pillari A",
      "referenceId" : "RGD:A35848"
    }, {
      "firstName" : "E",
      "lastName" : "Israel",
      "authorRank" : 7,
      "name" : "Israel E",
      "referenceId" : "RGD:A35849"
    }, {
      "firstName" : "N",
      "lastName" : "Schork",
      "authorRank" : 8,
      "name" : "Schork N",
      "referenceId" : "RGD:A161910"
    }, {
      "firstName" : "ES",
      "lastName" : "Silverman",
      "authorRank" : 9,
      "name" : "Silverman ES",
      "referenceId" : "RGD:A35851"
    }, {
      "firstName" : "DA",
      "lastName" : "Katz",
      "authorRank" : 10,
      "name" : "Katz DA",
      "referenceId" : "RGD:A35852"
    }, {
      "firstName" : "J",
      "lastName" : "Drajesk",
      "authorRank" : 11,
      "name" : "Drajesk J",
      "referenceId" : "RGD:A35853"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734557"
    } ]
  }, {
    "primaryId" : "PMID:10369262",
    "title" : "Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Drenth JP, etal., Nat Genet. 1999 Jun;22(2):178-81.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:29:21.000-05:00",
    "volume" : "22",
    "pages" : "178-81",
    "abstract" : "Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS; MIM 260920) is a rare, apparently monogenic, autosomal recessive disorder characterized by recurrent episodes of fever accompanied with lymphadenopathy, abdominal distress, joint involvement and skin lesions. All patients have high serum IgD values (>100 U/ml) and HIDS 'attacks' are associated with an intense acute phase reaction whose exact pathophysiology remains obscure. Two other hereditary febrile disorders have been described. Familial Mediterranean fever (MIM 249100) is an autosomal recessive disorder affecting mostly populations from the Mediterranean  basin and is caused by mutations in the gene MEFV (refs 5,6). Familial Hibernian  fever (MIM 142680), also known as autosomal dominant familial recurrent fever, is caused by missense mutations in the gene encoding type I tumour necrosis factor receptor. Here we perform a genome-wide search to map the HIDS gene. Haplotype analysis placed the gene at 12q24 between D12S330 and D12S79. We identified the gene MVK, encoding mevalonate kinase (MK, ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36), as a candidate gene. We characterized 3 missense mutations, a 92-bp loss stemming from a deletion or from exon skipping, and the absence of expression of one allele. Functional analysis demonstrated diminished MK activity in fibroblasts from HIDS patients. Our data establish MVK as the gene responsible for HIDS.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JP",
      "lastName" : "Drenth",
      "authorRank" : 1,
      "name" : "Drenth JP",
      "referenceId" : "RGD:A74173"
    }, {
      "firstName" : "L",
      "lastName" : "Cuisset",
      "authorRank" : 2,
      "name" : "Cuisset L",
      "referenceId" : "RGD:A10110"
    }, {
      "firstName" : "G",
      "lastName" : "Grateau",
      "authorRank" : 3,
      "name" : "Grateau G",
      "referenceId" : "RGD:A81937"
    }, {
      "firstName" : "C",
      "lastName" : "Vasseur",
      "authorRank" : 4,
      "name" : "Vasseur",
      "referenceId" : "RGD:A257956"
    }, {
      "firstName" : "SD",
      "lastName" : "Van de Velde-Visser",
      "authorRank" : 5,
      "name" : "Van de Velde-Visser",
      "referenceId" : "RGD:A257957"
    }, {
      "firstName" : "JG",
      "lastName" : "De Jong",
      "authorRank" : 6,
      "name" : "De Jong",
      "referenceId" : "RGD:A257958"
    }, {
      "firstName" : "JS",
      "lastName" : "Beckmann",
      "authorRank" : 7,
      "name" : "Beckmann",
      "referenceId" : "RGD:A397798"
    }, {
      "firstName" : "JW",
      "lastName" : "Van der Meer",
      "authorRank" : 8,
      "name" : "Van der Meer JW",
      "referenceId" : "RGD:A148866"
    }, {
      "firstName" : "M",
      "lastName" : "Delpech",
      "authorRank" : 9,
      "name" : "Delpech M",
      "referenceId" : "RGD:A10114"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064252"
    } ]
  }, {
    "primaryId" : "PMID:10369263",
    "title" : "The gene mutated in bare patches and striated mice encodes a novel 3beta-hydroxysteroid dehydrogenase.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Liu XY, etal., Nat Genet 1999 Jun;22(2):182-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-18T10:22:05.000-06:00",
    "volume" : "22",
    "pages" : "182-7",
    "abstract" : "X-linked dominant disorders that are exclusively lethal prenatally in hemizygous males have been described in human and mouse. None of the genes responsible has been isolated in either species. The bare patches (Bpa) and striated (Str) mouse mutations were originally identified in female offspring of X-irradiated males. Subsequently, additional independent alleles were described. We have previously mapped these X-linked dominant, male-lethal mutations to an overlapping region of 600 kb that is homologous to human Xq28 (ref. 4) and identified several candidate genes in this interval. Here we report mutations in one of these genes, Nsdhl, encoding an NAD(P)H steroid dehydrogenase-like protein, in two independent Bpa and three independent Str alleles. Quantitative analysis of sterols from tissues of affected Bpa mice support a role for Nsdhl in cholesterol biosynthesis. Our results demonstrate that Bpa and Str are allelic mutations and identify the first mammalian locus associated with an X-linked dominant, male-lethal phenotype. They also expand the spectrum of phenotypes associated with abnormalities of cholesterol metabolism.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "XY",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu XY",
      "referenceId" : "RGD:A57406"
    }, {
      "firstName" : "AW",
      "lastName" : "Dangel",
      "authorRank" : 2,
      "name" : "Dangel AW",
      "referenceId" : "RGD:A50058"
    }, {
      "firstName" : "RI",
      "lastName" : "Kelley",
      "authorRank" : 3,
      "name" : "Kelley RI",
      "referenceId" : "RGD:A37883"
    }, {
      "firstName" : "W",
      "lastName" : "Zhao",
      "authorRank" : 4,
      "name" : "Zhao W",
      "referenceId" : "RGD:A403995"
    }, {
      "firstName" : "P",
      "lastName" : "Denny",
      "authorRank" : 5,
      "name" : "Denny P",
      "referenceId" : "RGD:A6627"
    }, {
      "firstName" : "M",
      "lastName" : "Botcherby",
      "authorRank" : 6,
      "name" : "Botcherby M",
      "referenceId" : "RGD:A57408"
    }, {
      "firstName" : "B",
      "lastName" : "Cattanach",
      "authorRank" : 7,
      "name" : "Cattanach B",
      "referenceId" : "RGD:A57409"
    }, {
      "firstName" : "J",
      "lastName" : "Peters",
      "authorRank" : 8,
      "name" : "Peters J",
      "referenceId" : "RGD:A10667"
    }, {
      "firstName" : "PR",
      "lastName" : "Hunsicker",
      "authorRank" : 9,
      "name" : "Hunsicker PR",
      "referenceId" : "RGD:A57410"
    }, {
      "firstName" : "AM",
      "lastName" : "Mallon",
      "authorRank" : 10,
      "name" : "Mallon AM",
      "referenceId" : "RGD:A57411"
    }, {
      "firstName" : "MA",
      "lastName" : "Strivens",
      "authorRank" : 11,
      "name" : "Strivens MA",
      "referenceId" : "RGD:A6610"
    }, {
      "firstName" : "R",
      "lastName" : "Bate",
      "authorRank" : 12,
      "name" : "Bate R",
      "referenceId" : "RGD:A57412"
    }, {
      "firstName" : "W",
      "lastName" : "Miller",
      "authorRank" : 13,
      "name" : "Miller W",
      "referenceId" : "RGD:A42820"
    }, {
      "firstName" : "M",
      "lastName" : "Rhodes",
      "authorRank" : 14,
      "name" : "Rhodes M",
      "referenceId" : "RGD:A57413"
    }, {
      "firstName" : "SD",
      "lastName" : "Brown",
      "authorRank" : 15,
      "name" : "Brown SD",
      "referenceId" : "RGD:A6625"
    }, {
      "firstName" : "GE",
      "lastName" : "Herman",
      "authorRank" : 16,
      "name" : "Herman GE",
      "referenceId" : "RGD:A38029"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556806"
    } ]
  }, {
    "primaryId" : "PMID:10369266",
    "title" : "Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Wallis DE, etal., Nat Genet. 1999 Jun;22(2):196-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-30T14:48:49.000-06:00",
    "volume" : "22",
    "pages" : "196-8",
    "abstract" : "Holoprosencephaly (HPE) is a common, severe malformation of the brain that involves separation of the central nervous system into left and right halves. Mild HPE can consist of signs such as a single central incisor, hypotelorism, microcephaly, or other craniofacial findings that can be present with or without associated brain malformations. The aetiology of HPE is extremely heterogeneous, with the proposed participation of a minimum of 12 HPE-associated genetic loci as well as the causal involvement of specific teratogens acting at the earliest stages of neurulation. The HPE2 locus was recently characterized as a 1-Mb interval on human chromosome 2p21 that contained a gene associated with HPE. A minimal critical region was defined by a set of six overlapping deletions and three clustered translocations in HPE patients. We describe here the isolation and characterization of the human homeobox-containing SIX3 gene from the HPE2 minimal critical region (MCR). We show that at least 2 of the HPE-associated translocation breakpoints in 2p21 are less than 200 kb from the 5' end of SIX3. Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE. We propose that SIX3 is the HPE2 gene, essential for the development of the anterior neural plate and eye in humans.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DE",
      "lastName" : "Wallis",
      "authorRank" : 1,
      "name" : "Wallis DE",
      "referenceId" : "RGD:A73402"
    }, {
      "firstName" : "E",
      "lastName" : "Roessler",
      "authorRank" : 2,
      "name" : "Roessler E",
      "referenceId" : "RGD:A73403"
    }, {
      "firstName" : "U",
      "lastName" : "Hehr",
      "authorRank" : 3,
      "name" : "Hehr U",
      "referenceId" : "RGD:A63221"
    }, {
      "firstName" : "L",
      "lastName" : "Nanni",
      "authorRank" : 4,
      "name" : "Nanni L",
      "referenceId" : "RGD:A73404"
    }, {
      "firstName" : "T",
      "lastName" : "Wiltshire",
      "authorRank" : 5,
      "name" : "Wiltshire T",
      "referenceId" : "RGD:A73405"
    }, {
      "firstName" : "A",
      "lastName" : "Richieri-Costa",
      "authorRank" : 6,
      "name" : "Richieri-Costa A",
      "referenceId" : "RGD:A73406"
    }, {
      "firstName" : "G",
      "lastName" : "Gillessen-Kaesbach",
      "authorRank" : 7,
      "name" : "Gillessen-Kaesbach G",
      "referenceId" : "RGD:A57947"
    }, {
      "firstName" : "EH",
      "lastName" : "Zackai",
      "authorRank" : 8,
      "name" : "Zackai EH",
      "referenceId" : "RGD:A73407"
    }, {
      "firstName" : "J",
      "lastName" : "Rommens",
      "authorRank" : 9,
      "name" : "Rommens J",
      "referenceId" : "RGD:A63236"
    }, {
      "firstName" : "M",
      "lastName" : "Muenke",
      "authorRank" : 10,
      "name" : "Muenke M",
      "referenceId" : "RGD:A36395"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599336"
    } ]
  }, {
    "primaryId" : "PMID:10369267",
    "title" : "A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Stone EM, etal., Nat Genet. 1999 Jun;22(2):199-202.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-20T09:51:17.000-06:00",
    "volume" : "22",
    "pages" : "199-202",
    "abstract" : "Malattia Leventinese (ML) and Doyne honeycomb retinal dystrophy (DHRD) refer to two autosomal dominant diseases characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium (RPE). Both loci were mapped to chromosome 2p16-21 (refs 5,6) and this genetic interval has been subsequently narrowed. The importance of these diseases is due in large part to their close phenotypic similarity to age-related macular degeneration (AMD), a disorder with a strong genetic component that accounts for approximately 50% of registered blindness in the Western world. Just as in ML and DHRD, the early hallmark of AMD is the presence of drusen. Here we use a combination of positional and candidate gene methods to identify a single non-conservative mutation (Arg345Trp) in the gene EFEMP1 (for EGF-containing fibrillin-like extracellular matrix protein 1) in all families studied. This change was not present in 477 control individuals or in 494 patients with age-related macular degeneration. Identification of this mutation may aid in the development of an animal model for drusen, as well as in the identification of other genes involved in human macular degeneration.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EM",
      "lastName" : "Stone",
      "authorRank" : 1,
      "name" : "Stone EM",
      "referenceId" : "RGD:A9702"
    }, {
      "firstName" : "AJ",
      "lastName" : "Lotery",
      "authorRank" : 2,
      "name" : "Lotery AJ",
      "referenceId" : "RGD:A71614"
    }, {
      "firstName" : "FL",
      "lastName" : "Munier",
      "authorRank" : 3,
      "name" : "Munier FL",
      "referenceId" : "RGD:A71615"
    }, {
      "firstName" : "E",
      "lastName" : "Heon",
      "authorRank" : 4,
      "name" : "Heon E",
      "referenceId" : "RGD:A9698"
    }, {
      "firstName" : "B",
      "lastName" : "Piguet",
      "authorRank" : 5,
      "name" : "Piguet B",
      "referenceId" : "RGD:A71616"
    }, {
      "firstName" : "RH",
      "lastName" : "Guymer",
      "authorRank" : 6,
      "name" : "Guymer RH",
      "referenceId" : "RGD:A71617"
    }, {
      "firstName" : "K",
      "lastName" : "Vandenburgh",
      "authorRank" : 7,
      "name" : "Vandenburgh K",
      "referenceId" : "RGD:A71618"
    }, {
      "firstName" : "P",
      "lastName" : "Cousin",
      "authorRank" : 8,
      "name" : "Cousin P",
      "referenceId" : "RGD:A71619"
    }, {
      "firstName" : "D",
      "lastName" : "Nishimura",
      "authorRank" : 9,
      "name" : "Nishimura D",
      "referenceId" : "RGD:A27215"
    }, {
      "firstName" : "RE",
      "lastName" : "Swiderski",
      "authorRank" : 10,
      "name" : "Swiderski RE",
      "referenceId" : "RGD:A9691"
    }, {
      "firstName" : "G",
      "lastName" : "Silvestri",
      "authorRank" : 11,
      "name" : "Silvestri G",
      "referenceId" : "RGD:A63841"
    }, {
      "firstName" : "DA",
      "lastName" : "Mackey",
      "authorRank" : 12,
      "name" : "Mackey DA",
      "referenceId" : "RGD:A71620"
    }, {
      "firstName" : "GS",
      "lastName" : "Hageman",
      "authorRank" : 13,
      "name" : "Hageman GS",
      "referenceId" : "RGD:A45418"
    }, {
      "firstName" : "AC",
      "lastName" : "Bird",
      "authorRank" : 14,
      "name" : "Bird AC",
      "referenceId" : "RGD:A39524"
    }, {
      "firstName" : "VC",
      "lastName" : "Sheffield",
      "authorRank" : 15,
      "name" : "Sheffield VC",
      "referenceId" : "RGD:A4262"
    }, {
      "firstName" : "DF",
      "lastName" : "Schorderet",
      "authorRank" : 16,
      "name" : "Schorderet DF",
      "referenceId" : "RGD:A71621"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598888"
    } ]
  }, {
    "primaryId" : "PMID:10369669",
    "title" : "Glycoprotein reglucosylation and nucleotide sugar utilization in the secretory pathway: identification of a nucleoside diphosphatase in the endoplasmic reticulum.",
    "datePublished" : "1999-06-15T00:00:00.000-05:00",
    "citation" : "Trombetta ES and Helenius A, EMBO J. 1999 Jun 15;18(12):3282-92. doi: 10.1093/emboj/18.12.3282.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-12-17T17:08:04.000-06:00",
    "volume" : "18",
    "pages" : "3282-92",
    "abstract" : "UDP is generated in the lumen of the endoplasmic reticulum (ER) as a product of the UDP-glucose-dependent glycoprotein reglucosylation in the calnexin/calreticulin cycle. We describe here the identification, purification and characterization of an ER enzyme that hydrolyzes UDP to UMP. This nucleoside diphosphatase is a ubiquitously expressed, soluble 45 kDa glycoprotein devoid of transmembrane domains and KDEL-related ER localization sequences. It requires divalent cations for activity and hydrolyzes UDP, GDP and IDP but not any other nucleoside di-, mono- or triphosphates, nor thiamine pyrophosphate. By eliminating UDP, which is an inhibitory product of the UDP-Glc:glycoprotein glucosyltransferase, it is likely to promote reglucosylation reactions involved in glycoprotein folding and quality control in the ER.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E S",
      "lastName" : "Trombetta",
      "authorRank" : 1,
      "name" : "Trombetta ES",
      "referenceId" : "RGD:A492610"
    }, {
      "firstName" : "A",
      "lastName" : "Helenius",
      "authorRank" : 2,
      "name" : "Helenius A",
      "referenceId" : "RGD:A27790"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:40902965"
    } ]
  }, {
    "primaryId" : "PMID:10369701",
    "title" : "Hereditary colorectal cancer in the general population: from cancer registration  to molecular diagnosis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "de Leon MP, etal., Gut. 1999 Jul;45(1):32-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:56:39.000-05:00",
    "volume" : "45",
    "pages" : "32-8",
    "abstract" : "BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common inherited disorders predisposing to cancer. The genes responsible for the  disease have recently been cloned and characterised; their mutations induce a generalised genomic instability which is particularly evident at microsatellite loci (replication error (RER)+ phenotype). AIMS: To investigate how to select individuals and families in the general population who should be screened for constitutional mutations predisposing to colorectal cancer. PATIENTS/METHODS: Between 1984 and 1995, 1899 colorectal malignancies in 1831 patients were registered, and in 1721 of these (94%), family trees could be obtained. Patients  and families were classified into five categories according to a more or less likely genetic basis: HNPCC; \"suspected\" HNPCC; juvenile cases; aspecific cancer  aggregation; sporadic cases. In 18 families with HNPCC as well as in 18 with suspected HNPCC, microsatellite instability in tumour tissues and constitutional  mutations of two DNA mismatch repair genes (MSH2 and MLH1) could be evaluated. RER status was studied with five markers (BAT40, D2S123, D18S57, D17S787, and BAT26) in paraffin embedded tissues. Germline mutations of MSH2 or MLH1 genes were assessed on DNA and RNA extracted from lymphomonocytic cells, using reverse  transcription polymerase chain reaction, single strand conformation polymorphism  analysis, and direct DNA sequencing. RESULTS: HNPCC represented 2.6% and suspected HNPCC 4.6% of all registered colorectal neoplasms. Eleven out of 18 HNPCC families (61%) showed microsatellite instability as opposed to four (of 18) suspected HNPCC (22%; p<0.02). Three germline mutations (two in MSH2 and one in MLH1 gene) were found in three different large HNPCC families, whereas no mutations were detected in suspected HNPCC. CONCLUSIONS: In this study of cancer  genetic epidemiology, data from a tumour registry were analysed and this ultimately led to the identification and selection of families that should be tested for mutator gene mutations. With the use of a population based approach, the incidence of mutations was appreciably lower than previously reported and limited to families with full blown HNPCC. It is possible that in most families with a clinical spectrum of HNPCC (or suspected HNPCC) other DNA mismatch repair  genes are involved in the pathogenesis of the disease.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MP",
      "lastName" : "De Leon",
      "authorRank" : 1,
      "name" : "De Leon",
      "referenceId" : "RGD:A256732"
    }, {
      "firstName" : "M",
      "lastName" : "Pedroni",
      "authorRank" : 2,
      "name" : "Pedroni",
      "referenceId" : "RGD:A251063"
    }, {
      "firstName" : "P",
      "lastName" : "Benatti",
      "authorRank" : 3,
      "name" : "Benatti P",
      "referenceId" : "RGD:A124675"
    }, {
      "firstName" : "A",
      "lastName" : "Percesepe",
      "authorRank" : 4,
      "name" : "Percesepe",
      "referenceId" : "RGD:A262532"
    }, {
      "firstName" : "C",
      "lastName" : "Di Gregorio",
      "authorRank" : 5,
      "name" : "Di Gregorio C",
      "referenceId" : "RGD:A139251"
    }, {
      "firstName" : "M",
      "lastName" : "Foroni",
      "authorRank" : 6,
      "name" : "Foroni",
      "referenceId" : "RGD:A274121"
    }, {
      "firstName" : "G",
      "lastName" : "Rossi",
      "authorRank" : 7,
      "name" : "Rossi G",
      "referenceId" : "RGD:A61787"
    }, {
      "firstName" : "M",
      "lastName" : "Genuardi",
      "authorRank" : 8,
      "name" : "Genuardi M",
      "referenceId" : "RGD:A37061"
    }, {
      "firstName" : "G",
      "lastName" : "Neri",
      "authorRank" : 9,
      "name" : "Neri G",
      "referenceId" : "RGD:A30375"
    }, {
      "firstName" : "F",
      "lastName" : "Leonardi",
      "authorRank" : 10,
      "name" : "Leonardi",
      "referenceId" : "RGD:A274122"
    }, {
      "firstName" : "A",
      "lastName" : "Viel",
      "authorRank" : 11,
      "name" : "Viel A",
      "referenceId" : "RGD:A122297"
    }, {
      "firstName" : "E",
      "lastName" : "Capozzi",
      "authorRank" : 12,
      "name" : "Capozzi",
      "referenceId" : "RGD:A256730"
    }, {
      "firstName" : "M",
      "lastName" : "Boiocchi",
      "authorRank" : 13,
      "name" : "Boiocchi M",
      "referenceId" : "RGD:A116643"
    }, {
      "firstName" : "L",
      "lastName" : "Roncucci",
      "authorRank" : 14,
      "name" : "Roncucci",
      "referenceId" : "RGD:A251070"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069510"
    } ]
  }, {
    "primaryId" : "PMID:10369863",
    "title" : "Abundant expression and cytoplasmic aggregations of 1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Ishikawa K, etal., Hum Mol Genet. 1999 Jul;8(7):1185-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-05T15:24:35.000-05:00",
    "volume" : "8",
    "pages" : "1185-93",
    "abstract" : "Spinocerebellar ataxia type 6 (SCA6) is one of the eight neurodegenerative diseases caused by a tri-nucleotide (CAG) repeat expansion coding polyglutamine (CAG repeat/polyglutamine diseases) and is characterized by late onset autosomal  dominant cerebellar ataxia and predominant loss of cerebellar Purkinje cells. Although the causative, small and stable CAG repeat expansion for this disease has been identified in the [alpha]1A voltage-dependent calcium channel gene (CACNA1A), the mechanism which leads to predominant Purkinje cell degeneration is totally unknown. In this study, we show that the calcium channel mRNA/protein containing the CAG repeat/polyglutamine tract is most intensely expressed in Purkinje cells of human brains. In SCA6 brains, numerous oval or rod-shaped aggregates were seen exclusively in the cytoplasm of Purkinje cells. These cytoplasmic inclusions were not ubiquitinated, which contrasts with the neuronal  intra-nuclear inclusions of other CAG repeat/polyglutamine diseases. In cultured  cells, formation of perinuclear aggregates of the channel protein and apoptotic cell death were seen when transfected with full-length CACNA1A coding an expanded polyglutamine tract. The present study indicates that the mechanism of neurodegeneration in SCA6 is associated with cytoplasmic aggregations of the [alpha]1A calcium channel protein caused by a small CAG repeat/polyglutamine expansion in CACNA1A.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Ishikawa",
      "authorRank" : 1,
      "name" : "Ishikawa K",
      "referenceId" : "RGD:A16618"
    }, {
      "firstName" : "H",
      "lastName" : "Fujigasaki",
      "authorRank" : 2,
      "name" : "Fujigasaki",
      "referenceId" : "RGD:A205022"
    }, {
      "firstName" : "H",
      "lastName" : "Saegusa",
      "authorRank" : 3,
      "name" : "Saegusa H",
      "referenceId" : "RGD:A36600"
    }, {
      "firstName" : "K",
      "lastName" : "Ohwada",
      "authorRank" : 4,
      "name" : "Ohwada K",
      "referenceId" : "RGD:A142663"
    }, {
      "firstName" : "T",
      "lastName" : "Fujita",
      "authorRank" : 5,
      "name" : "Fujita T",
      "referenceId" : "RGD:A6425"
    }, {
      "firstName" : "H",
      "lastName" : "Iwamoto",
      "authorRank" : 6,
      "name" : "Iwamoto H",
      "referenceId" : "RGD:A29614"
    }, {
      "firstName" : "Y",
      "lastName" : "Komatsuzaki",
      "authorRank" : 7,
      "name" : "Komatsuzaki Y",
      "referenceId" : "RGD:A159760"
    }, {
      "firstName" : "S",
      "lastName" : "Toru",
      "authorRank" : 8,
      "name" : "Toru",
      "referenceId" : "RGD:A205023"
    }, {
      "firstName" : "H",
      "lastName" : "Toriyama",
      "authorRank" : 9,
      "name" : "Toriyama",
      "referenceId" : "RGD:A205024"
    }, {
      "firstName" : "M",
      "lastName" : "Watanabe",
      "authorRank" : 10,
      "name" : "Watanabe",
      "referenceId" : "RGD:A417010"
    }, {
      "firstName" : "N",
      "lastName" : "Ohkoshi",
      "authorRank" : 11,
      "name" : "Ohkoshi N",
      "referenceId" : "RGD:A36584"
    }, {
      "firstName" : "S",
      "lastName" : "Shoji",
      "authorRank" : 12,
      "name" : "Shoji S",
      "referenceId" : "RGD:A26583"
    }, {
      "firstName" : "I",
      "lastName" : "Kanazawa",
      "authorRank" : 13,
      "name" : "Kanazawa",
      "referenceId" : "RGD:A394117"
    }, {
      "firstName" : "T",
      "lastName" : "Tanabe",
      "authorRank" : 14,
      "name" : "Tanabe T",
      "referenceId" : "RGD:A9839"
    }, {
      "firstName" : "H",
      "lastName" : "Mizusawa",
      "authorRank" : 15,
      "name" : "Mizusawa",
      "referenceId" : "RGD:A335845"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10054421"
    } ]
  }, {
    "primaryId" : "PMID:10369864",
    "title" : "The cytotoxic T lymphocyte antigen-4 is a major Graves' disease locus.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Vaidya B, etal., Hum Mol Genet 1999 Jul;8(7):1195-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T14:20:38.000-05:00",
    "volume" : "8",
    "pages" : "1195-9",
    "abstract" : "Graves' disease (GD) is an autoimmune thyroid disorder that is inherited as a complex trait. We have genotyped 77 affected sib-pairs with autoimmune thyroid disease for eight polymorphic markers spanning the cytotoxic T lymphocyte antigen-4 ( CTLA-4 ) region of chromosome 2q31-q33, and for five markers spanning the major histocompatibility complex ( MHC ) region of chromosome 6p21. Non-parametric analysis showed linkage of GD to the CTLA-4 region with a peak non-parametric linkage (NPL) score of 3.43 ( P = 0.0004) at the marker D2S117. The proportion of affected full-sibs sharing zero alleles (z0) reached a minimum of 0.113 close to D2S117, giving a locus-specific lambdas for this region of 2.2. Families with brother-sister sib-pairs showed a peak NPL of 3.46 ( P = 0.0003, lambdas > 10) at D2S117, compared with 2.00 ( P = 0.02, lambdas = 1.9) in the families with only affected females, suggesting a stronger influence in families with affected males. Association between GD and the G allele of the Thr17Ala polymorphism within the CTLA-4 gene ( CTLA4A/G ) was observed using unaffected sib controls ( P = 0.005). Lesser evidence for linkage was found at the MHC locus, with a peak NPL score of 1.95 ( P = 0.026), between the markers D6S273 and TNFalpha. We demonstrate that the CTLA-4 locus (lambdas = 2.2) and the MHC locus (lambdas = 1.6) together confer approximately 50% of the inherited susceptibility to GD disease in our population.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Vaidya",
      "authorRank" : 1,
      "name" : "Vaidya B",
      "referenceId" : "RGD:A44986"
    }, {
      "firstName" : "H",
      "lastName" : "Imrie",
      "authorRank" : 2,
      "name" : "Imrie H",
      "referenceId" : "RGD:A58456"
    }, {
      "firstName" : "P",
      "lastName" : "Perros",
      "authorRank" : 3,
      "name" : "Perros P",
      "referenceId" : "RGD:A44988"
    }, {
      "firstName" : "ET",
      "lastName" : "Young",
      "authorRank" : 4,
      "name" : "Young ET",
      "referenceId" : "RGD:A44989"
    }, {
      "firstName" : "WF",
      "lastName" : "Kelly",
      "authorRank" : 5,
      "name" : "Kelly WF",
      "referenceId" : "RGD:A44990"
    }, {
      "firstName" : "D",
      "lastName" : "Carr",
      "authorRank" : 6,
      "name" : "Carr D",
      "referenceId" : "RGD:A44991"
    }, {
      "firstName" : "DM",
      "lastName" : "Large",
      "authorRank" : 7,
      "name" : "Large DM",
      "referenceId" : "RGD:A44992"
    }, {
      "firstName" : "AD",
      "lastName" : "Toft",
      "authorRank" : 8,
      "name" : "Toft AD",
      "referenceId" : "RGD:A44993"
    }, {
      "firstName" : "MI",
      "lastName" : "McCarthy",
      "authorRank" : 9,
      "name" : "McCarthy MI",
      "referenceId" : "RGD:A39906"
    }, {
      "firstName" : "P",
      "lastName" : "Kendall-Taylor",
      "authorRank" : 10,
      "name" : "Kendall-Taylor P",
      "referenceId" : "RGD:A44994"
    }, {
      "firstName" : "SH",
      "lastName" : "Pearce",
      "authorRank" : 11,
      "name" : "Pearce SH",
      "referenceId" : "RGD:A44995"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300388"
    } ]
  }, {
    "primaryId" : "PMID:10369867",
    "title" : "Identification of survival motor neuron as a transcriptional activator-binding protein.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Strasswimmer J, etal., Hum Mol Genet. 1999 Jul;8(7):1219-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:21:02.000-05:00",
    "volume" : "8",
    "pages" : "1219-26",
    "abstract" : "Spinal muscular atrophy (SMA) is an inherited neuro-muscular disease characterized by specific degeneration of spinal cord anterior horn cells and subsequent muscle atrophy. Survival motor neuron ( SMN ), located on chromosome 5q13, is the SMA-determining gene. In the nucleus, SMN is present in large foci called gems, the function of which is not yet known, while cytoplasmic SMN has been implicated in snRNP biogenesis. In SMA patients, SMN protein levels and the  number of gems generally correlate with disease severity, suggesting a critical nuclear function for SMN. In a screen for proteins associated with the nuclear transcription activator 'E2' of papillomavirus, two independent SMN cDNAs were isolated. The E2 and SMN proteins were found to associate specifically in vitro and in vivo. Expression of SMN enhanced E2-dependent transcriptional activation,  and patient-derived SMN missense mutations reduced E2 gene expression. Our results demonstrate that SMN interacts with a nuclear transcription factor and imply that SMN may serve a role in regulating gene expression. These observations suggest that SMA may in part result from abnormal gene expression and that E2 may influence viral gene expression through SMN interaction.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Strasswimmer",
      "authorRank" : 1,
      "name" : "Strasswimmer",
      "referenceId" : "RGD:A233188"
    }, {
      "firstName" : "CL",
      "lastName" : "Lorson",
      "authorRank" : 2,
      "name" : "Lorson CL",
      "referenceId" : "RGD:A49787"
    }, {
      "firstName" : "DE",
      "lastName" : "Breiding",
      "authorRank" : 3,
      "name" : "Breiding",
      "referenceId" : "RGD:A227620"
    }, {
      "firstName" : "JJ",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen JJ",
      "referenceId" : "RGD:A47901"
    }, {
      "firstName" : "T",
      "lastName" : "Le",
      "authorRank" : 5,
      "name" : "Le T",
      "referenceId" : "RGD:A80896"
    }, {
      "firstName" : "AH",
      "lastName" : "Burghes",
      "authorRank" : 6,
      "name" : "Burghes AH",
      "referenceId" : "RGD:A23241"
    }, {
      "firstName" : "EJ",
      "lastName" : "Androphy",
      "authorRank" : 7,
      "name" : "Androphy EJ",
      "referenceId" : "RGD:A49786"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11056175"
    } ]
  }, {
    "primaryId" : "PMID:10369869",
    "title" : "A missense mutation in connexin26, D66H, causes mutilating keratoderma with sensorineural deafness (Vohwinkel's syndrome) in three unrelated families.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Maestrini E, etal., Hum Mol Genet. 1999 Jul;8(7):1237-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-10-01T13:49:57.000-05:00",
    "volume" : "8",
    "pages" : "1237-43",
    "abstract" : "The multiplicity of functions served by intercellular gap junctions is reflected  by the variety of phenotypes caused by mutations in the connexins of which they are composed. Mutations in the connexin26 (Cx26) gene ( GJB2 ) at 13q11-q13 are a major cause of autosomal recessive hearing loss (DFNB1), but have also been reported in autosomal dominant deafness (DFNA3). We now report a Cx26 mutation in three families with mutilating keratoderma and deafness [Vohwinkel's syndrome (VS; MIM 124500), as originally described]. VS is characterized by papular and honeycomb keratoderma associated with constrictions of digits leading to autoamputation, distinctive starfish-like acral keratoses and moderate degrees of deafness. In a large British pedigree, we have mapped the defect to the Cx26 locus. All 10 affected members were heterozygous for a non-conservative mutation, D66H, in Cx26. The same mutation was found subsequently in affected individuals from two unrelated Spanish and Italian pedigrees segregating VS, suggesting that  D66H in Cx26 is a common mutation in classical VS. This mutation occurs at a highly conserved residue in the first extracellular domain of the Cx26 molecule,  and may exert its effects by interfering with assembly into connexons, docking with adjacent cells or gating properties of the gap junction. Our results provide evidence that a specific mutation in Cx26 can impair epidermal differentiation, as well as inner ear function.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Maestrini",
      "authorRank" : 1,
      "name" : "Maestrini E",
      "referenceId" : "RGD:A55548"
    }, {
      "firstName" : "BP",
      "lastName" : "Korge",
      "authorRank" : 2,
      "name" : "Korge",
      "referenceId" : "RGD:A173643"
    }, {
      "firstName" : "J",
      "lastName" : "Ocana-Sierra",
      "authorRank" : 3,
      "name" : "Ocana-Sierra",
      "referenceId" : "RGD:A173644"
    }, {
      "firstName" : "E",
      "lastName" : "Calzolari",
      "authorRank" : 4,
      "name" : "Calzolari",
      "referenceId" : "RGD:A173645"
    }, {
      "firstName" : "S",
      "lastName" : "Cambiaghi",
      "authorRank" : 5,
      "name" : "Cambiaghi",
      "referenceId" : "RGD:A173646"
    }, {
      "firstName" : "PM",
      "lastName" : "Scudder",
      "authorRank" : 6,
      "name" : "Scudder",
      "referenceId" : "RGD:A173647"
    }, {
      "firstName" : "A",
      "lastName" : "Hovnanian",
      "authorRank" : 7,
      "name" : "Hovnanian A",
      "referenceId" : "RGD:A36214"
    }, {
      "firstName" : "AP",
      "lastName" : "Monaco",
      "authorRank" : 8,
      "name" : "Monaco AP",
      "referenceId" : "RGD:A36213"
    }, {
      "firstName" : "CS",
      "lastName" : "Munro",
      "authorRank" : 9,
      "name" : "Munro CS",
      "referenceId" : "RGD:A36207"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7364824"
    } ]
  }, {
    "primaryId" : "PMID:10369870",
    "title" : "Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Warner LE, etal., Hum Mol Genet. 1999 Jul;8(7):1245-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-03T12:36:37.000-05:00",
    "volume" : "8",
    "pages" : "1245-51",
    "abstract" : "The early growth response 2 gene ( EGR2 ) is a Cys2His2zinc finger transcription factor which is thought to play a role in the regulation of peripheral nervous system myelination. This idea is based partly on the phenotype of homozygous Krox20 ( Egr2 ) knockout mice, which display hypomyelination of the PNS and a block of Schwann cells at an early stage of differentiation. Mutations in the human EGR2 gene have recently been associated with the inherited peripheral neuropathies Charcot-Marie-Tooth type 1, Dejerine-Sottas syndrome and congenital hypomyelinating neuropathy. Three of the four EGR2 mutations are dominant and occur within the zinc finger DNA-binding domain. The fourth mutation is recessive and affects the inhibitory domain (R1) that binds the NAB transcriptional co-repressors. A combination of DNA-binding assays and transcriptional analysis was used to determine the functional consequences of these mutations. The zinc finger mutations affect DNA binding and the amount of residual binding directly correlates with disease severity. The R1 domain mutation prevents interaction of EGR2 with the NAB co-repressors and thereby increases transcriptional activity. These data provide insight into the possible disease mechanisms underlying EGR2 mutations and the reason for varying severity and differences in inheritance patterns.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LE",
      "lastName" : "Warner",
      "authorRank" : 1,
      "name" : "Warner LE",
      "referenceId" : "RGD:A37923"
    }, {
      "firstName" : "J",
      "lastName" : "Svaren",
      "authorRank" : 2,
      "name" : "Svaren J",
      "referenceId" : "RGD:A6394"
    }, {
      "firstName" : "J",
      "lastName" : "Milbrandt",
      "authorRank" : 3,
      "name" : "Milbrandt J",
      "referenceId" : "RGD:A25994"
    }, {
      "firstName" : "JR",
      "lastName" : "Lupski",
      "authorRank" : 4,
      "name" : "Lupski JR",
      "referenceId" : "RGD:A38115"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601012"
    } ]
  }, {
    "primaryId" : "PMID:10369871",
    "title" : "A complex pattern of evolutionary conservation and alternative polyadenylation within the long 3\"-untranslated region of the methyl-CpG-binding protein 2 gene (MeCP2) suggests a regulatory role in gene expression.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Coy JF, etal., Hum Mol Genet 1999 Jul;8(7):1253-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:06.000-06:00",
    "volume" : "8",
    "pages" : "1253-62",
    "abstract" : "A systematic search for expressed sequences in the human Xq28 region resulted in the isolation of 8.5 kb large contigs of human and murine cDNAs with no apparent conserved open reading frames. These cDNAs were found to be derived from the 3\"-untranslated region (3\"-UTR) of the methyl-CpG-binding protein 2 gene ( MeCP2 ). This long 3\"-UTR is part of an alternatively polyadenylated, 10.1 kb MeCP2 transcript which is differentially expressed in human brain and other tissues. RNA in situ hybridization to sections of mouse embryo and adult tissues of an Mecp2 3\"-UTR probe showed ubiquitous low level expression in early organogenesis and enhanced expression in the hippocampus during formation of the differentiated brain. Sequence comparison between the human and mouse homologues revealed several blocks of very high conservation separated by less conserved sequences. Additional support for a domain-like conservation pattern of the long 3\"-UTR of the MeCP2 gene was obtained by examining conservation in the chimpanzee, orangutan, macaque, hamster, rat and kangaroo. The minimum free energy distribution for the predicted RNA secondary structure was very similar in human and mouse sequences. In particular, the conserved blocks were predicted to be of high minimum free energy, which suggests weak secondary structure with respect to RNA folding. The fact that both the sequence and predicted secondary structure have been highly conserved during evolution suggests that both the primary sequence and the three-dimensional structure of the 3\"-UTR may be important for its function in post-transcriptional regulation of MeCP2 expression.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JF",
      "lastName" : "Coy",
      "authorRank" : 1,
      "name" : "Coy JF",
      "referenceId" : "RGD:A7553"
    }, {
      "firstName" : "Z",
      "lastName" : "Sedlacek",
      "authorRank" : 2,
      "name" : "Sedlacek Z",
      "referenceId" : "RGD:A7554"
    }, {
      "firstName" : "D",
      "lastName" : "Bachner",
      "authorRank" : 3,
      "name" : "Bachner D",
      "referenceId" : "RGD:A4896"
    }, {
      "firstName" : "H",
      "lastName" : "Delius",
      "authorRank" : 4,
      "name" : "Delius H",
      "referenceId" : "RGD:A7555"
    }, {
      "firstName" : "A",
      "lastName" : "Poustka",
      "authorRank" : 5,
      "name" : "Poustka A",
      "referenceId" : "RGD:A7556"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69888"
    } ]
  }, {
    "primaryId" : "PMID:10369874",
    "title" : "Allelic and locus heterogeneity in inherited venous malformations.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Calvert JT, etal., Hum Mol Genet. 1999 Jul;8(7):1279-89. doi: 10.1093/hmg/8.7.1279.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:31:51.000-05:00",
    "volume" : "8",
    "pages" : "1279-89",
    "abstract" : "Venous malformations are low-flow vascular lesions consisting of disorganized thin-walled vascular channels. These can occur sporadically but also as an autosomal dominant condition termed venous malformations, cutaneous and mucosal (VMCM; OMIM 600195). In two large unrelated kindreds mapping to chromosome 9, the identical R849W missense mutation was identified in the first kinase domain of Tie2, an endothelial cell-specific receptor tyrosine kinase. We report here the identification of four new kindreds with inherited venous malformations. Unlike the initial two families described, these four families demonstrate allelic and locus heterogeneity. In one of these families, the R849W mutation co-segregates with the disease phenotype. Three other families with venous malformations lack this mutation. One of these families is linked to markers near TIE2 on chromosome 9. In this family, we identified a novel mutation within the first kinase domain of Tie2 resulting in a Y897S change. Results from COS-1 cell transfections using expression constructs containing either the R849W or the Y897S mutation suggest that the receptors containing either mutation show ligand-independent hyperphosphorylation. These results suggest a gain-of-function mechanism for development of venous malformations in these families. Of the two remaining families, one excludes linkage to the TIE2 locus, establishing the existence of at least one additional locus for dominantly inherited venous malformations.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J T",
      "lastName" : "Calvert",
      "authorRank" : 1,
      "name" : "Calvert JT",
      "referenceId" : "RGD:A603251"
    }, {
      "firstName" : "T J",
      "lastName" : "Riney",
      "authorRank" : 2,
      "name" : "Riney TJ",
      "referenceId" : "RGD:A603252"
    }, {
      "firstName" : "C D",
      "lastName" : "Kontos",
      "authorRank" : 3,
      "name" : "Kontos CD",
      "referenceId" : "RGD:A603253"
    }, {
      "firstName" : "E H",
      "lastName" : "Cha",
      "authorRank" : 4,
      "name" : "Cha EH",
      "referenceId" : "RGD:A603254"
    }, {
      "firstName" : "V G",
      "lastName" : "Prieto",
      "authorRank" : 5,
      "name" : "Prieto VG",
      "referenceId" : "RGD:A603255"
    }, {
      "firstName" : "C R",
      "lastName" : "Shea",
      "authorRank" : 6,
      "name" : "Shea CR",
      "referenceId" : "RGD:A603256"
    }, {
      "firstName" : "J N",
      "lastName" : "Berg",
      "authorRank" : 7,
      "name" : "Berg JN",
      "referenceId" : "RGD:A591721"
    }, {
      "firstName" : "N C",
      "lastName" : "Nevin",
      "authorRank" : 8,
      "name" : "Nevin NC",
      "referenceId" : "RGD:A603257"
    }, {
      "firstName" : "S A",
      "lastName" : "Simpson",
      "authorRank" : 9,
      "name" : "Simpson SA",
      "referenceId" : "RGD:A603258"
    }, {
      "firstName" : "K A",
      "lastName" : "Pasyk",
      "authorRank" : 10,
      "name" : "Pasyk KA",
      "referenceId" : "RGD:A603259"
    }, {
      "firstName" : "M C",
      "lastName" : "Speer",
      "authorRank" : 11,
      "name" : "Speer MC",
      "referenceId" : "RGD:A603260"
    }, {
      "firstName" : "K G",
      "lastName" : "Peters",
      "authorRank" : 12,
      "name" : "Peters KG",
      "referenceId" : "RGD:A603261"
    }, {
      "firstName" : "D A",
      "lastName" : "Marchuk",
      "authorRank" : 13,
      "name" : "Marchuk DA",
      "referenceId" : "RGD:A599765"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119990"
    } ]
  }, {
    "primaryId" : "PMID:10369879",
    "title" : "Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Coucke PJ, etal., Hum Mol Genet. 1999 Jul;8(7):1321-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-06T16:11:07.000-06:00",
    "volume" : "8",
    "pages" : "1321-8",
    "abstract" : "We have previously found linkage to chromosome 1p34 in five large families with autosomal dominant non-syndromic hearing impairment (DFNA2). In all five families, the connexin31 gene ( GJB3 ), located at 1p34 and responsible for non-syndromic autosomal dominant hearing loss in two small Chinese families, has been excluded as the responsible gene. Recently, a fourth member of the KCNQ branch of the K+channel family, KCNQ4, has been cloned. KCNQ4 was mapped to chromosome 1p34 and a single mutation was found in three patients from a small French family with non-syndromic autosomal dominant hearing loss. In this study, we have analysed the KCNQ4 gene for mutations in our five DFNA2 families. Missense mutations altering conserved amino acids were found in three families and an inactivating deletion was present in a fourth family. No KCNQ4 mutation could be found in a single DFNA2 family of Indonesian origin. These results indicate that at least two and possibly three genes responsible for hearing impairment are located close together on chromosome 1p34 and suggest that KCNQ4 mutations may be a relatively frequent cause of autosomal dominant hearing loss.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PJ",
      "lastName" : "Coucke",
      "authorRank" : 1,
      "name" : "Coucke PJ",
      "referenceId" : "RGD:A75944"
    }, {
      "firstName" : "P",
      "lastName" : "Van Hauwe",
      "authorRank" : 2,
      "name" : "Van Hauwe P",
      "referenceId" : "RGD:A73595"
    }, {
      "firstName" : "PM",
      "lastName" : "Kelley",
      "authorRank" : 3,
      "name" : "Kelley PM",
      "referenceId" : "RGD:A75641"
    }, {
      "firstName" : "H",
      "lastName" : "Kunst",
      "authorRank" : 4,
      "name" : "Kunst H",
      "referenceId" : "RGD:A76879"
    }, {
      "firstName" : "I",
      "lastName" : "Schatteman",
      "authorRank" : 5,
      "name" : "Schatteman I",
      "referenceId" : "RGD:A73593"
    }, {
      "firstName" : "D",
      "lastName" : "Van Velzen",
      "authorRank" : 6,
      "name" : "Van Velzen D",
      "referenceId" : "RGD:A76880"
    }, {
      "firstName" : "J",
      "lastName" : "Meyers",
      "authorRank" : 7,
      "name" : "Meyers J",
      "referenceId" : "RGD:A60188"
    }, {
      "firstName" : "RJ",
      "lastName" : "Ensink",
      "authorRank" : 8,
      "name" : "Ensink RJ",
      "referenceId" : "RGD:A76881"
    }, {
      "firstName" : "M",
      "lastName" : "Verstreken",
      "authorRank" : 9,
      "name" : "Verstreken M",
      "referenceId" : "RGD:A73594"
    }, {
      "firstName" : "F",
      "lastName" : "DeClau",
      "authorRank" : 10,
      "name" : "DeClau F",
      "referenceId" : "RGD:A71749"
    }, {
      "firstName" : "H",
      "lastName" : "Marres",
      "authorRank" : 11,
      "name" : "Marres H",
      "referenceId" : "RGD:A76882"
    }, {
      "firstName" : "K",
      "lastName" : "Kastury",
      "authorRank" : 12,
      "name" : "Kastury K",
      "referenceId" : "RGD:A44996"
    }, {
      "firstName" : "S",
      "lastName" : "Bhasin",
      "authorRank" : 13,
      "name" : "Bhasin S",
      "referenceId" : "RGD:A41715"
    }, {
      "firstName" : "WT",
      "lastName" : "McGuirt",
      "authorRank" : 14,
      "name" : "McGuirt WT",
      "referenceId" : "RGD:A75055"
    }, {
      "firstName" : "RJ",
      "lastName" : "Smith",
      "authorRank" : 15,
      "name" : "Smith RJ",
      "referenceId" : "RGD:A4612"
    }, {
      "firstName" : "CW",
      "lastName" : "Cremers",
      "authorRank" : 16,
      "name" : "Cremers CW",
      "referenceId" : "RGD:A72706"
    }, {
      "firstName" : "P",
      "lastName" : "Van de Heyning",
      "authorRank" : 17,
      "name" : "Van de Heyning P",
      "referenceId" : "RGD:A73598"
    }, {
      "firstName" : "PJ",
      "lastName" : "Willems",
      "authorRank" : 18,
      "name" : "Willems PJ",
      "referenceId" : "RGD:A72004"
    }, {
      "firstName" : "SD",
      "lastName" : "Smith",
      "authorRank" : 19,
      "name" : "Smith SD",
      "referenceId" : "RGD:A75640"
    }, {
      "firstName" : "G",
      "lastName" : "Van Camp",
      "authorRank" : 20,
      "name" : "Van Camp G",
      "referenceId" : "RGD:A43492"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600303"
    } ]
  }, {
    "primaryId" : "PMID:10370077",
    "title" : "Studies on the topology of the renal type II NaPi-cotransporter.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Lambert G, etal., Pflugers Arch. 1999 May;437(6):972-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-10T16:18:01.000-05:00",
    "volume" : "437",
    "pages" : "972-8",
    "abstract" : "The rat type II sodium/phosphate cotransporter (NaPi-2) is a 85- to 90-kDa glycosylated protein located at the proximal tubular brush border membrane. Hydropathy predictions suggest eight transmembrane domains (sTM) with a large glycosylated loop between sTM 3 and sTM 4. We have studied the membrane topology  of NaPi-2 expressed in oocytes. A 33-amino-acid fragment containing the FLAG epitope was inserted into seven loops connecting the sTMs and into the NH2- and COOH-ends of the protein. FLAG-antibody binding suggested that the loops connecting sTM 1 and sTM 2 as well as sTM 3 and sTM 4 are located extracellularly. Based on the lack of FLAG-antibody binding we suggest intracellular locations for the NH2- and COOH-termini and the region connecting sTM 4 and sTM 5. Immunoprecipitation studies of in vitro translated protein also  suggest that the NH2-terminus is sited extracellularly. In immunohistochemical studies with NaPi-2-transfected MDCK cells, an interaction with NH2- and COOH- terminal antipeptide antibodies could only be obtained after membrane permeabilization. The presented data are an experimental documentation of the intracellular location of the NH2- and COOH-termini, and of the extracellular location of extracellular loops 1 and 2.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Lambert",
      "authorRank" : 1,
      "name" : "Lambert",
      "referenceId" : "RGD:A169737"
    }, {
      "firstName" : "M",
      "lastName" : "Traebert",
      "authorRank" : 2,
      "name" : "Traebert",
      "referenceId" : "RGD:A169472"
    }, {
      "firstName" : "N",
      "lastName" : "Hernando",
      "authorRank" : 3,
      "name" : "Hernando",
      "referenceId" : "RGD:A169747"
    }, {
      "firstName" : "J",
      "lastName" : "Biber",
      "authorRank" : 4,
      "name" : "Biber",
      "referenceId" : "RGD:A403617"
    }, {
      "firstName" : "H",
      "lastName" : "Murer",
      "authorRank" : 5,
      "name" : "Murer",
      "referenceId" : "RGD:A341576"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7243175"
    } ]
  }, {
    "primaryId" : "PMID:10370372",
    "title" : "C/EBP beta in rheumatoid arthritis: correlation with inflammation, not disease specificity.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Pope RM, etal., Clin Immunol. 1999 Jun;91(3):271-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-10-01T16:14:32.000-05:00",
    "volume" : "91",
    "pages" : "271-82",
    "abstract" : "Rheumatoid arthritis synovial tissue was examined and compared with osteoarthritis tissue for the presence of the nuclear transcription factor C/EBP  beta (NF-IL-6). The region (lining or sublining), cell type, and subcellular distribution (cytoplasmic or nuclear) of the expression of C/EBP beta was characterized. Rheumatoid arthritis synovial fluid and blood and normal peripheral blood were also examined. C/EBP beta was detected in the synovial lining and in sublining cells of synovial tissue from patients with both rheumatoid and osteoarthritis. A significant (P < 0.001 and < 0.05, respectively) increase in the percentage of cells with nuclear staining was seen in the lining  layer, compared to cells in the sublining region, in rheumatoid and osteoarthritis. In both diseases a strong correlation (r = 0.79, P < 0.001) was observed between the percentage of cells in the synovial lining that were positive for nuclear C/EBP beta and lining cell depth. Two-color immunohistochemistry demonstrated that both macrophages and fibroblast-like synoviocytes were positive for nuclear C/EBP beta. The presence of C/EBP beta was confirmed by immunohistochemistry and Western blot analysis with isolated synovial fibroblasts. Nuclear C/EBP beta was also detected in rheumatoid synovial fluid monocytes/macrophages, but not in lymphocytes or neutrophils. Western blot  analysis confirmed the presence of C/EBP beta in these cells. The intensity of C/EBP beta staining was greater (P < 0.001) in synovial fluid monocytes than in those from normal or rheumatoid peripheral blood. In conclusion, the enhanced nuclear staining for C/EBP beta in the synovial lining, compared to the sublining, suggesting activation in the lining, and the positive correlation of lining layer depth with the percentage of cells in the lining positive for nuclear C/EBP beta, suggest a potential role for C/EBP beta in chronic inflammation. The regulation of the production or activity of C/EBP beta, to inhibit inflammatory mediator expression by synovial macrophages and fibroblasts, offers a novel approach to therapeutic intervention.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RM",
      "lastName" : "Pope",
      "authorRank" : 1,
      "name" : "Pope RM",
      "referenceId" : "RGD:A103650"
    }, {
      "firstName" : "R",
      "lastName" : "Lovis",
      "authorRank" : 2,
      "name" : "Lovis",
      "referenceId" : "RGD:A206556"
    }, {
      "firstName" : "S",
      "lastName" : "Mungre",
      "authorRank" : 3,
      "name" : "Mungre",
      "referenceId" : "RGD:A206557"
    }, {
      "firstName" : "H",
      "lastName" : "Perlman",
      "authorRank" : 4,
      "name" : "Perlman",
      "referenceId" : "RGD:A167335"
    }, {
      "firstName" : "AE",
      "lastName" : "Koch",
      "authorRank" : 5,
      "name" : "Koch AE",
      "referenceId" : "RGD:A60793"
    }, {
      "firstName" : "3RD",
      "lastName" : "Haines GK",
      "authorRank" : 6,
      "name" : "Haines GK 3RD",
      "referenceId" : "RGD:A120966"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10401215"
    } ]
  }, {
    "primaryId" : "PMID:10371078",
    "title" : "White matter dementia in CADASIL.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Filley CM, etal., J Neurol Sci. 1999 Mar 1;163(2):163-7. doi: 10.1016/s0022-510x(99)00038-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:56:36.000-05:00",
    "volume" : "163",
    "pages" : "163-7",
    "abstract" : "Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. Neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. Magnetic resonance imaging of the brain revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This case illustrates that CADASIL can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with CADASIL closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C M",
      "lastName" : "Filley",
      "authorRank" : 1,
      "name" : "Filley CM",
      "referenceId" : "RGD:A607312"
    }, {
      "firstName" : "L L",
      "lastName" : "Thompson",
      "authorRank" : 2,
      "name" : "Thompson LL",
      "referenceId" : "RGD:A607313"
    }, {
      "firstName" : "C I",
      "lastName" : "Sze",
      "authorRank" : 3,
      "name" : "Sze CI",
      "referenceId" : "RGD:A607314"
    }, {
      "firstName" : "J A",
      "lastName" : "Simon",
      "authorRank" : 4,
      "name" : "Simon JA",
      "referenceId" : "RGD:A607315"
    }, {
      "firstName" : "J F",
      "lastName" : "Paskavitz",
      "authorRank" : 5,
      "name" : "Paskavitz JF",
      "referenceId" : "RGD:A607316"
    }, {
      "firstName" : "B K",
      "lastName" : "Kleinschmidt-DeMasters",
      "authorRank" : 6,
      "name" : "Kleinschmidt-DeMasters BK",
      "referenceId" : "RGD:A607317"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598120731"
    } ]
  }, {
    "primaryId" : "PMID:10371165",
    "title" : "Identification of a novel alternatively spliced septin.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Fung ET and Scheller RH, FEBS Lett 1999 May 21;451(2):203-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T17:24:05.000-05:00",
    "volume" : "451",
    "pages" : "203-8",
    "abstract" : "Septins are a family of cytoskeletal proteins involved in cytokinesis, targeting of proteins to specific sites on the plasma membrane, and cellular morphogenesis. While many aspects of their function in cytokinesis in yeast cells have been investigated, the function of septins in mammalian cells is less well understood. For example, septins are present in post-mitotic neurons, suggesting they have other roles in, for example, establishing cell polarity. The full extent of the septin gene family is not known in mammalian cells. To better understand the septin gene family, we have cloned and characterized a novel mammalian septin.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ET",
      "lastName" : "Fung",
      "authorRank" : 1,
      "name" : "Fung ET",
      "referenceId" : "RGD:A19279"
    }, {
      "firstName" : "RH",
      "lastName" : "Scheller",
      "authorRank" : 2,
      "name" : "Scheller RH",
      "referenceId" : "RGD:A116018"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299505"
    } ]
  }, {
    "primaryId" : "PMID:10371349",
    "title" : "Molecular mediators of tumor angiogenesis: enhanced expression and activation of vascular endothelial growth factor receptor KDR in primary breast cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kranz A, etal., Int J Cancer. 1999 Jun 21;84(3):293-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-04T18:09:18.000-05:00",
    "volume" : "84",
    "pages" : "293-8",
    "abstract" : "The progression of breast cancer growth and its ability to metastasize are associated with the process of angiogenesis. In this study, we examined the protein expression of vascular endothelial growth factor (VEGF) and its specific and functional receptor KDR in human breast tissue. We investigated a total of 13 mammary carcinomas, 3 fibroadenomas, 5 specimens with fibrocystic breast disease as well as normal (adjacent to malignant) breast tissue using immunohistochemistry and Western blot analysis. In all carcinomas examined, functional KDR protein was present independent of tumor type, tumor stage and histological grade as demonstrated by tyrosine phosphorylation analysis of KDR. When malignant tissues were compared with their neighboring non-neoplastic regions, activated KDR was found to be expressed to a much higher extent within the malignant tissue samples. In fibroadenomas, KDR was barely detectable, whereas in fibrocystic breast disease KDR expression was variable. Immunostaining of KDR was localized to endothelium and epithelium of mammary ducts in malignant and benign breast tissue, while VEGF immunoreactivity was primarily found in the endothelium and also in tumor cells and macrophages. Our data demonstrate that KDR activation is enhanced in breast cancer in vivo and emphasize the functional role of VEGF and KDR in the development of malignant breast disease.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Kranz",
      "authorRank" : 1,
      "name" : "Kranz A",
      "referenceId" : "RGD:A93975"
    }, {
      "firstName" : "T",
      "lastName" : "Mattfeldt",
      "authorRank" : 2,
      "name" : "Mattfeldt T",
      "referenceId" : "RGD:A93976"
    }, {
      "firstName" : "J",
      "lastName" : "Waltenberger",
      "authorRank" : 3,
      "name" : "Waltenberger J",
      "referenceId" : "RGD:A27398"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2291951"
    } ]
  }, {
    "primaryId" : "PMID:10372552",
    "title" : "Chondroitin sulphate and heparan sulfate proteoglycan are sequentially expressed in the uterine extracellular matrix during early pregnancy in the rat.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Slater M and Murphy CR, Matrix Biol. 1999 Apr;18(2):125-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-05-07T12:35:24.000-05:00",
    "volume" : "18",
    "pages" : "125-31",
    "abstract" : "Chondroitin sulfate proteoglycan (CSPG) and heparan sulfate proteoglycan (HSPG) are extracellular matrix proteins that regulate cell adhesion, growth, migration, differentiation and gene expression in many systems. In this study, stromal CSPG label was intense within 10 microm of the uterine lumen. From that distance to the myometrium, CSPG was de-expressed. From the time of implantation on Day 6, this pattern was reversed. CSPG was de-expressed from the uterine epithelium to a distance of approximately 10 microm from the uterine lumen. From that region to the myometrium, labeling was homogeneously intense. This finding suggests that CSPG may inhibit attachment and implantation. Heparan sulfate core proteoglycan (perlecan) was increasingly expressed in the uterine epithelium from the time of implantation, commencing in the basement membrane on Day 6 and extending to the apical epithelium and lateral plasma membranes by Day 7. Perlecan thus appears to facilitate trophoblast attachment and implantation. We propose that attachment and implantation is regulated, at least in part, by the selective and sequential expression of CSPG and perlecan.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Slater",
      "authorRank" : 1,
      "name" : "Slater M",
      "referenceId" : "RGD:A82216"
    }, {
      "firstName" : "CR",
      "lastName" : "Murphy",
      "authorRank" : 2,
      "name" : "Murphy CR",
      "referenceId" : "RGD:A67072"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1624264"
    } ]
  }, {
    "primaryId" : "PMID:10372566",
    "title" : "Hippocampal alterations of apolipoprotein E and D mRNA levels in vivo and in vitro following kainate excitotoxicity.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Montpied P, etal., Epilepsy Res. 1999 Jun;35(2):135-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-06-29T15:49:12.000-05:00",
    "volume" : "35",
    "pages" : "135-46",
    "abstract" : "Alteration in the expression of apolipoprotein E (ApoE) and apolipoprotein D (ApoD) genes was evaluated in rat, 7 days following status epilepticus (SE) induced by intra-amygdala injection of kainate (KA), and in organotypic hippocampal cultures, 2 days after a single 1 h exposure to KA. Global polyadenylated RNA (poly A+) steady state, assessing global regulation of mRNA transcription was first measured in cortices and hippocampi from each animal and in the organotypic cultures. No alteration due to KA treatment was observed and individual concentrations of ApoE and ApoD mRNA species were therefore measured and comparative analysis performed. In the cortices of KA-treated animals, ApoE and ApoD mRNA levels did not show statistically significant changes. In contrast, in hippocampi, 7 days after SE, ApoE and ApoD mRNA levels were significantly increased, respectively, by 123 and 138%. This in vivo effect was confirmed in vitro on organotypic cultures, where KA treatment increased ApoE and ApoD mRNA expressions, respectively, by 72 and 61%. These observations indicate that lipidic metabolism is modified in the lesioned structure and suggest an increased traffic of lipids and a need for more ApoE and D in the hippocampus during the period of recovery and restructuration that follows severe seizures.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Montpied",
      "authorRank" : 1,
      "name" : "Montpied P",
      "referenceId" : "RGD:A108863"
    }, {
      "firstName" : "F",
      "lastName" : "De Bock",
      "authorRank" : 2,
      "name" : "De Bock F",
      "referenceId" : "RGD:A108864"
    }, {
      "firstName" : "M",
      "lastName" : "Lerner-Natoli",
      "authorRank" : 3,
      "name" : "Lerner-Natoli M",
      "referenceId" : "RGD:A108865"
    }, {
      "firstName" : "J",
      "lastName" : "Bockaert",
      "authorRank" : 4,
      "name" : "Bockaert J",
      "referenceId" : "RGD:A15096"
    }, {
      "firstName" : "G",
      "lastName" : "Rondouin",
      "authorRank" : 5,
      "name" : "Rondouin G",
      "referenceId" : "RGD:A108866"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311203"
    } ]
  }, {
    "primaryId" : "PMID:10373016",
    "title" : "Facial development and type III collagen RNA expression: concurrent repression in the osteopetrotic (Toothless,tl) rat and rescue after treatment with colony-stimulating factor-1.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Marks SC Jr, etal., Dev Dyn 1999 Jun;215(2):117-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-18T13:31:07.000-05:00",
    "volume" : "215",
    "pages" : "117-25",
    "abstract" : "The toothless (osteopetrotic) mutation in the rat is characterized by retarded development of the anterior facial skeleton. Growth of the anterior face in rats occurs at the premaxillary-maxillary suture (PMMS). To identify potential mechanisms for stunted facial growth in this mutation we compared the temporospatial expression of collagen I (Col I) and collagen III (Col III) RNA around this suture in toothless (tl) rats and normal littermates by in situ hybridization of specific riboprobes in sagittal sections of the head. In normal rats, the suture is S shaped at birth and becomes highly convoluted by 10 days with cells in the center (fibroblasts and osteoblast progenitors) expressing Col III RNA and those at the periphery (osteoblasts) expressing no Col III RNA but high amounts of Col I RNA throughout the growth phase (the first 2 postnatal weeks). In the mutant PMMS, cells were reduced in number, less differentiated, and fewer osteoblasts were encountered. Expression of Col I RNA was at normal levels, but centrosutural cells expressed Col III RNA only after day 6 and then only weakly. A highly convoluted sutural shape was never achieved in mutants during the first 2 postnatal weeks. Treatment of tl rats with the cytokine CSF-1 improved facial growth and restored cellular diversity and Col III RNA expression in the PMMS to normal levels. Taken together, these data suggest that normal facial growth in rats is related to expression of Col III RNAby osteoblast precursors in the PMMS, that these cells are deficient in the tl mutation and are rescued following treatment with CSF-1.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JR",
      "lastName" : "Marks SC",
      "authorRank" : 1,
      "name" : "Marks SC JR",
      "referenceId" : "RGD:A13249"
    }, {
      "firstName" : "C",
      "lastName" : "Lundmark",
      "authorRank" : 2,
      "name" : "Lundmark C",
      "referenceId" : "RGD:A9828"
    }, {
      "firstName" : "T",
      "lastName" : "Wurtz",
      "authorRank" : 3,
      "name" : "Wurtz T",
      "referenceId" : "RGD:A9826"
    }, {
      "firstName" : "PR",
      "lastName" : "Odgren",
      "authorRank" : 4,
      "name" : "Odgren PR",
      "referenceId" : "RGD:A13243"
    }, {
      "firstName" : "CA",
      "lastName" : "MacKay",
      "authorRank" : 5,
      "name" : "MacKay CA",
      "referenceId" : "RGD:A13244"
    }, {
      "firstName" : "A",
      "lastName" : "Mason-Savas",
      "authorRank" : 6,
      "name" : "Mason-Savas A",
      "referenceId" : "RGD:A25523"
    }, {
      "firstName" : "SN",
      "lastName" : "Popoff",
      "authorRank" : 7,
      "name" : "Popoff SN",
      "referenceId" : "RGD:A13247"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:704391"
    } ]
  }, {
    "primaryId" : "PMID:10373119",
    "title" : "Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Holash J, etal., Science. 1999 Jun 18;284(5422):1994-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-11-10T10:17:29.000-06:00",
    "volume" : "284",
    "pages" : "1994-8",
    "abstract" : "In contrast with the prevailing view that most tumors and metastases begin as avascular masses, evidence is presented here that a subset of tumors instead initially grows by coopting existing host vessels. This coopted host vasculature does not immediately undergo angiogenesis to support the tumor but instead regresses, leading to a secondarily avascular tumor and massive tumor cell loss. Ultimately, however, the remaining tumor is rescued by robust angiogenesis at the tumor margin. The expression patterns of the angiogenic antagonist angiopoietin-2 and of pro-angiogenic vascular endothelial growth factor (VEGF) suggest that these proteins may be critical regulators of this balance between vascular regression and growth.",
    "issueName" : "5422",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Holash",
      "authorRank" : 1,
      "name" : "Holash J",
      "referenceId" : "RGD:A114802"
    }, {
      "firstName" : "PC",
      "lastName" : "Maisonpierre",
      "authorRank" : 2,
      "name" : "Maisonpierre PC",
      "referenceId" : "RGD:A15009"
    }, {
      "firstName" : "D",
      "lastName" : "Compton",
      "authorRank" : 3,
      "name" : "Compton D",
      "referenceId" : "RGD:A114803"
    }, {
      "firstName" : "P",
      "lastName" : "Boland",
      "authorRank" : 4,
      "name" : "Boland P",
      "referenceId" : "RGD:A114804"
    }, {
      "firstName" : "CR",
      "lastName" : "Alexander",
      "authorRank" : 5,
      "name" : "Alexander CR",
      "referenceId" : "RGD:A114805"
    }, {
      "firstName" : "D",
      "lastName" : "Zagzag",
      "authorRank" : 6,
      "name" : "Zagzag D",
      "referenceId" : "RGD:A114806"
    }, {
      "firstName" : "GD",
      "lastName" : "Yancopoulos",
      "authorRank" : 7,
      "name" : "Yancopoulos GD",
      "referenceId" : "RGD:A120397"
    }, {
      "firstName" : "SJ",
      "lastName" : "Wiegand",
      "authorRank" : 8,
      "name" : "Wiegand SJ",
      "referenceId" : "RGD:A19445"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2314294"
    } ]
  }, {
    "primaryId" : "PMID:10373309",
    "title" : "Spag4, a novel sperm protein, binds outer dense-fiber protein Odf1 and localizes to microtubules of manchette and axoneme.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Shao X, etal., Dev Biol 1999 Jul 1;211(1):109-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:54:42.000-06:00",
    "volume" : "211",
    "pages" : "109-23",
    "abstract" : "Outer dense fibers are structures unique to the sperm tail. No definite function for these fibers has been found, but they may play a role in motility and provide elastic recoil. Their composition had been described before, but only two of the fiber proteins, Odf1 and Odf2, are cloned. We cloned Odf2 by virtue of its functional and specific interaction with Odf1, which, we show, is mediated by a leucine zipper. Further work demonstrated that the 84-kDa Odf2 protein localizes to both the cortex and the medulla of the fibers, whereas the 27-kDa Odf1 protein is present only in the medulla. Here we report the cloning and characterization of a new Odf1-interacting protein, Spag4. Spag4 mRNA is spermatid specific, and the 49-kDa Spag4 protein complexes specifically with Odf1, but not Odf2, mediated by a leucine zipper. It also self-associates. In contrast to Odf1 and Odf2, Spag4 protein localizes to two microtubule-containing spermatid structures. Spag4 is detectable in the transient manchette and it is associated with the axoneme in elongating spermatids and epididymal sperm. Our data suggest a role for Spag4 in protein localization to two major sperm tail structures.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Shao",
      "authorRank" : 1,
      "name" : "Shao X",
      "referenceId" : "RGD:A7642"
    }, {
      "firstName" : "HA",
      "lastName" : "Tarnasky",
      "authorRank" : 2,
      "name" : "Tarnasky HA",
      "referenceId" : "RGD:A19856"
    }, {
      "firstName" : "JP",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee JP",
      "referenceId" : "RGD:A27191"
    }, {
      "firstName" : "R",
      "lastName" : "Oko",
      "authorRank" : 4,
      "name" : "Oko R",
      "referenceId" : "RGD:A7644"
    }, {
      "firstName" : "FA",
      "lastName" : "Van der Hoorn",
      "authorRank" : 5,
      "name" : "Van der Hoorn FA",
      "referenceId" : "RGD:A7643"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727271"
    } ]
  }, {
    "primaryId" : "PMID:10373320",
    "title" : "Genetic dissection of \"OLETF,\" a rat model for non-insulin-dependent diabetes mellitus: quantitative trait locus analysis of (OLETF x BN) x OLETF.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Watanabe TK, etal., Genomics 1999 Jun 15;58(3):233-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-05T14:31:21.000-05:00",
    "volume" : "58",
    "pages" : "233-9",
    "abstract" : "To identify genetic determinants relevant to non-insulin-dependent diabetes mellitus (NIDDM), we performed a genome-wide analysis for quantitative trait loci (QTLs) using 359 backcross progeny of the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF strain is a well-studied animal model of obese NIDDM, with features of hyperinsulinemia, hyperglycemia, insulin resistance, and abundant abdominal fat. Our extensive genomic scanning with 218 markers revealed nine significant QTLs, including a strong determinant of obesity on chromosome 1 (Dmo1: LOD = 13.99, for body weight). Two highly significant QTLs for glucose homeostasis were found, one on chromosome 1 (Dmo4 LOD = 7.16, for postprandial glucose level) and the other on chromosome X (Dmo11/Odb1: LOD = 7.81, for postprandial glucose level). These data are comparable to results of our previous studies of the OLETF rat.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TK",
      "lastName" : "Watanabe",
      "authorRank" : 1,
      "name" : "Watanabe TK",
      "referenceId" : "RGD:A88768"
    }, {
      "firstName" : "S",
      "lastName" : "Okuno",
      "authorRank" : 2,
      "name" : "Okuno S",
      "referenceId" : "RGD:A162349"
    }, {
      "firstName" : "K",
      "lastName" : "Oga",
      "authorRank" : 3,
      "name" : "Oga K",
      "referenceId" : "RGD:A162347"
    }, {
      "firstName" : "A",
      "lastName" : "Mizoguchi-Miyakita",
      "authorRank" : 4,
      "name" : "Mizoguchi-Miyakita A",
      "referenceId" : "RGD:A162346"
    }, {
      "firstName" : "A",
      "lastName" : "Tsuji",
      "authorRank" : 5,
      "name" : "Tsuji A",
      "referenceId" : "RGD:A162343"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamasaki",
      "authorRank" : 6,
      "name" : "Yamasaki Y",
      "referenceId" : "RGD:A162345"
    }, {
      "firstName" : "H",
      "lastName" : "Hishigaki",
      "authorRank" : 7,
      "name" : "Hishigaki H",
      "referenceId" : "RGD:A162342"
    }, {
      "firstName" : "N",
      "lastName" : "Kanemoto",
      "authorRank" : 8,
      "name" : "Kanemoto N",
      "referenceId" : "RGD:A162350"
    }, {
      "firstName" : "T",
      "lastName" : "Takagi",
      "authorRank" : 9,
      "name" : "Takagi T",
      "referenceId" : "RGD:A296859"
    }, {
      "firstName" : "E",
      "lastName" : "Takahashi",
      "authorRank" : 10,
      "name" : "Takahashi E",
      "referenceId" : "RGD:A162351"
    }, {
      "firstName" : "Y",
      "lastName" : "Irie",
      "authorRank" : 11,
      "name" : "Irie Y",
      "referenceId" : "RGD:A5729"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakamura",
      "authorRank" : 12,
      "name" : "Nakamura Y",
      "referenceId" : "RGD:A161073"
    }, {
      "firstName" : "A",
      "lastName" : "Tanigami",
      "authorRank" : 13,
      "name" : "Tanigami A",
      "referenceId" : "RGD:A10455"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619678"
    } ]
  }, {
    "primaryId" : "PMID:10373359",
    "title" : "Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of flexible regions of the prion protein.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Wopfner F, etal., J Mol Biol 1999 Jun 25;289(5):1163-78.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:47.000-05:00",
    "volume" : "289",
    "pages" : "1163-78",
    "abstract" : "Prion diseases are fatal neurodegenerative disorders in man and animal associated with conformational conversion of a cellular prion protein (PrPc) into the pathologic isoform (PrPSc). The function of PrPcand the tertiary structure of PrPScare unclear. Various data indicate which parts of PrP might control the species barrier in prion diseases and the binding of putative factors to PrP. To elucidate these features, we analyzed the evolutionary conservation of the prion protein. Here, we add the primary PrP structures of 20 ungulates, three rodents, three carnivores, one maritime mammal, and nine birds. Within mammals and birds we found a high level of amino acid sequence identity, whereas between birds and mammals the overall homology was low. Various structural elements were conserved between mammals and birds. Using the CONRAD space-scale alignment, which predicts conserved and variable blocks, we observed similar patterns in avian and mammalian PrPs, although 130 million years of separate evolution lie in between. Our data support the suggestion that the repeat elements might have expanded differently within the various classes of vertebrates. Of note is the N-terminal part of PrP (amino acid residues 23-90), which harbors insertions and deletions, whereas in the C-terminal portion (91-231) mainly point mutations are found. Strikingly, we found a high level of conservation of sequences that are not part of the structured segment 121-231 of PrPcand of the structural elements therein, e.g. the N-terminal region from amino acid residue 23-90 and the regions located upstream of alpha-helices 1 and 3.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Wopfner",
      "authorRank" : 1,
      "name" : "Wopfner F",
      "referenceId" : "RGD:A33150"
    }, {
      "firstName" : "G",
      "lastName" : "Weidenhofer",
      "authorRank" : 2,
      "name" : "Weidenhofer G",
      "referenceId" : "RGD:A33151"
    }, {
      "firstName" : "R",
      "lastName" : "Schneider",
      "authorRank" : 3,
      "name" : "Schneider R",
      "referenceId" : "RGD:A33152"
    }, {
      "firstName" : "A",
      "lastName" : "Von Brunn",
      "authorRank" : 4,
      "name" : "Von Brunn A",
      "referenceId" : "RGD:A33153"
    }, {
      "firstName" : "S",
      "lastName" : "Gilch",
      "authorRank" : 5,
      "name" : "Gilch S",
      "referenceId" : "RGD:A33154"
    }, {
      "firstName" : "TF",
      "lastName" : "Schwarz",
      "authorRank" : 6,
      "name" : "Schwarz TF",
      "referenceId" : "RGD:A33155"
    }, {
      "firstName" : "T",
      "lastName" : "Werner",
      "authorRank" : 7,
      "name" : "Werner T",
      "referenceId" : "RGD:A33156"
    }, {
      "firstName" : "HM",
      "lastName" : "Schatzl",
      "authorRank" : 8,
      "name" : "Schatzl HM",
      "referenceId" : "RGD:A33157"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:729621"
    } ]
  }, {
    "primaryId" : "PMID:10373430",
    "title" : "The p56(lck)-interacting protein p62 stimulates transcription via the SV40 enhancer.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Rachubinski RA, etal., J Biol Chem. 1999 Jun 25;274(26):18278-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-24T20:35:56.000-05:00",
    "volume" : "274",
    "pages" : "18278-84",
    "abstract" : "p62 is a recently identified ubiquitin-binding, cytosolic phosphoprotein that interacts with several signal transduction molecules including the tyrosine kinase p56(lck) and the protein kinase C-zeta. p62 is therefore suggested to serve an important role in signal transduction in the cell, although the physiological function of p62 remains undefined. Here we demonstrate by transient transfection assays that p62 stimulates the transcription of reporter genes linked to the simian virus 40 (SV40) enhancer. A putative p62-responsive element  was localized to the B domain of the distal 72-base pair repeat of the SV40 enhancer. p62 was unable to bind this element in vitro, nor was it able to activate transcription when directly tethered to a promoter, suggesting that p62  stimulates transcription via an indirect mechanism. Stimulation of transcription  mediated by p62 was dependent on its amino-terminal region, which is also necessary for interaction with cell surface signaling molecules. These findings indicate that p62 may link extracellular signals directly to transcriptional responses, and identify the SV40 enhancer as a downstream target for signal transduction pathways in which p62 participates.",
    "issueName" : "26",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RA",
      "lastName" : "Rachubinski",
      "authorRank" : 1,
      "name" : "Rachubinski RA",
      "referenceId" : "RGD:A42219"
    }, {
      "firstName" : "SL",
      "lastName" : "Marcus",
      "authorRank" : 2,
      "name" : "Marcus",
      "referenceId" : "RGD:A374132"
    }, {
      "firstName" : "JP",
      "lastName" : "Capone",
      "authorRank" : 3,
      "name" : "Capone",
      "referenceId" : "RGD:A374133"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11531026"
    } ]
  }, {
    "primaryId" : "PMID:10373432",
    "title" : "The subcellular localizations of atypical synaptotagmins III and VI. Synaptotagmin III is enriched in synapses and synaptic plasma membranes but not in synaptic vesicles.",
    "datePublished" : "1999-06-25T00:00:00.000-05:00",
    "citation" : "Butz S, etal., J Biol Chem. 1999 Jun 25;274(26):18290-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T02:01:36.000-05:00",
    "volume" : "274",
    "pages" : "18290-6",
    "abstract" : "Multiple synaptotagmins are expressed in brain, but only synaptotagmins I and II have known functions in fast, synchronous Ca2+-triggered neurotransmitter release. Synaptotagmin III was proposed to regulate other aspects of synaptic vesicle exocytosis, particularly its slow component. Such a function predicts that synaptotagmin III should be an obligatory synaptic vesicle protein, as would also be anticipated from its high homology to synaptotagmins I and II. To test this hypothesis, we studied the distribution, developmental expression, and localization of synaptotagmin III and its closest homolog, synaptotagmin VI. We find that synaptotagmins III and VI are present in all brain regions in heterogeneous distributions and that their levels increase during development in parallel with synaptogenesis. Furthermore, we show by immunocytochemistry that synaptotagmin III is concentrated in synapses, as expected. Surprisingly, however, we observed that synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles. Synaptotagmin VI was also found to be relatively excluded from synaptic vesicles. Our data suggest that synaptotagmins III and VI perform roles in neurons that are not linked to synaptic vesicle exocytosis but to other Ca2+-related nerve terminal events, indicating that the functions of synaptotagmins are more diverse than originally thought.",
    "issueName" : "26",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Butz",
      "authorRank" : 1,
      "name" : "Butz S",
      "referenceId" : "RGD:A93805"
    }, {
      "firstName" : "R",
      "lastName" : "Fernandez-Chacon",
      "authorRank" : 2,
      "name" : "Fernandez-Chacon R",
      "referenceId" : "RGD:A5124"
    }, {
      "firstName" : "F",
      "lastName" : "Schmitz",
      "authorRank" : 3,
      "name" : "Schmitz F",
      "referenceId" : "RGD:A4723"
    }, {
      "firstName" : "R",
      "lastName" : "Jahn",
      "authorRank" : 4,
      "name" : "Jahn R",
      "referenceId" : "RGD:A160905"
    }, {
      "firstName" : "T C",
      "lastName" : "Südhof",
      "authorRank" : 5,
      "name" : "Südhof TC",
      "referenceId" : "RGD:A435850"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702215"
    } ]
  }, {
    "primaryId" : "PMID:10373452",
    "title" : "EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis?",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Okamoto M, etal., J Biol Chem 1999 Jun 25;274(26):18446-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:05.000-06:00",
    "volume" : "274",
    "pages" : "18446-54",
    "abstract" : "In yeast two-hybrid screens for proteins that bind to SNAP-25 and may be involved in exocytosis, we isolated a protein called EHSH1 (for EH domain/SH3 domain-containing protein). Cloning of full-length cDNAs revealed that EHSH1 is composed of an N-terminal region with two EH domains, a central region that is enriched in lysine, leucine, glutamate, arginine, and glutamine (KLERQ domain), and a C-terminal region comprised of five SH3 domains. The third SH3 domain is alternatively spliced. Data bank searches demonstrated that EHSH1 is very similar to Xenopus and human intersectins and to human SH3P17. In addition, we identified expressed sequence tags that encode a second isoform of EHSH1, called EHSH2. EHSH1 is abundantly expressed in brain and at lower levels in all other tissues tested. In binding studies, we found that the central KLERQ domain of EHSH1 binds to recombinant or native brain SNAP-25 and SNAP-23. The C-terminal SH3 domains, by contrast, quantitatively interact with dynamin, a protein involved in endocytosis. Dynamin strongly binds to the alternatively spliced central SH3 domain (SH3C) and the two C-terminal SH3 domains (SH3D and SH3E) but not to the N-terminal SH3 domains (SH3A and SH3B). Immunoprecipitations confirmed that both dynamin and SNAP-25 are complexed to EHSH1 in brain. Our data suggest that EHSH1/intersectin may be a novel adaptor protein that couples endocytic membrane traffic to exocytosis. The ability of multiple SH3 domains in EHSH1 to bind to dynamin suggests that EHSH1 can cluster several dynamin molecules in a manner that is regulated by alternative splicing.",
    "issueName" : "26",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Okamoto",
      "authorRank" : 1,
      "name" : "Okamoto M",
      "referenceId" : "RGD:A159261"
    }, {
      "firstName" : "S",
      "lastName" : "Schoch",
      "authorRank" : 2,
      "name" : "Schoch S",
      "referenceId" : "RGD:A7450"
    }, {
      "firstName" : "TC",
      "lastName" : "Sudhof",
      "authorRank" : 3,
      "name" : "Sudhof TC",
      "referenceId" : "RGD:A116148"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69862"
    } ]
  }, {
    "primaryId" : "PMID:10373468",
    "title" : "GPI1 stabilizes an enzyme essential in the first step of glycosylphosphatidylinositol biosynthesis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Hong Y, etal., J Biol Chem 1999 Jun 25;274(26):18582-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-31T15:20:37.000-05:00",
    "volume" : "274",
    "pages" : "18582-8",
    "abstract" : "Attachment of glycosylphosphatidylinositol (GPI) is essential for the surface expression of many proteins. Biosynthesis of glycosylphosphatidylinositol is initiated by the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol. In mammalian cells, this reaction is mediated by a complex of PIG-A, PIG-H, PIG-C, and GPI1. This complexity may be relevant for regulation and for usage of a particular phosphatidylinositol. However, the functions of the respective components have been unclear. Here we cloned the mouse GPI1 gene and disrupted it in F9 embryonal carcinoma cells. Disruption of the GPI1 gene caused a severe but not complete defect in the generation of glycosylphosphatidylinositol-anchored proteins, indicating some residual biosynthetic activity. A complex of PIG-A, PIG-H, and PIG-C decreased to a nearly undetectable level, whereas a complex of PIG-A and PIG-H was easily detected. A lack of GPI1 also caused partial decreases of PIG-C and PIG-H. Therefore, GPI1 stabilizes the enzyme by tying up PIG-C with a complex of PIG-A and PIG-H.",
    "issueName" : "26",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Hong",
      "authorRank" : 1,
      "name" : "Hong Y",
      "referenceId" : "RGD:A9485"
    }, {
      "firstName" : "K",
      "lastName" : "Ohishi",
      "authorRank" : 2,
      "name" : "Ohishi K",
      "referenceId" : "RGD:A7310"
    }, {
      "firstName" : "R",
      "lastName" : "Watanabe",
      "authorRank" : 3,
      "name" : "Watanabe R",
      "referenceId" : "RGD:A7309"
    }, {
      "firstName" : "Y",
      "lastName" : "Endo",
      "authorRank" : 4,
      "name" : "Endo Y",
      "referenceId" : "RGD:A20549"
    }, {
      "firstName" : "Y",
      "lastName" : "Maeda",
      "authorRank" : 5,
      "name" : "Maeda Y",
      "referenceId" : "RGD:A7307"
    }, {
      "firstName" : "T",
      "lastName" : "Kinoshita",
      "authorRank" : 6,
      "name" : "Kinoshita T",
      "referenceId" : "RGD:A7311"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549492"
    } ]
  }, {
    "primaryId" : "PMID:10373470",
    "title" : "The cloning and analysis of LEK1 identifies variations in the LEK/centromere protein F/mitosin gene family.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Goodwin RL, etal., J Biol Chem 1999 Jun 25;274(26):18597-604.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-07-24T22:59:22.000-05:00",
    "volume" : "274",
    "pages" : "18597-604",
    "abstract" : "We report the cloning of a novel murine cDNA, LEK1, that is related to human CENP-F and mitosin and more distantly to chicken CMF1. The proteins from these three organisms have significant homology, yet differ in their temporal, spatial, and subcellular localizations. The human proteins bind the kinetochore in mitotic cells, whereas the chicken protein is found only in skeletal and cardiac muscle and is developmentally regulated. Mouse LEK1 is a single copy gene that codes for two developmentally regulated transcripts. The LEK1 protein is expressed early and ubiquitously in mouse development and is generally down-regulated as development proceeds in a manner that correlates to a cessation of mitosis. In adult tissues, the LEK1 protein is detected exclusively in the pronucleus of the oocyte and was not observed in other actively dividing tissues. Subcellular localization revealed that the LEK1 protein in mitotic cells does not bind the kinetochore. From these data, we hypothesize that chicken CMF1, human CENP-F, mitosin, and mouse LEK1 are members of an emerging family of genes that have important and functionally distinct roles in development and cell division.",
    "issueName" : "26",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RL",
      "lastName" : "Goodwin",
      "authorRank" : 1,
      "name" : "Goodwin RL",
      "referenceId" : "RGD:A54313"
    }, {
      "firstName" : "LM",
      "lastName" : "Pabon-Pena",
      "authorRank" : 2,
      "name" : "Pabon-Pena LM",
      "referenceId" : "RGD:A16029"
    }, {
      "firstName" : "GC",
      "lastName" : "Foster",
      "authorRank" : 3,
      "name" : "Foster GC",
      "referenceId" : "RGD:A54314"
    }, {
      "firstName" : "D",
      "lastName" : "Bader",
      "authorRank" : 4,
      "name" : "Bader D",
      "referenceId" : "RGD:A54315"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1359063"
    } ]
  }, {
    "primaryId" : "PMID:10373478",
    "title" : "Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Mochizuki T, etal., J Biol Chem 1999 Jun 25;274(26):18659-66.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-13T16:52:35.000-05:00",
    "volume" : "274",
    "pages" : "18659-66",
    "abstract" : "The pim-1 oncogene encodes a serine/threonine kinase (Pim-1) involved in the transduction of cytokine-triggered mitogenic signals. Pim-1 is unique in that it closely cooperates with c-Myc not only in oncogenesis, but also in apoptosis induction. However, the molecular basis of Pim-1 function remains poorly understood, largely because the downstream effector molecule(s) for Pim-1 kinase has not been identified. Here we provide several lines of evidence that Cdc25A cell cycle phosphatase, a direct transcriptional target for c-Myc, is a substrate for Pim-1 kinase and functions as an effector for Pim-1. We found that Pim-1 physically interacts with Cdc25A both in vitro and in vivo and phosphorylates Cdc25A. We also observed that Pim-1-mediated phosphorylation of Cdc25A increases its phosphatase activity. In addition, wild-type Pim-1, but not kinase-inactive Pim-1, enhanced Cdc25A-mediated cellular transformation and apoptosis. Our results indicate that Cdc25A might be a key molecule that links Pim-1 and c-Myc and that also ties Pim-1-mediated mitogenic signals to cell cycle machinery.",
    "issueName" : "26",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Mochizuki",
      "authorRank" : 1,
      "name" : "Mochizuki T",
      "referenceId" : "RGD:A26487"
    }, {
      "firstName" : "C",
      "lastName" : "Kitanaka",
      "authorRank" : 2,
      "name" : "Kitanaka C",
      "referenceId" : "RGD:A10184"
    }, {
      "firstName" : "K",
      "lastName" : "Noguchi",
      "authorRank" : 3,
      "name" : "Noguchi K",
      "referenceId" : "RGD:A7776"
    }, {
      "firstName" : "T",
      "lastName" : "Muramatsu",
      "authorRank" : 4,
      "name" : "Muramatsu T",
      "referenceId" : "RGD:A22404"
    }, {
      "firstName" : "A",
      "lastName" : "Asai",
      "authorRank" : 5,
      "name" : "Asai A",
      "referenceId" : "RGD:A6323"
    }, {
      "firstName" : "Y",
      "lastName" : "Kuchino",
      "authorRank" : 6,
      "name" : "Kuchino Y",
      "referenceId" : "RGD:A6326"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:724654"
    } ]
  }, {
    "primaryId" : "PMID:10373510",
    "title" : "Ras-specific exchange factor GRF: oligomerization through its Dbl homology domain and calcium-dependent activation of Raf.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Anborgh PH, etal., Mol Cell Biol. 1999 Jul;19(7):4611-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-05-04T13:53:22.000-05:00",
    "volume" : "19",
    "pages" : "4611-22",
    "abstract" : "The full-length versions of the Ras-specific exchange factors Ras-GRF1 (GRF1) and Ras-GRF2 (GRF2), which are expressed in brain and a restricted number of other organs, possess an ionomycin-dependent activation of Erk mitogen-activated protein kinase activity in 293T cells (C. L. Farnsworth et al., Nature 376:524-527, 1995; N. P. Fam et al., Mol. Cell. Biol. 17:1396-1406, 1996). Each GRF protein contains a Dbl homology (DH) domain. A yeast two-hybrid screen was used to identify polypeptides that associate with the DH domain of GRF1. In this  screen, a positive cDNA clone from a human brain cDNA library was isolated which  consisted of the GRF2 DH domain and its adjacent ilimaquinone domain. Deletion analysis verified that the two-hybrid interaction required only the DH domains, and mutation of Leu-263 to Gln (L263Q) in the N terminus of the GRF1 DH domain abolished the two-hybrid interaction, while a cluster of more C-terminally located mutations in the DH domain did not eliminate the interaction. Oligomers between GRF1 and GRF2 were detected in a rat brain extract, and forced expression of GRF1 and GRF2 in cultured mammalian cells formed homo- and hetero-oligomers. Introduction of the L263Q mutation in GRF1 led to a protein that was deficient in oligomer formation, while GRF1 containing the DH cluster mutations formed homo-oligomers with an efficiency similar to that of wild type. Compared to wild-type GRF1, the focus-forming activity on NIH 3T3 cells of the GRF1 DH cluster mutant was reduced, while the L263Q mutant was inactive. Both mutants were impaired in their ability to mediate ionomycin-dependent Erk activity in 293T cells. In the absence of ionomycin, 293T cells expressing wild-type GRF1 contained much higher levels of Ras-GTP than control cells; the increase in Erk activity induced by ionomycin in the GRF1-expressing cells also induced a concomitant increase in Raf kinase activity, but without a further increase in the level Ras-GTP. We conclude that GRF1 and GRF2 can form homo- and hetero-oligomers via their DH domains, that mutational inactivation of oligomer formation by GRF1 is associated with impaired biological and signaling activities, and that in 293T cells GRF1 mediates at least two pathways for Raf activation: one a constitutive signal that is mainly Ras-dependent, and one an ionomycin-induced signal that cooperates with the constitutive signal without further augmenting the level of GTP-Ras.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PH",
      "lastName" : "Anborgh",
      "authorRank" : 1,
      "name" : "Anborgh PH",
      "referenceId" : "RGD:A99266"
    }, {
      "firstName" : "X",
      "lastName" : "Qian",
      "authorRank" : 2,
      "name" : "Qian X",
      "referenceId" : "RGD:A5932"
    }, {
      "firstName" : "AG",
      "lastName" : "Papageorge",
      "authorRank" : 3,
      "name" : "Papageorge",
      "referenceId" : "RGD:A201356"
    }, {
      "firstName" : "WC",
      "lastName" : "Vass",
      "authorRank" : 4,
      "name" : "Vass",
      "referenceId" : "RGD:A201357"
    }, {
      "firstName" : "JE",
      "lastName" : "DeClue",
      "authorRank" : 5,
      "name" : "DeClue",
      "referenceId" : "RGD:A201358"
    }, {
      "firstName" : "DR",
      "lastName" : "Lowy",
      "authorRank" : 6,
      "name" : "Lowy",
      "referenceId" : "RGD:A201359"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10003124"
    } ]
  }, {
    "primaryId" : "PMID:10374321",
    "title" : "Zhonghua bing li xue za zhi Chinese journal of pathology",
    "datePublished" : "1997-12-01T00:00:00.000-06:00",
    "citation" : "Niu Y, etal., Zhonghua Bing Li Xue Za Zhi. 1997 Dec;26(6):337-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-12-11T15:32:40.000-06:00",
    "volume" : "26",
    "pages" : "337-9",
    "abstract" : "OBJECTIVE: To investigate the expression of proliferating cell nuclear antigen (PCNA) in breast phylloides cystosarcoma and its clinicopathological signification. METHODS: Immunohistochemistry (SP method) with monoclonal antibodies PC10 against PCNA was performed in 100 cases of phylloides cystosarcoma and 39 cases of adenofibroma. RESULTS: The positive rate of PCNA in phylloides cystosarcoma was 86%. The average PCNA index (PI) of phylloides cystosarcoma was significantly different among every histologic grading (F = 85.33, P < 0.01). The degree of differentiation was lower, the PI was higher. The PI was closely correlated with histologic grading (r's = 0.77). The PI in grade I phylloides cystosarcoma was higher than that in the group of adenofibroma with abundant mesenchymal cells (t = 3.42, P < 0.01). There was only a low correlation between PI and mitotic figures in phylloides cystosarcoma (r = 0.39). CONCLUSIONS: These findings suggest that the detection of PCNA has considerable practical value in reflecting the proliferation of activity of phylloides cystosarcoma, assisting the pathologists to make histologic grading; distinguishing the malignancy from benign ones (differential diagnosis) and evaluating the prognosis.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Niu",
      "authorRank" : 1,
      "name" : "Niu Y",
      "referenceId" : "RGD:A90707"
    }, {
      "firstName" : "X",
      "lastName" : "Fu",
      "authorRank" : 2,
      "name" : "Fu X",
      "referenceId" : "RGD:A56313"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhao",
      "authorRank" : 3,
      "name" : "Zhao Y",
      "referenceId" : "RGD:A161223"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2315010"
    } ]
  }, {
    "primaryId" : "PMID:10374842",
    "title" : "Expression of highly polysialylated neural cell adhesion molecule in pancreatic cancer neural invasive lesion.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kameda K, etal., Cancer Lett. 1999 Apr 1;137(2):201-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-21T14:55:43.000-05:00",
    "volume" : "137",
    "pages" : "201-7",
    "abstract" : "Neurotropism of pancreatic cancer is one of the hypotheses explaining neural invasion, which is one of the characteristics of pancreatic cancer. In these studies, we immunohistochemically examined neural cell adhesion molecules (NCAM), homophilic adhesion molecules expressed on the nerve cells, as a factor of neurotropism, in 15 pancreatic cancer operatively obtained, especially in neural invasive lesions. We also investigated the role of polysialic acid (PSA), which is attached to NCAM and related to the malignant potential of cancers. NCAM was detected in 66.7% of pancreatic cancers, and in all 9 cases with massive perineural invasion. In neural invasive lesions, however, there were perineurium and endoneurium, which do not express NCAM, between the cancer and nerve cells. PSA was also detected in the pancreatic cancers expressing NCAM. Moreover, PSA expression was stronger in the perineural invasive lesions than in the main tumor and was related to the cancer cell proliferation investigated by Ki-67 staining. It is unlikely therefore, that NCAM plays an important role in neurotropism. However, the NCAM expressed on the pancreatic cancer was attached to PSA, which itself plays an important role in the malignant potential of this disease.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Kameda",
      "authorRank" : 1,
      "name" : "Kameda K",
      "referenceId" : "RGD:A61342"
    }, {
      "firstName" : "H",
      "lastName" : "Shimada",
      "authorRank" : 2,
      "name" : "Shimada H",
      "referenceId" : "RGD:A6499"
    }, {
      "firstName" : "T",
      "lastName" : "Ishikawa",
      "authorRank" : 3,
      "name" : "Ishikawa T",
      "referenceId" : "RGD:A299703"
    }, {
      "firstName" : "A",
      "lastName" : "Takimoto",
      "authorRank" : 4,
      "name" : "Takimoto A",
      "referenceId" : "RGD:A125304"
    }, {
      "firstName" : "N",
      "lastName" : "Momiyama",
      "authorRank" : 5,
      "name" : "Momiyama N",
      "referenceId" : "RGD:A125305"
    }, {
      "firstName" : "S",
      "lastName" : "Hasegawa",
      "authorRank" : 6,
      "name" : "Hasegawa S",
      "referenceId" : "RGD:A7936"
    }, {
      "firstName" : "K",
      "lastName" : "Misuta",
      "authorRank" : 7,
      "name" : "Misuta K",
      "referenceId" : "RGD:A125306"
    }, {
      "firstName" : "A",
      "lastName" : "Nakano",
      "authorRank" : 8,
      "name" : "Nakano A",
      "referenceId" : "RGD:A67330"
    }, {
      "firstName" : "Y",
      "lastName" : "Nagashima",
      "authorRank" : 9,
      "name" : "Nagashima Y",
      "referenceId" : "RGD:A21778"
    }, {
      "firstName" : "Y",
      "lastName" : "Ichikawa",
      "authorRank" : 10,
      "name" : "Ichikawa Y",
      "referenceId" : "RGD:A41945"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2326075"
    } ]
  }, {
    "primaryId" : "PMID:10374863",
    "title" : "Hepatocyte growth inhibitory factor derived from HTLV-I(+) T-cell line is identical to IL-6.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kawai Y, etal., Leuk Res. 1999 May;23(5):489-97.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-20T14:54:47.000-05:00",
    "volume" : "23",
    "pages" : "489-97",
    "abstract" : "We previously reported that the culture supernatant of the human T-cell leukemia  virus (HTLV-I) infected-T-cell line--ATL-2--included factor(s), which had an inhibitory effect on epidermal growth factor (EGF)-stimulated proliferation of primary cultured rat hepatocytes. After crude purification, we arbitrarily named  it hepatocyte growth inhibitory factor (HGI). In this study, we further purified  HGI and determined its amino acid sequence. For purification, we used 4-steps column chromatography and SDS-PAGE. The purified proteins consisted of two bands  of 20 and 27 kDa in SDS-PAGE analysis. Protein extracted from each band had an inhibitory effect on rat hepatocyte growth. Amino acid analysis of the purified 20 kDa band revealed that the 34 amino acids were identical to those of IL-6. The inhibitory effect of the factor was neutralized by an anti IL-6 neutralizing antibody. Using Western blot analysis of HGI, an anti IL-6 antibody recognized both 20 and 27 kDa bands. Consequently HGI was determined to be identical to IL-6, which occurred in higher levels in the sera of adult T-cell leukemia (ATL)  patients.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Kawai",
      "authorRank" : 1,
      "name" : "Kawai Y",
      "referenceId" : "RGD:A19187"
    }, {
      "firstName" : "A",
      "lastName" : "Yamauchi",
      "authorRank" : 2,
      "name" : "Yamauchi A",
      "referenceId" : "RGD:A141772"
    }, {
      "firstName" : "H",
      "lastName" : "Nakamura",
      "authorRank" : 3,
      "name" : "Nakamura",
      "referenceId" : "RGD:A401423"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakamura",
      "authorRank" : 4,
      "name" : "Nakamura",
      "referenceId" : "RGD:A415572"
    }, {
      "firstName" : "T",
      "lastName" : "Hirose",
      "authorRank" : 5,
      "name" : "Hirose T",
      "referenceId" : "RGD:A9841"
    }, {
      "firstName" : "S",
      "lastName" : "Tsuyuki",
      "authorRank" : 6,
      "name" : "Tsuyuki",
      "referenceId" : "RGD:A189820"
    }, {
      "firstName" : "N",
      "lastName" : "Shinkura",
      "authorRank" : 7,
      "name" : "Shinkura",
      "referenceId" : "RGD:A243576"
    }, {
      "firstName" : "K",
      "lastName" : "Okawa",
      "authorRank" : 8,
      "name" : "Okawa K",
      "referenceId" : "RGD:A54434"
    }, {
      "firstName" : "A",
      "lastName" : "Iwamatsu",
      "authorRank" : 9,
      "name" : "Iwamatsu A",
      "referenceId" : "RGD:A15137"
    }, {
      "firstName" : "Y",
      "lastName" : "Maeda",
      "authorRank" : 10,
      "name" : "Maeda Y",
      "referenceId" : "RGD:A7307"
    }, {
      "firstName" : "I",
      "lastName" : "Ikai",
      "authorRank" : 11,
      "name" : "Ikai I",
      "referenceId" : "RGD:A129858"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamaoka",
      "authorRank" : 12,
      "name" : "Yamaoka Y",
      "referenceId" : "RGD:A44870"
    }, {
      "firstName" : "T",
      "lastName" : "Inamoto",
      "authorRank" : 13,
      "name" : "Inamoto T",
      "referenceId" : "RGD:A96686"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11060275"
    } ]
  }, {
    "primaryId" : "PMID:10374894",
    "title" : "ProMMP-9 (92 kDa gelatinase) in vitreous fluid of patients with proliferative diabetic retinopathy.",
    "datePublished" : "1000-02-01T00:00:00.000-06:00",
    "citation" : "Kosano H, etal., Life Sci. 1999;64(25):2307-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-24T16:54:40.000-06:00",
    "volume" : "64",
    "pages" : "2307-15",
    "abstract" : "Matrix metalloproteinases (MMPs) are implicated in tissue destruction during various pathophysiologic conditions. The vitreous body is a gel-like extracellular matrix that undergoes liquefaction during aging and pathological processes. To investigate the pathogenic role of MMPs in proliferative diabetic retinopathy (PDR), we studied 73 eyes from PDR patients and 25 eyes from patients with non-diabetic ocular diseases. Vitreous MMPs were measured by zymography. Retinopathy was assessed by ophthalmoscopy and PDR was classified into 3 stages,  'naked', 'active', and 'quiescent'. Although proMMP-9 was expressed in only 8% (2/25) of non-diabetic patients, it was expressed in more than 80% (38/47) of 'active' PDR patients and still expressed in 60% (9/15) of those with 'quiescent' PDR. Vascular endothelial growth factor (VEGF) in vitreous fluids was undetectable (<0.16 ng/ml) in most of the non-diabetic patients, and was maximally elevated in the 'active' PDR patients (mean=2.20 ng/ml, range; 0.16-7.61), declining in patients with 'quiescent' PDR (1.04 ng/ml, 0.16-3.77). These results suggest that MMP-9 is one of the noteworthy factors in relation to  the progress of PDR, as well as angiogenic cytokines such as VEGF.",
    "issueName" : "25",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Kosano",
      "authorRank" : 1,
      "name" : "Kosano",
      "referenceId" : "RGD:A180040"
    }, {
      "firstName" : "T",
      "lastName" : "Okano",
      "authorRank" : 2,
      "name" : "Okano T",
      "referenceId" : "RGD:A14784"
    }, {
      "firstName" : "Y",
      "lastName" : "Katsura",
      "authorRank" : 3,
      "name" : "Katsura",
      "referenceId" : "RGD:A180041"
    }, {
      "firstName" : "M",
      "lastName" : "Noritake",
      "authorRank" : 4,
      "name" : "Noritake",
      "referenceId" : "RGD:A180042"
    }, {
      "firstName" : "S",
      "lastName" : "Kado",
      "authorRank" : 5,
      "name" : "Kado",
      "referenceId" : "RGD:A180043"
    }, {
      "firstName" : "T",
      "lastName" : "Matsuoka",
      "authorRank" : 6,
      "name" : "Matsuoka T",
      "referenceId" : "RGD:A30935"
    }, {
      "firstName" : "H",
      "lastName" : "Nishigori",
      "authorRank" : 7,
      "name" : "Nishigori H",
      "referenceId" : "RGD:A78917"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547815"
    } ]
  }, {
    "primaryId" : "PMID:10374970",
    "title" : "Human papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Thomas M and Banks L, J Gen Virol. 1999 Jun;80 ( Pt 6):1513-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T13:54:18.000-05:00",
    "volume" : "80 ( Pt 6)",
    "pages" : "1513-7",
    "abstract" : "Human papillomavirus (HPV) replication occurs in terminally differentiating epithelium, and requires the activation of cellular DNA replication proteins. Unscheduled DNA replication can result in the induction of apoptosis, and the viral E6 protein induces the degradation of p53 to prevent this. It has recently  been shown that HPV-18 E6 can also stimulate the degradation of Bak, a pro-apoptotic member of the Bcl-2 family. This report shows that the E6 proteins  from HPV-18, HPV-16 and HPV-11 can all bind to Bak in vitro, stimulate its degradation in vivo and reduce Bak-induced apoptosis. However, the non-oncogenic  HPV-11 E6 is less effective than the oncogenic E6 proteins in each of these assays, indicating that the ability of HPV to circumvent the apoptosis induced by Bak may contribute to the oncogenic potential of the virus.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Thomas",
      "authorRank" : 1,
      "name" : "Thomas M",
      "referenceId" : "RGD:A99598"
    }, {
      "firstName" : "L",
      "lastName" : "Banks",
      "authorRank" : 2,
      "name" : "Banks L",
      "referenceId" : "RGD:A106344"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11054465"
    } ]
  }, {
    "primaryId" : "PMID:10375024",
    "title" : "The rat intraovarian interleukin (IL)-1 system: cellular localization, cyclic variation and hormonal regulation of IL-1beta and of the type I and type II IL-1 receptors.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kol S, etal., Mol Cell Endocrinol. 1999 Mar 25;149(1-2):115-28.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-06-24T16:38:03.000-05:00",
    "volume" : "149",
    "pages" : "115-28",
    "abstract" : "An increasing body of evidence supports the possibility that intraovarian interleukin (IL)-1 plays an intermediary role in the periovulatory cascade. To gain further insight into the intraovarian IL-1 hypothesis, we studied the cellular localization cyclic variation and hormonal regulation of IL-1beta, as well as of the type I and type II IL-1 receptors (IL-1R) in immature rats. In situ hybridization localized IL-1beta and type I IL-1R transcripts to the granulosa cell compartment, the innermost layers of the theca interna and to the oocyte of the untreated immature ovary. Molecular probing of whole ovarian material in the course of a simulated estrous cycle revealed a progressive preovulatory increase in IL-1beta and type I IL-1R transcripts to an in vivo peak at the time of ovulation (3.0- and 2.5-fold increases over untreated controls; P < 0.05). Comparable efforts to localize and probe for type II IL-IR transcripts failed to elicit a detectable signal. The basal in vitro expression pattern of IL-1beta and type II IL-1R transcripts by whole ovarian dispersates revealed an early (4 h) spontaneous increase to a peak (2.1- and 5.8-fold increases over time 0: P < 0.05) followed by a gradual decline to a 48 h nadir. Treatment of whole ovarian dispersates with the IL-1 receptor antagonist (IL-1RA) or with IL-1beta failed to alter the initial (4 h) burst of IL-1beta or of type II IL-1R expression thereby suggesting IL-1-independence. Treatment with hCG proved equally ineffective. However, longer-term treatment of whole ovarian dispersates with IL-1beta produced a significant secondary increase (5.9-fold over time 0; P < 0.05) in IL-1beta (but not type II IL-1R) transcripts by 48 h. This IL-1 effect was completely blocked by co-treatment with IL-1RA thereby suggesting mediation via a specific IL-1 receptor. Qualitatively comparable but quantitatively reduced results obtained for isolated granulosa cells. The basal in vitro expression pattern of type I IL-1R transcripts by whole ovarian dispersates revealed a progressive spontaneous increase (3.1-fold increase overall) over the 48 h culture. Treatment with IL-1beta produced a significant (P < 0.05) increase (5-fold) in type I IL-1R transcripts by 48 h, an effect which was completely blocked by co-treatment with IL-1RA. Taken together, these observations: (1) localize IL-1beta and its type I receptor to granulosa cells, the innermost layers of the theca interna and to the oocyte; (2) confirm their periovulatory in vivo expression pattern; (3) document their expression by untreated cultured whole ovarian dispersates; and (4) demonstrate their in vitro responsiveness to receptor-mediated/IL-1-driven autocrine amplification. The type II IL-1R was undetectable in vivo, its in vitro expression pattern proving IL-1- and hCG-independent. The periovulatory expression pattern of IL-1beta and its receptor (type I) is compatible with the notion that the intraovarian IL-1 system may play an intermediary role in the ovulatory process.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kol",
      "authorRank" : 1,
      "name" : "Kol S",
      "referenceId" : "RGD:A108607"
    }, {
      "firstName" : "K",
      "lastName" : "Ruutiainen-Altman",
      "authorRank" : 2,
      "name" : "Ruutiainen-Altman K",
      "referenceId" : "RGD:A108608"
    }, {
      "firstName" : "WJ",
      "lastName" : "Scherzer",
      "authorRank" : 3,
      "name" : "Scherzer WJ",
      "referenceId" : "RGD:A108609"
    }, {
      "firstName" : "I",
      "lastName" : "Ben-Shlomo",
      "authorRank" : 4,
      "name" : "Ben-Shlomo I",
      "referenceId" : "RGD:A108610"
    }, {
      "firstName" : "M",
      "lastName" : "Ando",
      "authorRank" : 5,
      "name" : "Ando M",
      "referenceId" : "RGD:A51647"
    }, {
      "firstName" : "RM",
      "lastName" : "Rohan",
      "authorRank" : 6,
      "name" : "Rohan RM",
      "referenceId" : "RGD:A108611"
    }, {
      "firstName" : "EY",
      "lastName" : "Adashi",
      "authorRank" : 7,
      "name" : "Adashi EY",
      "referenceId" : "RGD:A28683"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311108"
    } ]
  }, {
    "primaryId" : "PMID:10375411",
    "title" : "Limited proteolysis of tyrosine hydroxylase identifies residues 33-50 as conformationally sensitive to phosphorylation state and dopamine binding.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "McCulloch RI and Fitzpatrick PF, Arch Biochem Biophys. 1999 Jul 1;367(1):143-5. doi: 10.1006/abbi.1999.1259.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-06-29T01:56:22.000-05:00",
    "volume" : "367",
    "pages" : "143-5",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R I",
      "lastName" : "McCulloch",
      "authorRank" : 1,
      "name" : "McCulloch RI",
      "referenceId" : "RGD:A517722"
    }, {
      "firstName" : "P F",
      "lastName" : "Fitzpatrick",
      "authorRank" : 2,
      "name" : "Fitzpatrick PF",
      "referenceId" : "RGD:A517723"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:152995565"
    } ]
  }, {
    "primaryId" : "PMID:10375453",
    "title" : "Changes of GABA metabolic enzymes in acute retinal ischemia.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Kobayashi N, etal., Exp Eye Res. 1999 Jul;69(1):91-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-02T09:26:49.000-06:00",
    "volume" : "69",
    "pages" : "91-6",
    "abstract" : "It is reported that GABA accumulates in Muller cells in ischemic and diabetic rat retina. To investigate the mechanism of GABA accumulation in Muller cells, we localized GABA and glutamate in ischemic rat retina and measured the activity of GAD and GABA-T, enzymes involved in GABA metabolism. Using general anesthesia, we incised the bulbar conjunctiva of the rat around the limbus and clamped the left optic nerve. A sham operation was performed on the right eyes. Ocular ischemia was sustained for 30, 60 and 90 minutes. Rat eyes were enucleated immediately after ischemia and prepared for immunohistochemistry and enzyme activity measurement. Glutamate-like immunoreactivity (Glu-IR) in the sham-operated rat retina was observed in all retinal layers, showing intense staining in the nerve fiber layer (NFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Glu-IR increased in the outer plexiform layer (OPL) and outer nuclear layer (ONL) in an ischemic time-dependent manner. GABA-like immunoreactivity (GABA-IR) in sham-operated rat retina was observed in NFL, GCL, IPL and inner nuclear layer (INL). When the ischemic time was extended, GABA-IR intensely stained Muller cells. GAD activity was not changed in ischemic rat retina as compared to normal rat retina, but GABA-T activity was significantly decreased in ischemic rat retina. These results suggested that glutamate was induced by ischemia and was converted to GABA by GAD activity. Increased GABA was not metabolized because GABA-T activity was decreased. GABA accumulation in Muller cells progressed during the change in activity of these metabolic enzymes.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Kobayashi",
      "authorRank" : 1,
      "name" : "Kobayashi N",
      "referenceId" : "RGD:A70588"
    }, {
      "firstName" : "S",
      "lastName" : "Ishiguro",
      "authorRank" : 2,
      "name" : "Ishiguro S",
      "referenceId" : "RGD:A67379"
    }, {
      "firstName" : "H",
      "lastName" : "Tomita",
      "authorRank" : 3,
      "name" : "Tomita H",
      "referenceId" : "RGD:A70589"
    }, {
      "firstName" : "S",
      "lastName" : "Nishikawa",
      "authorRank" : 4,
      "name" : "Nishikawa S",
      "referenceId" : "RGD:A15562"
    }, {
      "firstName" : "M",
      "lastName" : "Tamai",
      "authorRank" : 5,
      "name" : "Tamai M",
      "referenceId" : "RGD:A25202"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598516"
    } ]
  }, {
    "primaryId" : "PMID:10375621",
    "title" : "Metastatic rat carcinoma cells express a new retrotransposon.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Grassi M, etal., Gene 1999 Jun 11;233(1-2):59-66.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:49:43.000-05:00",
    "volume" : "233",
    "pages" : "59-66",
    "abstract" : "Genes differentially expressed by a rat bladder carcinoma NBT-II cells and their in-vivo-selected metastatic M-NBT-II variant were analysed. Amplification and cloning of a 277-bp B sequence, exclusively expressed by the M-NBT-II cells, were performed, and this sequence was detected as a 6.7-kb RNA. This fragment shares 46-50% identities with the gag-related protein of mouse and hamster Intracisternal A Particles (IAPs). Screening of a M-NBT-II cDNA library with the B probe selected a 1671-bp sequence corresponding to the 5' end of a novel retrotransposon member of the rat IAP family. This sequence has a strong identity with the Ecker Rat IAP (ERA-IAP) except for the B portion and has an open reading frame potentially encoding a 114-amino-acid gag retrovirus-related protein. Rearrangement of this new retrotransposon could be relevant with the tumor progression in our model system since it is only expressed in the M-NBT-II in-vivo-selected carcinoma metastasis.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Grassi",
      "authorRank" : 1,
      "name" : "Grassi M",
      "referenceId" : "RGD:A43434"
    }, {
      "firstName" : "JM",
      "lastName" : "Girault",
      "authorRank" : 2,
      "name" : "Girault JM",
      "referenceId" : "RGD:A30834"
    }, {
      "firstName" : "WP",
      "lastName" : "Wang",
      "authorRank" : 3,
      "name" : "Wang WP",
      "referenceId" : "RGD:A43435"
    }, {
      "firstName" : "JP",
      "lastName" : "Thiery",
      "authorRank" : 4,
      "name" : "Thiery JP",
      "referenceId" : "RGD:A17457"
    }, {
      "firstName" : "J",
      "lastName" : "Jouanneau",
      "authorRank" : 5,
      "name" : "Jouanneau J",
      "referenceId" : "RGD:A18153"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299565"
    } ]
  }, {
    "primaryId" : "PMID:10375868",
    "title" : "HLA-DMA and HLA-DMB genotyping in patients with rheumatic diseases.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Yen JH, etal., Kaohsiung J Med Sci. 1999 May;15(5):263-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-11-17T17:20:28.000-06:00",
    "volume" : "15",
    "pages" : "263-7",
    "abstract" : "To investigate the correlation of HLA-DMA and DMB alleles to some rheumatic diseases, HLA-DMA and DMB genes were detected in 11 patients with juvenile rheumatoid arthritis (JRA), 22 patients with psoriatic arthritis, 26 patients with Behcet's disease, 62 patients with ankylosing spondylitis (AS), and 138 unrelated healthy controls. There was no significant difference in phenotypic frequencies of HLA-DMA and DMB alleles between controls and patients with these rheumatic diseases. HLA-DMA and DMB genes are not related to the susceptibility of JRA, psoriatic arthritis, Behcet's disease, and AS.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JH",
      "lastName" : "Yen",
      "authorRank" : 1,
      "name" : "Yen JH",
      "referenceId" : "RGD:A66017"
    }, {
      "firstName" : "WC",
      "lastName" : "Tsai",
      "authorRank" : 2,
      "name" : "Tsai WC",
      "referenceId" : "RGD:A66018"
    }, {
      "firstName" : "JJ",
      "lastName" : "Tsai",
      "authorRank" : 3,
      "name" : "Tsai JJ",
      "referenceId" : "RGD:A69975"
    }, {
      "firstName" : "CJ",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen CJ",
      "referenceId" : "RGD:A33260"
    }, {
      "firstName" : "CH",
      "lastName" : "Lin",
      "authorRank" : 5,
      "name" : "Lin CH",
      "referenceId" : "RGD:A54321"
    }, {
      "firstName" : "TT",
      "lastName" : "Ou",
      "authorRank" : 6,
      "name" : "Ou TT",
      "referenceId" : "RGD:A66019"
    }, {
      "firstName" : "CC",
      "lastName" : "Wu",
      "authorRank" : 7,
      "name" : "Wu CC",
      "referenceId" : "RGD:A69976"
    }, {
      "firstName" : "HW",
      "lastName" : "Liu",
      "authorRank" : 8,
      "name" : "Liu HW",
      "referenceId" : "RGD:A66021"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1582700"
    } ]
  }, {
    "primaryId" : "PMID:10376119",
    "title" : "Functional PAX-6 gene-linked polymorphic region: potential association with paranoid schizophrenia.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Stober G, etal., Biol Psychiatry 1999 Jun 15;45(12):1585-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-15T16:50:59.000-05:00",
    "volume" : "45",
    "pages" : "1585-91",
    "abstract" : "BACKGROUND: Early differentiation of the nervous system and adult CNS neuroplasticity is modulated by PAX-6. We have shown previously that a highly polymorphic, functional AC/AG repeat in the 5' regulatory region of the gene showed significantly increased promoter activity, if containing > or = 29 repeats, and that the heterozygous genotype (< or = 28/> or = 29) revealed increased mRNA PAX-6 levels in human brain tissue compared to the homozygous short variant. METHODS: In a case-control study of 655 unrelated individuals, allele frequencies and genotype distributions of the functional PAX-6 promoter polymorphism were investigated comprising patients with DSM-IV schizophrenia, patients with affective disorders, and population controls. RESULTS: No allelic or genotypic association of the PAX-6 promoter polymorphism to affective disorder or to schizophrenia as one disease entity was observed. After subtyping schizophrenia into paranoid and nonparanoid forms, potential evidence was found for a genotypic association of the high-activity variant with the paranoid subtype of schizophrenia (p = .02). The estimated odds ratio was 1.7 (95% CI .98 to 2.95) for those heterozygous and 1.4 (95% CI .82 to 2.42) for those heterozygous or homozygous for the high-activity variant compared to the homozygous low-activity variant. CONCLUSIONS: Our finding indicates that early developmental genes may be involved in the etiopathogenesis of schizophrenia subtypes via variable transcriptional regulation in the developing and adult human brain.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Stober",
      "authorRank" : 1,
      "name" : "Stober G",
      "referenceId" : "RGD:A52839"
    }, {
      "firstName" : "YV",
      "lastName" : "Syagailo",
      "authorRank" : 2,
      "name" : "Syagailo YV",
      "referenceId" : "RGD:A53004"
    }, {
      "firstName" : "O",
      "lastName" : "Okladnova",
      "authorRank" : 3,
      "name" : "Okladnova O",
      "referenceId" : "RGD:A53005"
    }, {
      "firstName" : "G",
      "lastName" : "Jungkunz",
      "authorRank" : 4,
      "name" : "Jungkunz G",
      "referenceId" : "RGD:A53006"
    }, {
      "firstName" : "M",
      "lastName" : "Knapp",
      "authorRank" : 5,
      "name" : "Knapp M",
      "referenceId" : "RGD:A52840"
    }, {
      "firstName" : "H",
      "lastName" : "Beckmann",
      "authorRank" : 6,
      "name" : "Beckmann H",
      "referenceId" : "RGD:A52841"
    }, {
      "firstName" : "KP",
      "lastName" : "Lesch",
      "authorRank" : 7,
      "name" : "Lesch KP",
      "referenceId" : "RGD:A33883"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358554"
    } ]
  }, {
    "primaryId" : "PMID:10376215",
    "title" : "A comparative study of rat and human Tmp21 (p23) reveals the pseudogene-like features of human Tmp21-II.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Horer J, etal., DNA Seq 1999;10(2):121-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:54:44.000-06:00",
    "volume" : "10",
    "pages" : "121-6",
    "abstract" : "Tmp21 (p23) is involved in biosynthetic transport from the endoplasmic reticulum to the Golgi complex. We have recently characterized two cDNA-variants of human Tmp21, the Tmp21-isoforms-I and -II. Because of the lack of cDNA sequence data and protein expression data, it was not clear if Tmp21-II encodes a functional Tmp21-protein. Here we describe the cloning of the full length human Tmp21-II transcript. The putative open reading frame of Tmp21-II contains a reading frame jump and a nonsense mutation in comparison to all other Tmp21-I (p23) members. Our data indicate that hum-Tmp21-II is transcribed, but not translated. We conclude that Tmp21-II cDNA derives from a neutral pseudogene, which originates from a duplication event of the human Tmp21-isoform-I.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Horer",
      "authorRank" : 1,
      "name" : "Horer J",
      "referenceId" : "RGD:A27192"
    }, {
      "firstName" : "R",
      "lastName" : "Blum",
      "authorRank" : 2,
      "name" : "Blum R",
      "referenceId" : "RGD:A6095"
    }, {
      "firstName" : "P",
      "lastName" : "Feick",
      "authorRank" : 3,
      "name" : "Feick P",
      "referenceId" : "RGD:A6096"
    }, {
      "firstName" : "W",
      "lastName" : "Nastainczyk",
      "authorRank" : 4,
      "name" : "Nastainczyk W",
      "referenceId" : "RGD:A6100"
    }, {
      "firstName" : "I",
      "lastName" : "Schulz",
      "authorRank" : 5,
      "name" : "Schulz I",
      "referenceId" : "RGD:A6101"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727272"
    } ]
  }, {
    "primaryId" : "PMID:10376216",
    "title" : "Unique 5'-end of a Na(+)-K(+)-2Cl- cotransporter-like mRNA expressed in rat skeletal muscle.",
    "datePublished" : "2002-08-01T00:00:00.000-05:00",
    "citation" : "Fu L, etal., DNA Seq 1999;10(2):127-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:14:21.000-05:00",
    "volume" : "10",
    "pages" : "127-32",
    "abstract" : "Functional evidence presented by others indicates that rat slow-twitch skeletal muscle lacks typical Na(+)-K(+)-2Cl- cotransporter activity, as determined by loop diuretic-sensitive potassium transport. This report presents a unique 5' mRNA sequence of a Na(+)-K(+)-2Cl- cotransporter-like molecule expressed in the rat soleus muscle and the deduced N-terminus of the protein. In addition to its unique 5' mRNA sequence, the coding region of the N-terminus is quite short compared with other known Na(+)-K(+)-2Cl- cotransporters. Nonetheless, the mRNA possesses conserved cotransporter-like membrane spanning domains, though one domains corresponding to a reported exon is divergent. Therefore, it appears that skeletal muscle does express a Na(+)-K(+)-2Cl- cotransporter-like mRNA that may code for a protein with atypical Na(+)-K(+)-2Cl- cotransporter properties.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Fu",
      "authorRank" : 1,
      "name" : "Fu L",
      "referenceId" : "RGD:A23013"
    }, {
      "firstName" : "JA",
      "lastName" : "Wong",
      "authorRank" : 2,
      "name" : "Wong JA",
      "referenceId" : "RGD:A23014"
    }, {
      "firstName" : "EG",
      "lastName" : "Schneider",
      "authorRank" : 3,
      "name" : "Schneider EG",
      "referenceId" : "RGD:A23015"
    }, {
      "firstName" : "DB",
      "lastName" : "Thomason",
      "authorRank" : 4,
      "name" : "Thomason DB",
      "referenceId" : "RGD:A12563"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634062"
    } ]
  }, {
    "primaryId" : "PMID:10376574",
    "title" : "Carrier rates in the midwestern United States for GJB2 mutations causing inherited deafness.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Green GE, etal., JAMA. 1999 Jun 16;281(23):2211-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:40:05.000-05:00",
    "volume" : "281",
    "pages" : "2211-6",
    "abstract" : "CONTEXT: Mutations in the GJB2 gene are the most common known cause of inherited  congenital severe-to-profound deafness. The carrier frequency of these mutations  is not known. OBJECTIVES: To determine the carrier rate of deafness-causing mutations in GJB2 in the midwestern United States and the prevalence of these mutations in persons with congenital sensorineural hearing loss ranging in severity from moderate to profound, and to derive revised data for counseling purposes. DESIGN: Laboratory analysis, performed in 1998, of samples from probands with hearing loss for mutations in GJB2 using an allele-specific polymerase chain reaction assay, single-strand conformation polymorphism analysis, and direct sequencing. SETTING AND SUBJECTS: Fifty-two subjects younger than 19 years sequentially referred to a midwestern tertiary referral center for  hearing loss or cochlear implantation, with moderate-to-profound congenital hearing loss of unknown cause, parental nonconsanguinity, and nonsyndromic deafness with hearing loss limited to a single generation; 560 control neonates were screened for the 35delG mutation. MAIN OUTCOME MEASURE: Prevalence of mutations in the GJB2 gene by congenital deafness status. RESULTS: Of 52 sequential probands referred for congenital sensorineural hearing loss, 22 (42%)  were found to have GJB2 mutations. The 35delG mutation was identified in 29 of the 41 mutant alleles. Of probands' sibs, all homozygotes and compound heterozygotes had deafness. Fourteen of 560 controls were 35delG heterozygotes, for a carrier rate expressed as a mean (SE) of 2.5% (0.66%). The carrier rate for all recessive deafness-causing GJB2 mutations was determined to be 3.01% (probable range, 2.54%-3.56%). Calculated sensitivity and specificity for a screening test based on 35delG mutation alone were 96.9% and 97.4%, respectively, and observed values were 94% and 97%, respectively. CONCLUSIONS: Our data suggest that mutations in GJB2 are the leading cause of moderate-to-profound congenital inherited deafness in the midwestern United States. Screening of the GJB2 mutation can be offered to individuals with congenital deafness with high sensitivity and specificity by screening only for the 35delG mutation. A positive finding should establish an etiologic diagnosis and affect genetic counseling.",
    "issueName" : "23",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GE",
      "lastName" : "Green",
      "authorRank" : 1,
      "name" : "Green",
      "referenceId" : "RGD:A175771"
    }, {
      "firstName" : "DA",
      "lastName" : "Scott",
      "authorRank" : 2,
      "name" : "Scott",
      "referenceId" : "RGD:A232444"
    }, {
      "firstName" : "JM",
      "lastName" : "McDonald",
      "authorRank" : 3,
      "name" : "McDonald",
      "referenceId" : "RGD:A267923"
    }, {
      "firstName" : "GG",
      "lastName" : "Woodworth",
      "authorRank" : 4,
      "name" : "Woodworth",
      "referenceId" : "RGD:A273133"
    }, {
      "firstName" : "VC",
      "lastName" : "Sheffield",
      "authorRank" : 5,
      "name" : "Sheffield VC",
      "referenceId" : "RGD:A4262"
    }, {
      "firstName" : "RJ",
      "lastName" : "Smith",
      "authorRank" : 6,
      "name" : "Smith RJ",
      "referenceId" : "RGD:A4612"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069177"
    } ]
  }, {
    "primaryId" : "PMID:10376919",
    "title" : "Functional effects of mutations in KvLQT1 that cause long QT syndrome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wang Z, etal., J Cardiovasc Electrophysiol. 1999 Jun;10(6):817-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:44:25.000-05:00",
    "volume" : "10",
    "pages" : "817-26",
    "abstract" : "INTRODUCTION: The long QT syndrome (LQT) is caused by mutations in genes encoding ion channels that modulate the duration of ventricular action potentials. One of  these genes, KVLQT1, encodes an alpha subunit that coassembles with another subunit, hminK, to form the cardiac slow delayed rectifier (I(Ks)) K+ channel. METHODS AND RESULTS: The functional effects of seven mutations in KVLQT1 were assessed using two-microelectrode voltage clamp and the Xenopus oocyte expression system. Most mutations in KVLQT1 caused loss of function when expressed alone. Oocytes were also injected with equal amounts of wild-type (WT) KVLQT1 and mutant KVLQT1 cRNA (with or without coinjection of hminK) and the resulting currents compared to currents induced by WT KvLQT1 alone. A341V, R190Q, or G189R KVLQT1 subunits did not affect expression of WT KvLQT1. The other mutations in KVLQT1 caused a variable degree of dominant-negative suppression of I(Ks). The order of  potency for this effect was G345E > G306R = V254M > A341E. CONCLUSIONS: LQT1-associated mutations in KVLQT1 caused a spectrum of dysfunction in I(Ks) and KvLQT1 channels. The degree of I(Ks) dysfunction did not correlate with the QTc interval or the presence of symptoms in the respective gene carriers. In contrast to previous reports, we found that loss of function mutations are not exclusive to recessively inherited LQT.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang",
      "referenceId" : "RGD:A416946"
    }, {
      "firstName" : "M",
      "lastName" : "Tristani-Firouzi",
      "authorRank" : 2,
      "name" : "Tristani-Firouzi",
      "referenceId" : "RGD:A254108"
    }, {
      "firstName" : "Q",
      "lastName" : "Xu",
      "authorRank" : 3,
      "name" : "Xu",
      "referenceId" : "RGD:A416817"
    }, {
      "firstName" : "M",
      "lastName" : "Lin",
      "authorRank" : 4,
      "name" : "Lin M",
      "referenceId" : "RGD:A12788"
    }, {
      "firstName" : "MT",
      "lastName" : "Keating",
      "authorRank" : 5,
      "name" : "Keating MT",
      "referenceId" : "RGD:A18685"
    }, {
      "firstName" : "MC",
      "lastName" : "Sanguinetti",
      "authorRank" : 6,
      "name" : "Sanguinetti MC",
      "referenceId" : "RGD:A61429"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064785"
    } ]
  }, {
    "primaryId" : "PMID:10377006",
    "title" : "Increased occurrence of cleft lip in glycogen storage disease type II (GSDII): exclusion of a contiguous gene syndrome in two patients by presence of intragenic mutations including a novel nonsense mutation Gln58Stop.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Huie ML, etal., Am J Med Genet. 1999 Jul 2;85(1):5-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:43:54.000-05:00",
    "volume" : "85",
    "pages" : "5-8",
    "abstract" : "Genetic deficiency of lysosomal acid alpha-glucosidase (acid maltase) results in  the autosomal recessive disorder glycogen storage disease type II (GSDII) in which intralysosomal accumulation of glycogen primarily affects function of skeletal and cardiac muscle. During an earlier review we noted 3 in 100 cases of  GSDII with incidental description of cleft lip. In addition, we identified 2 of 35 GSDII patients referred to us for molecular studies with co-occurence of cleft lip, considerably greater than the estimated frequency of nonsyndromic cleft lip  with or without cleft palate of 1 in 700 to 1,000. Because several lines of evidence support a minor cleft lip/palate (Cl/P) locus on chromosome 17q close to the locus for GSDII, we defined the molecular basis for the GSDII in these two patients to determine if they represented a contiguous gene syndrome. Patient I (of Dutch descent) was homozygous and the parents heterozygous for an intragenic  deletion of exon 18 (deltaex18), common in Dutch patients. Patient II was heterozygous for delta525T, a mutation also common in Dutch patients and a novel  nonsense mutation (172 [corrected] C-->T; Gln58Stop) in exon 2, the first coding  exon. The mother was heterozygous for the delta525T and the father for the 172 [corrected] C-->T; Gln58Stop. The finding that both patients carried intragenic mutations eliminates a contiguous gene syndrome. Whereas the presence of cleft lip/cleft palate in a patient with GSDII could be coincidental, these co-occurences could represent a modifying action of acid alpha-glucosidase deficiency on unlinked or linked genes that result in increased susceptibility for cleft lip.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ML",
      "lastName" : "Huie",
      "authorRank" : 1,
      "name" : "Huie ML",
      "referenceId" : "RGD:A44037"
    }, {
      "firstName" : "JS",
      "lastName" : "Kasper",
      "authorRank" : 2,
      "name" : "Kasper JS",
      "referenceId" : "RGD:A44038"
    }, {
      "firstName" : "PH",
      "lastName" : "Arn",
      "authorRank" : 3,
      "name" : "Arn",
      "referenceId" : "RGD:A264949"
    }, {
      "firstName" : "CR",
      "lastName" : "Greenberg",
      "authorRank" : 4,
      "name" : "Greenberg CR",
      "referenceId" : "RGD:A39179"
    }, {
      "firstName" : "R",
      "lastName" : "Hirschhorn",
      "authorRank" : 5,
      "name" : "Hirschhorn R",
      "referenceId" : "RGD:A44036"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066446"
    } ]
  }, {
    "primaryId" : "PMID:10377013",
    "title" : "Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Bellus GA, etal., Am J Med Genet. 1999 Jul 2;85(1):53-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-07T13:49:40.000-06:00",
    "volume" : "85",
    "pages" : "53-65",
    "abstract" : "We previously discovered a novel missense mutation (Lys650Met) in the tyrosine kinase domain of the fibroblast growth factor receptor 3 (FGFR3) gene in four unrelated individuals with a condition we called \"severe achondroplasia with developmental delay and acanthosis nigricans\" (SADDAN) [Tavormina et al., 1999: Am. J. Hum. Genet. 64:722-731]. Here we present a more detailed clinical account  of the SADDAN phenotype. The FGFR3 Lys650Met mutation results in severe disturbances in endochondral bone growth that approach and overlap those observed in thanatophoric dysplasia, type I. However, this mutation is most often compatible with survival into adulthood. Other unusual bone deformities, such as  femoral bowing with reverse (i.e., posterior apex) tibial and fibular bowing and  \"ram's horn\" bowing of the clavicle, are also seen in some patients. In addition  to skeletal dysplasia, progressive acanthosis nigricans, and central nervous system structural anomalies, seizures and severe developmental delays are observed in surviving SADDAN patients. Despite its location within the same FGFR3 codon as the thanatophoric dysplasia type II mutation (Lys650Glu) and a similar effect on constitutive activation of the FGFR3 tyrosine kinase, the Lys650Met is  not associated with cloverleaf skull or craniosynostosis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GA",
      "lastName" : "Bellus",
      "authorRank" : 1,
      "name" : "Bellus",
      "referenceId" : "RGD:A267750"
    }, {
      "firstName" : "MJ",
      "lastName" : "Bamshad",
      "authorRank" : 2,
      "name" : "Bamshad MJ",
      "referenceId" : "RGD:A85609"
    }, {
      "firstName" : "KA",
      "lastName" : "Przylepa",
      "authorRank" : 3,
      "name" : "Przylepa",
      "referenceId" : "RGD:A414571"
    }, {
      "firstName" : "J",
      "lastName" : "Dorst",
      "authorRank" : 4,
      "name" : "Dorst",
      "referenceId" : "RGD:A414620"
    }, {
      "firstName" : "RR",
      "lastName" : "Lee",
      "authorRank" : 5,
      "name" : "Lee",
      "referenceId" : "RGD:A414621"
    }, {
      "firstName" : "O",
      "lastName" : "Hurko",
      "authorRank" : 6,
      "name" : "Hurko",
      "referenceId" : "RGD:A414622"
    }, {
      "firstName" : "EW",
      "lastName" : "Jabs",
      "authorRank" : 7,
      "name" : "Jabs EW",
      "referenceId" : "RGD:A15495"
    }, {
      "firstName" : "CJ",
      "lastName" : "Curry",
      "authorRank" : 8,
      "name" : "Curry",
      "referenceId" : "RGD:A227317"
    }, {
      "firstName" : "WR",
      "lastName" : "Wilcox",
      "authorRank" : 9,
      "name" : "Wilcox WR",
      "referenceId" : "RGD:A37391"
    }, {
      "firstName" : "RS",
      "lastName" : "Lachman",
      "authorRank" : 10,
      "name" : "Lachman RS",
      "referenceId" : "RGD:A37392"
    }, {
      "firstName" : "DL",
      "lastName" : "Rimoin",
      "authorRank" : 11,
      "name" : "Rimoin DL",
      "referenceId" : "RGD:A37393"
    }, {
      "firstName" : "CA",
      "lastName" : "Francomano",
      "authorRank" : 12,
      "name" : "Francomano CA",
      "referenceId" : "RGD:A39144"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568054"
    } ]
  }, {
    "primaryId" : "PMID:10377182",
    "title" : "Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Wilkinson RJ, etal., J Exp Med. 1999 Jun 21;189(12):1863-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-20T13:06:33.000-05:00",
    "volume" : "189",
    "pages" : "1863-74",
    "abstract" : "Several lines of evidence suggest that host genetic factors controlling the immune response influence infection by Mycobacterium tuberculosis. The proinflammatory cytokine interleukin (IL)-1beta and its antagonist, IL-1Ra (IL-1 receptor agonist), are strongly induced by M. tuberculosis and are encoded by polymorphic genes. The induction of both IL-1Ra mRNA and secreted protein by M. tuberculosis in IL-1Ra allele A2-positive (IL-1Ra A2(+)) healthy subjects was 1.9-fold higher than in IL-1Ra A2(-) subjects. The M. tuberculosis-induced expression of mRNA for IL-1beta was higher in subjects of the IL-1beta (+3953) A1(+) haplotype (P = 0.04). The molar ratio of IL-1Ra/IL-1beta induced by M. tuberculosis was markedly higher in IL-1Ra A2(+) individuals (P < 0.05), with minor overlap between the groups, reflecting linkage between the IL-1Ra A2 and IL-1beta (+3953) A2 alleles. In M. tuberculosis-stimulated peripheral blood mononuclear cells, the addition of IL-4 increased IL-1Ra secretion, whereas interferon gamma increased and IL-10 decreased IL-1beta production, indicative of a differential influence on the IL-1Ra/IL-1beta ratio by cytokines. In a study of 114 healthy purified protein derivative-reactive subjects and 89 patients with tuberculosis, the frequency of allelic variants at two positions (-511 and +3953) in the IL-1beta and IL-1Ra genes did not differ between the groups. However, the proinflammatory IL-1Ra A2(-)/IL-1beta (+3953) A1(+) haplotype was unevenly distributed, being more common in patients with tuberculous pleurisy (92%) in comparison with healthy M. tuberculosis-sensitized control subjects or patients with other disease forms (57%, P = 0.028 and 56%, P = 0. 024, respectively). Furthermore, the IL-1Ra A2(+) haplotype was associated with a reduced Mantoux response to purified protein derivative of M. tuberculosis: 60% of tuberculin-nonreactive patients were of this type. Thus, the polymorphism at the IL-1 locus influences the cytokine response and may be a determinant of delayed-type hypersensitivity and disease expression in human tuberculosis.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RJ",
      "lastName" : "Wilkinson",
      "authorRank" : 1,
      "name" : "Wilkinson RJ",
      "referenceId" : "RGD:A127665"
    }, {
      "firstName" : "P",
      "lastName" : "Patel",
      "authorRank" : 2,
      "name" : "Patel P",
      "referenceId" : "RGD:A127666"
    }, {
      "firstName" : "M",
      "lastName" : "Llewelyn",
      "authorRank" : 3,
      "name" : "Llewelyn M",
      "referenceId" : "RGD:A127667"
    }, {
      "firstName" : "CS",
      "lastName" : "Hirsch",
      "authorRank" : 4,
      "name" : "Hirsch CS",
      "referenceId" : "RGD:A127668"
    }, {
      "firstName" : "G",
      "lastName" : "Pasvol",
      "authorRank" : 5,
      "name" : "Pasvol G",
      "referenceId" : "RGD:A127669"
    }, {
      "firstName" : "G",
      "lastName" : "Snounou",
      "authorRank" : 6,
      "name" : "Snounou G",
      "referenceId" : "RGD:A127670"
    }, {
      "firstName" : "RN",
      "lastName" : "Davidson",
      "authorRank" : 7,
      "name" : "Davidson RN",
      "referenceId" : "RGD:A127671"
    }, {
      "firstName" : "Z",
      "lastName" : "Toossi",
      "authorRank" : 8,
      "name" : "Toossi Z",
      "referenceId" : "RGD:A127672"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4143226"
    } ]
  }, {
    "primaryId" : "PMID:10377218",
    "title" : "Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Strickland CL, etal., J Med Chem. 1999 Jun 17;42(12):2125-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:35:20.000-05:00",
    "volume" : "42",
    "pages" : "2125-35",
    "abstract" : "Crystallographic and thermodynamic studies of farnesyl protein transferase (FPT)  complexed with novel tricyclic inhibitors provide insights into the observed SAR  for this unique class of nonpeptidic FPT inhibitors. The crystallographic structures reveal a binding pattern conserved across the mono-, di-, and trihalogen series. In the complexes, the tricycle spans the FPT active site cavity and interacts with both protein atoms and the isoprenoid portion of bound  farnesyl diphosphate. An amide carbonyl, common to the tricyclic compounds described here, participates in a water-mediated hydrogen bond to the protein backbone. Ten high-resolution crystal structures of inhibitors complexed with FPT are reported. Included are crystallographic data for FPT complexed with SCH 66336, a compound currently undergoing clinical trials as an anticancer agent (SCH 66336, 4-[2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5, 6]cyclohepta[1, 2-b]pyridin-11-yl)-1-piperidinyl]-2-oxoethyl]-1-piperidinecarbo xamide ). Thermodynamic binding parameters show favorable enthalpies of complex formation and small net entropic contributions as observed for 4-[2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-11H-benzo[5, 6]cyclohepta[1, 2-b]pyridin-11-ylidene)-1-piperidinyl]-2-oxoethyl]pyridine N-oxide where DeltaH degrees bind = -12.5 kcal/mol and TDeltaS degrees bind = -1.5 kcal/mol.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CL",
      "lastName" : "Strickland",
      "authorRank" : 1,
      "name" : "Strickland",
      "referenceId" : "RGD:A184541"
    }, {
      "firstName" : "PC",
      "lastName" : "Weber",
      "authorRank" : 2,
      "name" : "Weber",
      "referenceId" : "RGD:A184542"
    }, {
      "firstName" : "WT",
      "lastName" : "Windsor",
      "authorRank" : 3,
      "name" : "Windsor",
      "referenceId" : "RGD:A184543"
    }, {
      "firstName" : "Z",
      "lastName" : "Wu",
      "authorRank" : 4,
      "name" : "Wu Z",
      "referenceId" : "RGD:A15127"
    }, {
      "firstName" : "HV",
      "lastName" : "Le",
      "authorRank" : 5,
      "name" : "Le HV",
      "referenceId" : "RGD:A37019"
    }, {
      "firstName" : "MM",
      "lastName" : "Albanese",
      "authorRank" : 6,
      "name" : "Albanese",
      "referenceId" : "RGD:A184544"
    }, {
      "firstName" : "CS",
      "lastName" : "Alvarez",
      "authorRank" : 7,
      "name" : "Alvarez",
      "referenceId" : "RGD:A184545"
    }, {
      "firstName" : "D",
      "lastName" : "Cesarz",
      "authorRank" : 8,
      "name" : "Cesarz",
      "referenceId" : "RGD:A184546"
    }, {
      "firstName" : "J",
      "lastName" : "Del Rosario",
      "authorRank" : 9,
      "name" : "Del Rosario",
      "referenceId" : "RGD:A184547"
    }, {
      "firstName" : "J",
      "lastName" : "Deskus",
      "authorRank" : 10,
      "name" : "Deskus",
      "referenceId" : "RGD:A184548"
    }, {
      "firstName" : "AK",
      "lastName" : "Mallams",
      "authorRank" : 11,
      "name" : "Mallams",
      "referenceId" : "RGD:A184549"
    }, {
      "firstName" : "FG",
      "lastName" : "Njoroge",
      "authorRank" : 12,
      "name" : "Njoroge",
      "referenceId" : "RGD:A184550"
    }, {
      "firstName" : "JJ",
      "lastName" : "Piwinski",
      "authorRank" : 13,
      "name" : "Piwinski",
      "referenceId" : "RGD:A184551"
    }, {
      "firstName" : "S",
      "lastName" : "Remiszewski",
      "authorRank" : 14,
      "name" : "Remiszewski",
      "referenceId" : "RGD:A184552"
    }, {
      "firstName" : "RR",
      "lastName" : "Rossman",
      "authorRank" : 15,
      "name" : "Rossman",
      "referenceId" : "RGD:A184553"
    }, {
      "firstName" : "AG",
      "lastName" : "Taveras",
      "authorRank" : 16,
      "name" : "Taveras",
      "referenceId" : "RGD:A184554"
    }, {
      "firstName" : "B",
      "lastName" : "Vibulbhan",
      "authorRank" : 17,
      "name" : "Vibulbhan",
      "referenceId" : "RGD:A184555"
    }, {
      "firstName" : "RJ",
      "lastName" : "Doll",
      "authorRank" : 18,
      "name" : "Doll",
      "referenceId" : "RGD:A184556"
    }, {
      "firstName" : "VM",
      "lastName" : "Girijavallabhan",
      "authorRank" : 19,
      "name" : "Girijavallabhan",
      "referenceId" : "RGD:A184557"
    }, {
      "firstName" : "AK",
      "lastName" : "Ganguly",
      "authorRank" : 20,
      "name" : "Ganguly",
      "referenceId" : "RGD:A184558"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553653"
    } ]
  }, {
    "primaryId" : "PMID:10377344",
    "title" : "The native rat olfactory cyclic nucleotide-gated channel is composed of three distinct subunits.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Bonigk W, etal., J Neurosci 1999 Jul 1;19(13):5332-47.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:30.000-05:00",
    "volume" : "19",
    "pages" : "5332-47",
    "abstract" : "Cyclic nucleotide-gated (CNG) channels play central roles in visual and olfactory signal transduction. In the retina, rod photoreceptors express the subunits CNCalpha1 and CNCbeta1a. In cone photoreceptors, only CNCalpha2 expression has been demonstrated so far. Rat olfactory sensory neurons (OSNs) express two homologous subunits, here designated CNCalpha3 and CNCalpha4. This paper describes the characterization of CNCbeta1b, a third subunit expressed in OSNs and establishes it as a component of the native channel. CNCbeta1b is an alternate splice form of the rod photoreceptor CNCbeta1a subunit. Analysis of mRNA and protein expression together suggest co-expression of all three subunits in sensory cilia of OSNs. From single-channel analyses of native rat olfactory channels and of channels expressed heterologously from all possible combinations of the CNCalpha3, -alpha4, and -beta1b subunits, we conclude that the native CNG channel in OSNs is composed of all three subunits. Thus, CNG channels in both rod photoreceptors and olfactory sensory neurons result from coassembly of specific alpha subunits with various forms of an alternatively spliced beta subunit.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Bonigk",
      "authorRank" : 1,
      "name" : "Bonigk W",
      "referenceId" : "RGD:A17157"
    }, {
      "firstName" : "J",
      "lastName" : "Bradley",
      "authorRank" : 2,
      "name" : "Bradley J",
      "referenceId" : "RGD:A17103"
    }, {
      "firstName" : "F",
      "lastName" : "Muller",
      "authorRank" : 3,
      "name" : "Muller F",
      "referenceId" : "RGD:A9848"
    }, {
      "firstName" : "F",
      "lastName" : "Sesti",
      "authorRank" : 4,
      "name" : "Sesti F",
      "referenceId" : "RGD:A17158"
    }, {
      "firstName" : "I",
      "lastName" : "Boekhoff",
      "authorRank" : 5,
      "name" : "Boekhoff I",
      "referenceId" : "RGD:A17159"
    }, {
      "firstName" : "GV",
      "lastName" : "Ronnett",
      "authorRank" : 6,
      "name" : "Ronnett GV",
      "referenceId" : "RGD:A17106"
    }, {
      "firstName" : "UB",
      "lastName" : "Kaupp",
      "authorRank" : 7,
      "name" : "Kaupp UB",
      "referenceId" : "RGD:A9847"
    }, {
      "firstName" : "S",
      "lastName" : "Frings",
      "authorRank" : 8,
      "name" : "Frings S",
      "referenceId" : "RGD:A17160"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632392"
    } ]
  }, {
    "primaryId" : "PMID:10378403",
    "title" : "Congenital alveolar proteinosis caused by a novel mutation of the surfactant protein B gene and misalignment of lung vessels in consanguineous kindred infants.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Wallot M, etal., Eur J Pediatr. 1999 Jun;158(6):513-8. doi: 10.1007/s004310051132.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-04-11T16:00:54.000-05:00",
    "volume" : "158",
    "pages" : "513-8",
    "abstract" : "<br><b>UNLABELLED: </b>Congenital alveolar proteinosis and misalignment of lung vessels are rare disorders. We report on five infants of consanguineous kindred. All infants were delivered at term after uneventful pregnancies. Shortly after birth they developed respiratory failure and severe persistent pulmonary hypertension. All died despite intensive care. Lung tissue of two infants was studied. Histological examination revealed combination of alveolar proteinosis and misalignment of lung vessels in one patient, alveolar proteinosis in the other. Immunostaining demonstrated surfactant protein B (SP-B) deficiency in both patients' lungs. In a further sibling, analysis of broncho-alveolar lavage fluid showed decreased surfactant protein. PCR and direct sequence analysis of the SP-B gene revealed three novel mutations. One of them, a single base deletion, shifts the reading frame at amino acid 122 and creates a premature termination of translation in exon 6. No mature SP-B protein is produced.<br><b>CONCLUSION: </b>Surfactant protein B deficiency caused by mutations of the respective gene and misalignment of lung vessels can concur. Both diseases may have a pathogenetic factor in common.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Wallot",
      "authorRank" : 1,
      "name" : "Wallot M",
      "referenceId" : "RGD:A514396"
    }, {
      "firstName" : "C",
      "lastName" : "Wagenvoort",
      "authorRank" : 2,
      "name" : "Wagenvoort C",
      "referenceId" : "RGD:A514397"
    }, {
      "firstName" : "D",
      "lastName" : "deMello",
      "authorRank" : 3,
      "name" : "deMello D",
      "referenceId" : "RGD:A514398"
    }, {
      "firstName" : "K M",
      "lastName" : "Müller",
      "authorRank" : 4,
      "name" : "Müller KM",
      "referenceId" : "RGD:A514399"
    }, {
      "firstName" : "J",
      "lastName" : "Floros",
      "authorRank" : 5,
      "name" : "Floros J",
      "referenceId" : "RGD:A128342"
    }, {
      "firstName" : "C",
      "lastName" : "Roll",
      "authorRank" : 6,
      "name" : "Roll C",
      "referenceId" : "RGD:A514400"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:151667447"
    } ]
  }, {
    "primaryId" : "PMID:10378475",
    "title" : "Impairment of TNF-alpha expression and secretion in primary rat liver cell cultures by acetaminophen treatment.",
    "datePublished" : "1999-04-15T00:00:00.000-05:00",
    "citation" : "Nastevska C, etal., Toxicology. 1999 Apr 15;133(2-3):85-92. doi: 10.1016/s0300-483x(99)00007-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-10-16T13:07:52.000-05:00",
    "volume" : "133",
    "pages" : "85-92",
    "abstract" : "Tumor necrosis factor-alpha (TNF-alpha) is assumed to act as a mediator in toxic liver injury, aggravating the primary damage to the parenchymal liver cell, but also stimulating liver regeneration. Reports on the effect of acetaminophen in vivo on TNF-alpha transcript concentrations and serum TNF-alpha concentrations, under different experimental, or clinical conditions have yielded controversial results. We used primary rat hepatocyte and Kupffer cell cultures to test the direct action of subtoxic and toxic concentrations of acetaminophen on TNF-alpha expression and release. We observed a dose-dependent decrease of TNF-alpha mRNA in the hepatocytes, and of TNF-alpha release into the medium of hepatocyte cultures. The data also indicate an impairment of TNF-alpha release in Kupffer cell cultures after treatment with nontoxic, as well as with toxic, acetaminophen concentrations. The results suggest that inhibition of TNF-alpha expression and release in the liver is a consequence of acetaminophen exposure. It is at present unknown how this effect modulates the course of acetaminophen intoxication.",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Nastevska",
      "authorRank" : 1,
      "name" : "Nastevska C",
      "referenceId" : "RGD:A475490"
    }, {
      "firstName" : "E",
      "lastName" : "Gerber",
      "authorRank" : 2,
      "name" : "Gerber E",
      "referenceId" : "RGD:A475491"
    }, {
      "firstName" : "M",
      "lastName" : "Horbach",
      "authorRank" : 3,
      "name" : "Horbach M",
      "referenceId" : "RGD:A475492"
    }, {
      "firstName" : "E",
      "lastName" : "Röhrdanz",
      "authorRank" : 4,
      "name" : "Röhrdanz E",
      "referenceId" : "RGD:A475493"
    }, {
      "firstName" : "R",
      "lastName" : "Kahl",
      "authorRank" : 5,
      "name" : "Kahl R",
      "referenceId" : "RGD:A475494"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14994702"
    } ]
  }, {
    "primaryId" : "PMID:10379914",
    "title" : "Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Cornea-Hebert V, etal., J Comp Neurol. 1999 Jun 28;409(2):187-209.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-05-10T16:50:13.000-05:00",
    "volume" : "409",
    "pages" : "187-209",
    "abstract" : "Light and electron microscope immunocytochemistry with a monoclonal antibody against the N-terminal domain of the human protein was used to determine the cellular and subcellular localization of serotonin 5-HT2A receptors in the central nervous system of adult rat. Following immunoperoxidase or silver-intensified immunogold labeling, neuronal, somatodendritic, and/or axonal immunoreactivity was detected in numerous brain regions, including all those in which ligand binding sites and 5-HT2A mRNA had previously been reported. The distribution of 5-HT2A-immunolabeled soma/dendrites was characterized in cerebral cortex, olfactory system, septum, hippocampal formation, basal ganglia, amygdala, diencephalon, cerebellum, brainstem, and spinal cord. Labeled axons were visible in every myelinated tract known to arise from immunoreactive cell body groups. In immunopositive soma/dendrites as well as axons, the 5-HT2A receptor appeared mainly cytoplasmic rather than membrane bound. Even though the dendritic labeling was generally stronger than the somatic, it did not extend to dendritic spines in such regions as the cerebral and piriform cortex, the neostriatum, or the molecular layer of the cerebellum. Similarly, there were no labeled axon terminals in numerous regions known to be strongly innervated by the immunoreactive somata and their axons (e.g., molecular layer of piriform cortex). It was concluded that the 5-HT2A receptor is mostly intracellular and transported in dendrites and axons, but does not reach into dendritic spines or axon terminals. Because it has previously been shown that this serotonin receptor is transported retrogradely as well as anterogradely, activates intracellular transduction pathways and intervenes in the regulation of the expression of many genes, it is suggested that one of its main functions is to participate in retrograde signaling systems activated by serotonin.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Cornea-Hebert",
      "authorRank" : 1,
      "name" : "Cornea-Hebert V",
      "referenceId" : "RGD:A82693"
    }, {
      "firstName" : "M",
      "lastName" : "Riad",
      "authorRank" : 2,
      "name" : "Riad M",
      "referenceId" : "RGD:A82694"
    }, {
      "firstName" : "C",
      "lastName" : "Wu",
      "authorRank" : 3,
      "name" : "Wu C",
      "referenceId" : "RGD:A44065"
    }, {
      "firstName" : "SK",
      "lastName" : "Singh",
      "authorRank" : 4,
      "name" : "Singh SK",
      "referenceId" : "RGD:A82695"
    }, {
      "firstName" : "L",
      "lastName" : "Descarries",
      "authorRank" : 5,
      "name" : "Descarries L",
      "referenceId" : "RGD:A82696"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1624400"
    } ]
  }, {
    "primaryId" : "PMID:10380012",
    "title" : "cDNA sequence analysis of monoclonal antibody FU-MK-1 specific for a transmembrane carcinoma-associated antigen, and construction of a mouse/human chimeric antibody.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Arakawa F, etal., Hybridoma. 1999 Apr;18(2):131-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:35:33.000-05:00",
    "volume" : "18",
    "pages" : "131-8",
    "abstract" : "Mouse monoclonal antibody (MAb) FU-MK-1, raised against a human gastric adenocarcinoma, recognizes a transmembrane antigen, GA733-2, present on most adenocarcinomas and seems to be of potential utility for immunodiagnosis and immunotherapy of those cancers. However, an inherent problem in their in vivo application is the human anti-mouse antibody response. In this study, we cloned and sequenced the variable region genes of the heavy and light chains (V(H) and Vkappa) of FU-MK-1 using the reverse transcription-polymerase chain reaction method. Then, we constructed a mouse/human chimeric antibody, designated as Ch FU-MK-1, by fusing the FU-MK-1 V(H) and Vkappa genes to the human Cgamma1 and Ckappa genes, respectively, and by ligating the chimeric H and L chain genes to each other in a mammalian cell expression vector. The final gene construct was transfected into mouse non-Ig-producing hybridoma cells by electroporation. The Ch FU-MK-1 antibody thus prepared bound to human adenocarcinoma cells and competitively inhibited the binding of the parental FU-MK-1 to the adenocarcinoma cells. Ch FU-MK-1 also showed a potent antibody-dependent cell-mediated cytotoxicity (ADCC) with human peripheral blood mononuclear cells as effectors against the adenocarcinoma cells, indicating that this chimeric antibody seems to be suitable for in vivo therapeutic approaches.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Arakawa",
      "authorRank" : 1,
      "name" : "Arakawa",
      "referenceId" : "RGD:A242026"
    }, {
      "firstName" : "T",
      "lastName" : "Yamamoto",
      "authorRank" : 2,
      "name" : "Yamamoto",
      "referenceId" : "RGD:A414894"
    }, {
      "firstName" : "H",
      "lastName" : "Kanda",
      "authorRank" : 3,
      "name" : "Kanda H",
      "referenceId" : "RGD:A46070"
    }, {
      "firstName" : "T",
      "lastName" : "Watanabe",
      "authorRank" : 4,
      "name" : "Watanabe",
      "referenceId" : "RGD:A411303"
    }, {
      "firstName" : "M",
      "lastName" : "Kuroki",
      "authorRank" : 5,
      "name" : "Kuroki M",
      "referenceId" : "RGD:A13849"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340616"
    } ]
  }, {
    "primaryId" : "PMID:10380019",
    "title" : "Construction and characterization of a chimeric fusion protein consisting of an anti-idiotype antibody mimicking a breast cancer-associated antigen and the cytokine GM-CSF.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Tripathi PK, etal., Hybridoma. 1999 Apr;18(2):193-202.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T20:05:24.000-05:00",
    "volume" : "18",
    "pages" : "193-202",
    "abstract" : "Anti-idiotype antibody, 11D10 mimics biologically and antigenically a distinct and specific epitope of the high molecular weight human milk fat globule (HMFG),  a cancer-associated antigen present in over 90% of breast tumor samples. To augment the immunogenicity of 11D10 without the aid of a carrier protein or adjuvant, we made a chimeric 11D10-GM-CSF fusion protein for use as a vaccine. An expression plasmid for 11D10 was made by ligation of the DNA sequences of the 11D10 light-chain variable region upstream of the human kappa constant region. The heavy-chain plasmid carrying GM-CSF was made by ligation of the heavy-chain variable region sequences upstream of the human gamma1 constant region CH1 fused  to the DNA fragment encoding the mature GM-CSF peptide 3' to the CH3 exon. NS1 plasmacytoma cells were transfected with the light and heavy-chain vectors by electroporation. Fusion protein secreted in the culture medium was purified and was characterized by gel electrophoresis as well as by determination of the biological activity of the fused GM-CSF. In nonreducing SDS-polyacrylamide gels,  a single band approximately 200 Kd reacted with anti-human kappa, anti-human lambda1 and anti-GM-CSF antibodies. In reducing polyacrylamide gels, a approximately 74 kd protein reacted with anti-human lambda1 and anti-GM-CSF antibodies. The fusion protein induced proliferation of GM-CSF dependent NFS-60 cells. These results suggest that the protein is a chimeric anti-idiotype antibody consisting of 11D10 variable domains, human kappa and lambda1 constant domains and that the GM-CSF moiety fused to the constant region lambda1 is biologically active.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PK",
      "lastName" : "Tripathi",
      "authorRank" : 1,
      "name" : "Tripathi",
      "referenceId" : "RGD:A333569"
    }, {
      "firstName" : "H",
      "lastName" : "Qin",
      "authorRank" : 2,
      "name" : "Qin H",
      "referenceId" : "RGD:A116121"
    }, {
      "firstName" : "M",
      "lastName" : "Bhattacharya-Chatterjee",
      "authorRank" : 3,
      "name" : "Bhattacharya-Chatterjee",
      "referenceId" : "RGD:A333570"
    }, {
      "firstName" : "RL",
      "lastName" : "Ceriani",
      "authorRank" : 4,
      "name" : "Ceriani",
      "referenceId" : "RGD:A333571"
    }, {
      "firstName" : "KA",
      "lastName" : "Foon",
      "authorRank" : 5,
      "name" : "Foon",
      "referenceId" : "RGD:A333572"
    }, {
      "firstName" : "SK",
      "lastName" : "Chatterjee",
      "authorRank" : 6,
      "name" : "Chatterjee",
      "referenceId" : "RGD:A333573"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11341444"
    } ]
  }, {
    "primaryId" : "PMID:10380116",
    "title" : "3-Thia fatty acid treatment, in contrast to eicosapentaenoic acid and starvation, induces gene expression of carnitine palmitoyltransferase-II in rat liver.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Madsen L and Berge RK, Lipids. 1999 May;34(5):447-56. doi: 10.1007/s11745-999-0384-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-03-25T14:10:55.000-05:00",
    "volume" : "34",
    "pages" : "447-56",
    "abstract" : "The aim of the present study was to investigate the hepatic regulation and beta-oxidation of long-chain fatty acids in peroxisomes and mitochondria, after 3-thia- tetradecylthioacetic acid (C14-S-acetic acid) treatment. When palmitoyl-CoA and palmitoyl-L-carnitine were used as substrates, hepatic formation of acid-soluble products was significantly increased in C14-S-acetic acid treated rats. Administration of C14-S-acetic acid resulted in increased enzyme activity and mRNA levels of hepatic mitochondrial carnitine palmitoyltransferase (CPT)-II. CPT-II activity correlated with both palmitoyl-CoA and palmitoyl-L-carnitine oxidation in rats treated with different chain-length 3-thia fatty acids. CPT-I activity and mRNA levels were, however, marginally affected. The hepatic CPT-II activity was mainly localized in the mitochondrial fraction, whereas the CPT-I activity was enriched in the mitochondrial, peroxisomal, and microsomal fractions. In C14-S-acetic acid-treated rats, the specific activity of peroxisomal and microsomal CPT-I increased, whereas the mitochondrial activity tended to decrease. C14-S-Acetyl-CoA inhibited CPT-I activity in vitro. The sensitivity of CPT-I to malonyl-CoA was unchanged, and the hepatic malonyl-CoA concentration increased after C14-S-acetic acid treatment. The mRNA levels of acetyl-CoA carboxylase increased. In hepatocytes cultured from palmitic acid- and C14-S-acetic acid-treated rats, the CPT-I inhibitor etomoxir inhibited the formation of acid-soluble products 91 and 21%, respectively. In contrast to 3-thia fatty acid treatment, eicosapentaenoic acid treatment and starvation increased the mitochondrial CPT-I activity and reduced its malonyl-CoA sensitivity. Palmitoyl-L-carnitine oxidation and CPT-II activity were, however, unchanged after either EPA treatment or starvation. The results from this study open the possibility that the rate control of mitochondrial beta-oxidation under mitochondrion and peroxisome proliferation is distributed between an enzyme or enzymes of the pathway beyond the CPT-I site after 3-thia fatty acid treatment. It is suggested that fatty acids are partly oxidized in the peroxisomes before entering the mitochondria as acylcarnitines for further oxidation.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Madsen",
      "authorRank" : 1,
      "name" : "Madsen L",
      "referenceId" : "RGD:A125328"
    }, {
      "firstName" : "R K",
      "lastName" : "Berge",
      "authorRank" : 2,
      "name" : "Berge RK",
      "referenceId" : "RGD:A477050"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:21410186"
    } ]
  }, {
    "primaryId" : "PMID:10380882",
    "title" : "MBP1: a novel mutant p53-specific protein partner with oncogenic properties.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Gallagher WM, etal., Oncogene 1999 Jun 17;18(24):3608-16.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-06T11:15:56.000-05:00",
    "volume" : "18",
    "pages" : "3608-16",
    "abstract" : "Using a yeast two-hybrid screening strategy with a common tumour-derived p53 mutant as bait, we identified several mutant p53-interacting partners including the known proteins wild-type (wt) p53, hUBC9 and GBP/PIAS1. In addition, a novel protein partner was identified which we have termed MBP1, for Mutant p53-Binding Protein 1. MBP1 is a new member of the emerging fibulin gene family, which currently comprises fibulin-1, fibulin-2 and S1-5. Expression of MBP1 mRNA is differentially regulated both temporally during development of the mouse embryo and in a tissue-specific manner within the adult. Specific interaction between MBP1 and mutant p53 was illustrated by both two-hybrid analysis in yeast and co-immunoprecipitation in mammalian cells. MBP1 displayed the following order of binding specificity towards different p53 forms: H175 > G281 > H273 > or = W248>wt p53. Thus, MBP1 appears to bind preferentially to p53 mutants of the 'structural' rather than 'contact' class, reflecting a potential bias towards those mutants having a significant alteration in conformation from that assumed by wt p53. We propose that MBP1 is the product of a candidate oncogene as rates of both neoplastic transformation and tumour cell growth were shown to be significantly enhanced when the protein is ectopically overexpressed. Furthermore, MBP1 may play a role in determining if a 'gain of function' effect is seen with certain p53 mutants.",
    "issueName" : "24",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WM",
      "lastName" : "Gallagher",
      "authorRank" : 1,
      "name" : "Gallagher WM",
      "referenceId" : "RGD:A55695"
    }, {
      "firstName" : "M",
      "lastName" : "Argentini",
      "authorRank" : 2,
      "name" : "Argentini M",
      "referenceId" : "RGD:A55696"
    }, {
      "firstName" : "V",
      "lastName" : "Sierra",
      "authorRank" : 3,
      "name" : "Sierra V",
      "referenceId" : "RGD:A55697"
    }, {
      "firstName" : "L",
      "lastName" : "Bracco",
      "authorRank" : 4,
      "name" : "Bracco L",
      "referenceId" : "RGD:A55698"
    }, {
      "firstName" : "L",
      "lastName" : "Debussche",
      "authorRank" : 5,
      "name" : "Debussche L",
      "referenceId" : "RGD:A55699"
    }, {
      "firstName" : "E",
      "lastName" : "Conseiller",
      "authorRank" : 6,
      "name" : "Conseiller E",
      "referenceId" : "RGD:A55700"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549640"
    } ]
  }, {
    "primaryId" : "PMID:10380922",
    "title" : "Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Trommsdorff M, etal., Cell. 1999 Jun 11;97(6):689-701.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-01-27T10:52:35.000-06:00",
    "volume" : "97",
    "pages" : "689-701",
    "abstract" : "Layering of neurons in the cerebral cortex and cerebellum requires Reelin, an extracellular matrix protein, and mammalian Disabled (mDab1), a cytosolic protein that activates tyrosine kinases. Here, we report the requirement for two other proteins, cell surface receptors termed very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). Both receptors can bind mDab1 on their cytoplasmic tails and are expressed in cortical and cerebellar layers adjacent to layers that express Reelin. mDab1 expression is upregulated in knockout mice that lack both VLDLR and ApoER2. Inversion of cortical layers and absence of cerebellar foliation in these animals precisely mimic the phenotype of mice lacking Reelin or mDab1. These findings suggest that VLDLR and ApoER2 participate in transmitting the extracellular Reelin signal to intracellular signaling processes initiated by mDab1.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Trommsdorff",
      "authorRank" : 1,
      "name" : "Trommsdorff M",
      "referenceId" : "RGD:A58103"
    }, {
      "firstName" : "M",
      "lastName" : "Gotthardt",
      "authorRank" : 2,
      "name" : "Gotthardt M",
      "referenceId" : "RGD:A51083"
    }, {
      "firstName" : "T",
      "lastName" : "Hiesberger",
      "authorRank" : 3,
      "name" : "Hiesberger T",
      "referenceId" : "RGD:A26187"
    }, {
      "firstName" : "J",
      "lastName" : "Shelton",
      "authorRank" : 4,
      "name" : "Shelton J",
      "referenceId" : "RGD:A58104"
    }, {
      "firstName" : "W",
      "lastName" : "Stockinger",
      "authorRank" : 5,
      "name" : "Stockinger W",
      "referenceId" : "RGD:A58105"
    }, {
      "firstName" : "J",
      "lastName" : "Nimpf",
      "authorRank" : 6,
      "name" : "Nimpf J",
      "referenceId" : "RGD:A58106"
    }, {
      "firstName" : "RE",
      "lastName" : "Hammer",
      "authorRank" : 7,
      "name" : "Hammer RE",
      "referenceId" : "RGD:A14042"
    }, {
      "firstName" : "JA",
      "lastName" : "Richardson",
      "authorRank" : 8,
      "name" : "Richardson JA",
      "referenceId" : "RGD:A14041"
    }, {
      "firstName" : "J",
      "lastName" : "Herz",
      "authorRank" : 9,
      "name" : "Herz J",
      "referenceId" : "RGD:A33909"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1559371"
    } ]
  }, {
    "primaryId" : "PMID:10380929",
    "title" : "A striking organization of a large family of human neural cadherin-like cell adhesion genes.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wu Q and Maniatis T, Cell. 1999 Jun 11;97(6):779-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T13:55:50.000-05:00",
    "volume" : "97",
    "pages" : "779-90",
    "abstract" : "We have identified 52 novel human cadherin-like genes organized into three closely linked clusters. Comparison of the genomic DNA sequences with those of representative cDNAs reveals a striking genomic organization similar to that of immunoglobulin and T cell receptor gene clusters. The N-terminal extracellular and transmembrane domains of each cadherin protein are encoded by a distinct and  unusually large exon. These exons are organized in a tandem array. By contrast, the C-terminal cytoplasmic domain of each protein is identical and is encoded by  three small exons located downstream from the cluster of N-terminal exons. This unusual organization has interesting implications regarding the molecular code required to establish complex networks of neuronal connections in the brain and the mechanisms of cell-specific cadherin-like gene expression.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Wu",
      "authorRank" : 1,
      "name" : "Wu Q",
      "referenceId" : "RGD:A46188"
    }, {
      "firstName" : "T",
      "lastName" : "Maniatis",
      "authorRank" : 2,
      "name" : "Maniatis",
      "referenceId" : "RGD:A216416"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11054619"
    } ]
  }, {
    "primaryId" : "PMID:10380986",
    "title" : "Association of the androgen receptor gene (AR) with ADHD and conduct disorder.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Comings DE, etal., Neuroreport. 1999 May 14;10(7):1589-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-10-30T10:31:46.000-05:00",
    "volume" : "10",
    "pages" : "1589-92",
    "abstract" : "The male predominance of externalizing behaviors suggests that the X-linked androgen gene might be involved. Since the shorter alleles of the CAG and GGC polymorphisms of the AR gene are associated with increased gene expression we sought to determine whether they were also associated with externalizing behaviors. We examined 302 subjects consisting of Tourette syndrome probands and  controls. ANOVA showed a significant association between the AR haplotypes and ADHD (p < 0.0001), conduct disorder (CD; p < 0.017), and oppositional defiant disorder (ODD; p < 0.004) with the lowest scores in those with the longer alleles at both polymorphisms. These results suggest that genetic variation at the human  AR gene plays a role in human externalizing disorders.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DE",
      "lastName" : "Comings",
      "authorRank" : 1,
      "name" : "Comings DE",
      "referenceId" : "RGD:A52202"
    }, {
      "firstName" : "C",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen C",
      "referenceId" : "RGD:A161909"
    }, {
      "firstName" : "S",
      "lastName" : "Wu",
      "authorRank" : 3,
      "name" : "Wu S",
      "referenceId" : "RGD:A5677"
    }, {
      "firstName" : "D",
      "lastName" : "Muhleman",
      "authorRank" : 4,
      "name" : "Muhleman D",
      "referenceId" : "RGD:A52525"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6907129"
    } ]
  }, {
    "primaryId" : "PMID:10381141",
    "title" : "Inhibition by retinoids of benzo(A)pyrene metabolism catalyzed by 3-methylcholanthrene-induced rat cytochrome P-450 1A1.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Huang DY, etal., Metabolism. 1999 Jun;48(6):689-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-04-30T09:44:30.000-05:00",
    "volume" : "48",
    "pages" : "689-92",
    "abstract" : "Benzo(a)pyrene, a well-known procarcinogen, is believed to be activated by microsomal cytochrome P-450 1A1 (CYP 1A1). We recently reported that rat CYP 1A1 induced by 3-methylcholanthrene (3-MC) catalyzed the conversion of retinal to retinoic acid. In this study, we investigated retinoid inhibition of the metabolism of benzo(a)pyrene and 7-ethoxyresorufin, another specific substrate of CYP 1A1, using liver microsomes prepared from control and 3-MC-pretreated rats as the enzyme source. In 3-MC-treated rats, retinal and retinol, but not retinoic acid, inhibited benzo(a)pyrene metabolism. The 50% inhibitory concentration (IC50) of retinal was about 11.5 micromol/L and the inhibition was competitive, with a Ki value of 5.8 micromol/L. Retinol is a more potent inhibitor than retinal. The IC50 was about 5 micromol/L and the inhibition was mixed, with a Ki value of 19.2 micromol/L and a Ki' value of 4.2 micromol/L. Almost the same results were obtained for the reaction of 7-ethoxyresorufin deethylation. In contrast, the metabolic activity of both benzo(a)pyrene and 7-ethoxyresorufin was much lower in untreated versus 3-MC-treated rats, and only weak inhibition by the retinoids was observed. The results suggest that retinoids inhibit the activation of benzo(a)pyrene and that the substrate specificity of cytochrome P-450 isozymes associated with retinoid metabolism should be taken into account when studying the anticarcinogenic action of retinoids.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DY",
      "lastName" : "Huang",
      "authorRank" : 1,
      "name" : "Huang DY",
      "referenceId" : "RGD:A85441"
    }, {
      "firstName" : "T",
      "lastName" : "Ohnishi",
      "authorRank" : 2,
      "name" : "Ohnishi T",
      "referenceId" : "RGD:A27748"
    }, {
      "firstName" : "H",
      "lastName" : "Jiang",
      "authorRank" : 3,
      "name" : "Jiang H",
      "referenceId" : "RGD:A4102"
    }, {
      "firstName" : "A",
      "lastName" : "Furukawa",
      "authorRank" : 4,
      "name" : "Furukawa A",
      "referenceId" : "RGD:A41943"
    }, {
      "firstName" : "Y",
      "lastName" : "Ichikawa",
      "authorRank" : 5,
      "name" : "Ichikawa Y",
      "referenceId" : "RGD:A41945"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306682"
    } ]
  }, {
    "primaryId" : "PMID:10381153",
    "title" : "Elevated atrial natriuretic peptides and early renal failure in type 2 diabetic Goto-Kakizaki rats.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Vesely DL, etal., Metabolism. 1999 Jun;48(6):771-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-10-02T15:37:46.000-05:00",
    "volume" : "48",
    "pages" : "771-8",
    "abstract" : "The present investigation was designed to determine if atrial natriuretic peptides (ANPs) are increased in a spontaneous model of non-obese type 2 diabetes, the Goto-Kakizaki (GK) rat. Four peptide hormones originating from the ANP prohormone were increased twofold (P < .05) to sixfold (P < .01) in the circulation of GK rats compared with nondiabetic Wistar rats from which the GK colony was originally derived. Thus, ANP, long-acting natriuretic peptide (LANP), vessel dilator, and kaliuretic peptide were (mean +/- SE) 497 +/- 78, 1,285 +/- 105, 457 +/- 45, and 385 +/- 87 pg/mL in GK rats, versus 78 +/- 23, 542 +/- 77, 137 +/- 26, and 134 +/- 33 pg/mL, respectively, in Wistar rats. In evaluating the cause of the increased ANPs, the blood volume of GK rats (16.2 +/- 0.4 mL) was significantly (P < .01) increased compared with Wistar rats (9.5 +/- 0.3 mL). The ventricles of GK rats were not dilated when examined by transthoracic echocardiography, but the venous system was markedly distended. GK rats had a 48% to 79% decrease in renal function (ie, increased serum creatinine and blood urea nitrogen [BUN]) compared with Wistar rats. These results indicate that circulating ANPs are increased in the GK spontaneously diabetic rat secondary to (1) increased blood volume, which leads to increased synthesis and release of ANPs, and (2) renal failure, which results in a delayed metabolic processing of these peptides. The early combined increases of the four atrial peptides collectively may contribute to the hyperfiltration that occurs in early diabetes mellitus.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DL",
      "lastName" : "Vesely",
      "authorRank" : 1,
      "name" : "Vesely DL",
      "referenceId" : "RGD:A59647"
    }, {
      "firstName" : "JR",
      "lastName" : "Gower WR",
      "authorRank" : 2,
      "name" : "Gower WR JR",
      "referenceId" : "RGD:A59642"
    }, {
      "firstName" : "JR",
      "lastName" : "Dietz",
      "authorRank" : 3,
      "name" : "Dietz JR",
      "referenceId" : "RGD:A113062"
    }, {
      "firstName" : "RM",
      "lastName" : "Overton",
      "authorRank" : 4,
      "name" : "Overton RM",
      "referenceId" : "RGD:A113063"
    }, {
      "firstName" : "LC",
      "lastName" : "Clark",
      "authorRank" : 5,
      "name" : "Clark LC",
      "referenceId" : "RGD:A113064"
    }, {
      "firstName" : "EK",
      "lastName" : "Antwi",
      "authorRank" : 6,
      "name" : "Antwi EK",
      "referenceId" : "RGD:A113065"
    }, {
      "firstName" : "RV",
      "lastName" : "Farese",
      "authorRank" : 7,
      "name" : "Farese RV",
      "referenceId" : "RGD:A59646"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313592"
    } ]
  }, {
    "primaryId" : "PMID:10381256",
    "title" : "Cutaneous rat wounds express c49a, a novel gene with homology to the human melanoma differentiation associated gene, mda-7.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Soo C, etal., J Cell Biochem 1999 Jul 1;74(1):1-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:32.000-05:00",
    "volume" : "74",
    "pages" : "1-10",
    "abstract" : "We have used DD-PCR (differential display-polymerase chain reaction) to identify new genes that are over- or underexpressed during wound repair. DD-PCR performed on excisional wounds identified the expression of rat c49a. Cloning and sequence analysis of the rat c49a gene revealed high homology to a novel human melanoma differentiation associated gene, mda-7. The human mda-7gene isolated from melanoma cell lines, has been linked with human melanoma differentiation, and growth suppression. Moreover, transfection of human mda-7 constructs into human tumor cells suppresses the growth and colony formation of tumor cells from diverse origins. To confirm and relatively quantitate expression of rat c49a gene during repair, specific primer, reduced cycle RT-PCR (reverse transcription-PCR) was performed. RT-PCR showed an approximately 9 to 12-fold elevation of rat c49a mRNA at 12 h to 5 days above nonwounded controls that gradually decreased to approximately 1.5 to 3-fold by day 14. Cloning and sequence analysis of the entire 1200 base pair c49a gene product showed 78% nucleotide homology to human mda-7. Immunohistochemistry studies localized rat C49A expression primarily to fibroblast-like cells at the wound edge and base. The marked up-regulation of rat c49a transcripts during the inflammatory and early granulation tissue phases of wound repair where cellular processes such as re-epithelialization, angiogenesis, and fibroplasia predominate--suggest that c49a is associated with proliferation of fibroblasts in wound healing.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Soo",
      "authorRank" : 1,
      "name" : "Soo C",
      "referenceId" : "RGD:A19735"
    }, {
      "firstName" : "WW",
      "lastName" : "Shaw",
      "authorRank" : 2,
      "name" : "Shaw WW",
      "referenceId" : "RGD:A19736"
    }, {
      "firstName" : "E",
      "lastName" : "Freymiller",
      "authorRank" : 3,
      "name" : "Freymiller E",
      "referenceId" : "RGD:A19737"
    }, {
      "firstName" : "MT",
      "lastName" : "Longaker",
      "authorRank" : 4,
      "name" : "Longaker MT",
      "referenceId" : "RGD:A19738"
    }, {
      "firstName" : "CN",
      "lastName" : "Bertolami",
      "authorRank" : 5,
      "name" : "Bertolami CN",
      "referenceId" : "RGD:A19739"
    }, {
      "firstName" : "R",
      "lastName" : "Chiu",
      "authorRank" : 6,
      "name" : "Chiu R",
      "referenceId" : "RGD:A19740"
    }, {
      "firstName" : "A",
      "lastName" : "Tieu",
      "authorRank" : 7,
      "name" : "Tieu A",
      "referenceId" : "RGD:A19741"
    }, {
      "firstName" : "K",
      "lastName" : "Ting",
      "authorRank" : 8,
      "name" : "Ting K",
      "referenceId" : "RGD:A19742"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633079"
    } ]
  }, {
    "primaryId" : "PMID:10381328",
    "title" : "Metachromatic leukodystrophy: subtype genotype/phenotype correlations and identification of novel missense mutations (P148L and P191T) causing the juvenile-onset disease.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Qu Y, etal., Mol Genet Metab. 1999 Jul;67(3):206-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:41:56.000-05:00",
    "volume" : "67",
    "pages" : "206-12",
    "abstract" : "Metachromatic leukodystrophy (MLD) is a lysosomal storage disease resulting from  the deficient activity of arylsulfatase A (ASA) and the accumulation of sulfatides. The disease is characterized by several subtypes, designated by age at onset: the late-infantile-, juvenile-, and adult-onset variants. Mutation analysis of genomic DNA from a proband with each variant was performed to identify and characterize their causative ASA mutations. Two sisters with the infantile-onset disease were homoallelic for the missense mutation D335V, a juvenile-onset proband was heteroallelic for two novel missense mutations, P148L  and P191T, and an adult-onset patient was heteroallelic for the H397Y and P426L mutations. The novel mutations were not identified in 108 normal alleles indicating that these base substitutions were not common polymorphisms. To further characterize the mutant gene products, the mutant enzymes were partially  purified from cultured fibroblasts and their molecular weights and charges were compared by immunoblotting following SDS-PAGE or isoelectric focusing (IEF). Normal fibroblast ASA had a single, broad band at 54 kDa. The enzyme from the late-infantile-onset patient had distinct bands of 36 and 78 kDa, but lacked the  normal 54-kDa species. The juvenile- and adult-onset patients each had a faint band of 54 kDa and several other bands ranging from 29 to 64 kDa. IEF revealed several bands for the partially purified normal enzyme with a relatively narrow pH range around 4.0, whereas numerous bands with a wider range of isoelectric points were observed with the enzymes from the juvenile- and adult-onset fibroblasts. In contrast, the enzyme from the late-infantile-onset proband had four bands with more acidic isoelectric points, none corresponding to those of the normal enzyme. These results document changes in both size and charge of the  mutant enzymes from patients with different mutations and MLD subtypes.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Qu",
      "authorRank" : 1,
      "name" : "Qu Y",
      "referenceId" : "RGD:A22766"
    }, {
      "firstName" : "E",
      "lastName" : "Shapira",
      "authorRank" : 2,
      "name" : "Shapira",
      "referenceId" : "RGD:A259506"
    }, {
      "firstName" : "RJ",
      "lastName" : "Desnick",
      "authorRank" : 3,
      "name" : "Desnick RJ",
      "referenceId" : "RGD:A15118"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064693"
    } ]
  }, {
    "primaryId" : "PMID:10381332",
    "title" : "Association of the serotonin transporter gene with serum cholesterol levels and heart disease.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Comings DE, etal., Mol Genet Metab. 1999 Jul;67(3):248-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-18T08:34:41.000-05:00",
    "volume" : "67",
    "pages" : "248-53",
    "abstract" : "In a study of a group of elderly athletes we observed an unexpected association between serum cholesterol levels and the HTTLPR insertion/deletion polymorphism of the promoter region of the serotonin transporter gene (HTT, SLC6A4). As a follow-up we examined the potential association of this polymorphism with cholesterol and triglyceride levels, or heart disease, in two other groups of subjects. We examined the possible association between cholesterol levels and heart disease and genotypes of the HTTLPR insertion/deletion polymorphism of the promoter region of the HTT gene, in three independent study populations ranging from 42 to 90 years of age. For subjects 55 to 70 years of age in Group 1, cholesterol levels were significantly greater in the LS heterozygotes than either LL or SS homozygotes, indicating a heterosis effect (P </= 0.0001). This was replicated in Group 2 (P </= 0.015). Triglyceride levels were also significantly elevated in the LS subjects (P </= 0.001). In Groups 1 and 3 there was a significant association between LS heterozygosity and heart disease, angina, and heart attacks in subjects 70 years of age or less. All of these associations were absent in subjects >70 years of age. While these studies are preliminary and exploratory, they are consistent with a relationship of the HTT gene in cholesterol levels and a risk for heart disease. Replication of these findings in independent, epidemiologically based studies is required.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DE",
      "lastName" : "Comings",
      "authorRank" : 1,
      "name" : "Comings DE",
      "referenceId" : "RGD:A52202"
    }, {
      "firstName" : "JP",
      "lastName" : "MacMurray",
      "authorRank" : 2,
      "name" : "MacMurray JP",
      "referenceId" : "RGD:A52783"
    }, {
      "firstName" : "N",
      "lastName" : "Gonzalez",
      "authorRank" : 3,
      "name" : "Gonzalez N",
      "referenceId" : "RGD:A63407"
    }, {
      "firstName" : "L",
      "lastName" : "Ferry",
      "authorRank" : 4,
      "name" : "Ferry L",
      "referenceId" : "RGD:A53222"
    }, {
      "firstName" : "WR",
      "lastName" : "Peters",
      "authorRank" : 5,
      "name" : "Peters WR",
      "referenceId" : "RGD:A63408"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580639"
    } ]
  }, {
    "primaryId" : "PMID:10381337",
    "title" : "Heterogeneous nuclear ribonucleoprotein A2 interacts with protein kinase CK2.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Pancetti F, etal., Biochem Biophys Res Commun. 1999 Jun 24;260(1):17-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-11-29T14:51:51.000-06:00",
    "volume" : "260",
    "pages" : "17-22",
    "abstract" : "The catalytic subunit of protein kinase CK2 (CK2alpha) was found associated with  heterogeneous nuclear ribonucleoprotein particles (hnRNPs) that contain the core  proteins A2 and C1-C2. High levels of CK2 activity were also detected in these complexes. Phosphopeptide patterns of hnRNP A2 phosphorylated in vivo and in vitro by protein kinase CK2 were similar, suggesting that this kinase can phosphorylate hnRNPA2 in vivo. Binding experiments using human recombinant hnRNP  A2, free human recombinant CK2alpha or CK2beta subunits, reconstituted CK2 holoenzyme and purified native rat liver CK2 indicated that hnRNP A2 associated with both catalytic and regulatory CK2 subunits, and that the interaction was independent of the presence of RNA. However, the capability of hnRNP A2 to bind to CK2 holoenzyme was lower than its binding to the isolated subunits. These data indicate that the association of CK2alpha with CK2beta interferes with the subsequent binding of hnRNP A2. HnRNP A2 inhibited the autophosphorylation of CK2beta. This effect was stronger with reconstituted human recombinant CK2 than with purified native rat liver CK2.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Pancetti",
      "authorRank" : 1,
      "name" : "Pancetti",
      "referenceId" : "RGD:A412760"
    }, {
      "firstName" : "R",
      "lastName" : "Bosser",
      "authorRank" : 2,
      "name" : "Bosser",
      "referenceId" : "RGD:A201547"
    }, {
      "firstName" : "A",
      "lastName" : "Krehan",
      "authorRank" : 3,
      "name" : "Krehan",
      "referenceId" : "RGD:A413937"
    }, {
      "firstName" : "W",
      "lastName" : "Pyerin",
      "authorRank" : 4,
      "name" : "Pyerin W",
      "referenceId" : "RGD:A21873"
    }, {
      "firstName" : "E",
      "lastName" : "Itarte",
      "authorRank" : 5,
      "name" : "Itarte",
      "referenceId" : "RGD:A170416"
    }, {
      "firstName" : "O",
      "lastName" : "Bachs",
      "authorRank" : 6,
      "name" : "Bachs O",
      "referenceId" : "RGD:A46205"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11565844"
    } ]
  }, {
    "primaryId" : "PMID:10381377",
    "title" : "Molecular cloning of rat SH2-containing inositol phosphatase 2 (SHIP2) and its role in the regulation of insulin signaling.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Ishihara H, etal., Biochem Biophys Res Commun 1999 Jun 24;260(1):265-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-07-31T12:14:22.000-05:00",
    "volume" : "260",
    "pages" : "265-72",
    "abstract" : "SH2-containing inositol 5'-phosphatase (SHIP) plays a negative regulatory role in hematopoietic cells. We have now cloned the rat SHIP isozyme (SHIP2) cDNA from skeletal muscle, which is one of the most important target tissue of insulin action. Rat SHIP2 cDNA encodes a 1183-amino-acid protein that is 45% identical with rat SHIP. Rat SHIP2 contains an amino-terminal SH2 domain, a central 5'-phosphoinositol phosphatase activity domain, and a phosphotyrosine binding (PTB) consensus sequence and a proline-rich region at the carboxyl tail. Specific antibodies to SHIP2 were raised and the function of SHIP2 was studied by stably overexpressing rat SHIP2 in Rat1 fibroblasts expressing human insulin receptors (HIRc). Endogenous SHIP2 underwent insulin-mediated tyrosine phosphorylation and phosphorylation was markedly increased when SHIP2 was overexpressed. Although overexpression of SHIP2 did not affect insulin-induced tyrosine phosphorylation of the insulin receptor beta-subunit and Shc, subsequent association of Shc with Grb2 was inhibited, possibly by competition between the SH2 domains of SHIP2 and Grb2 for the Shc phosphotyrosine. As a result, insulin-stimulated MAP kinase activation was reduced in SHIP2-overexpressing cells. Insulin-induced tyrosine phosphorylation of IRS-1, IRS-1 association with the p85 subunit of PI3-kinase, and PI3-kinase activation were not affected by overexpression of SHIP2. Interestingly, although both PtdIns-(3,4,5)P3 and PtdIns(3,4)P2 have been implicated in the regulation of Akt activity in vitro, overexpression of SHIP2 inhibited insulin-induced Akt activation, presumably by its 5'-inositol phosphatase activity. Furthermore, insulin-induced thymidine incorporation was decreased by overexpression of SHIP2. These results indicate that SHIP2 plays a negative regulatory role in insulin-induced mitogenesis, and regulation of the Shc. Grb2 complex and of the downstream products of PI3-kinase provides possible mechanisms of SHIP2 action in insulin signaling.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Ishihara",
      "authorRank" : 1,
      "name" : "Ishihara H",
      "referenceId" : "RGD:A125704"
    }, {
      "firstName" : "T",
      "lastName" : "Sasaoka",
      "authorRank" : 2,
      "name" : "Sasaoka T",
      "referenceId" : "RGD:A4933"
    }, {
      "firstName" : "H",
      "lastName" : "Hori",
      "authorRank" : 3,
      "name" : "Hori H",
      "referenceId" : "RGD:A4934"
    }, {
      "firstName" : "T",
      "lastName" : "Wada",
      "authorRank" : 4,
      "name" : "Wada T",
      "referenceId" : "RGD:A4935"
    }, {
      "firstName" : "H",
      "lastName" : "Hirai",
      "authorRank" : 5,
      "name" : "Hirai H",
      "referenceId" : "RGD:A4936"
    }, {
      "firstName" : "T",
      "lastName" : "Haruta",
      "authorRank" : 6,
      "name" : "Haruta T",
      "referenceId" : "RGD:A4937"
    }, {
      "firstName" : "WJ",
      "lastName" : "Langlois",
      "authorRank" : 7,
      "name" : "Langlois WJ",
      "referenceId" : "RGD:A4938"
    }, {
      "firstName" : "M",
      "lastName" : "Kobayashi",
      "authorRank" : 8,
      "name" : "Kobayashi M",
      "referenceId" : "RGD:A4939"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68267"
    } ]
  }, {
    "primaryId" : "PMID:10381487",
    "title" : "Anti-inflammatory effects of systemic anti-tumour necrosis factor alpha treatment in human/murine SCID arthritis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Schadlich H, etal., Ann Rheum Dis. 1999 Jul;58(7):428-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-08T16:53:55.000-05:00",
    "volume" : "58",
    "pages" : "428-34",
    "abstract" : "OBJECTIVES: To evaluate in vivo the contribution of tumour necrosis factor alpha  (TNFalpha) to the chimeric transfer model of human rheumatoid arthritis synovial  membrane into SCID mice (hu/mu SCID arthritis), systemic anti-TNFalpha treatment  was performed and the clinical, serological, and histopathological effects of this treatment assessed. METHODS: Animals were treated with the rat-antimouse TNFalpha monoclonal antibody V1q, starting on day 1 after hu/mu engraftment, twice weekly for 12 weeks. Joint swelling, serum concentrations of human and murine interleukin 6 (IL6), and serum amyloid P (SAP) were measured. Histopathological and immunohistochemical analyses of the joints were also performed at the end of treatment. RESULTS: Neutralisation of murine TNFalpha induced the following effects: (a) reduction of extent and duration of the acute  arthritis phase, with significant reduction of joint swelling at two weeks; (b) decrease of murine SAP concentrations after the first antibody administration; and (c) increase of murine IL6 in the serum. At the end of treatment, there was a significant reduction of the inflammatory infiltration in the engrafted joints. Because of the mild degree of joint erosion, no treatment effects could be demonstrated on the destructive process. CONCLUSION: In the lymphocyte independent hu/mu SCID arthritis, anti-TNFalpha treatment reduces local and systemic signs of inflammation.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Schadlich",
      "authorRank" : 1,
      "name" : "Schadlich",
      "referenceId" : "RGD:A215876"
    }, {
      "firstName" : "J",
      "lastName" : "Ermann",
      "authorRank" : 2,
      "name" : "Ermann",
      "referenceId" : "RGD:A215877"
    }, {
      "firstName" : "M",
      "lastName" : "Biskop",
      "authorRank" : 3,
      "name" : "Biskop",
      "referenceId" : "RGD:A215878"
    }, {
      "firstName" : "W",
      "lastName" : "Falk",
      "authorRank" : 4,
      "name" : "Falk W",
      "referenceId" : "RGD:A61015"
    }, {
      "firstName" : "F",
      "lastName" : "Sperling",
      "authorRank" : 5,
      "name" : "Sperling",
      "referenceId" : "RGD:A215879"
    }, {
      "firstName" : "A",
      "lastName" : "Jungel",
      "authorRank" : 6,
      "name" : "Jungel A",
      "referenceId" : "RGD:A149739"
    }, {
      "firstName" : "J",
      "lastName" : "Lehmann",
      "authorRank" : 7,
      "name" : "Lehmann J",
      "referenceId" : "RGD:A99190"
    }, {
      "firstName" : "F",
      "lastName" : "Emmrich",
      "authorRank" : 8,
      "name" : "Emmrich",
      "referenceId" : "RGD:A205112"
    }, {
      "firstName" : "U",
      "lastName" : "Sack",
      "authorRank" : 9,
      "name" : "Sack U",
      "referenceId" : "RGD:A135448"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11049553"
    } ]
  }, {
    "primaryId" : "PMID:10381505",
    "title" : "Differentiation of the mononuclear phagocyte system during mouse embryogenesis: the role of transcription factor PU.1.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Lichanska AM, etal., Blood 1999 Jul 1;94(1):127-38.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-01T08:41:42.000-05:00",
    "volume" : "94",
    "pages" : "127-38",
    "abstract" : "During mouse embryogenesis, macrophage-like cells arise first in the yolk sac and are produced subsequently in the liver. The onset of liver hematopoiesis is associated with the transition from primitive to definitive erythrocyte production. This report addresses the hypothesis that a similar transition in phenotype occurs in myelopoiesis. We have used whole mount in situ hybridization to detect macrophage-specific genes expressed during mouse development. The mouse c-fms mRNA, encoding the receptor for macrophage colony-stimulating factor (CSF-1), was expressed on phagocytic cells in the yolk sac and throughout the embryo before the onset of liver hematopoiesis. Similar cells were detected using the mannose receptor, the complement receptor (CR3), or the Microphthalmia transcription factor (MITF) as mRNA markers. By contrast, other markers including the F4/80 antigen, the macrophage scavenger receptor, the S-100 proteins, S100A8 and S100A9, and the secretory product lysozyme appeared later in development and appeared restricted to only a subset of c-fms-positive cells. Two-color immunolabeling on disaggregated cells confirmed that CR3 and c-fms proteins are expressed on the same cells. Among the genes appearing later in development was the macrophage-restricted transcription factor, PU.1, which has been shown to be required for normal adult myelopoiesis. Mice with null mutations in PU.1 had normal numbers of c-fms-positive phagocytes at 11.5dpc. PU.1(-/-) embryonic stem cells were able to give rise to macrophage-like cells after cultivation in vitro. The results support previous evidence that yolk sac-derived fetal phagocytes are functionally distinct from those arising in the liver and develop via a different pathway.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AM",
      "lastName" : "Lichanska",
      "authorRank" : 1,
      "name" : "Lichanska AM",
      "referenceId" : "RGD:A55192"
    }, {
      "firstName" : "CM",
      "lastName" : "Browne",
      "authorRank" : 2,
      "name" : "Browne CM",
      "referenceId" : "RGD:A55193"
    }, {
      "firstName" : "GW",
      "lastName" : "Henkel",
      "authorRank" : 3,
      "name" : "Henkel GW",
      "referenceId" : "RGD:A55194"
    }, {
      "firstName" : "KM",
      "lastName" : "Murphy",
      "authorRank" : 4,
      "name" : "Murphy KM",
      "referenceId" : "RGD:A55195"
    }, {
      "firstName" : "MC",
      "lastName" : "Ostrowski",
      "authorRank" : 5,
      "name" : "Ostrowski MC",
      "referenceId" : "RGD:A55196"
    }, {
      "firstName" : "SR",
      "lastName" : "McKercher",
      "authorRank" : 6,
      "name" : "McKercher SR",
      "referenceId" : "RGD:A55197"
    }, {
      "firstName" : "RA",
      "lastName" : "Maki",
      "authorRank" : 7,
      "name" : "Maki RA",
      "referenceId" : "RGD:A16124"
    }, {
      "firstName" : "DA",
      "lastName" : "Hume",
      "authorRank" : 8,
      "name" : "Hume DA",
      "referenceId" : "RGD:A31524"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549495"
    } ]
  }, {
    "primaryId" : "PMID:10381583",
    "title" : "Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Bendahhou S, etal., J Physiol. 1999 Jul 15;518 ( Pt 2):337-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:33:54.000-05:00",
    "volume" : "518 ( Pt 2)",
    "pages" : "337-44",
    "abstract" : "1. Paramyotonia congenita is a temperature-sensitive skeletal muscle disorder caused by missense mutations that occur in the adult skeletal muscle voltage-gated sodium channel. We report here the identification of a new genetic  mutation in a family with the paramyotonia congenita phenotype. 2. Single-strand  conformation polymorphism analysis and DNA sequencing showed that the defect was  linked to a single nucleotide substitution causing an amino acid change from an arginine to a serine at position 1448 in the human sodium channel alpha-subunit.  3. Expression of the altered protein in human embryonic kidney (HEK) 293 cells revealed several defects in channel function: (i) the rate of fast inactivation was slower in the mutant channel compared with wild-type, (ii) steady-state fast  inactivation was shifted towards hyperpolarizing potentials, (iii) the R1448S channels deactivated much more slowly, and (iv) the mutant channels recovered from the fast inactivated state more rapidly. 4. By contrast, the activation curve, steady-state slow inactivation and the rate of onset and recovery from slow inactivation were not altered by the R1448S mutation. 5. These data show that the defects observed in the sodium channel function could well explain the onset of the paramyotonia congenita in this family and emphasize the role of segment S4 of domain IV in sodium channel inactivation.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Bendahhou",
      "authorRank" : 1,
      "name" : "Bendahhou S",
      "referenceId" : "RGD:A62785"
    }, {
      "firstName" : "TR",
      "lastName" : "Cummins",
      "authorRank" : 2,
      "name" : "Cummins TR",
      "referenceId" : "RGD:A40668"
    }, {
      "firstName" : "H",
      "lastName" : "Kwiecinski",
      "authorRank" : 3,
      "name" : "Kwiecinski H",
      "referenceId" : "RGD:A161150"
    }, {
      "firstName" : "SG",
      "lastName" : "Waxman",
      "authorRank" : 4,
      "name" : "Waxman SG",
      "referenceId" : "RGD:A7917"
    }, {
      "firstName" : "LJ",
      "lastName" : "Ptacek",
      "authorRank" : 5,
      "name" : "Ptacek LJ",
      "referenceId" : "RGD:A75980"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072440"
    } ]
  }, {
    "primaryId" : "PMID:10381586",
    "title" : "Modulation of rat cardiac sodium channel by the stimulatory G protein alpha subunit.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Lu T, etal., J Physiol. 1999 Jul 15;518 ( Pt 2):371-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-11-08T15:31:09.000-06:00",
    "volume" : "518 ( Pt 2)",
    "pages" : "371-84",
    "abstract" : "1. Modulation of cardiac sodium currents (INa) by the G protein stimulatory alpha subunit (Gsalpha) was studied using patch-clamp techniques on freshly dissociated rat ventricular myocytes. 2. Whole-cell recordings showed that stimulation of beta-adrenergic receptors with 10 microM isoprenaline (isoproterenol, ISO) enhanced INa by 68.4 +/- 9.6 % (mean +/- s.e.m.; n = 7, P < 0.05 vs. baseline). With the addition of 22 microgram ml-1 protein kinase A inhibitor (PKI) to the pipette solution, 10 microM ISO enhanced INa by 30.5 +/- 7.0 % (n = 7, P < 0.05 vs. baseline). With the pipette solution containing both PKI and 20 microgram ml-1 anti-Gsalpha IgG or 20 microgram ml-1 anti-Gsalpha IgG alone, 10 microM ISO produced no change in INa. 3. The effect of Gsalpha on INa was not due to changes in the steady-state activation or inactivation curves, the time course of current decay, the development of inactivation, or the recovery from inactivation. 4. Whole-cell INa was increased by 45.2 +/- 5.3% (n = 13, P < 0.05 vs. control) with pipette solution containing 1 microM Gsalpha27-42 peptide (amino acids 27-42 of rat brain Gsalpha) without altering the properties of Na+ channel kinetics. Furthermore, application of 1 nM Gsalpha27-42 to Na+ channels in inside-out macropatches increased the ensemble-averaged INa by 32.5 +/- 6.8 % (n = 8, P < 0.05 vs. baseline). The increase in INa was reversible upon Gsalpha27-42 peptide washout. Single channel experiments showed that the Gsalpha27-42 peptide did not alter the Na+ single channel current amplitude, the mean open time or the mean closed time, but increased the number of functional channels (N) in the patch. 5. Application of selected short amino acid segments (Gsalpha27-36, Gsalpha33-42 and Gsalpha30-39) of the 16 amino acid Gsalpha peptide (Gsalpha27-42 peptide) showed that only the C-terminal segment of this peptide (Gsalpha33-42) significantly increased INa in a dose-dependent fashion. These results show that cardiac INa is regulated by Gsalpha via a mechanism independent of PKA that results in an increase in the number of functional Na+ channels. In addition, a 10 residue domain (amino acids 33-42) near the N-terminus of Gsalpha is important in modulating cardiac Na+ channels.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Lu",
      "authorRank" : 1,
      "name" : "Lu T",
      "referenceId" : "RGD:A69792"
    }, {
      "firstName" : "HC",
      "lastName" : "Lee",
      "authorRank" : 2,
      "name" : "Lee HC",
      "referenceId" : "RGD:A20512"
    }, {
      "firstName" : "JA",
      "lastName" : "Kabat",
      "authorRank" : 3,
      "name" : "Kabat JA",
      "referenceId" : "RGD:A147392"
    }, {
      "firstName" : "EF",
      "lastName" : "Shibata",
      "authorRank" : 4,
      "name" : "Shibata EF",
      "referenceId" : "RGD:A147393"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5509841"
    } ]
  }, {
    "primaryId" : "PMID:10381597",
    "title" : "Presynaptic serotonergic inhibition of GABAergic synaptic transmission in mechanically dissociated rat basolateral amygdala neurons.",
    "datePublished" : "1999-07-15T00:00:00.000-05:00",
    "citation" : "Koyama S, etal., J Physiol. 1999 Jul 15;518 ( Pt 2):525-38.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T02:01:25.000-05:00",
    "volume" : "518 ( Pt 2)",
    "pages" : "525-38",
    "abstract" : "1. The basolateral amygdala (ABL) nuclei contribute to the process of anxiety. GABAergic transmission is critical in these nuclei and serotonergic inputs from dorsal raphe nuclei also significantly regulate GABA release. In mechanically dissociated rat ABL neurons, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) arising from attached GABAergic presynaptic nerve terminals were recorded with the nystatin-perforated patch method and pharmacological isolation. 2. 5-HT reversibly reduced the GABAergic mIPSC frequency without affecting the mean amplitude. The serotonergic effect was mimicked by the 5-HT1A specific agonist 8-OH DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) and blocked by the 5-HT1A antagonist spiperone. 3. The GTP-binding protein inhibitor N-ethylmaleimide removed the serotonergic inhibition of mIPSC frequency. In either K+-free or Ca2+-free external solution, 5-HT could inhibit mIPSC frequency. 4. High K+ stimulation increased mIPSC frequency and 8-OH DPAT inhibited this increase even in the presence of Cd2+. 5. Forskolin, an activator of adenylyl cyclase (AC), significantly increased synaptic GABA release frequency. Pretreatment with forskolin prevented the serotonergic inhibition of mIPSC frequency in both the standard and high K+ external solution. 6. Ruthenium Red (RR), an agent facilitating the secretory process in a Ca2+-independent manner, increased synaptic GABA release. 5-HT also suppressed RR-facilitated mIPSC frequency. 7. We conclude that 5-HT inhibits GABAergic mIPSCs by inactivating the AC-cAMP signal transduction pathway via a G-protein-coupled 5-HT1A receptor and this intracellular pathway directly acts on the GABA-releasing process independent of K+ and Ca2+ channels in the presynaptic nerve terminals.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Koyama",
      "authorRank" : 1,
      "name" : "Koyama S",
      "referenceId" : "RGD:A5606"
    }, {
      "firstName" : "C",
      "lastName" : "Kubo",
      "authorRank" : 2,
      "name" : "Kubo C",
      "referenceId" : "RGD:A460489"
    }, {
      "firstName" : "J S",
      "lastName" : "Rhee",
      "authorRank" : 3,
      "name" : "Rhee JS",
      "referenceId" : "RGD:A460490"
    }, {
      "firstName" : "N",
      "lastName" : "Akaike",
      "authorRank" : 4,
      "name" : "Akaike N",
      "referenceId" : "RGD:A13317"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702211"
    } ]
  }, {
    "primaryId" : "PMID:10381813",
    "title" : "Efficacy of keratinocyte growth factor-2 in dextran sulfate sodium-induced murine colitis.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Miceli R, etal., J Pharmacol Exp Ther. 1999 Jul;290(1):464-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-05-27T14:52:51.000-05:00",
    "volume" : "290",
    "pages" : "464-71",
    "abstract" : "The purpose of this study was to determine the efficacy of a novel human protein, keratinocyte growth factor-2 (KGF-2), in a model of murine colitis induced by ad libitum exposure to a 4% solution of dextran sulfate sodium (DSS) in the drinking water. Initial evaluation of KGF-2 was based on its ability to reduce weight loss, stool score, and histological score in mice exposed to DSS for 7 days. When KGF-2 (0.1-10.0 mg/kg i.p. or s.c.) was injected daily into DSS-treated mice from day 0 to 7, it significantly reduced all three parameters in a dose-response fashion, with a minimum effective dose of between 1 and 3 mg/kg. When KGF-2 was given therapeutically, starting 4 days after initiation of the 7-day DSS treatment, the 3- but not the 0.5-mg/kg dose significantly enhanced weight recovery after discontinuation of DSS treatment. When DSS treatment was prolonged beyond the normal 7 days, therapeutic intervention on day 2 or 4 also significantly reduced mortality, weight loss, and stool score at the 1- and 3-mg/kg dose. Therapeutic treatment also resulted in reduction of colon myloperoxidase levels by more than 50%. These experiments suggest that KGF-2 may be clinically useful in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Miceli",
      "authorRank" : 1,
      "name" : "Miceli R",
      "referenceId" : "RGD:A500000"
    }, {
      "firstName" : "M",
      "lastName" : "Hubert",
      "authorRank" : 2,
      "name" : "Hubert M",
      "referenceId" : "RGD:A500001"
    }, {
      "firstName" : "G",
      "lastName" : "Santiago",
      "authorRank" : 3,
      "name" : "Santiago G",
      "referenceId" : "RGD:A500002"
    }, {
      "firstName" : "D L",
      "lastName" : "Yao",
      "authorRank" : 4,
      "name" : "Yao DL",
      "referenceId" : "RGD:A500003"
    }, {
      "firstName" : "T A",
      "lastName" : "Coleman",
      "authorRank" : 5,
      "name" : "Coleman TA",
      "referenceId" : "RGD:A500004"
    }, {
      "firstName" : "K A",
      "lastName" : "Huddleston",
      "authorRank" : 6,
      "name" : "Huddleston KA",
      "referenceId" : "RGD:A500005"
    }, {
      "firstName" : "K",
      "lastName" : "Connolly",
      "authorRank" : 7,
      "name" : "Connolly K",
      "referenceId" : "RGD:A35473"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:126928132"
    } ]
  }, {
    "primaryId" : "PMID:10381889",
    "title" : "Neuregulin signaling in the heart. Dynamic targeting of erbB4 to caveolar microdomains in cardiac myocytes.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Zhao YY, etal., Circ Res. 1999 Jun 25;84(12):1380-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-02-22T15:34:05.000-06:00",
    "volume" : "84",
    "pages" : "1380-7",
    "abstract" : "Two of the neuregulins (NRG1 and NRG2) and their receptors (erbB2 and erbB4) are essential for normal cardiac development and can mediate hypertrophic growth and enhance survival of embryonic, postnatal, and adult rat ventricular myocytes. The expression of erbB4, the predominant NRG receptor in postnatal rat ventricular muscle, declines after midembryogenesis, and its expression is limited to cardiac myocytes. A full-length erbB4 rat cDNA isolated from neonatal ventricular muscle was found to be highly homologous to human erbB4 and contained a caveolin binding motif within the cytoplasmic kinase domain. Using the complementary techniques of detergent-free density-gradient ultracentrifugation of myocyte lysates and coimmunoprecipitation of erbB4 and caveolin-3, the caveolin isoform expressed in cardiac myocytes, erbB4 could be localized (using both approaches) to caveolar microdomains. Moreover, addition of a soluble NRG1, recombinant human glial growth factor 2, resulted in rapid (2-minute) translocation of erbB4 out of caveolar microdomain in cardiac myocytes. Thus, erbB4 is dynamically targeted to caveolar microdomains within cardiac myocytes. Its rapid translocation after NRG1 binding may contribute to receptor desensitization in the continuous presence of ligand.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YY",
      "lastName" : "Zhao",
      "authorRank" : 1,
      "name" : "Zhao YY",
      "referenceId" : "RGD:A36768"
    }, {
      "firstName" : "O",
      "lastName" : "Feron",
      "authorRank" : 2,
      "name" : "Feron O",
      "referenceId" : "RGD:A92458"
    }, {
      "firstName" : "C",
      "lastName" : "Dessy",
      "authorRank" : 3,
      "name" : "Dessy C",
      "referenceId" : "RGD:A92459"
    }, {
      "firstName" : "X",
      "lastName" : "Han",
      "authorRank" : 4,
      "name" : "Han X",
      "referenceId" : "RGD:A27674"
    }, {
      "firstName" : "MA",
      "lastName" : "Marchionni",
      "authorRank" : 5,
      "name" : "Marchionni MA",
      "referenceId" : "RGD:A65015"
    }, {
      "firstName" : "RA",
      "lastName" : "Kelly",
      "authorRank" : 6,
      "name" : "Kelly RA",
      "referenceId" : "RGD:A8136"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2290016"
    } ]
  }, {
    "primaryId" : "PMID:10382588",
    "title" : "An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Cassell PG, etal., Diabetologia. 1999 Jun;42(6):688-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-29T18:21:28.000-05:00",
    "volume" : "42",
    "pages" : "688-92",
    "abstract" : "AIMS/HYPOTHESIS: Linkage between markers close to the uncoupling protein 2 and 3 genes (11q13) and resting metabolic rate and a pre-diabetic phenotype have been found. The syntenic region in mouse has been found to be linked to quantitative traits associated with obesity and diabetes. UCP2 and UCP3 could therefore have an important role in body weight regulation and susceptibility to diabetes. We investigated a recently identified variant of the UCP2 gene in exon 8 as a marker for glucose and weight homeostasis. METHODS: Length variation of the UCP2 exon 8 variant was studied by the polymerase chain reaction and agarose gel electrophoresis. Sequence variants of the UCP3 gene were sought by semi-automated DNA sequencing. RESULTS: In 453 South Indian subjects, we found an association in women between the UCP2 exon variant and body mass index (p = 0.018). These findings were replicated in a separate group of South Indian subjects (n = 143, p < 0.001) irrespective of sex. Although no association was found between the UCP2 exon 8 variant and overt obesity in British subjects, the UCP2 genotype of obese women (n = 83) correlated with fasting serum leptin concentration (p = 0.006) in the presence of extreme obesity. These observations could not be explained by tight linkage disequilibrium with a coding region variant in the region of the UCP3 gene of biological significance. Lastly, no association was found between UCP2 and Type II (non-insulin-dependent) diabetes using either a family based design (85 families) or case control study (normal glucose tolerance n = 335, impaired glucose tolerance n = 42, Type II diabetes n = 76). CONCLUSION/INTERPRETATION: We have described a UCP2 gene exon 8 variant that may affect susceptibility to weight gain by influencing regulation of leptin.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PG",
      "lastName" : "Cassell",
      "authorRank" : 1,
      "name" : "Cassell PG",
      "referenceId" : "RGD:A40296"
    }, {
      "firstName" : "M",
      "lastName" : "Neverova",
      "authorRank" : 2,
      "name" : "Neverova M",
      "referenceId" : "RGD:A112823"
    }, {
      "firstName" : "S",
      "lastName" : "Janmohamed",
      "authorRank" : 3,
      "name" : "Janmohamed S",
      "referenceId" : "RGD:A112824"
    }, {
      "firstName" : "N",
      "lastName" : "Uwakwe",
      "authorRank" : 4,
      "name" : "Uwakwe N",
      "referenceId" : "RGD:A112825"
    }, {
      "firstName" : "A",
      "lastName" : "Qureshi",
      "authorRank" : 5,
      "name" : "Qureshi A",
      "referenceId" : "RGD:A12590"
    }, {
      "firstName" : "MI",
      "lastName" : "McCarthy",
      "authorRank" : 6,
      "name" : "McCarthy MI",
      "referenceId" : "RGD:A39906"
    }, {
      "firstName" : "PJ",
      "lastName" : "Saker",
      "authorRank" : 7,
      "name" : "Saker PJ",
      "referenceId" : "RGD:A40297"
    }, {
      "firstName" : "L",
      "lastName" : "Albon",
      "authorRank" : 8,
      "name" : "Albon L",
      "referenceId" : "RGD:A112826"
    }, {
      "firstName" : "P",
      "lastName" : "Kopelman",
      "authorRank" : 9,
      "name" : "Kopelman P",
      "referenceId" : "RGD:A112827"
    }, {
      "firstName" : "K",
      "lastName" : "Noonan",
      "authorRank" : 10,
      "name" : "Noonan K",
      "referenceId" : "RGD:A112828"
    }, {
      "firstName" : "J",
      "lastName" : "Easlick",
      "authorRank" : 11,
      "name" : "Easlick J",
      "referenceId" : "RGD:A112829"
    }, {
      "firstName" : "A",
      "lastName" : "Ramachandran",
      "authorRank" : 12,
      "name" : "Ramachandran A",
      "referenceId" : "RGD:A60051"
    }, {
      "firstName" : "C",
      "lastName" : "Snehalatha",
      "authorRank" : 13,
      "name" : "Snehalatha C",
      "referenceId" : "RGD:A79276"
    }, {
      "firstName" : "C",
      "lastName" : "Pecqueur",
      "authorRank" : 14,
      "name" : "Pecqueur C",
      "referenceId" : "RGD:A39306"
    }, {
      "firstName" : "D",
      "lastName" : "Ricquier",
      "authorRank" : 15,
      "name" : "Ricquier D",
      "referenceId" : "RGD:A27583"
    }, {
      "firstName" : "C",
      "lastName" : "Warden",
      "authorRank" : 16,
      "name" : "Warden C",
      "referenceId" : "RGD:A112830"
    }, {
      "firstName" : "GA",
      "lastName" : "Hitman",
      "authorRank" : 17,
      "name" : "Hitman GA",
      "referenceId" : "RGD:A39902"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313525"
    } ]
  }, {
    "primaryId" : "PMID:10382592",
    "title" : "Involvement of Smad proteins in the differentiation of pancreatic AR42J cells induced by activin A.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Zhang YQ, etal., Diabetologia 1999 Jun;42(6):719-27.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:05.000-06:00",
    "volume" : "42",
    "pages" : "719-27",
    "abstract" : "AIMS/HYPOTHESIS: Activin A induces differentiation of amylase-secreting pancreatic AR42J cells into endocrine cells. This study assesses the role of Smad proteins in the actions of activin A in AR42J cells. METHODS: The expression of Smad proteins was determined by northern blotting. Phosphorylation and translocation of Smad2 was measured by transfecting flag-tagged Smad2. Involvement of Smad2 was examined by transfecting cDNA encoding N-terminal and C-terminal domains of Smad2. RESULTS: The mRNAs for Smad2 and Smad4 were abundantly expressed whereas the expression of mRNA for Smad1 and Smad3 was very low. Activin A induced serine-phosphorylation and the subsequent accumulation of the Smad2 in nuclei. Transfection of the N-terminal domain of Smad2, which acts as a dominantly negative mutant (Smad2-N), blocked the morphological changes induced by activin A whereas the C-terminal domain of Smad2, which acts as a constitutively active mutant (Smad2-C), reproduced the activin-induced morphological changes. Similarly, Smad2-N blocked apoptosis induced by activin A and Smad2-C induced apoptosis. Activin A converted AR42J into insulin-secreting cells in the presence of hepatocyte growth factor and introduction of Smad2-N inhibited the differentiation. Smad2-C, however, did not induce differentiation in the presence of hepatocyte growth factor. CONCLUSIONS/INTERPRETATION: Activation of the Smad2 pathway is necessary and sufficient to induce apoptosis and morphological changes. Although activation of the Smad2 pathway is required, it is not solely sufficient for the differentiation of AR42J into endocrine cells.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YQ",
      "lastName" : "Zhang",
      "authorRank" : 1,
      "name" : "Zhang YQ",
      "referenceId" : "RGD:A7499"
    }, {
      "firstName" : "M",
      "lastName" : "Kanzaki",
      "authorRank" : 2,
      "name" : "Kanzaki M",
      "referenceId" : "RGD:A7500"
    }, {
      "firstName" : "M",
      "lastName" : "Furukawa",
      "authorRank" : 3,
      "name" : "Furukawa M",
      "referenceId" : "RGD:A7501"
    }, {
      "firstName" : "H",
      "lastName" : "Shibata",
      "authorRank" : 4,
      "name" : "Shibata H",
      "referenceId" : "RGD:A7502"
    }, {
      "firstName" : "M",
      "lastName" : "Ozeki",
      "authorRank" : 5,
      "name" : "Ozeki M",
      "referenceId" : "RGD:A7503"
    }, {
      "firstName" : "I",
      "lastName" : "Kojima",
      "authorRank" : 6,
      "name" : "Kojima I",
      "referenceId" : "RGD:A7504"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69876"
    } ]
  }, {
    "primaryId" : "PMID:10382763",
    "title" : "NILR-1, a novel immunoglobulin-like receptor expressed by neutrophilic granulocytes, is encoded by a leukocyte receptor gene complex on rat chromosome 1.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Berg SF, etal., Eur J Immunol 1999 Jun;29(6):2000-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:14:55.000-05:00",
    "volume" : "29",
    "pages" : "2000-6",
    "abstract" : "Several receptors expressed by subsets of leukocytes and with sequence homology to the killer cell inhibitory receptors have recently been identified both in man and mouse. Here we describe a rat cDNA that encodes a novel receptor of this group, designated neutrophil immunoglobulin-like receptor-1 (NILR-1). The predicted 58.7-kDa mature NILR-1 protein is a type I integral membrane protein, with three C2-type immunoglobulin superfamily domains, a transmembrane region devoid of charged amino acids, and a cytoplasmic tail containing four immunoreceptor tyrosine-based inhibition motif-like regions. NILR-1 shows greatest sequence homology to the mouse paired immunoglobulin-like receptor-B and members of the human leukocyte immunoglobulin-like receptor/immunoglobulin-like transcript group of receptors. As shown by Northern blot analysis, NILR-1 was transcribed by neutrophilic granulocytes. Although weaker transcription was found with a macrophage cell line, no signal was detected with peritoneal macrophage or spleen RNA. Linkage analysis localized Nilr1 to chromosome 1, closely linked to a locus encoding a rat NKp46 orthologue. The two loci define a rat leukocyte receptor gene complex, in a region syntenic to human chromosome 19q13.4 and the proximal part of mouse chromosome 7, that harbors the human and mouse leukocyte receptor gene complexes.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SF",
      "lastName" : "Berg",
      "authorRank" : 1,
      "name" : "Berg SF",
      "referenceId" : "RGD:A54401"
    }, {
      "firstName" : "S",
      "lastName" : "Fossum",
      "authorRank" : 2,
      "name" : "Fossum S",
      "referenceId" : "RGD:A88266"
    }, {
      "firstName" : "E",
      "lastName" : "Dissen",
      "authorRank" : 3,
      "name" : "Dissen E",
      "referenceId" : "RGD:A88263"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70628"
    } ]
  }, {
    "primaryId" : "PMID:10382909",
    "title" : "Genotype-phenotype analysis in X-linked Emery-Dreifuss muscular dystrophy and identification of a missense mutation associated with a milder phenotype.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Yates JR, etal., Neuromuscul Disord. 1999 May;9(3):159-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:19:19.000-05:00",
    "volume" : "9",
    "pages" : "159-65",
    "abstract" : "Direct sequencing of the emerin gene in 22 families with Emery-Dreifuss muscular  dystrophy (EMD) revealed mutations in 21 (95%), confirming that emerin mutations  can be identified in the majority of families with X-linked EMD. Most emerin mutations result in absence of the protein. In this study three mutations (a missense mutation Pro183Thr and two in-frame deletions removing residues 95-99 and 236-241, respectively) were unusual in being associated with expression of mutant protein. The phenotype in these families was compared in detail with the clinical features in cases with typical null mutations. For the in-frame deletions there were no significant differences. In the family with the missense  mutation the phenotype was milder. Age at onset was later for first symptoms and  for development of ankle contractures and muscle weakness. These findings have diagnostic implications as well as pointing to functionally important regions of  the emerin protein.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JR",
      "lastName" : "Yates",
      "authorRank" : 1,
      "name" : "Yates JR",
      "referenceId" : "RGD:A37371"
    }, {
      "firstName" : "J",
      "lastName" : "Bagshaw",
      "authorRank" : 2,
      "name" : "Bagshaw",
      "referenceId" : "RGD:A267367"
    }, {
      "firstName" : "VM",
      "lastName" : "Aksmanovic",
      "authorRank" : 3,
      "name" : "Aksmanovic",
      "referenceId" : "RGD:A265904"
    }, {
      "firstName" : "E",
      "lastName" : "Coomber",
      "authorRank" : 4,
      "name" : "Coomber",
      "referenceId" : "RGD:A267368"
    }, {
      "firstName" : "R",
      "lastName" : "McMahon",
      "authorRank" : 5,
      "name" : "McMahon R",
      "referenceId" : "RGD:A115501"
    }, {
      "firstName" : "JL",
      "lastName" : "Whittaker",
      "authorRank" : 6,
      "name" : "Whittaker JL",
      "referenceId" : "RGD:A44648"
    }, {
      "firstName" : "PJ",
      "lastName" : "Morrison",
      "authorRank" : 7,
      "name" : "Morrison",
      "referenceId" : "RGD:A205790"
    }, {
      "firstName" : "J",
      "lastName" : "Kendrick-Jones",
      "authorRank" : 8,
      "name" : "Kendrick-Jones J",
      "referenceId" : "RGD:A41464"
    }, {
      "firstName" : "JA",
      "lastName" : "Ellis",
      "authorRank" : 9,
      "name" : "Ellis JA",
      "referenceId" : "RGD:A12429"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067205"
    } ]
  }, {
    "primaryId" : "PMID:10383132",
    "title" : "Elevated and biallelic expression of p73 is associated withprogression of human bladder cancer.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Chi SG, etal., Cancer Res. 1999 Jun 15;59(12):2791-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-03-31T17:00:29.000-05:00",
    "volume" : "59",
    "pages" : "2791-3",
    "abstract" : "p73, a member of the p53 family at 1p36.3, has been demonstrated to be expressed monoallelically and induce apoptosis or G1 arrest of the cell cycle. To explore the candidacy of p73 as a suppressor in bladder tumorigenesis, we examined expression level, allelic origin, and mutation of p73 mRNA in 45 primary bladder carcinomas. Quantitative PCR analysis showed no allelic loss of the gene but showed various levels of mRNA expression in both carcinoma and noncancerous tissues. Elevated expression of p73 was frequently observed in carcinoma tissues [18 (40.0%) of 45] and showed a strong correlation with tumor stage or grade. Allotyping analysis using a StyI polymorphism detected biallelic expression in 12 (52.2%) of 23 heterozygous carcinomas but none in 4 noncancerous tissues. Tumor-specific biallelic expression was also identified from one matched set. In addition, 8 (66.7%) of these 12 expressed high levels of p73 mRNA, whereas only 2 (18.2%) of 11 monoallelic expressors showed high expression, which suggests that the increased expression of p73 might be caused by the transcriptional activation of a silent allele in carcinomas. Single-strand conformational polymorphism analysis of the entire coding region of p73 revealed no mutation, whereas 12 (26.7%) of the same set showed p53 alterations. No relationship between expression of p73 and p53 mutation or expression of p21Waf1 or MDM2 was identified. Taken together, our data argue that p73 does not play a role as a tumor suppressor in bladder carcinogenesis and suggest that the activation of a silent allele may contribute to the progression of bladder tumors.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SG",
      "lastName" : "Chi",
      "authorRank" : 1,
      "name" : "Chi SG",
      "referenceId" : "RGD:A93568"
    }, {
      "firstName" : "SG",
      "lastName" : "Chang",
      "authorRank" : 2,
      "name" : "Chang SG",
      "referenceId" : "RGD:A93569"
    }, {
      "firstName" : "SJ",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee SJ",
      "referenceId" : "RGD:A1210"
    }, {
      "firstName" : "CH",
      "lastName" : "Lee",
      "authorRank" : 4,
      "name" : "Lee CH",
      "referenceId" : "RGD:A18605"
    }, {
      "firstName" : "JI",
      "lastName" : "Kim",
      "authorRank" : 5,
      "name" : "Kim JI",
      "referenceId" : "RGD:A93570"
    }, {
      "firstName" : "JH",
      "lastName" : "Park",
      "authorRank" : 6,
      "name" : "Park JH",
      "referenceId" : "RGD:A18126"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2291836"
    } ]
  }, {
    "primaryId" : "PMID:10383153",
    "title" : "Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Longuemaux S, etal., Cancer Res. 1999 Jun 15;59(12):2903-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-10-17T16:36:27.000-05:00",
    "volume" : "59",
    "pages" : "2903-8",
    "abstract" : "The steady increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the notion that certain carcinogens present in  the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may  affect the occurrence of RCC. Many of the enzymes dealing with such environmental factors are polymorphic and may, therefore, confer variable susceptibility to RCC. This case-control study was designed to test for an association between genetic polymorphism of enzymes involved in xenobiotic metabolism and the risk of sporadic RCC. Genomic DNA was obtained from 173 patients with RCC and 211 controls of Caucasian origin. We used PCR-RFLP to investigate polymorphism for the most common alleles at two cytochrome-P450 mono-oxygenases (CYP1A1 and CYP2D6), one NAD[P]H:quinone oxidoreductase (NQO1), three glutathione S-transferases (GSTM1, GSTT1, and GSTP1), and one N-acetyltransferase (NAT2) loci. The CYP1A1 (m) \"variant\" genotype, which contains at least one copy of the  CYP1A1 variant alleles, was found to be associated with a 2.1-fold [95% confidence interval (CI), 1.1-3.9] increase in the risk of RCC. There was also a  higher risk of RCC for subjects with the CYP1A1 (m) variant genotype combined with any of the following genotypes: GSTT1 (+) \"active\" [odds ratio (OR), 2.3; 95% CI, 1.2-4.5], GSTP1 (m) variant (OR, 2.4; 95% CI, 1.0-5.4), or NAT2 (-) \"slow acetylator\" (OR, 2.5; 95% CI, 1.1-5.5). A significant association was also found  for the GSTM1 (-) \"null\" and GSTP1 (m) genotypes combined with either NAT2 (-) (OR, 2.6; 95% CI, 1.2-5.8) or CYP1A1 (m) (OR, 3.5; 95% CI, 1.1-11.2). The CYP2D6  (-) \"poor metabolizer \" and the NQO1 (-) \"defective\" genotypes were not clearly associated with a higher risk of RCC. Our data demonstrate for the first time a significant association between a group of pharmacogenetic polymorphisms and RCC  risk. These positive findings suggest that interindividual variation in the metabolic pathways involved in the functionalization and detoxification of specific xenobiotics is an important susceptibility factor for RCC in Caucasians.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Longuemaux",
      "authorRank" : 1,
      "name" : "Longuemaux S",
      "referenceId" : "RGD:A158854"
    }, {
      "firstName" : "C",
      "lastName" : "Delomenie",
      "authorRank" : 2,
      "name" : "Delomenie C",
      "referenceId" : "RGD:A158855"
    }, {
      "firstName" : "C",
      "lastName" : "Gallou",
      "authorRank" : 3,
      "name" : "Gallou C",
      "referenceId" : "RGD:A158856"
    }, {
      "firstName" : "A",
      "lastName" : "Mejean",
      "authorRank" : 4,
      "name" : "Mejean A",
      "referenceId" : "RGD:A158857"
    }, {
      "firstName" : "M",
      "lastName" : "Vincent-Viry",
      "authorRank" : 5,
      "name" : "Vincent-Viry M",
      "referenceId" : "RGD:A158858"
    }, {
      "firstName" : "R",
      "lastName" : "Bouvier",
      "authorRank" : 6,
      "name" : "Bouvier R",
      "referenceId" : "RGD:A71575"
    }, {
      "firstName" : "D",
      "lastName" : "Droz",
      "authorRank" : 7,
      "name" : "Droz D",
      "referenceId" : "RGD:A158859"
    }, {
      "firstName" : "R",
      "lastName" : "Krishnamoorthy",
      "authorRank" : 8,
      "name" : "Krishnamoorthy R",
      "referenceId" : "RGD:A134316"
    }, {
      "firstName" : "MM",
      "lastName" : "Galteau",
      "authorRank" : 9,
      "name" : "Galteau MM",
      "referenceId" : "RGD:A158860"
    }, {
      "firstName" : "C",
      "lastName" : "Junien",
      "authorRank" : 10,
      "name" : "Junien C",
      "referenceId" : "RGD:A60289"
    }, {
      "firstName" : "C",
      "lastName" : "Beroud",
      "authorRank" : 11,
      "name" : "Beroud C",
      "referenceId" : "RGD:A158861"
    }, {
      "firstName" : "JM",
      "lastName" : "Dupret",
      "authorRank" : 12,
      "name" : "Dupret JM",
      "referenceId" : "RGD:A37511"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6906878"
    } ]
  }, {
    "primaryId" : "PMID:10383386",
    "title" : "Synaptogyrins regulate Ca2+-dependent exocytosis in PC12 cells.",
    "datePublished" : "1999-07-02T00:00:00.000-05:00",
    "citation" : "Sugita S, etal., J Biol Chem. 1999 Jul 2;274(27):18893-901.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-09-02T06:12:55.000-05:00",
    "volume" : "274",
    "pages" : "18893-901",
    "abstract" : "Synaptogyrins constitute a family of synaptic vesicle proteins of unknown function. With the full-length structure of a new brain synaptogyrin isoform, we now show that the synaptogyrin family in vertebrates includes two neuronal and one ubiquitous isoform. All of these synaptogyrins are composed of a short conserved N-terminal cytoplasmic sequence, four homologous transmembrane regions, and a variable cytoplasmic C-terminal tail that is tyrosine-phosphorylated. The localization, abundance, and conservation of synaptogyrins suggest a function in exocytosis. To test this, we employed a secretion assay in PC12 cells expressing transfected human growth hormone (hGH) as a reporter protein. When Ca2+-dependent hGH secretion from PC12 cells was triggered by high K+ or alpha-latrotoxin, co-transfection of all synaptogyrins with hGH inhibited hGH exocytosis as strongly as co-transfection of tetanus toxin light chain. Synaptophysin I, which is distantly related to synaptogyrins, was also inhibitory but less active. Inhibition was independent of the amount of hGH expressed but correlated with the amount of synaptogyrin transfected. Inhibition of exocytosis was not observed with several other synaptic proteins, suggesting specificity. Analysis of the regions of synaptogyrin required for inhibition revealed that the conserved N-terminal domain of synaptogyrin is essential for inhibition, whereas the long C-terminal cytoplasmic tail is largely dispensable. Our results suggest that synaptogyrins are conserved components of the exocytotic apparatus, which function as regulators of Ca2+-dependent exocytosis.",
    "issueName" : "27",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Sugita",
      "authorRank" : 1,
      "name" : "Sugita S",
      "referenceId" : "RGD:A14274"
    }, {
      "firstName" : "R",
      "lastName" : "Janz",
      "authorRank" : 2,
      "name" : "Janz R",
      "referenceId" : "RGD:A8101"
    }, {
      "firstName" : "T C",
      "lastName" : "Südhof",
      "authorRank" : 3,
      "name" : "Südhof TC",
      "referenceId" : "RGD:A435850"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13210524"
    } ]
  }, {
    "primaryId" : "PMID:10383413",
    "title" : "Functional interaction between Oct-1 and retinoid X receptor.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Kakizawa T, etal., J Biol Chem. 1999 Jul 2;274(27):19103-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-02-17T14:49:55.000-06:00",
    "volume" : "274",
    "pages" : "19103-8",
    "abstract" : "The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and heterodimerizes with a variety of other family members such as the thyroid hormone receptor (TR),1 retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor. Therefore, RXR is supposed to play a key role in a ligand-dependent regulation of gene transcription by nuclear receptors. In this study, we have identified the octamer-binding transcription factor-1 (Oct-1) as a novel interaction factor of RXR. In vitro pull-down assays  using RXR deletion mutants showed that the interaction surfaces were located in the region encompassing the DNA binding domain (C domain) and the hinge domain (D domain) of RXR. We also showed that RXR interacted with the POU homeodomain but not with the POU-specific domain of Oct-1. Gel shift analysis revealed that Oct-1 reduced the binding of TR/RXR heterodimers to the thyroid hormone response element (TRE). In transient transfection assays using COS1 cells, Oct-1 repressed the T3-dependent transcriptional activity of TR/RXR heterodimers, consistent with in vitro DNA binding data; however, transcriptional activation by Gal4-TR(LBD) (LBD, ligand binding domain), which lacks its own DNA binding domain but retains  responsiveness to T3, was not influenced by Oct-1. These results suggest that Oct-1 functionally interacts with RXR and negatively regulates the nuclear receptor signaling pathway by altering the DNA binding ability of the receptors.",
    "issueName" : "27",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kakizawa",
      "authorRank" : 1,
      "name" : "Kakizawa T",
      "referenceId" : "RGD:A94169"
    }, {
      "firstName" : "T",
      "lastName" : "Miyamoto",
      "authorRank" : 2,
      "name" : "Miyamoto T",
      "referenceId" : "RGD:A6918"
    }, {
      "firstName" : "K",
      "lastName" : "Ichikawa",
      "authorRank" : 3,
      "name" : "Ichikawa K",
      "referenceId" : "RGD:A48178"
    }, {
      "firstName" : "A",
      "lastName" : "Kaneko",
      "authorRank" : 4,
      "name" : "Kaneko A",
      "referenceId" : "RGD:A31750"
    }, {
      "firstName" : "S",
      "lastName" : "Suzuki",
      "authorRank" : 5,
      "name" : "Suzuki S",
      "referenceId" : "RGD:A9090"
    }, {
      "firstName" : "M",
      "lastName" : "Hara",
      "authorRank" : 6,
      "name" : "Hara M",
      "referenceId" : "RGD:A32682"
    }, {
      "firstName" : "T",
      "lastName" : "Nagasawa",
      "authorRank" : 7,
      "name" : "Nagasawa T",
      "referenceId" : "RGD:A12123"
    }, {
      "firstName" : "T",
      "lastName" : "Takeda",
      "authorRank" : 8,
      "name" : "Takeda T",
      "referenceId" : "RGD:A17662"
    }, {
      "firstName" : "JI",
      "lastName" : "Mori",
      "authorRank" : 9,
      "name" : "Mori",
      "referenceId" : "RGD:A199237"
    }, {
      "firstName" : "M",
      "lastName" : "Kumagai",
      "authorRank" : 10,
      "name" : "Kumagai M",
      "referenceId" : "RGD:A64908"
    }, {
      "firstName" : "K",
      "lastName" : "Hashizume",
      "authorRank" : 11,
      "name" : "Hashizume K",
      "referenceId" : "RGD:A65822"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9727451"
    } ]
  }, {
    "primaryId" : "PMID:10383417",
    "title" : "Possible involvement of a novel STAM-associated molecule \"AMSH\" in intracellular signal transduction mediated by cytokines.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Tanaka N, etal., J Biol Chem 1999 Jul 2;274(27):19129-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-01T08:06:54.000-05:00",
    "volume" : "274",
    "pages" : "19129-35",
    "abstract" : "STAM containing an SH3 (Src homology 3) domain and an immunoreceptor tyrosine-based activation motif was previously revealed to be implicated in signaling pathways immediately downstream of Jak2 and Jak3 tyrosine kinases associated with cytokine receptors. We molecularly cloned a novel molecule interacting with the SH3 domain of STAM, which was named AMSH (associated molecule with the SH3 domain of STAM). AMSH contains a putative bipartite nuclear localization signal and a homologous region of a c-Jun activation domain-binding protein 1 (JAB1) subdomain in addition to a binding site for the SH3 domain of STAM. AMSH mutant deleted of the C-terminal half conferred dominant negative effects on signaling for DNA synthesis and c-myc induction mediated by interleukin 2 and granulocyte macrophage-colony-stimulating factor. These results suggest that AMSH plays a critical role in the cytokine-mediated intracellular signal transduction downstream of the Jak2/Jak3.STAM complex.",
    "issueName" : "27",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Tanaka",
      "authorRank" : 1,
      "name" : "Tanaka N",
      "referenceId" : "RGD:A8912"
    }, {
      "firstName" : "K",
      "lastName" : "Kaneko",
      "authorRank" : 2,
      "name" : "Kaneko K",
      "referenceId" : "RGD:A5732"
    }, {
      "firstName" : "H",
      "lastName" : "Asao",
      "authorRank" : 3,
      "name" : "Asao H",
      "referenceId" : "RGD:A24300"
    }, {
      "firstName" : "H",
      "lastName" : "Kasai",
      "authorRank" : 4,
      "name" : "Kasai H",
      "referenceId" : "RGD:A24301"
    }, {
      "firstName" : "Y",
      "lastName" : "Endo",
      "authorRank" : 5,
      "name" : "Endo Y",
      "referenceId" : "RGD:A20549"
    }, {
      "firstName" : "T",
      "lastName" : "Fujita",
      "authorRank" : 6,
      "name" : "Fujita T",
      "referenceId" : "RGD:A6425"
    }, {
      "firstName" : "T",
      "lastName" : "Takeshita",
      "authorRank" : 7,
      "name" : "Takeshita T",
      "referenceId" : "RGD:A24302"
    }, {
      "firstName" : "K",
      "lastName" : "Sugamura",
      "authorRank" : 8,
      "name" : "Sugamura K",
      "referenceId" : "RGD:A24303"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634548"
    } ]
  }, {
    "primaryId" : "PMID:10383464",
    "title" : "Arcadlin is a neural activity-regulated cadherin involved in long term potentiation.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Yamagata K, etal., J Biol Chem 1999 Jul 2;274(27):19473-1979.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:54.000-05:00",
    "volume" : "274",
    "pages" : "19473-1979",
    "abstract" : "Neural activity results in long term changes that underlie synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here, we identify a novel cadherin molecule Arcadlin (activity-regulated cadherin-like protein). arcadlin mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by N-methyl-D-aspartate-dependent synaptic activity in long term potentiation. The extracellular domain of Arcadlin is most homologous to protocadherin-8; however, the cytoplasmic region is distinct from that of any cadherin family member. Arcadlin protein is expressed at the synapses and shows a homophilic binding activity in a Ca2+-dependent manner. Furthermore, application of Arcadlin antibody reduces excitatory postsynaptic potential amplitude and blocks long term potentiation in hippocampal slices. Its close homology with cadherins, its rapid inducibility by neural activity, and its involvement in synaptic transmission suggest that Arcadlin may play an important role in activity-induced synaptic reorganization underlying long term memory.",
    "issueName" : "27",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Yamagata",
      "authorRank" : 1,
      "name" : "Yamagata K",
      "referenceId" : "RGD:A125327"
    }, {
      "firstName" : "KI",
      "lastName" : "Andreasson",
      "authorRank" : 2,
      "name" : "Andreasson KI",
      "referenceId" : "RGD:A5725"
    }, {
      "firstName" : "H",
      "lastName" : "Sugiura",
      "authorRank" : 3,
      "name" : "Sugiura H",
      "referenceId" : "RGD:A5726"
    }, {
      "firstName" : "E",
      "lastName" : "Maru",
      "authorRank" : 4,
      "name" : "Maru E",
      "referenceId" : "RGD:A5727"
    }, {
      "firstName" : "M",
      "lastName" : "Dominique",
      "authorRank" : 5,
      "name" : "Dominique M",
      "referenceId" : "RGD:A5728"
    }, {
      "firstName" : "Y",
      "lastName" : "Irie",
      "authorRank" : 6,
      "name" : "Irie Y",
      "referenceId" : "RGD:A5729"
    }, {
      "firstName" : "N",
      "lastName" : "Miki",
      "authorRank" : 7,
      "name" : "Miki N",
      "referenceId" : "RGD:A5707"
    }, {
      "firstName" : "Y",
      "lastName" : "Hayashi",
      "authorRank" : 8,
      "name" : "Hayashi Y",
      "referenceId" : "RGD:A299696"
    }, {
      "firstName" : "M",
      "lastName" : "Yoshioka",
      "authorRank" : 9,
      "name" : "Yoshioka M",
      "referenceId" : "RGD:A5731"
    }, {
      "firstName" : "K",
      "lastName" : "Kaneko",
      "authorRank" : 10,
      "name" : "Kaneko K",
      "referenceId" : "RGD:A5732"
    }, {
      "firstName" : "H",
      "lastName" : "Kato",
      "authorRank" : 11,
      "name" : "Kato H",
      "referenceId" : "RGD:A158249"
    }, {
      "firstName" : "PF",
      "lastName" : "Worley",
      "authorRank" : 12,
      "name" : "Worley PF",
      "referenceId" : "RGD:A49791"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68758"
    } ]
  }, {
    "primaryId" : "PMID:10383487",
    "title" : "Impact of testosterone and oestradiol on region specificity of skeletal muscle-ATP, creatine phosphokinase and myokinase in male and female Wistar rats.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Ramamani A, etal., Acta Physiol Scand. 1999 Jun;166(2):91-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-09-08T08:48:45.000-05:00",
    "volume" : "166",
    "pages" : "91-7",
    "abstract" : "The main aim of the present study was to test the hypothesis that skeletal muscle ATP concentration, creatine phosphokinase and myokinase enzyme activities are stimulated by the sex steroids in both male and female rats (animals were not subjected to any kind of exercise or any training). To test the hypothesis healthy mature (90-120 days old, weighing about 160-180 g) male and female rats were gonadectomized. Gonadectomized male and female rats were administered with testosterone (Sigma Chemical, St Louis, MO, USA) at a dose of 100 microg (100 g body weight)-1 day-1 for males and 5 microg (100 g body weight)-1 day-1 for females for 30 days from day 31 post-castration onwards; and oestradiol at a dose of 5 microg (100 g body weight)-1 day-1 for 30 days from day 31 post-castration onwards for both males and females (17beta oestradiol, Sigma Chemical Company, St Louis, MO, USA). The ATP content, creatine phosphokinase and myokinase enzyme activities of skeletal muscles were significantly higher than that of skeletal muscles of female control rats. Gonadectomy resulted in a significant decrease in ATP content and creatine phosphokinase myokinase enzyme activities in both male and female rats. Testosterone treatment to gonadectomized male rats brought back the parameters to normalcy whereas the same to the female rats enhanced the enzyme activities and ATP contents to the level of control male rats. Oestradiol treatment to castrated male rats did not bring about any significant alterations whereas the same in gonadectomized female rats brought them back to normalcy. Therefore from the present study it is concluded that testosterone is effective in both males and females whereas oestradiol was effective only in the females in enhancing skeletal muscle energy metabolism.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Ramamani",
      "authorRank" : 1,
      "name" : "Ramamani A",
      "referenceId" : "RGD:A144464"
    }, {
      "firstName" : "MM",
      "lastName" : "Aruldhas",
      "authorRank" : 2,
      "name" : "Aruldhas MM",
      "referenceId" : "RGD:A34414"
    }, {
      "firstName" : "P",
      "lastName" : "Govindarajulu",
      "authorRank" : 3,
      "name" : "Govindarajulu P",
      "referenceId" : "RGD:A34413"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5490212"
    } ]
  }, {
    "primaryId" : "PMID:10383730",
    "title" : "Basal transepidermal water loss is increased in platelet-type 12-lipoxygenase deficient mice.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Johnson EN, etal., J Invest Dermatol. 1999 Jun;112(6):861-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-02T15:20:34.000-06:00",
    "volume" : "112",
    "pages" : "861-5",
    "abstract" : "The roles of fatty acids in the skin have been under investigation since early reports of the phenotypic abnormalities of mice fed a diet deficient in essential fatty acids. Little is known about the functional significance of fatty acid metabolism by lipoxygenases in epidermis. Here, we have examined the role of platelet-type 12-lipoxygenase which converts arachidonic acid to the oxygenated metabolite 12-hydroperoxyeicosatetraenoic acid, in the skin using platelet-type 12-lipoxygenase-deficient mice generated by gene targeting. Platelet-type 12-lipoxygenase in wild-type mice was localized to the stratum granulosum by immunohistochemical analysis. Platelet-type 12-lipoxygenase-deficient mice lacked immunodetectable platelet-type 12-lipoxygenase in platelets and epidermis, appeared grossly normal, and exhibited an increase in basal transepidermal water loss without alteration in basal mitotic activity. Water loss and mitotic activity in mice with an acetone-disrupted membrane barrier were normal. No defect in ultrastructural properties or content of major fatty acids in dorsal skin or ear inflammation response was apparent in platelet-type 12-lipoxygenase-deficient mice. These results indicate that the platelet-type 12-lipoxygenase pathway in mice is partly responsible for normal permeability barrier function but the mechanism awaits further elucidation.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EN",
      "lastName" : "Johnson",
      "authorRank" : 1,
      "name" : "Johnson EN",
      "referenceId" : "RGD:A58503"
    }, {
      "firstName" : "LB",
      "lastName" : "Nanney",
      "authorRank" : 2,
      "name" : "Nanney LB",
      "referenceId" : "RGD:A58505"
    }, {
      "firstName" : "J",
      "lastName" : "Virmani",
      "authorRank" : 3,
      "name" : "Virmani J",
      "referenceId" : "RGD:A58506"
    }, {
      "firstName" : "JA",
      "lastName" : "Lawson",
      "authorRank" : 4,
      "name" : "Lawson JA",
      "referenceId" : "RGD:A46850"
    }, {
      "firstName" : "CD",
      "lastName" : "Funk",
      "authorRank" : 5,
      "name" : "Funk CD",
      "referenceId" : "RGD:A58504"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578313"
    } ]
  }, {
    "primaryId" : "PMID:10383750",
    "title" : "A premature stop codon mutation in the 2B helix termination peptide of keratin 5 in a German epidermolysis bullosa simplex Dowling-Meara case.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Müller FB, etal., J Invest Dermatol. 1999 Jun;112(6):988-90. doi: 10.1046/j.1523-1747.1999.00615.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:38:12.000-05:00",
    "volume" : "112",
    "pages" : "988-90",
    "abstract" : "Epidermolysis bullosa simplex (EBS) is caused by defective assembly of keratin intermediate filaments in basal keratinocytes and recent studies indicated causal mutations in the keratin KRT5 and KRT14 genes. In this study, we describe a novel KRT5 mutation in a German sporadic case of EBS Dowling-Meara. Transition of G to T (nucleotide position 2334) leads to a premature stop codon (E477stop, residue 93 of the 2B helix) in the last residue of the highly conserved helix-termination peptide K/LLEGE of the 2B rod domain of keratin K5. This represents the first premature stop codon mutation identified within the K/LLEGE motif of any disorder reported so far that is caused by keratin mutations.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F B",
      "lastName" : "Müller",
      "authorRank" : 1,
      "name" : "Müller FB",
      "referenceId" : "RGD:A594332"
    }, {
      "firstName" : "I",
      "lastName" : "Anton-Lamprecht",
      "authorRank" : 2,
      "name" : "Anton-Lamprecht I",
      "referenceId" : "RGD:A581060"
    }, {
      "firstName" : "W",
      "lastName" : "Küster",
      "authorRank" : 3,
      "name" : "Küster W",
      "referenceId" : "RGD:A593145"
    }, {
      "firstName" : "B P",
      "lastName" : "Korge",
      "authorRank" : 4,
      "name" : "Korge BP",
      "referenceId" : "RGD:A594333"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118451"
    } ]
  }, {
    "primaryId" : "PMID:10383826",
    "title" : "Rapid phosphorylation of Elk-1 transcription factor and activation of MAP kinase  signal transduction pathways in response to visual stimulation.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Kaminska B, etal., Mol Cell Neurosci. 1999 Jun;13(6):405-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-12-05T15:13:05.000-06:00",
    "volume" : "13",
    "pages" : "405-14",
    "abstract" : "The AP-1 transcription factor, which is composed of various combinations of Fos and Jun proteins, is believed to be a key participant in molecular processes that guide activity-dependent changes in gene expression. In this study, we investigated the activity of different MAP kinases that have been implicated in AP-1 activation. We examined the activities of ERK, JNK/SAPK, and p38 MAPK along  with their nuclear targets (Elk-1 and c-Jun) in rat visual cortex after light stimulation. The transcription factor Elk-1 (a possible regulator of c-fos expression) was found to be transiently modified by phosphorylation when visual stimulation was applied after a period of dark rearing. In vitro kinase assay with Elk-1 as substrate showed that light stimulation activated MAPK/ERK in visual cortex but not frontal cortex. Furthermore, ERK activation was temporally  matched to onset of Elk-1 phosphorylation. The activity of JNK1 (c-Jun N-terminal kinase 1) was elevated at 2-6 h after visual exposure and was also temporally correlated to increase of endogenous P-c-Jun levels and its appearance within the AP-1 DNA-binding complex. The activities of p38 MAP kinases did not change significantly. These results demonstrate the differential engagement of MAPK signaling pathways following sensory stimulation and their relative effects upon  AP-1 expression in the intact brain.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Kaminska",
      "authorRank" : 1,
      "name" : "Kaminska B",
      "referenceId" : "RGD:A11962"
    }, {
      "firstName" : "L",
      "lastName" : "Kaczmarek",
      "authorRank" : 2,
      "name" : "Kaczmarek L",
      "referenceId" : "RGD:A9136"
    }, {
      "firstName" : "S",
      "lastName" : "Zangenehpour",
      "authorRank" : 3,
      "name" : "Zangenehpour S",
      "referenceId" : "RGD:A19676"
    }, {
      "firstName" : "A",
      "lastName" : "Chaudhuri",
      "authorRank" : 4,
      "name" : "Chaudhuri A",
      "referenceId" : "RGD:A19677"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7488912"
    } ]
  }, {
    "primaryId" : "PMID:10383829",
    "title" : "A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Drosopoulos NE, etal., Mol Cell Neurosci 1999 Jun;13(6):441-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:01:23.000-05:00",
    "volume" : "13",
    "pages" : "441-9",
    "abstract" : "Receptor-like protein tyrosine phosphatase kappa (RPTPkappa) is expressed in the nervous system in a manner consistent with a role in axonal growth and guidance. The extracellular domain of RPTPkappa shares structural features with cell adhesion molecules and can support homophilic adhesion. In the present study we produced a soluble Fc-chimeric protein containing the full extracellular domain of RPTPkappa. Following affinity capture, the RPTPkappa-Fc was shown to promote the aggregation of Covasphere beads, confirming its homophilic binding activity. When added to cultures of cerebellar neurons as a soluble molecule, the RPTPkappa chimera stimulated neurite outgrowth. The neurite outgrowth response was substantially inhibited by a cell-permeable peptide inhibitor of Grb2 and by PD 098059, a drug that has been used to inhibit MEK1 activation in a wide range of cell types. These results demonstrate that RPTPkappa can stimulate neurite outgrowth and provide evidence that this might involve the coupling of Grb2 to a MAPK signal transduction cascade.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NE",
      "lastName" : "Drosopoulos",
      "authorRank" : 1,
      "name" : "Drosopoulos NE",
      "referenceId" : "RGD:A22851"
    }, {
      "firstName" : "FS",
      "lastName" : "Walsh",
      "authorRank" : 2,
      "name" : "Walsh FS",
      "referenceId" : "RGD:A12095"
    }, {
      "firstName" : "P",
      "lastName" : "Doherty",
      "authorRank" : 3,
      "name" : "Doherty P",
      "referenceId" : "RGD:A22852"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634006"
    } ]
  }, {
    "primaryId" : "PMID:10383892",
    "title" : "cDNA cloning, expression and activity of a second human aflatoxin B1-metabolizing member of the aldo-keto reductase superfamily, AKR7A3.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Knight LP, etal., Carcinogenesis. 1999 Jul;20(7):1215-23. doi: 10.1093/carcin/20.7.1215.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-03-15T06:05:49.000-05:00",
    "volume" : "20",
    "pages" : "1215-23",
    "abstract" : "The aflatoxin B1 (AFB1) aldehyde metabolite of AFB1 may contribute to the cytotoxicity of this hepatocarcinogen via protein adduction. Aflatoxin B1 aldehyde reductases, specifically the NADPH-dependent aldo-keto reductases of rat (AKR7A1) and human (AKR7A2), are known to metabolize the AFB1 dihydrodiol by forming AFB1 dialcohol. Using a rat AKR7A1 cDNA, we isolated and characterized a distinct aldo-keto reductase (AKR7A3) from an adult human liver cDNA library. The deduced amino acid sequence of AKR7A3 shares 80 and 88% identity with rat AKR7A1 and human AKR7A2, respectively. Recombinant rat AKR7A1 and human AKR7A3 were expressed and purified from Escherichia coli as hexa-histidine tagged fusion proteins. These proteins catalyzed the reduction of several model carbonyl-containing substrates. The NADPH-dependent formation of AFB1 dialcohol by recombinant human AKR7A3 was confirmed by liquid chromatography coupled to electrospray ionization mass spectrometry. Rabbit polyclonal antibodies produced using recombinant rat AKR7A1 protein were shown to detect nanogram amounts of rat and human AKR7A protein. The amount of AKR7A-related protein in hepatic cytosols of 1, 2-dithiole-3-thione-treated rats was 18-fold greater than in cytosols from untreated animals. These antibodies detected AKR7A-related protein in normal human liver samples ranging from 0.3 to 0.8 microg/mg cytosolic protein. Northern blot analysis showed varying levels of expression of AKR7A RNA in human liver and in several extrahepatic tissues, with relatively high levels in the stomach, pancreas, kidney and liver. Based on the kinetic parameters determined using recombinant human AKR7A3 and AFB1 dihydrodiol at pH 7.4, the catalytic efficiency of this reaction (k2/K, per M/s) equals or exceeds those reported for other enzymes, for example cytochrome P450s and glutathione S-transferases, known to metabolize AFB1 in vivo. These findings indicate that, depending on the extent of AFB1 dihydrodiol formation, AKR7A may contribute to the protection against AFB1-induced hepatotoxicity.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L P",
      "lastName" : "Knight",
      "authorRank" : 1,
      "name" : "Knight LP",
      "referenceId" : "RGD:A561758"
    }, {
      "firstName" : "T",
      "lastName" : "Primiano",
      "authorRank" : 2,
      "name" : "Primiano T",
      "referenceId" : "RGD:A17965"
    }, {
      "firstName" : "J D",
      "lastName" : "Groopman",
      "authorRank" : 3,
      "name" : "Groopman JD",
      "referenceId" : "RGD:A561759"
    }, {
      "firstName" : "T W",
      "lastName" : "Kensler",
      "authorRank" : 4,
      "name" : "Kensler TW",
      "referenceId" : "RGD:A486027"
    }, {
      "firstName" : "T R",
      "lastName" : "Sutter",
      "authorRank" : 5,
      "name" : "Sutter TR",
      "referenceId" : "RGD:A486026"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598092476"
    } ]
  }, {
    "primaryId" : "PMID:10383893",
    "title" : "Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasias.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Lemos MC, etal., Carcinogenesis. 1999 Jul;20(7):1225-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-25T11:39:59.000-06:00",
    "volume" : "20",
    "pages" : "1225-9",
    "abstract" : "Xenobiotic-metabolizing enzymes constitute an important line of defence against a variety of carcinogens. Many are polymorphic, constituting the basis for the wide inter-individual variation in metabolic capacity and possibly a source of variation in the susceptibility to chemical-induced carcinogenesis. The aim of this study was to determine the existence of any association between the main genetic polymorphisms of cytochrome P450 2D6 (CYP2D6), glutathione S-transferase  M1 (GSTM1) and N-acetyltransferase 2 (NAT2) and an altered risk for haematological neoplasias. A total of 160 patients and 128 controls were genotyped by means of PCR-RFLP-based assays. Mutated alleles comprising CYP2D6*4, GSTM1*0, NAT2*5A, *5B, *5C, *6 and *7 were analysed along with the wild-type alleles. The results showed a higher frequency of CYP2D6 extensive metabolizers carrying two functional alleles in the leukaemia group, when compared with controls (76.6 versus 57.0%, P = 0.008). No differences were found in the case of Hodgkin and non-Hodgkin lymphomas. Analysis of the GSTM1 and NAT2 polymorphisms failed to show an association with any of the neoplasias, although a near significant increase in fast acetylators was also found in the leukaemia group (50.0 versus 35.9%, P = 0.06). The results suggest an association of extensive metabolism with an increased risk for leukaemia, possibly by an increase in the metabolic activation of chemical carcinogens or linkage to another cancer-causing gene. Opposite findings presented in other studies may reflect geographical differences in the type of environmental carcinogens to which different populations are exposed.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MC",
      "lastName" : "Lemos",
      "authorRank" : 1,
      "name" : "Lemos MC",
      "referenceId" : "RGD:A120935"
    }, {
      "firstName" : "FJ",
      "lastName" : "Cabrita",
      "authorRank" : 2,
      "name" : "Cabrita",
      "referenceId" : "RGD:A210956"
    }, {
      "firstName" : "HA",
      "lastName" : "Silva",
      "authorRank" : 3,
      "name" : "Silva",
      "referenceId" : "RGD:A210957"
    }, {
      "firstName" : "M",
      "lastName" : "Vivan",
      "authorRank" : 4,
      "name" : "Vivan",
      "referenceId" : "RGD:A210958"
    }, {
      "firstName" : "F",
      "lastName" : "Placido",
      "authorRank" : 5,
      "name" : "Placido",
      "referenceId" : "RGD:A210959"
    }, {
      "firstName" : "FJ",
      "lastName" : "Regateiro",
      "authorRank" : 6,
      "name" : "Regateiro",
      "referenceId" : "RGD:A210960"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10755329"
    } ]
  }, {
    "primaryId" : "PMID:10383894",
    "title" : "Interaction between haemochromatosis and transferrin receptor genes in different  neoplastic disorders.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Beckman LE, etal., Carcinogenesis. 1999 Jul;20(7):1231-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-08-04T11:02:26.000-05:00",
    "volume" : "20",
    "pages" : "1231-3",
    "abstract" : "A number of genes are involved in iron metabolism, including the transferrin receptor (TFR) and haemochromatosis (HFE) genes. In previous investigations an increased risk for neoplastic disease has been observed in individuals homo- and  heterozygous for hereditary haemochromatosis. The HFE wild-type gene product complexes with the transferrin receptor (TF) and two different HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of TFR for TF and increase cellular iron uptake. In a recent study we found no associations for HFE and TFR separately, but an interaction between HFE and TFR genotypes in multiple myeloma. Individuals carrying the HFE Tyr282 allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser142 allele had an  increased risk. In the present study the same association was found in breast and colorectal cancer. The odds ratio for all three neoplasms combined was 2.0 (95% CI 1.0-3.8). The risk for neoplastic disease was further increased (OR 7.7, 95% CI = 1.0-59.9) when the analysis was restricted to HFE Tyr homozygotes and compound heterozygotes in combination with TFR Ser homozygosity. Thus, an interaction between HFE and TFR alleles may increase the risk for different neoplastic disorders.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LE",
      "lastName" : "Beckman",
      "authorRank" : 1,
      "name" : "Beckman",
      "referenceId" : "RGD:A192160"
    }, {
      "firstName" : "GF",
      "lastName" : "Van Landeghem",
      "authorRank" : 2,
      "name" : "Van Landeghem",
      "referenceId" : "RGD:A192161"
    }, {
      "firstName" : "C",
      "lastName" : "Sikstrom",
      "authorRank" : 3,
      "name" : "Sikstrom",
      "referenceId" : "RGD:A192162"
    }, {
      "firstName" : "A",
      "lastName" : "Wahlin",
      "authorRank" : 4,
      "name" : "Wahlin",
      "referenceId" : "RGD:A192163"
    }, {
      "firstName" : "B",
      "lastName" : "Markevarn",
      "authorRank" : 5,
      "name" : "Markevarn",
      "referenceId" : "RGD:A192164"
    }, {
      "firstName" : "G",
      "lastName" : "Hallmans",
      "authorRank" : 6,
      "name" : "Hallmans G",
      "referenceId" : "RGD:A70272"
    }, {
      "firstName" : "P",
      "lastName" : "Lenner",
      "authorRank" : 7,
      "name" : "Lenner",
      "referenceId" : "RGD:A192165"
    }, {
      "firstName" : "L",
      "lastName" : "Athlin",
      "authorRank" : 8,
      "name" : "Athlin",
      "referenceId" : "RGD:A192166"
    }, {
      "firstName" : "R",
      "lastName" : "Stenling",
      "authorRank" : 9,
      "name" : "Stenling",
      "referenceId" : "RGD:A192167"
    }, {
      "firstName" : "L",
      "lastName" : "Beckman",
      "authorRank" : 10,
      "name" : "Beckman",
      "referenceId" : "RGD:A187882"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8694350"
    } ]
  }, {
    "primaryId" : "PMID:10383909",
    "title" : "Immunohistochemical localization of inducible nitric oxide synthase and 3-nitrotyrosine in rat liver tumors induced by N-nitrosodiethylamine.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Ahn B, etal., Carcinogenesis. 1999 Jul;20(7):1337-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-05-28T08:27:31.000-05:00",
    "volume" : "20",
    "pages" : "1337-44",
    "abstract" : "Human liver cancers have been associated mainly with chronic inflammations such as viral hepatitis B or C. This suggests that prolonged cell damage by chronic inflammation is critical in cancer development. Overproduction of nitric oxide (NO.) and its derivative (NOx, peroxynitrite) has been implicated as a cause of tissue damage by inflammation, thus contributing to tumor promotion. We have demonstrated the expression of the inducible isoform of nitric oxide synthase (iNOS) and 3-nitrotyrosine, a marker of peroxynitrite formation, by immunohistochemistry in preneoplastic and neoplastic rat liver tissues induced by continuous infusion of N-nitrosodiethylamine with mini-pumps. The preneoplastic lesions were characterized by proliferation of phenotypically altered hepatic foci (PAHF), dysplastic hepatocytes and oval cells. Histologically, the tumors were hepatocellular carcinomas (HCCs) of trabecular, (pseudo)glandular and solid types with or without cholangiocellular involvement. iNOS was located mainly in oval cells, capillary endothelial and muscular cells, epithelia of cholangiomas and glandular HCCs. 3-Nitrotyrosine was observed in the cytoplasms of PAHF and dysplastic hepatocytes in preneoplasias and in the cytoplasms of some living or apoptotic HCC cells, connective tissues, proteinaceous fluids, sinusoidal endothelia of tumorous hepatocytes and cholangiomas in tumors. From these observations, we suggest that: (i) chronic tissue damage by chemical carcinogens may act to induce iNOS and peroxynitrite formation; (ii) oval cells play a key role in development and/or growth of tumor tissues by producing NO. via iNOS, which may also cause tissue damage by peroxynitrite; (iii) iNOS can be considered as a phenotypic marker in cells of oval cell lineage and neovascularized capillaries in tumor tissues.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Ahn",
      "authorRank" : 1,
      "name" : "Ahn B",
      "referenceId" : "RGD:A123976"
    }, {
      "firstName" : "BS",
      "lastName" : "Han",
      "authorRank" : 2,
      "name" : "Han BS",
      "referenceId" : "RGD:A123977"
    }, {
      "firstName" : "DJ",
      "lastName" : "Kim",
      "authorRank" : 3,
      "name" : "Kim DJ",
      "referenceId" : "RGD:A61287"
    }, {
      "firstName" : "H",
      "lastName" : "Ohshima",
      "authorRank" : 4,
      "name" : "Ohshima H",
      "referenceId" : "RGD:A49211"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2325277"
    } ]
  }, {
    "primaryId" : "PMID:10383933",
    "title" : "Expression pattern of notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand-receptor interactions in intrathymic T cell development.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Felli MP, etal., Int Immunol. 1999 Jul;11(7):1017-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:31:22.000-05:00",
    "volume" : "11",
    "pages" : "1017-25",
    "abstract" : "The suggested role of Notch1 or its mutants in thymocyte differentiation and T cell tumorigenesis raises the question of how the different members of the Notch  family influence distinct steps in T cell development and the role played by Notch ligands in the thymus. We report here that different Notch receptor-ligand  partnerships may occur inside the thymus, as we observed differential expression  of Notch1, 2 and 3 receptors, their ligands Jagged1 and 2, and downstream intracellular effectors hairy and Enhancer of Split homolog 1 (HES-1) and hairy and Enhancer of Split homolog 5 (HES-5), depending on ontogenetic stage and thymic cell populations. Indeed, while Jagged2 is expressed in both stromal cells and thymocytes, Jagged1 expression is restricted to stromal cells. Moreover, a differential distribution of Notch3, with respect to Notch1, was observed in distinct age-related thymocyte subsets. Finally, Notch3 was preferentially up-regulated in thymocytes, following the induction of their differentiation by interaction with thymic epithelial cells expressing the cognate Jagged1 and 2 ligands, suggesting that, besides Notch1, Notch3 may also be involved in distinct steps of thymocyte development. Our results suggest that the Notch signaling pathway is involved in a complex interplay of T cell developmental stages, as a consequence of the heterogeneity and specific expression of members of the Notch  receptor family and their cognate ligands, in distinct thymic cell compartments.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MP",
      "lastName" : "Felli",
      "authorRank" : 1,
      "name" : "Felli",
      "referenceId" : "RGD:A183597"
    }, {
      "firstName" : "M",
      "lastName" : "Maroder",
      "authorRank" : 2,
      "name" : "Maroder",
      "referenceId" : "RGD:A183598"
    }, {
      "firstName" : "TA",
      "lastName" : "Mitsiadis",
      "authorRank" : 3,
      "name" : "Mitsiadis",
      "referenceId" : "RGD:A183599"
    }, {
      "firstName" : "AF",
      "lastName" : "Campese",
      "authorRank" : 4,
      "name" : "Campese",
      "referenceId" : "RGD:A183600"
    }, {
      "firstName" : "D",
      "lastName" : "Bellavia",
      "authorRank" : 5,
      "name" : "Bellavia D",
      "referenceId" : "RGD:A149453"
    }, {
      "firstName" : "A",
      "lastName" : "Vacca",
      "authorRank" : 6,
      "name" : "Vacca",
      "referenceId" : "RGD:A183601"
    }, {
      "firstName" : "RS",
      "lastName" : "Mann",
      "authorRank" : 7,
      "name" : "Mann RS",
      "referenceId" : "RGD:A49904"
    }, {
      "firstName" : "L",
      "lastName" : "Frati",
      "authorRank" : 8,
      "name" : "Frati L",
      "referenceId" : "RGD:A34865"
    }, {
      "firstName" : "U",
      "lastName" : "Lendahl",
      "authorRank" : 9,
      "name" : "Lendahl U",
      "referenceId" : "RGD:A21177"
    }, {
      "firstName" : "A",
      "lastName" : "Gulino",
      "authorRank" : 10,
      "name" : "Gulino A",
      "referenceId" : "RGD:A66661"
    }, {
      "firstName" : "I",
      "lastName" : "Screpanti",
      "authorRank" : 11,
      "name" : "Screpanti I",
      "referenceId" : "RGD:A116450"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553281"
    } ]
  }, {
    "primaryId" : "PMID:10384040",
    "title" : "Linkage mapping of rat chromosome 5 markers generated from chromosome-specific libraries.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Lan H, etal., Mamm Genome 1999 Jul;10(7):687-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-17T13:11:43.000-05:00",
    "volume" : "10",
    "pages" : "687-91",
    "abstract" : "Seventy-six novel microsatellite markers with various simple sequence repeat (SSR) motifs are reported in this paper. They were generated on the basis of non-radioactive library screening procedures from flow-sorted rat Chromosome (Chr) 5-specific DNA, and were mapped in three rat backcross populations. Fifty-four of these markers mapped to Chr 5, while the other 22 mapped to other chromosomes of the rat genome. The marker D3Uwm8 is a new microsatellite marker for the rat syndecan 4 (ryudocan) gene. A genotyping protocol based on agarose gel electrophoresis is also provided in this paper.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Lan",
      "authorRank" : 1,
      "name" : "Lan H",
      "referenceId" : "RGD:A109790"
    }, {
      "firstName" : "LA",
      "lastName" : "Shepel",
      "authorRank" : 2,
      "name" : "Shepel LA",
      "referenceId" : "RGD:A67941"
    }, {
      "firstName" : "JD",
      "lastName" : "Haag",
      "authorRank" : 3,
      "name" : "Haag JD",
      "referenceId" : "RGD:A148404"
    }, {
      "firstName" : "MN",
      "lastName" : "Gould",
      "authorRank" : 4,
      "name" : "Gould MN",
      "referenceId" : "RGD:A153633"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68914"
    } ]
  }, {
    "primaryId" : "PMID:10384041",
    "title" : "Deletion in the beige gene of the beige rat owing to recombination between LINE1s.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Mori M, etal., Mamm Genome 1999 Jul;10(7):692-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:37:16.000-05:00",
    "volume" : "10",
    "pages" : "692-5",
    "abstract" : "We have determined the molecular genetic basis of the rat beige mutant, a model for human Chediak-Higashi syndrome. Deletion of a 578-bp sequence, which led to a frame shift and a presumably non-functional truncated BEIGE protein, was identified in beige cDNA. The beige rat had a deletion of about 20 kb of genomic DNA, including three exons, which constitute the deleted 578-bp cDNA fragment. LINE1s (Long Interspersed Nucleolar Element 1) were identified at the site of the deletion. Consensus recognition sequences for DNA topoisomerase I were clustered at the putative deletion junction sites in LINE1s. We conclude that the deletion in the beige gene mediated by recombination between LINE1s is the causative mutation in the beige rat. The recombination might have been induced by DNA topoisomerase I and the extensive sequence homology between LINE1s.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Mori",
      "authorRank" : 1,
      "name" : "Mori M",
      "referenceId" : "RGD:A7028"
    }, {
      "firstName" : "T",
      "lastName" : "Nishikawa",
      "authorRank" : 2,
      "name" : "Nishikawa T",
      "referenceId" : "RGD:A11119"
    }, {
      "firstName" : "K",
      "lastName" : "Higuchi",
      "authorRank" : 3,
      "name" : "Higuchi K",
      "referenceId" : "RGD:A20487"
    }, {
      "firstName" : "M",
      "lastName" : "Nishimura",
      "authorRank" : 4,
      "name" : "Nishimura M",
      "referenceId" : "RGD:A10995"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633300"
    } ]
  }, {
    "primaryId" : "PMID:10384042",
    "title" : "Genomic assignment of the warfarin resistance locus, Rw, in the rat.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Kohn MH and Pelz HJ, Mamm Genome 1999 Jul;10(7):696-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-01-11T10:51:02.000-06:00",
    "volume" : "10",
    "pages" : "696-8",
    "abstract" : "The locus responsible for resistance to the anticoagulants warfarin and bromadiolone (locus symbol Rw) was integrated into the rat (Rattus norvegicus) microsatellite genome map. Seventh-generation offspring of a segregating strain of rats heterozygous resistant to both compounds were tested with a blood-clotting-response (BCR) test. No recombination between resistance to warfarin and bromadiolone was observed, indicating a common genetic basis. No recombinants were found between Rw and D1Arb18 (Myl2) located at the MIT-microsatellite map position 95.90 (SHRSP x BN F2-cross) or 82.24 (FHH x ACI F2-cross). Resistance segregated in a ratio expected for single, dominant gene responses. An equal number of females and males were resistant, but females retained higher percentage blood coagulation activities (PCA) after anticoagulant administration. Partial synteny between rat, mouse, and human suggests that Myl2 may serve as anchor to map the Rw homologs in mouse and human.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MH",
      "lastName" : "Kohn",
      "authorRank" : 1,
      "name" : "Kohn MH",
      "referenceId" : "RGD:A50104"
    }, {
      "firstName" : "HJ",
      "lastName" : "Pelz",
      "authorRank" : 2,
      "name" : "Pelz HJ",
      "referenceId" : "RGD:A48315"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1304540"
    } ]
  }, {
    "primaryId" : "PMID:10384052",
    "title" : "Comparative analyses of the Dominant megacolon-SOX10 genomic interval in mouse and human.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Southard-Smith EM, etal., Mamm Genome 1999 Jul;10(7):744-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-01T15:11:57.000-05:00",
    "volume" : "10",
    "pages" : "744-9",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EM",
      "lastName" : "Southard-Smith",
      "authorRank" : 1,
      "name" : "Southard-Smith EM",
      "referenceId" : "RGD:A48484"
    }, {
      "firstName" : "JE",
      "lastName" : "Collins",
      "authorRank" : 2,
      "name" : "Collins JE",
      "referenceId" : "RGD:A35949"
    }, {
      "firstName" : "JS",
      "lastName" : "Ellison",
      "authorRank" : 3,
      "name" : "Ellison JS",
      "referenceId" : "RGD:A55314"
    }, {
      "firstName" : "KJ",
      "lastName" : "Smith",
      "authorRank" : 4,
      "name" : "Smith KJ",
      "referenceId" : "RGD:A19699"
    }, {
      "firstName" : "AD",
      "lastName" : "Baxevanis",
      "authorRank" : 5,
      "name" : "Baxevanis AD",
      "referenceId" : "RGD:A55315"
    }, {
      "firstName" : "JW",
      "lastName" : "Touchman",
      "authorRank" : 6,
      "name" : "Touchman JW",
      "referenceId" : "RGD:A48222"
    }, {
      "firstName" : "ED",
      "lastName" : "Green",
      "authorRank" : 7,
      "name" : "Green ED",
      "referenceId" : "RGD:A7697"
    }, {
      "firstName" : "I",
      "lastName" : "Dunham",
      "authorRank" : 8,
      "name" : "Dunham I",
      "referenceId" : "RGD:A35950"
    }, {
      "firstName" : "WJ",
      "lastName" : "Pavan",
      "authorRank" : 9,
      "name" : "Pavan WJ",
      "referenceId" : "RGD:A39411"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549531"
    } ]
  }, {
    "primaryId" : "PMID:10384061",
    "title" : "Expression of C-C chemokines in bronchoalveolar lavage cells from patients with granulomatous lung diseases.",
    "datePublished" : "1000-01-01T00:00:00.000-06:00",
    "citation" : "Oshima M, etal., Lung. 1999;177(4):229-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-13T14:01:15.000-06:00",
    "volume" : "177",
    "pages" : "229-40",
    "abstract" : "To determine the role of C-C chemokines in the pathogenesis of granulomatous lung diseases, we studied the mRNA levels of C-C chemokines, regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1 in bronchoalveolar lavage (BAL) cells obtained from patients with sarcoidosis (n = 17), hypersensitivity pneumonitis (HP) (n = 4), and cryptogenic fibrosing alveolitis (CFA) (n = 10) using the reverse transcription-polymerase chain reaction (RT-PCR) technique. The mRNA levels of RANTES, MIP-1alpha, and MIP-1beta in BAL cells were significantly correlated with the lavaged lymphocyte proportion, and a significant inverse correlation was observed between the mRNA level of MIP-1beta and the CD4/CD8 ratio of lavaged lymphocytes. Among the three diseases, the mRNA levels of RANTES and MIP-1alpha were significantly higher in the patients with sarcoidosis or HP compared with those in the patients with CFA. The level of MIP-1beta mRNA was significantly higher in the HP patients compared with that in the patients with sarcoidosis or CFA. No significant differences were observed in the level of MCP-1 mRNA among the three diseases. Thus, RANTES and MIP-1alpha were suggested to be important in the pathogenesis of granulomatous inflammation in sarcoidosis and HP. MIP-1beta might play an important role in the pathogenesis of HP, mediating the recruitment of lymphocytes specific to HP.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Oshima",
      "authorRank" : 1,
      "name" : "Oshima M",
      "referenceId" : "RGD:A29003"
    }, {
      "firstName" : "A",
      "lastName" : "Maeda",
      "authorRank" : 2,
      "name" : "Maeda A",
      "referenceId" : "RGD:A40054"
    }, {
      "firstName" : "S",
      "lastName" : "Ishioka",
      "authorRank" : 3,
      "name" : "Ishioka S",
      "referenceId" : "RGD:A97849"
    }, {
      "firstName" : "K",
      "lastName" : "Hiyama",
      "authorRank" : 4,
      "name" : "Hiyama K",
      "referenceId" : "RGD:A131424"
    }, {
      "firstName" : "M",
      "lastName" : "Yamakido",
      "authorRank" : 5,
      "name" : "Yamakido M",
      "referenceId" : "RGD:A133510"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4891436"
    } ]
  }, {
    "primaryId" : "PMID:10384097",
    "title" : "Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the \"resistant\" Brown Norway rat: disease susceptibility is  determined by MHC and MHC-linked effects on the B cell response.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Stefferl A, etal., J Immunol. 1999 Jul 1;163(1):40-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-05T16:38:21.000-06:00",
    "volume" : "163",
    "pages" : "40-9",
    "abstract" : "Experimental autoimmune encephalomyelitis (EAE) induced by active immunization with the myelin oligodendrocyte glycoprotein (MOG) is an Ab-mediated, T cell-dependent autoimmune disease that replicates the inflammatory demyelinating  pathology of multiple sclerosis. We report that disease susceptibility and severity are determined by MHC and MHC-linked effects on the MOG-specific B cell  response that mediate severe clinical EAE in the EAE-resistant Brown Norway (BN)  rat. Immunization with the extracellular domain of MOG in CFA induced fulminant clinical disease associated with widespread demyelination and with an inflammatory infiltrate containing large numbers of polymorphonuclear cells and eosinophils within 10 days of immunization. To analyze the effects of the MHC (RT1 system) we compared BN (RT1 n) rats with Lewis (LEW) (RT1 l) and two reciprocal MHC congenic strains, LEW.1N (RT1n) and BN.1L (RT1 l). This comparison revealed that disease severity and clinical course were strongly influenced by the MHC haplotype that modulated the pathogenic MOG-specific autoantibody response. The intra-MHC recombinant congenic strain LEW.1R38 demonstrated that gene loci located both within the centromeric segment of the MHC containing classical class I and class II genes and within the telomeric RT1.M region containing the MOG gene are involved in determining Ab production and disease susceptibility. This study indicates that the current T cell-centered interpretation of MHC-mediated effects on disease susceptibility must be reassessed in multiple sclerosis and other autoimmune diseases in which autoantibody is involved in disease pathogenesis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Stefferl",
      "authorRank" : 1,
      "name" : "Stefferl",
      "referenceId" : "RGD:A198062"
    }, {
      "firstName" : "U",
      "lastName" : "Brehm",
      "authorRank" : 2,
      "name" : "Brehm",
      "referenceId" : "RGD:A198063"
    }, {
      "firstName" : "M",
      "lastName" : "Storch",
      "authorRank" : 3,
      "name" : "Storch M",
      "referenceId" : "RGD:A6899"
    }, {
      "firstName" : "D",
      "lastName" : "Lambracht-Washington",
      "authorRank" : 4,
      "name" : "Lambracht-Washington D",
      "referenceId" : "RGD:A16761"
    }, {
      "firstName" : "C",
      "lastName" : "Bourquin",
      "authorRank" : 5,
      "name" : "Bourquin",
      "referenceId" : "RGD:A198064"
    }, {
      "firstName" : "K",
      "lastName" : "Wonigeit",
      "authorRank" : 6,
      "name" : "Wonigeit K",
      "referenceId" : "RGD:A22517"
    }, {
      "firstName" : "H",
      "lastName" : "Lassmann",
      "authorRank" : 7,
      "name" : "Lassmann H",
      "referenceId" : "RGD:A6901"
    }, {
      "firstName" : "C",
      "lastName" : "Linington",
      "authorRank" : 8,
      "name" : "Linington",
      "referenceId" : "RGD:A235488"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685372"
    } ]
  }, {
    "primaryId" : "PMID:10384126",
    "title" : "Genes encoding three new members of the leukocyte antigen 6 superfamily and a novel member of Ig superfamily, together with genes encoding the regulatory nuclear chloride ion channel protein (hRNCC) and an N omega-N omega-dimethylarginine dimethylaminohydrolase homologue, are found in a 30-kb segment of the MHC class III region.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Ribas G, etal., J Immunol 1999 Jul 1;163(1):278-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-01-07T14:49:11.000-06:00",
    "volume" : "163",
    "pages" : "278-87",
    "abstract" : "Many of the genes in the class III region of the human MHC encode proteins involved in the immune and inflammatory responses. We have sequenced a 30-kb segment of the MHC class III region lying between the heat shock protein 70 and TNF genes as part of a program aimed at identifying genes that could be involved in autoimmune disease susceptibility. The sequence analysis has revealed the localization of seven genes, whose precise position and order is cen-G7-G6-G6A-G6B-G6C-G6D-G6E-tel, five of which are fully encoded in the sequence, allowing their genomic structures to be defined. Three of them (G6C, G6D, and G6E) encode putative proteins that belong to the Ly-6 superfamily, known to be GPI-anchored proteins attached to the cell surface. Members of the family are specifically expressed and are important in leukocyte maturation. A fourth gene, G6B, encodes a novel member of the Ig superfamily containing a single Ig V-like domain and a cytoplasmic tail with several signal transduction features. The G6 gene encodes a regulatory nuclear chloride ion channel protein, while the G6A gene encodes a putative homologue of the enzyme N omega,N omega-dimethylarginine dimethylaminohydrolase, which is thought to be involved in regulating nitric oxide synthesis. In addition, three microsatellite markers, 9N-1, 82-2, and D6S273 are contained within the sequence, the last two of which have been reported to be strongly associated with the autoimmune disease ankylosing spondylitis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Ribas",
      "authorRank" : 1,
      "name" : "Ribas G",
      "referenceId" : "RGD:A50078"
    }, {
      "firstName" : "M",
      "lastName" : "Neville",
      "authorRank" : 2,
      "name" : "Neville M",
      "referenceId" : "RGD:A50079"
    }, {
      "firstName" : "JL",
      "lastName" : "Wixon",
      "authorRank" : 3,
      "name" : "Wixon JL",
      "referenceId" : "RGD:A50080"
    }, {
      "firstName" : "J",
      "lastName" : "Cheng",
      "authorRank" : 4,
      "name" : "Cheng J",
      "referenceId" : "RGD:A8791"
    }, {
      "firstName" : "RD",
      "lastName" : "Campbell",
      "authorRank" : 5,
      "name" : "Campbell RD",
      "referenceId" : "RGD:A40325"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1304532"
    } ]
  }, {
    "primaryId" : "PMID:10384142",
    "title" : "Mouse monocyte-derived chemokine is involved in airway hyperreactivity and lung inflammation.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Gonzalo JA, etal., J Immunol. 1999 Jul 1;163(1):403-11.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-14T16:01:19.000-06:00",
    "volume" : "163",
    "pages" : "403-11",
    "abstract" : "The cloning, expression, and function of the murine (m) homologue of human (h) monocyte-derived chemokine (MDC) is reported here. Like hMDC, mMDC is able to elicit the chemotactic migration in vitro of activated lymphocytes and monocytes. Among activated lymphocytes, Th2 cells were induced to migrate most efficiently. mMDC mRNA and protein expression is modulated during the course of an allergic reaction in the lung. Neutralization of mMDC with specific Abs in a model of lung inflammation resulted in prevention of airway hyperreactivity and significant reduction of eosinophils in the lung interstitium but not in the airway lumen. These data suggest that mMDC is essential in the transit/retention of leukocytes in the lung tissue rather than in their extravasation from the blood vessel or during their transepithelial migration into the airways. These results also highlight the relevance of factors, such as mMDC, that regulate the migration and accumulation of leukocytes within the tissue during the development of the key physiological endpoint of asthma, airway hyperreactivity.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Gonzalo",
      "authorRank" : 1,
      "name" : "Gonzalo JA",
      "referenceId" : "RGD:A55622"
    }, {
      "firstName" : "Y",
      "lastName" : "Pan",
      "authorRank" : 2,
      "name" : "Pan Y",
      "referenceId" : "RGD:A37937"
    }, {
      "firstName" : "CM",
      "lastName" : "Lloyd",
      "authorRank" : 3,
      "name" : "Lloyd CM",
      "referenceId" : "RGD:A128933"
    }, {
      "firstName" : "GQ",
      "lastName" : "Jia",
      "authorRank" : 4,
      "name" : "Jia GQ",
      "referenceId" : "RGD:A133647"
    }, {
      "firstName" : "G",
      "lastName" : "Yu",
      "authorRank" : 5,
      "name" : "Yu G",
      "referenceId" : "RGD:A20071"
    }, {
      "firstName" : "B",
      "lastName" : "Dussault",
      "authorRank" : 6,
      "name" : "Dussault B",
      "referenceId" : "RGD:A133648"
    }, {
      "firstName" : "CA",
      "lastName" : "Powers",
      "authorRank" : 7,
      "name" : "Powers CA",
      "referenceId" : "RGD:A133649"
    }, {
      "firstName" : "AE",
      "lastName" : "Proudfoot",
      "authorRank" : 8,
      "name" : "Proudfoot AE",
      "referenceId" : "RGD:A25019"
    }, {
      "firstName" : "AJ",
      "lastName" : "Coyle",
      "authorRank" : 9,
      "name" : "Coyle AJ",
      "referenceId" : "RGD:A55624"
    }, {
      "firstName" : "D",
      "lastName" : "Gearing",
      "authorRank" : 10,
      "name" : "Gearing D",
      "referenceId" : "RGD:A133650"
    }, {
      "firstName" : "JC",
      "lastName" : "Gutierrez-Ramos",
      "authorRank" : 11,
      "name" : "Gutierrez-Ramos JC",
      "referenceId" : "RGD:A55629"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4891475"
    } ]
  }, {
    "primaryId" : "PMID:10384387",
    "title" : "DNA-based prenatal diagnosis for very-long-chain acyl-CoA dehydrogenase deficiency.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Andresen BS, etal., J Inherit Metab Dis. 1999 May;22(3):281-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:54:46.000-05:00",
    "volume" : "22",
    "pages" : "281-5",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BS",
      "lastName" : "Andresen",
      "authorRank" : 1,
      "name" : "Andresen",
      "referenceId" : "RGD:A252075"
    }, {
      "firstName" : "S",
      "lastName" : "Olpin",
      "authorRank" : 2,
      "name" : "Olpin",
      "referenceId" : "RGD:A253483"
    }, {
      "firstName" : "EA",
      "lastName" : "Kvittingen",
      "authorRank" : 3,
      "name" : "Kvittingen",
      "referenceId" : "RGD:A265017"
    }, {
      "firstName" : "P",
      "lastName" : "Augoustides-Savvopoulou",
      "authorRank" : 4,
      "name" : "Augoustides-Savvopoulou",
      "referenceId" : "RGD:A273991"
    }, {
      "firstName" : "D",
      "lastName" : "Lindhout",
      "authorRank" : 5,
      "name" : "Lindhout D",
      "referenceId" : "RGD:A81725"
    }, {
      "firstName" : "DJ",
      "lastName" : "Halley",
      "authorRank" : 6,
      "name" : "Halley DJ",
      "referenceId" : "RGD:A126470"
    }, {
      "firstName" : "C",
      "lastName" : "Vianey-Saban",
      "authorRank" : 7,
      "name" : "Vianey-Saban",
      "referenceId" : "RGD:A252327"
    }, {
      "firstName" : "RJ",
      "lastName" : "Wanders",
      "authorRank" : 8,
      "name" : "Wanders RJ",
      "referenceId" : "RGD:A5204"
    }, {
      "firstName" : "L",
      "lastName" : "Ijlst",
      "authorRank" : 9,
      "name" : "Ijlst L",
      "referenceId" : "RGD:A44839"
    }, {
      "firstName" : "LD",
      "lastName" : "Schroeder",
      "authorRank" : 10,
      "name" : "Schroeder",
      "referenceId" : "RGD:A263819"
    }, {
      "firstName" : "L",
      "lastName" : "Bolund",
      "authorRank" : 11,
      "name" : "Bolund",
      "referenceId" : "RGD:A261404"
    }, {
      "firstName" : "N",
      "lastName" : "Gregersen",
      "authorRank" : 12,
      "name" : "Gregersen N",
      "referenceId" : "RGD:A28402"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069469"
    } ]
  }, {
    "primaryId" : "PMID:10384398",
    "title" : "Molecular and biochemical basis for variants and deficiency forms of galactose-1-phosphate uridyltransferase.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Shin YS, etal., J Inherit Metab Dis. 1999 May;22(3):327-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:15:35.000-05:00",
    "volume" : "22",
    "pages" : "327-9",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YS",
      "lastName" : "Shin",
      "authorRank" : 1,
      "name" : "Shin YS",
      "referenceId" : "RGD:A75477"
    }, {
      "firstName" : "J",
      "lastName" : "Zschocke",
      "authorRank" : 2,
      "name" : "Zschocke J",
      "referenceId" : "RGD:A68505"
    }, {
      "firstName" : "AM",
      "lastName" : "Das",
      "authorRank" : 3,
      "name" : "Das AM",
      "referenceId" : "RGD:A133675"
    }, {
      "firstName" : "T",
      "lastName" : "Podskarbi",
      "authorRank" : 4,
      "name" : "Podskarbi",
      "referenceId" : "RGD:A256374"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063782"
    } ]
  }, {
    "primaryId" : "PMID:10384880",
    "title" : "Mice lacking NT-3, and its receptor TrkC, exhibit profound deficiencies in CNS glial cells.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kahn MA, etal., Glia 1999 Apr;26(2):153-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-09T14:12:12.000-05:00",
    "volume" : "26",
    "pages" : "153-65",
    "abstract" : "Neurotrophin-3 (NT-3) and its receptor TrkC are known to be important for neuronal survival. More recently, NT-3 has been implicated as playing a role in oligodendrocyte (OL) proliferation and survival in vitro. Examination of NT-3 and TrkC knockout mice revealed a reduction in NT-3-dependent neurons. To date, no study has examined alterations in glial cell populations in these knockout mice. In this report, we demonstrate a decline in OL progenitor cell numbers within the CNS of NT-3 and TrkC knockout mice. We also observed that immature and mature OL-specific markers were attenuated in the NT-3 and TrkC knockout animals. Deficiencies in other CNS glial cells, including astrocytes and ameboid microglia, were also observed. The subventricular zone (SVZ), a highly proliferative region for progenitor glial cells, was reduced in size. Furthermore, a nuclear-specific stain revealed a decline in the numbers of pyknotic nuclei in and around the SVZ of the knockout mice. These data will support an in vivo NT-3-dependent mechanism for the normal development of CNS glial cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MA",
      "lastName" : "Kahn",
      "authorRank" : 1,
      "name" : "Kahn MA",
      "referenceId" : "RGD:A52114"
    }, {
      "firstName" : "S",
      "lastName" : "Kumar",
      "authorRank" : 2,
      "name" : "Kumar S",
      "referenceId" : "RGD:A5569"
    }, {
      "firstName" : "D",
      "lastName" : "Liebl",
      "authorRank" : 3,
      "name" : "Liebl D",
      "referenceId" : "RGD:A52115"
    }, {
      "firstName" : "R",
      "lastName" : "Chang",
      "authorRank" : 4,
      "name" : "Chang R",
      "referenceId" : "RGD:A52116"
    }, {
      "firstName" : "LF",
      "lastName" : "Parada",
      "authorRank" : 5,
      "name" : "Parada LF",
      "referenceId" : "RGD:A13864"
    }, {
      "firstName" : "J",
      "lastName" : "De Vellis",
      "authorRank" : 6,
      "name" : "De Vellis J",
      "referenceId" : "RGD:A52117"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358331"
    } ]
  }, {
    "primaryId" : "PMID:10384881",
    "title" : "Identification and localization of Ca(2+)-activated K+ channels in rat sciatic nerve.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Mi H, etal., Glia. 1999 Apr;26(2):166-75.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-10-07T10:48:24.000-05:00",
    "volume" : "26",
    "pages" : "166-75",
    "abstract" : "To understand the physiology of Schwann cells and myelinated nerve, we have been engaged in identifying K+ channels in sciatic nerve and determining their subcellular localization. In the present study, we examined the slo family of Ca(2+)-activated K+ channels, a class of channel that had not previously been identified in myelinated nerve. We have determined that these channels are indeed expressed in peripheral nerve, and have cloned rat homologues of slo that are more than 95% identical to the murine slo. We found that sciatic nerve RNA contained numerous alternatively spliced variants of the slo homologue, as has been seen in other tissues. We raised a polyclonal antibody against a peptide from the carboxyl terminal of the channels. Immunocytochemistry revealed that the channel proteins are in Schwann cells and are associated with canaliculi that run along the outer surface of the cells. They are also relatively concentrated near the node of Ranvier in the Schwann cell outer membrane. This staining pattern is quite similar to what we previously reported for the voltage-dependent K+ channel Kv 1.5. We did not observe staining of axons or connective tissue in the nerve and so it seems likely that most or all of the splicing variants are located in the Schwann cells. The localization of these channels also suggests that they may participate in maintaining the resting potential of the Schwann cells during K+ buffering.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Mi",
      "authorRank" : 1,
      "name" : "Mi H",
      "referenceId" : "RGD:A66937"
    }, {
      "firstName" : "RM",
      "lastName" : "Harris-Warrick",
      "authorRank" : 2,
      "name" : "Harris-Warrick RM",
      "referenceId" : "RGD:A66938"
    }, {
      "firstName" : "TJ",
      "lastName" : "Deerinck",
      "authorRank" : 3,
      "name" : "Deerinck TJ",
      "referenceId" : "RGD:A52307"
    }, {
      "firstName" : "I",
      "lastName" : "Inman",
      "authorRank" : 4,
      "name" : "Inman I",
      "referenceId" : "RGD:A66939"
    }, {
      "firstName" : "MH",
      "lastName" : "Ellisman",
      "authorRank" : 5,
      "name" : "Ellisman MH",
      "referenceId" : "RGD:A6388"
    }, {
      "firstName" : "TL",
      "lastName" : "Schwarz",
      "authorRank" : 6,
      "name" : "Schwarz TL",
      "referenceId" : "RGD:A66940"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581589"
    } ]
  }, {
    "primaryId" : "PMID:10384882",
    "title" : "Edg-2 in myelin-forming cells: isoforms, genomic mapping, and exclusion in Charcot-Marie-Tooth disease.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Allard J, etal., Glia. 1999 Apr;26(2):176-85.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-04-19T10:50:53.000-05:00",
    "volume" : "26",
    "pages" : "176-85",
    "abstract" : "Edg-2 is an heptahelical receptor whose spatio-temporal distribution during rat brain development is consistent with a role in the control of myelination. We have now identified two splice variants of Edg-2 mRNA in rat brain that encode two receptor isoforms differing by a stretch of 18 amino acids in the NH2-terminal extracellular tail of the receptor. Prenatally (i.e., before oligodendrocyte myelination), the two variants detected by selective in situ hybridization are equally abundant, vary in parallel, and remain restricted to proliferative zones in the brain. Postnatally, the long isoform becomes predominant in myelinating structures, where its abundance increases sharply during the period of myelination. In the adult human brain, only the long variant was detected, while in situ hybridization showed it selectively expressed in the white matter and in clusters of cells showing features of oligodendrocytes of the temporal cerebral cortex. Consequently, the human Edg-2 gene was studied to assess its possible contribution in inherited neuropathies. The coding sequence was found to be contained in three exons and to map to chromosome 9q31.3-32 by using radiation hybrid panel and Yeast-Artificial Chromosomes. Two intragenic bi-allelic polymorphisms and a rare mutation were identified. As a first application to molecular genetic studies, they were used to exclude the Edg-2 gene in six families with phenotype of demyelinating Charcot-Marie-Tooth disease of unknown origin.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Allard",
      "authorRank" : 1,
      "name" : "Allard J",
      "referenceId" : "RGD:A27644"
    }, {
      "firstName" : "S",
      "lastName" : "Barron",
      "authorRank" : 2,
      "name" : "Barron S",
      "referenceId" : "RGD:A27643"
    }, {
      "firstName" : "S",
      "lastName" : "Trottier",
      "authorRank" : 3,
      "name" : "Trottier S",
      "referenceId" : "RGD:A122237"
    }, {
      "firstName" : "P",
      "lastName" : "Cervera",
      "authorRank" : 4,
      "name" : "Cervera P",
      "referenceId" : "RGD:A122238"
    }, {
      "firstName" : "C",
      "lastName" : "Daumas-Duport",
      "authorRank" : 5,
      "name" : "Daumas-Duport C",
      "referenceId" : "RGD:A122239"
    }, {
      "firstName" : "E",
      "lastName" : "LeGuern",
      "authorRank" : 6,
      "name" : "LeGuern E",
      "referenceId" : "RGD:A27266"
    }, {
      "firstName" : "A",
      "lastName" : "Brice",
      "authorRank" : 7,
      "name" : "Brice A",
      "referenceId" : "RGD:A381290"
    }, {
      "firstName" : "JC",
      "lastName" : "Schwartz",
      "authorRank" : 8,
      "name" : "Schwartz JC",
      "referenceId" : "RGD:A122242"
    }, {
      "firstName" : "P",
      "lastName" : "Sokoloff",
      "authorRank" : 9,
      "name" : "Sokoloff P",
      "referenceId" : "RGD:A27648"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317715"
    } ]
  }, {
    "primaryId" : "PMID:10385124",
    "title" : "The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.",
    "datePublished" : "1999-06-17T00:00:00.000-05:00",
    "citation" : "Masutani C, etal., Nature. 1999 Jun 17;399(6737):700-4. doi: 10.1038/21447.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:32:16.000-05:00",
    "volume" : "399",
    "pages" : "700-4",
    "abstract" : "Xeroderma pigmentosum variant (XP-V) is an inherited disorder which is associated with increased incidence of sunlight-induced skin cancers. Unlike other xeroderma pigmentosum cells (belonging to groups XP-A to XP-G), XP-V cells carry out normal nucleotide-excision repair processes but are defective in their replication of ultraviolet-damaged DNA. It has been suspected for some time that the XPV gene encodes a protein that is involved in trans-lesion DNA synthesis, but the gene product has never been isolated. Using an improved cell-free assay for trans-lesion DNA synthesis, we have recently isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in XP-V cell extracts. Here we show that this polymerase is a human homologue of the yeast Rad30 protein, recently identified as DNA polymerase eta. This polymerase and yeast Rad30 are members of a family of damage-bypass replication proteins which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. We found that all XP-V cells examined carry mutations in their DNA polymerase eta gene. Recombinant human DNA polymerase eta corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. Together, these results indicate that DNA polymerase eta could be the XPV gene product.",
    "issueName" : "6737",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Masutani",
      "authorRank" : 1,
      "name" : "Masutani C",
      "referenceId" : "RGD:A581042"
    }, {
      "firstName" : "R",
      "lastName" : "Kusumoto",
      "authorRank" : 2,
      "name" : "Kusumoto R",
      "referenceId" : "RGD:A581043"
    }, {
      "firstName" : "A",
      "lastName" : "Yamada",
      "authorRank" : 3,
      "name" : "Yamada A",
      "referenceId" : "RGD:A14439"
    }, {
      "firstName" : "N",
      "lastName" : "Dohmae",
      "authorRank" : 4,
      "name" : "Dohmae N",
      "referenceId" : "RGD:A9496"
    }, {
      "firstName" : "M",
      "lastName" : "Yokoi",
      "authorRank" : 5,
      "name" : "Yokoi M",
      "referenceId" : "RGD:A30229"
    }, {
      "firstName" : "M",
      "lastName" : "Yuasa",
      "authorRank" : 6,
      "name" : "Yuasa M",
      "referenceId" : "RGD:A581044"
    }, {
      "firstName" : "M",
      "lastName" : "Araki",
      "authorRank" : 7,
      "name" : "Araki M",
      "referenceId" : "RGD:A28710"
    }, {
      "firstName" : "S",
      "lastName" : "Iwai",
      "authorRank" : 8,
      "name" : "Iwai S",
      "referenceId" : "RGD:A18863"
    }, {
      "firstName" : "K",
      "lastName" : "Takio",
      "authorRank" : 9,
      "name" : "Takio K",
      "referenceId" : "RGD:A9497"
    }, {
      "firstName" : "F",
      "lastName" : "Hanaoka",
      "authorRank" : 10,
      "name" : "Hanaoka F",
      "referenceId" : "RGD:A21665"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598116515"
    } ]
  }, {
    "primaryId" : "PMID:10385260",
    "title" : "Bradykinin down-regulates LPS-induced eosinophil accumulation in the pleural cavity of mice through type 2-kinin receptor activation: a role for prostaglandins.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Silva AR, etal., Br J Pharmacol. 1999 May;127(2):569-75.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-04T11:14:31.000-06:00",
    "volume" : "127",
    "pages" : "569-75",
    "abstract" : "1. The role of both exogenously administered and endogenously generated bradykinin (BK) on LPS-induced eosinophil accumulation in the mice pleural cavity was investigated by means of treatment with BK selective receptor agonists/antagonists and captopril. 2. Intrathoracic (i.t.) injection of LPS (250 ng cavity(-1)) induced eosinophil influx at 24 h as previously described (Bozza et al., 1993). Pretreatment with the B1 receptor antagonist des-Arg9-[leu-8]BK (0.025 and 0.25 nmol cavity(-1)) showed no effect on this phenomenon, whereas pretreatment with the B2 receptor antagonists, NPC 17731 (0.025 and 0.25 nmol cavity(-1)) or HOE 140 (2.5 nmol cavity(-1)), increased LPS-induced eosinophil influx. Accordingly, pretreatment with captopril at 10 mg kg(-1) i.p., inhibited eosinophil infiltration induced by LPS in the pleural cavity, suggesting that endogenous BK is down-regulating LPS-induced eosinophil accumulation. 3. BK administered at 15 and 25 nmol cavity(-1), i.t. or i.p. also inhibited LPS-induced eosinophil accumulation. BK alone had no effect on the basal number of leucocytes in the pleural or peritoneal cavity in doses up to 25 nmol cavity(-1). Nevertheless, when injected at doses of 50 and 100 nmol cavity(-1) BK induced leucocyte influx characterized by neutrophil and eosinophil accumulation at 24 h. 4. Similarly to what was observed with BK, a specific B2 receptor agonist, Tyr8BK, administered at 0.25 nmol cavity(-1) i.p., significantly inhibited the eosinophil influx induced by LPS. 5. The mechanism by which B2 receptor agonists inhibit LPS-induced eosinophil accumulation was investigated by pretreating the animals with indomethacin or a selective cyclooxygenase-2 inhibitor, NS-398. Pretreatment with either indomethacin or NS-398 had no effect on eosinophil influx induced by LPS alone, but those drugs were able to restore the LPS-induced eosinophil influx in Tyr8BK (0.25 nmol cavity(-1)) injected mice. 6. In conclusion, endogenously generated bradykinin seems to modulate, through activation of B2 receptors, eosinphil accumulation induced by LPS via a mechanism dependent on prostanoid synthesis.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AR",
      "lastName" : "Silva",
      "authorRank" : 1,
      "name" : "Silva AR",
      "referenceId" : "RGD:A133063"
    }, {
      "firstName" : "AP",
      "lastName" : "Larangeira",
      "authorRank" : 2,
      "name" : "Larangeira AP",
      "referenceId" : "RGD:A133064"
    }, {
      "firstName" : "P",
      "lastName" : "Pacheco",
      "authorRank" : 3,
      "name" : "Pacheco P",
      "referenceId" : "RGD:A126488"
    }, {
      "firstName" : "JB",
      "lastName" : "Calixto",
      "authorRank" : 4,
      "name" : "Calixto JB",
      "referenceId" : "RGD:A25484"
    }, {
      "firstName" : "MG",
      "lastName" : "Henriques",
      "authorRank" : 5,
      "name" : "Henriques MG",
      "referenceId" : "RGD:A132425"
    }, {
      "firstName" : "PT",
      "lastName" : "Bozza",
      "authorRank" : 6,
      "name" : "Bozza PT",
      "referenceId" : "RGD:A130629"
    }, {
      "firstName" : "HC",
      "lastName" : "Castro-Faria-Neto",
      "authorRank" : 7,
      "name" : "Castro-Faria-Neto HC",
      "referenceId" : "RGD:A130628"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4891039"
    } ]
  }, {
    "primaryId" : "PMID:10385363",
    "title" : "Evaluation of malignancy and the prognosis of esophageal cancer based on an immunohistochemical study (p53, E-cadherin, epidermal growth factor receptor).",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Inada S, etal., Surg Today. 1999;29(6):493-503.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-04-29T12:07:15.000-05:00",
    "volume" : "29",
    "pages" : "493-503",
    "abstract" : "The subjects in this study consisted of 40 preoperative untreated esophageal squamous cell carcinoma patients. While p53 did not significantly correlate with the clinicopathological factors, E-cadherin significantly correlated with lymphatic invasion, vascular invasion, the depth of invasion, the degree of lymph node metastasis, the histological stage, and the number of lymph node metastases. Epidermal growth factor receptor (EGFR) significantly correlated with age, the depth of invasion, and the number of lymph node metastases. The 5-year cumulative survival rate was 45.7% in the p53-positive cases and 61.9% in the p53-negative cases, with no significant difference, and 87.8% in the E-cadherin-positive cases and 19.1% in the -negative cases, and the difference was significant. The prognosis was significantly poor in EGFR-positive subjects: the 5-year survival rate was 38.6% in EGFR-positive cases and 68% in -negative cases. The 5-year survival rate in E-cadherin-negative, EGFR-positive cases was 0%, while it was 91.7% in the reverse pattern, and this difference was significant. These findings suggest that both E-cadherin and EGFR are important prognostic factors, and a more precise prognosis can thus be obtained by combining them. Such a combined technique may be very useful as an indicator for grading the biological malignancy of esophageal cancer.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Inada",
      "authorRank" : 1,
      "name" : "Inada S",
      "referenceId" : "RGD:A139729"
    }, {
      "firstName" : "T",
      "lastName" : "Koto",
      "authorRank" : 2,
      "name" : "Koto T",
      "referenceId" : "RGD:A139730"
    }, {
      "firstName" : "K",
      "lastName" : "Futami",
      "authorRank" : 3,
      "name" : "Futami K",
      "referenceId" : "RGD:A121222"
    }, {
      "firstName" : "S",
      "lastName" : "Arima",
      "authorRank" : 4,
      "name" : "Arima S",
      "referenceId" : "RGD:A6705"
    }, {
      "firstName" : "A",
      "lastName" : "Iwashita",
      "authorRank" : 5,
      "name" : "Iwashita A",
      "referenceId" : "RGD:A139731"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5131486"
    } ]
  }, {
    "primaryId" : "PMID:10385402",
    "title" : "Transcription activating and repressing functions of the androgen receptor are differentially influenced by mutations in the deoxyribonucleic acid-binding domain.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Aarnisalo P, etal., Endocrinology. 1999 Jul;140(7):3097-105.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-05-20T17:35:06.000-05:00",
    "volume" : "140",
    "pages" : "3097-105",
    "abstract" : "Despite the wide spectrum of androgen receptor (AR) mutants described in androgen insensitivity syndromes (AIS), their influence on transactivating and, in particular, transrepressing functions of AR are poorly defined. Rat AR mutants with substitutions in the DNA-binding domain, corresponding to several mutations  in AIS patients, were examined for these activities. AR variants (G551V and C562G) with mutations in the first zinc finger (ZF) exhibited reduced DNA binding activity and attenuated transactivation. An R590Q substitution in the second ZF diminished transcriptional activity only from a promoter with a single androgen response element, whereas activation at multiple androgen response element sites  was unaffected, despite the poor DNA-binding affinity of R590Q. Another substitution in the second ZF, A579T, yielded similar findings. In comparison to  wild-type AR, G551V, and C562G variants had markedly reduced ability to repress an NF-kappaB/RelA-activated promoter but R590Q behaved like the native receptor.  AP1 function was repressed not only by wild-type AR but also by the transactivating mutants A579T and R590Q as well as by the transcriptionally inactive mutants G551V and C562G. Furthermore, a Lys-to-Ala substitution in codon 563 of the first ZF switched AR into a ligand-dependent activator at AP1 sites but maintained the ability to repress NF-kappaB/RelA function. Taken together, DNA-binding domain mutations in AIS patients influence transcriptional activating and repressing functions of AR in a selective fashion, which probably contributes to the complexity in the presentation of the AIS phenotype.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Aarnisalo",
      "authorRank" : 1,
      "name" : "Aarnisalo",
      "referenceId" : "RGD:A202203"
    }, {
      "firstName" : "H",
      "lastName" : "Santti",
      "authorRank" : 2,
      "name" : "Santti H",
      "referenceId" : "RGD:A103256"
    }, {
      "firstName" : "H",
      "lastName" : "Poukka",
      "authorRank" : 3,
      "name" : "Poukka H",
      "referenceId" : "RGD:A7857"
    }, {
      "firstName" : "JJ",
      "lastName" : "Palvimo",
      "authorRank" : 4,
      "name" : "Palvimo JJ",
      "referenceId" : "RGD:A7860"
    }, {
      "firstName" : "OA",
      "lastName" : "Janne",
      "authorRank" : 5,
      "name" : "Janne OA",
      "referenceId" : "RGD:A7750"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10043317"
    } ]
  }, {
    "primaryId" : "PMID:10385480",
    "title" : "Gene expression of CC chemokines in experimental acute tubulointerstitial nephritis.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Ou ZL, etal., J Lab Clin Med. 1999 Jan;133(1):41-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-05-30T13:01:19.000-05:00",
    "volume" : "133",
    "pages" : "41-7",
    "abstract" : "The infiltration of mononuclear leukocytes into glomeruli or the interstitium is a feature in most forms of glomerular diseases. CC chemokines, mostly chemoattractants for mononuclear leukocytes, are molecules that are potentially responsible for the recruitment of these cells in the kidney. We previously reported that the gene expression of six CC chemokines-MCP-1, MCP-3, MIP-1alpha, MIP-1beta, RANTES, and TCA3-was enhanced in a rat model of crescentic glomerulonephritis, the most severe form of glomerulonephritis. In this study we analyzed their gene expression in a model of another type of kidney disease, acute nephrosis accompanied by tubulointerstitial lesions, which is induced by an injection of puromycin aminonucleoside. Because leukocyte infiltration in this model is much more prominent in the interstitium than in glomeruli, we analyzed their gene expression in the renal cortex. On day 3, when the level of urinary protein was slightly but significantly increased but the number of interstitial leukocytes was unchanged, the enhanced expression of mRNAs for MCP-1, MCP-3, and TCA3 was observed. On day 5, the numbers of interstitial monocytes and lymphocytes significantly increased, and the levels of the mRNA expression of the above chemokines were still higher than the control animals, whereas the levels of mRNAs for MIP- 1alpha, MIP-1beta, and RANTES were not higher or were only slightly higher than the control ones. These results suggest that multiple CC chemokines may play a role in the recruitment of leukocytes in this model and that the expression pattern of CC chemokines depends on the type of kidney injury.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z L",
      "lastName" : "Ou",
      "authorRank" : 1,
      "name" : "Ou ZL",
      "referenceId" : "RGD:A433652"
    }, {
      "firstName" : "Y",
      "lastName" : "Natori",
      "authorRank" : 2,
      "name" : "Natori Y",
      "referenceId" : "RGD:A24227"
    }, {
      "firstName" : "Y",
      "lastName" : "Natori",
      "authorRank" : 3,
      "name" : "Natori Y",
      "referenceId" : "RGD:A24227"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6483768"
    } ]
  }, {
    "primaryId" : "PMID:10385596",
    "title" : "Mild vitamin A deficiency delays fetal lung maturation in the rat.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Chailley-Heu B, etal., Am J Respir Cell Mol Biol. 1999 Jul;21(1):89-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-10-08T15:01:32.000-05:00",
    "volume" : "21",
    "pages" : "89-96",
    "abstract" : "During late pregnancy, the fetal lung stores surfactant in preparation for extrauterine life. Surfactant deficiency, most often due to prematurity, precipitates respiratory distress syndrome (RDS) of the neonate. Although vitamin A (retinol) and retinoic acid have been shown to enhance the synthesis of phospholipid surfactant components, their effect on surfactant-specific proteins is unclear. No attempt has been made to evaluate the consequences of vitamin A restriction on surfactant phospholipid storage or on the expression of the life-essential surfactant protein-B (SP-B). We induced in rats a partial vitamin A deficiency leading to a 30-60% reduction in blood retinol, a status compatible with maintenance of gestation and absence of gross abnormalities in offspring. At term, lung surfactant phospholipids were reduced by 21%, and the major surfactant phospholipid, disaturated phosphatidylcholine (DSPC), was reduced by 27% in vitamin A-deficient (VAD) fetuses. The decrease in surfactant phospholipids and DSPC correlated linearly with plasma retinol, and reached about 50% in fetuses with the lowest retinol concentrations; it was accompanied by reduced expression of the gene for fatty acid synthase, a key enzyme in the synthetic pathway for surfactant-phospholipid lipid precursors. The amounts of SP-A, SP-B, and SP-C messenger RNAs were decreased by 46%, 32%, and 28%, respectively, in VAD fetuses. Consistently, amounts of SP-A and SP-B proteins were diminished as assessed by Western blotting. The proportion of type II cells determined after SP-B labeling was unchanged in VAD as compared with control lungs. Vitamin A deficiency is therefore a cause of lung maturational delay. In view of its rather large incidence in human populations, it may represent an increased risk for RDS and an aggravating factor for prematurity.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Chailley-Heu",
      "authorRank" : 1,
      "name" : "Chailley-Heu B",
      "referenceId" : "RGD:A5391"
    }, {
      "firstName" : "N",
      "lastName" : "Chelly",
      "authorRank" : 2,
      "name" : "Chelly N",
      "referenceId" : "RGD:A5388"
    }, {
      "firstName" : "M",
      "lastName" : "Lelievre-Pegorier",
      "authorRank" : 3,
      "name" : "Lelievre-Pegorier M",
      "referenceId" : "RGD:A128763"
    }, {
      "firstName" : "AM",
      "lastName" : "Barlier-Mur",
      "authorRank" : 4,
      "name" : "Barlier-Mur AM",
      "referenceId" : "RGD:A81161"
    }, {
      "firstName" : "C",
      "lastName" : "Merlet-Benichou",
      "authorRank" : 5,
      "name" : "Merlet-Benichou C",
      "referenceId" : "RGD:A71174"
    }, {
      "firstName" : "JR",
      "lastName" : "Bourbon",
      "authorRank" : 6,
      "name" : "Bourbon JR",
      "referenceId" : "RGD:A5392"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4144157"
    } ]
  }, {
    "primaryId" : "PMID:10385646",
    "title" : "Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: identification of a human hepatic progenitor cell?",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Baumann U, etal., Hepatology. 1999 Jul;30(1):112-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-06-22T12:34:15.000-05:00",
    "volume" : "30",
    "pages" : "112-7",
    "abstract" : "The stem cell factor (SCF)/c-kit ligand/receptor system has been implicated in stem (oval) cell activation following liver injury in the rat. The aim of this study was to determine the role of the SCF/c-kit system in pediatric human liver during acute and chronic liver injury. Tissue was obtained from hepatectomy specimens of patients undergoing liver transplantation for extrahepatic biliary atresia (EHBA) and fulminant hepatic failure (FHF). Specific expression of mRNA for c-kit and beta-actin was measured by ribonuclease protection and by immunohistochemistry to localize c-kit in tissue sections. Expression of c-kit was detected at relatively consistent levels in normal and cirrhotic (EHBA) livers. However, in FHF, c-kit mRNA levels were elevated in 3 of 6 specimens. Immunolocalization highlighted the presence of small numbers of c-kit-positive cells in the portal tracts of normal livers with increased numbers in cirrhotic livers. The highest c-kit staining, however, was observed in FHF, in which, in addition to the cells in the portal tracts, discrete c-kit-positive cells were also found integrated into bile ducts. Colocalization studies demonstrated some of the c-kit-positive cells to be of mast cell, leukocyte, and hematopoietic cell origin. However, there remained a subset that was also negative for these markers. The up-regulation of c-kit receptor expression in diseased livers suggests an involvement of this receptor/ligand system in hepatic repair mechanisms, and we speculate that c-kit-positive cells may represent a hepatic progenitor cell population. The origin and growth/differentiation potential of these c-kit-positive cells is under investigation.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "U",
      "lastName" : "Baumann",
      "authorRank" : 1,
      "name" : "Baumann U",
      "referenceId" : "RGD:A445722"
    }, {
      "firstName" : "H A",
      "lastName" : "Crosby",
      "authorRank" : 2,
      "name" : "Crosby HA",
      "referenceId" : "RGD:A445723"
    }, {
      "firstName" : "P",
      "lastName" : "Ramani",
      "authorRank" : 3,
      "name" : "Ramani P",
      "referenceId" : "RGD:A445724"
    }, {
      "firstName" : "D A",
      "lastName" : "Kelly",
      "authorRank" : 4,
      "name" : "Kelly DA",
      "referenceId" : "RGD:A445725"
    }, {
      "firstName" : "A J",
      "lastName" : "Strain",
      "authorRank" : 5,
      "name" : "Strain AJ",
      "referenceId" : "RGD:A445726"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12910730"
    } ]
  }, {
    "primaryId" : "PMID:10385678",
    "title" : "Selective substrates for non-neuronal monoamine transporters.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Grundemann D, etal., Mol Pharmacol 1999 Jul;56(1):1-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:15:48.000-05:00",
    "volume" : "56",
    "pages" : "1-10",
    "abstract" : "The recently identified transport proteins organic cation transporter 1 (OCT1), OCT2, and extraneuronal monoamine transporter (EMT) accept dopamine, noradrenaline, adrenaline, and 5-hydroxytryptamine as substrates and hence qualify as non-neuronal monoamine transporters. In the present study, selective transport substrates were identified that allow, by analogy to receptor agonists, functional discrimination of these transporters. To contrast efficiency of solute transport, stably transfected 293 cell lines, each expressing a single transporter, were examined side by side in uptake experiments with radiolabeled substrates. Normalized uptake rates indicate that tetraethylammonium, with a rate of about 0.5 relative to 1-methyl-4-phenylpyridinium (MPP+), is a good substrate for OCT1 and OCT2. It was not, however, accepted as substrate by EMT. Choline was transported exclusively by OCT1, with a rate of about 0.5 relative to MPP+. Histamine was a good substrate with a rate of about 0.6 relative to MPP+ for OCT2 and EMT, but was not transported by OCT1. Guanidine was an excellent substrate for OCT2, with a rate as high as that of MPP+. Transport of guanidine by OCT1 was low, and transport by EMT was negligible. With the guanidine derivatives cimetidine and creatinine, a pattern strikingly similar to guanidine was observed. Collectively, these substrates reveal key differences in solute recognition and turnover and thus challenge the concept of \"polyspecific\" organic cation transporters. In addition, our data, when compared with previous studies, suggest that OCT2 corresponds to the organic cation/H+ antiport mechanism in renal brush-border membrane vesicles, and that EMT corresponds to the guanidine/H+ antiport mechanism in membrane vesicles from placenta and intestine.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Grundemann",
      "authorRank" : 1,
      "name" : "Grundemann D",
      "referenceId" : "RGD:A23021"
    }, {
      "firstName" : "G",
      "lastName" : "Liebich",
      "authorRank" : 2,
      "name" : "Liebich G",
      "referenceId" : "RGD:A23022"
    }, {
      "firstName" : "N",
      "lastName" : "Kiefer",
      "authorRank" : 3,
      "name" : "Kiefer N",
      "referenceId" : "RGD:A23023"
    }, {
      "firstName" : "S",
      "lastName" : "Koster",
      "authorRank" : 4,
      "name" : "Koster S",
      "referenceId" : "RGD:A23024"
    }, {
      "firstName" : "E",
      "lastName" : "Schomig",
      "authorRank" : 5,
      "name" : "Schomig E",
      "referenceId" : "RGD:A23025"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634067"
    } ]
  }, {
    "primaryId" : "PMID:10385696",
    "title" : "Abnormal regulation of the sympathetic nervous system in alpha2A-adrenergic receptor knockout mice.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Altman JD, etal., Mol Pharmacol. 1999 Jul;56(1):154-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-01-25T11:05:52.000-06:00",
    "volume" : "56",
    "pages" : "154-61",
    "abstract" : "alpha2-Adrenergic receptors (ARs) play a key role in regulating neurotransmitter release in the central and peripheral sympathetic nervous systems. To date, three subtypes of alpha2-ARs have been cloned (alpha2A, alpha2B, and alpha2C). Here we describe the physiological consequences of disrupting the gene for the alpha2A-AR. Mice lacking functional alpha2A subtypes were compared with wild-type (WT) mice, with animals lacking the alpha2B or alpha2C subtypes, and with mice carrying a point mutation in the alpha2A-AR gene (alpha2AD79N). Deletion of the alpha2A subtype led to an increase in sympathetic activity with resting tachycardia (knockout, 581 +/- 21 min-1; WT, 395 +/- 21 min-1), depletion of cardiac tissue norepinephrine concentration (knockout, 676 +/- 31 pg/mg protein; WT, 1178 +/- 98 pg/mg protein), and down-regulation of cardiac beta-ARs (Bmax: knockout, 23 +/- 1 fmol/mg protein; WT, 31 +/- 2 fmol/mg protein). The hypotensive effect of alpha2 agonists was completely absent in alpha2A-deficient mice. Presynaptic alpha2-AR function was tested in two isolated vas deferens preparations. The nonsubtype-selective alpha2 agonist dexmedetomidine completely blocked the contractile response to electrical stimulation in vas deferens from alpha2B-AR knockout, alpha2C-AR knockout, alpha2AD79N mutant, and WT mice. The maximal inhibition of vas deferens contraction by the alpha2 agonist in alpha2A-AR knockout mice was only 42 +/- 9%. [3H]Norepinephrine release studies performed in vas deferens confirmed these findings. The results indicate that the alpha2A-AR is a major presynaptic receptor subtype regulating norepinephrine release from sympathetic nerves; however, the residual alpha2-mediated effect in the alpha2A-AR knockout mice suggests that a second alpha2 subtype (alpha2B or alpha2C) also functions as a presynaptic autoreceptor to inhibit transmitter release.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JD",
      "lastName" : "Altman",
      "authorRank" : 1,
      "name" : "Altman JD",
      "referenceId" : "RGD:A58037"
    }, {
      "firstName" : "AU",
      "lastName" : "Trendelenburg",
      "authorRank" : 2,
      "name" : "Trendelenburg AU",
      "referenceId" : "RGD:A58038"
    }, {
      "firstName" : "L",
      "lastName" : "MacMillan",
      "authorRank" : 3,
      "name" : "MacMillan L",
      "referenceId" : "RGD:A58039"
    }, {
      "firstName" : "D",
      "lastName" : "Bernstein",
      "authorRank" : 4,
      "name" : "Bernstein D",
      "referenceId" : "RGD:A58032"
    }, {
      "firstName" : "L",
      "lastName" : "Limbird",
      "authorRank" : 5,
      "name" : "Limbird L",
      "referenceId" : "RGD:A58040"
    }, {
      "firstName" : "K",
      "lastName" : "Starke",
      "authorRank" : 6,
      "name" : "Starke K",
      "referenceId" : "RGD:A58041"
    }, {
      "firstName" : "BK",
      "lastName" : "Kobilka",
      "authorRank" : 7,
      "name" : "Kobilka BK",
      "referenceId" : "RGD:A39435"
    }, {
      "firstName" : "L",
      "lastName" : "Hein",
      "authorRank" : 8,
      "name" : "Hein L",
      "referenceId" : "RGD:A58030"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1559312"
    } ]
  }, {
    "primaryId" : "PMID:10386469",
    "title" : "Fas antigen/CD-95 upregulation and activation during castration-induced regression of the rat ventral prostate gland.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "de la Taille A, etal., Prostate. 1999 Jul 1;40(2):89-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-25T16:16:55.000-05:00",
    "volume" : "40",
    "pages" : "89-96",
    "abstract" : "BACKGROUND: Fas antigen/CD 95 is a 45-kDa transmembrane protein that can initiate intracellular signaling pathways, leading to apoptosis when it is clustered on the cell surface. A recent report claiming that the ventral prostate glands of lpr -/- mutant mice (lacking functional fas antigen) do not regress following castration prompted our analysis of the regressing rat ventral prostate gland for evidence that fas antigen might participate in the molecular process leading to prostate cell apoptosis after castration. METHODS: An RNase protection assay and  Western blotting analysis were used to quantify fas antigen mRNA and protein expression in the regressing rat ventral prostate gland. Immunoprecipitates of fas antigen from membrane preparations made from control or castrated rat prostates were analyzed for coprecipitation of FADD and RIP proteins to assess the activation state of the fas antigen before and after castration. Finally, prostate tissues obtained from two different strains of lpr -/- mutant mice were  analyzed for induced apoptosis after castration by the TUNEL staining method. RESULTS: Rat ventral prostate gland fas antigen mRNA and protein expression was upregulated approximately 3-5-fold in the 3-day castrated rat as compared to hormonally intact rats. Immunoprecipitates of fas antigen from membranes of ventral prostates from castrated rats contained significantly increased amounts of both FADD and RIP proteins when compared to those of intact or control operated rats. However, counts of TUNEL-labeled cells in the ventral prostate glands of castrated lpr -/- mice were not significantly different from those in castrated, genetically normal controls. Likewise, the morphology of apoptotic bodies formed in the prostates of castrated lpr -/- mice was indistinguishable from that in control animals. CONCLUSIONS: Fas antigen/CD-95, a protein that is involved in some forms of apoptosis, is upregulated during regression of the rat  ventral prostate gland and becomes functionally \"activated.\" However, our inability to distinguish any difference in the apoptosis rate or in the morphology of the apoptotic bodies formed in response to castration between lpr -/- mice and genetically normal controls indicates that, contrary to the prior report, functional fas protein is not required for castration-induced prostate cell apoptosis.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "De la Taille",
      "authorRank" : 1,
      "name" : "De la Taille A",
      "referenceId" : "RGD:A23665"
    }, {
      "firstName" : "MW",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen MW",
      "referenceId" : "RGD:A23663"
    }, {
      "firstName" : "A",
      "lastName" : "Shabsigh",
      "authorRank" : 3,
      "name" : "Shabsigh A",
      "referenceId" : "RGD:A23664"
    }, {
      "firstName" : "E",
      "lastName" : "Bagiella",
      "authorRank" : 4,
      "name" : "Bagiella E",
      "referenceId" : "RGD:A148633"
    }, {
      "firstName" : "A",
      "lastName" : "Kiss",
      "authorRank" : 5,
      "name" : "Kiss A",
      "referenceId" : "RGD:A28550"
    }, {
      "firstName" : "R",
      "lastName" : "Buttyan",
      "authorRank" : 6,
      "name" : "Buttyan R",
      "referenceId" : "RGD:A8389"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662865"
    } ]
  }, {
    "primaryId" : "PMID:10386556",
    "title" : "Novel hMLH1 and hMSH2 germline mutations in African Americans with colorectal cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Weber TK, etal., JAMA. 1999 Jun 23-30;281(24):2316-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:21:58.000-05:00",
    "volume" : "281",
    "pages" : "2316-20",
    "abstract" : "CONTEXT: Germline mutations of the DNA mismatch repair (MMR) genes hMLH1 and hMSH2 have been shown to cosegregate with the colorectal cancer phenotype in multiple hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. However, the frequency of these mutations among African American patients with colorectal  cancer is unknown. OBJECTIVE: To investigate the frequency of germline alterations of the DNA MMR genes hMLH1 and hMSH2 among African Americans affected by HNPCC and early-age onset colorectal cancer. DESIGN, SETTING, AND PATIENTS: Forty unrelated African American HNPCC and early-age onset colorectal cancer patients (8 women, 3 men) were identified from the cancer registry at a National  Cancer Institute-designated referral center, 11 of whom were available for and agreed to study participation from January 1997 to February 1998. The mean age of the subjects was 44 years. An additional 50 age- and sex-matched African Americans without personal or family history of colorectal, endometrial, ovarian, urinary tract, or upper gastrointestinal tract malignancy were also studied as a  polymorphism control population. In all subjects, genomic DNA was amplified by polymerase chain reaction for all hMLH1 and hMSH2 exons and screened using single-strand conformation polymorphism (SSCP) analysis. Samples demonstrating significant SSCP shifts underwent automated nucleotide sequencing analysis. MAIN  OUTCOME MEASURE: Frequency of hMLH1 and hMSH2 germline alterations in the affected and control subjects. RESULTS: Germline hMLH1 and hMSH2 mutations were detected in 3 (27%) of the African American colorectal cancer probands studied. Each mutation was novel. Two hMLH1 (an A-->T transversion at codon 26 and a GG-->AT substitution across codons 177 and 178) mutations and 1 hMSH2 mutation (a C-->T transition at codon 389) were identified in 3 female study subjects. Six other hMLH1 and hMSH2 alterations were detected but were presumed to be polymorphisms. Neither missense mutation (at codons 26 and 389) was detected in the control population. CONCLUSIONS: The results of our analysis support an association between the 3 mutations reported and predisposition to colorectal cancer. Further studies are needed to define DNA MMR gene-associated colorectal cancer in African Americans, an understudied population at increased risk of fatal colorectal cancer.",
    "issueName" : "24",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TK",
      "lastName" : "Weber",
      "authorRank" : 1,
      "name" : "Weber",
      "referenceId" : "RGD:A284146"
    }, {
      "firstName" : "HM",
      "lastName" : "Chin",
      "authorRank" : 2,
      "name" : "Chin HM",
      "referenceId" : "RGD:A32044"
    }, {
      "firstName" : "M",
      "lastName" : "Rodriguez-Bigas",
      "authorRank" : 3,
      "name" : "Rodriguez-Bigas",
      "referenceId" : "RGD:A284147"
    }, {
      "firstName" : "B",
      "lastName" : "Keitz",
      "authorRank" : 4,
      "name" : "Keitz",
      "referenceId" : "RGD:A284148"
    }, {
      "firstName" : "R",
      "lastName" : "Gilligan",
      "authorRank" : 5,
      "name" : "Gilligan",
      "referenceId" : "RGD:A284149"
    }, {
      "firstName" : "L",
      "lastName" : "O'Malley",
      "authorRank" : 6,
      "name" : "O'Malley",
      "referenceId" : "RGD:A256952"
    }, {
      "firstName" : "E",
      "lastName" : "Urf",
      "authorRank" : 7,
      "name" : "Urf",
      "referenceId" : "RGD:A284150"
    }, {
      "firstName" : "N",
      "lastName" : "Diba",
      "authorRank" : 8,
      "name" : "Diba",
      "referenceId" : "RGD:A284151"
    }, {
      "firstName" : "J",
      "lastName" : "Pazik",
      "authorRank" : 9,
      "name" : "Pazik",
      "referenceId" : "RGD:A284152"
    }, {
      "firstName" : "NJ",
      "lastName" : "Petrelli",
      "authorRank" : 10,
      "name" : "Petrelli",
      "referenceId" : "RGD:A284153"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073298"
    } ]
  }, {
    "primaryId" : "PMID:10386582",
    "title" : "3-Hydroxy-3-methylglutaryl CoA reductase inhibitors reduce serum triglyceride levels through modulation of apolipoprotein C-III and lipoprotein lipase.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Schoonjans K, etal., FEBS Lett. 1999 Jun 11;452(3):160-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-07-27T11:17:28.000-05:00",
    "volume" : "452",
    "pages" : "160-4",
    "abstract" : "Statins are hypolipidemic drugs which not only improve cholesterol but also triglyceride levels. Whereas their cholesterol-reducing effect involves inhibition of de novo biosynthesis of cellular cholesterol through competitive inhibition of its rate-limiting enzyme 3-hydroxy-3-methylglutaryl CoA reductase,  the mechanism by which they lower triglycerides remains unknown and forms the subject of the current study. Treatment of normal rats for 4 days with simvastatin decreased serum triglycerides significantly, whereas it increased high density lipoprotein cholesterol moderately. The decrease in triglyceride concentrations after simvastatin was caused by a reduction in the amount of very  low density lipoprotein particles which were of an unchanged lipid composition. Simvastatin administration increased the lipoprotein lipase mRNA and activity in  adipose tissue and heart. This effect on lipoprotein lipase was accompanied by decreased mRNA as well as plasma levels of the lipoprotein lipase inhibitor apolipoprotein C-III. These results suggest that the triglyceride-lowering effect of statins involves a stimulation of lipoprotein lipase-mediated clearance of triglyceride-rich lipoproteins.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Schoonjans",
      "authorRank" : 1,
      "name" : "Schoonjans K",
      "referenceId" : "RGD:A143984"
    }, {
      "firstName" : "J",
      "lastName" : "Peinado-Onsurbe",
      "authorRank" : 2,
      "name" : "Peinado-Onsurbe J",
      "referenceId" : "RGD:A86985"
    }, {
      "firstName" : "JC",
      "lastName" : "Fruchart",
      "authorRank" : 3,
      "name" : "Fruchart JC",
      "referenceId" : "RGD:A16018"
    }, {
      "firstName" : "A",
      "lastName" : "Tailleux",
      "authorRank" : 4,
      "name" : "Tailleux",
      "referenceId" : "RGD:A182905"
    }, {
      "firstName" : "C",
      "lastName" : "Fievet",
      "authorRank" : 5,
      "name" : "Fievet C",
      "referenceId" : "RGD:A44178"
    }, {
      "firstName" : "J",
      "lastName" : "Auwerx",
      "authorRank" : 6,
      "name" : "Auwerx J",
      "referenceId" : "RGD:A44563"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10054089"
    } ]
  }, {
    "primaryId" : "PMID:10386602",
    "title" : "Anisoosmotic regulation of the Nopp140 mRNA in H4IIE rat hepatoma cells and primary hepatocytes.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Warskulat U, etal., FEBS Lett. 1999 Jun 11;452(3):259-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-02-27T14:59:10.000-06:00",
    "volume" : "452",
    "pages" : "259-62",
    "abstract" : "Using the differential display polymerase chain reaction osmosensitive regulation of mRNA levels of the nucleolar phosphoprotein of 140 kDa (Nopp140) was found in H4IIE rat hepatoma cells. These levels were downregulated after hypoosmotic exposure in H4IIE cells and primary rat hepatocytes. Hyperosmotic incubation increased Nopp140 mRNA levels in H4IIE cells but not in hepatocytes. Inhibition of p38MAPK or MAP kinase kinase upstream of Erk-1 and Erk-2 decreased Nopp140 mRNA levels but did not prevent their osmosensitivity. Because Nopp140 is involved in the regulation of transcriptional activity it could play a role in the osmosignalling pathway towards gene expression in H4IIE cells and hepatocytes.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "U",
      "lastName" : "Warskulat",
      "authorRank" : 1,
      "name" : "Warskulat U",
      "referenceId" : "RGD:A17362"
    }, {
      "firstName" : "R",
      "lastName" : "Hammermann",
      "authorRank" : 2,
      "name" : "Hammermann R",
      "referenceId" : "RGD:A16043"
    }, {
      "firstName" : "D",
      "lastName" : "Haussinger",
      "authorRank" : 3,
      "name" : "Haussinger D",
      "referenceId" : "RGD:A17363"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303816"
    } ]
  }, {
    "primaryId" : "PMID:10386614",
    "title" : "Effect of mutations found in carbohydrate-deficient glycoprotein syndrome type IA on the activity of phosphomannomutase 2.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Pirard M, etal., FEBS Lett. 1999 Jun 11;452(3):319-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:18:29.000-05:00",
    "volume" : "452",
    "pages" : "319-22",
    "abstract" : "Seven mutant forms of human phosphomannomutase 2 were produced in Escherichia coli and purified. These mutants had a Vmax of 0.2-50% of the wild enzyme and were unstable. The least active protein (R141H) bears a very frequent mutation, which has never been found in the homozygous state whereas the second least active protein (D188G) corresponds to a mutation associated with a particularly severe phenotype. We conclude that total lack of phosphomannomutase 2 is incompatible with life. Another conclusion is that the elevated residual phosphomannomutase activity found in fibroblasts of some patients is contributed  by their mutated phosphomannomutase 2.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Pirard",
      "authorRank" : 1,
      "name" : "Pirard",
      "referenceId" : "RGD:A271825"
    }, {
      "firstName" : "G",
      "lastName" : "Matthijs",
      "authorRank" : 2,
      "name" : "Matthijs G",
      "referenceId" : "RGD:A72378"
    }, {
      "firstName" : "L",
      "lastName" : "Heykants",
      "authorRank" : 3,
      "name" : "Heykants",
      "referenceId" : "RGD:A271826"
    }, {
      "firstName" : "E",
      "lastName" : "Schollen",
      "authorRank" : 4,
      "name" : "Schollen",
      "referenceId" : "RGD:A250586"
    }, {
      "firstName" : "S",
      "lastName" : "Grunewald",
      "authorRank" : 5,
      "name" : "Grunewald S",
      "referenceId" : "RGD:A30807"
    }, {
      "firstName" : "J",
      "lastName" : "Jaeken",
      "authorRank" : 6,
      "name" : "Jaeken J",
      "referenceId" : "RGD:A52148"
    }, {
      "firstName" : "E",
      "lastName" : "Van Schaftingen",
      "authorRank" : 7,
      "name" : "Van Schaftingen E",
      "referenceId" : "RGD:A17332"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068696"
    } ]
  }, {
    "primaryId" : "PMID:10386951",
    "title" : "A PC12 variant lacking regulated secretory organelles: aberrant protein targeting and evidence for a factor inhibiting neuroendocrine gene expression.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Pance A, etal., J Neurochem. 1999 Jul;73(1):21-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-05-18T15:32:19.000-05:00",
    "volume" : "73",
    "pages" : "21-30",
    "abstract" : "A variant of the PC12 pheochromocytoma cell line (termed A35C) has been isolated  that lacks regulated secretory organelles and several constituent proteins. Northern and Southern blot analyses suggested a block at the transcriptional level. The proprotein-converting enzyme carboxypeptidase H was synthesised in the A35C cell line but was secreted by the constitutive pathway. Transient transfection of A35C cells with cDNAs encoding the regulated secretory proteins dopamine beta-hydroxylase and synaptotagmin I resulted in distinct patterns of mistargeting of these proteins. It is surprising that hybrid cells created by fusing normal PC12 cells with A35C cells exhibited the variant phenotype, suggesting that A35C cells express an inhibitory factor that represses neuroendocrine-specific gene expression.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Pance",
      "authorRank" : 1,
      "name" : "Pance A",
      "referenceId" : "RGD:A49634"
    }, {
      "firstName" : "K",
      "lastName" : "Morgan",
      "authorRank" : 2,
      "name" : "Morgan K",
      "referenceId" : "RGD:A161992"
    }, {
      "firstName" : "PC",
      "lastName" : "Guest",
      "authorRank" : 3,
      "name" : "Guest PC",
      "referenceId" : "RGD:A76229"
    }, {
      "firstName" : "K",
      "lastName" : "Bowers",
      "authorRank" : 4,
      "name" : "Bowers K",
      "referenceId" : "RGD:A154741"
    }, {
      "firstName" : "GE",
      "lastName" : "Dean",
      "authorRank" : 5,
      "name" : "Dean GE",
      "referenceId" : "RGD:A154742"
    }, {
      "firstName" : "DF",
      "lastName" : "Cutler",
      "authorRank" : 6,
      "name" : "Cutler DF",
      "referenceId" : "RGD:A154743"
    }, {
      "firstName" : "AP",
      "lastName" : "Jackson",
      "authorRank" : 7,
      "name" : "Jackson AP",
      "referenceId" : "RGD:A6986"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6483348"
    } ]
  }, {
    "primaryId" : "PMID:10386996",
    "title" : "Expression of the SM-20 gene promotes death in nerve growth factor-dependent sympathetic neurons.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Lipscomb EA, etal., J Neurochem. 1999 Jul;73(1):429-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-23T17:06:24.000-05:00",
    "volume" : "73",
    "pages" : "429-32",
    "abstract" : "Sympathetic neurons undergo apoptosis when deprived of nerve growth factor (NGF). Inhibitors of RNA or protein synthesis block this death, suggesting that gene expression is important for apoptosis in this system. We have identified SM-20 as a new gene that increases in expression in sympathetic neurons after NGF withdrawal. Expression of SM-20 also increases during neuronal death caused by cytosine arabinoside or the phosphatidylinositol 3-kinase inhibitor LY294002. In  addition, SM-20 protein synthesis is elevated in NGF-deprived neurons compared with neurons maintained with NGF. Importantly, expression of SM-20 in sympathetic neurons causes cell death in the presence of NGF. These results suggest that SM-20 may function to regulate cell death in neurons.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EA",
      "lastName" : "Lipscomb",
      "authorRank" : 1,
      "name" : "Lipscomb",
      "referenceId" : "RGD:A329885"
    }, {
      "firstName" : "PD",
      "lastName" : "Sarmiere",
      "authorRank" : 2,
      "name" : "Sarmiere",
      "referenceId" : "RGD:A204162"
    }, {
      "firstName" : "RJ",
      "lastName" : "Crowder",
      "authorRank" : 3,
      "name" : "Crowder RJ",
      "referenceId" : "RGD:A49037"
    }, {
      "firstName" : "RS",
      "lastName" : "Freeman",
      "authorRank" : 4,
      "name" : "Freeman RS",
      "referenceId" : "RGD:A29738"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11252089"
    } ]
  }, {
    "primaryId" : "PMID:10387044",
    "title" : "Binding of biliverdin, bilirubin, and thyroid hormones to lipocalin-type prostaglandin D synthase.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Beuckmann CT, etal., Biochemistry. 1999 Jun 22;38(25):8006-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:37:18.000-05:00",
    "volume" : "38",
    "pages" : "8006-13",
    "abstract" : "Lipocalin-type prostaglandin D synthase is a major protein of the cerebrospinal fluid and was originally known as beta-trace. We investigated the binding ability of prostaglandin D synthase toward bile pigments, thyroid hormones, steroid hormones, and fatty acids in this present study. We found that the recombinant enzyme binds bile pigments and thyroid hormones, resulting in quenching of the intrinsic tryptophan fluorescence, the appearance of induced circular dichroism of the lipophilic ligands, and a red shift of the absorption spectra of bilirubin and biliverdin. The binding of prostaglandin D synthase to lipophilic ligands was also demonstrated by the resonant mirror technique and surface plasmon resonance  detection. The dissociation constants were calculated to be 33 nM, 37 nM, 660 nM, 820 nM, and 2.08 microM for biliverdin, bilirubin, L-thyroxine, 3,3',5'-triiodo-L-thyronine, and 3,3', 5-triiodo-L-thyronine, respectively. Biliverdin and bilirubin underwent a shift in their absorption peaks from 375 to  380 nm and from 439 to 446 nm, respectively, after binding to prostaglandin D synthase. Bilirubin bound to the enzyme showed a bisignate CD spectrum with a (-) Cotton effect at 422 nm and a (+) Cotton effect at 472 nm, indicating a right-handed chirality. The ligands also inhibited prostaglandin D synthase activity noncompetitively in a concentration-dependent manner, with IC50 values between 3.9 and 10. 9 microM. Epididymal retinoic acid-binding protein and beta-lactoglobulin, two other lipocalin proteins that bind retinoids such as prostaglandin D synthase, did not show any significant interaction with bile pigments or thyroid hormones. These results show that prostaglandin D synthase binds small lipophilic ligands with a specificity distinct from that of other lipocalins.",
    "issueName" : "25",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CT",
      "lastName" : "Beuckmann",
      "authorRank" : 1,
      "name" : "Beuckmann CT",
      "referenceId" : "RGD:A22364"
    }, {
      "firstName" : "M",
      "lastName" : "Aoyagi",
      "authorRank" : 2,
      "name" : "Aoyagi M",
      "referenceId" : "RGD:A47803"
    }, {
      "firstName" : "I",
      "lastName" : "Okazaki",
      "authorRank" : 3,
      "name" : "Okazaki I",
      "referenceId" : "RGD:A30156"
    }, {
      "firstName" : "T",
      "lastName" : "Hiroike",
      "authorRank" : 4,
      "name" : "Hiroike",
      "referenceId" : "RGD:A185016"
    }, {
      "firstName" : "H",
      "lastName" : "Toh",
      "authorRank" : 5,
      "name" : "Toh H",
      "referenceId" : "RGD:A6088"
    }, {
      "firstName" : "O",
      "lastName" : "Hayaishi",
      "authorRank" : 6,
      "name" : "Hayaishi O",
      "referenceId" : "RGD:A6090"
    }, {
      "firstName" : "Y",
      "lastName" : "Urade",
      "authorRank" : 7,
      "name" : "Urade Y",
      "referenceId" : "RGD:A6089"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553833"
    } ]
  }, {
    "primaryId" : "PMID:10387075",
    "title" : "The HELLGH motif of rat liver dipeptidyl peptidase III is involved in zinc coordination and the catalytic activity of the enzyme.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Fukasawa K, etal., Biochemistry 1999 Jun 29;38(26):8299-303.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-19T13:10:49.000-06:00",
    "volume" : "38",
    "pages" : "8299-303",
    "abstract" : "The role of the HELLGH (residues 450-455) motif in the sequence of rat dipeptidyl peptidase III (EC 3.4.14.4) was investigated by replacing Glu451 with an alanine or an aspartic acid residue and by replacing His450 and His455 with a tyrosine residue by site-directed mutagenesis. Mutated cDNAs were expressed three or four times in Escherichia coli, and the resulting proteins were purified to apparent homogeneity. None of the expressed mutated proteins exhibited DPP III activity. The mutants of Glu451 contained 1 mol of zinc per mole of protein, but mutants His450 and His455 did not contain significant amounts of zinc as determined by atomic absorption spectrometry. The Leu453-deleted enzyme (having the zinc aminopeptidase motif HExxH-18-E) had almost the same order of binding affinity (for Arg-Arg-2-naphthylamide) as the wild-type enzyme, but the specificity constant was about 10%. These results provide evidence that the suitable number of amino acids included between Glu451 and His455 is three residues for the enzyme activity and confirm that residues His450, His455, and Glu451 are involved in zinc coordination and catalytic activity.",
    "issueName" : "26",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Fukasawa",
      "authorRank" : 1,
      "name" : "Fukasawa K",
      "referenceId" : "RGD:A9425"
    }, {
      "firstName" : "KM",
      "lastName" : "Fukasawa",
      "authorRank" : 2,
      "name" : "Fukasawa KM",
      "referenceId" : "RGD:A9424"
    }, {
      "firstName" : "H",
      "lastName" : "Iwamoto",
      "authorRank" : 3,
      "name" : "Iwamoto H",
      "referenceId" : "RGD:A29614"
    }, {
      "firstName" : "J",
      "lastName" : "Hirose",
      "authorRank" : 4,
      "name" : "Hirose J",
      "referenceId" : "RGD:A29615"
    }, {
      "firstName" : "M",
      "lastName" : "Harada",
      "authorRank" : 5,
      "name" : "Harada M",
      "referenceId" : "RGD:A314640"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:728455"
    } ]
  }, {
    "primaryId" : "PMID:10388558",
    "title" : "Comparative sequence analysis of the complete human sarcomeric myosin heavy chain family: implications for functional diversity.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Weiss A, etal., J Mol Biol 1999 Jul 2;290(1):61-75.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-08-15T23:00:50.000-05:00",
    "volume" : "290",
    "pages" : "61-75",
    "abstract" : "The conventional myosin motor proteins that drive mammalian skeletal and cardiac muscle contraction include eight sarcomeric myosin heavy chain (MyHC) isoforms. Six skeletal MyHCs are encoded by genes found in tightly linked clusters on human and mouse chromosomes 17 and 11, respectively. The full coding regions of only two out of six mammalian skeletal MyHCs had been sequenced prior to this work. In an effort to assess the extent of sequence diversity within the human MyHC family we present new full-length coding sequences corresponding to four additional human genes: MyHC-IIb, MyHC-extraocular, MyHC-IIa and MyHC-IIx/d. This represents the first opportunity to compare the full coding sequences of all eight sarcomeric MyHC isoforms within a vertebrate organism. Sequence variability has been analyzed in the context of available structure/function data with an emphasis on potential functional diversity within the family. Results indicate that functional diversity among MyHCs is likely to be accomplished by having small pockets of sequence diversity in an otherwise highly conserved molecule.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Weiss",
      "authorRank" : 1,
      "name" : "Weiss A",
      "referenceId" : "RGD:A24450"
    }, {
      "firstName" : "S",
      "lastName" : "Schiaffino",
      "authorRank" : 2,
      "name" : "Schiaffino S",
      "referenceId" : "RGD:A120422"
    }, {
      "firstName" : "LA",
      "lastName" : "Leinwand",
      "authorRank" : 3,
      "name" : "Leinwand LA",
      "referenceId" : "RGD:A70993"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302214"
    } ]
  }, {
    "primaryId" : "PMID:10389840",
    "title" : "No correlation of plasma cell 1 overexpression with insulin resistance in diabetic rats and 3T3-L1 adipocytes.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Sakoda H, etal., Diabetes 1999 Jul;48(7):1365-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-19T13:10:52.000-06:00",
    "volume" : "48",
    "pages" : "1365-71",
    "abstract" : "Membrane glycoprotein plasma cell 1 (PC-1) has been shown to be increased in type 2 diabetes and involved in insulin resistance through inhibiting the insulin receptor tyrosine kinase, which was demonstrated using cultured breast cancer cells. However, other reports have shown contradictory results in Chinese hamster ovary cells and in vitro kinase assay. Thus, we considered it necessary to investigate the effect of PC-1 using highly insulin-sensitive cells. Here, we used two of the following approaches: 1) investigating PC-1 expression levels in insulin-responsive tissues in rat models of diabetes and 2) overexpressing PC-1 in 3T3-L1 adipocytes. We found that PC-1 was highly expressed in insulin-responsive tissues, such as liver and adipose tissue, in normal rats. However, high-fat feeding or streptozotocin-induced diabetes did not change its expression levels in liver, adipose tissue, and skeletal muscle. Thus, PC-1 expression levels were not associated with high-fat-diet-induced insulin resistance or hyperglycemia. Although PC-1 was increased in adipose tissue in Zucker fatty rats (protein level, by 50%; mRNA level, by 90%), its expression levels in liver and skeletal muscle, tissues that are more responsible for whole body glucose metabolism than adipose tissue, did not significantly differ from those in normal rats. Next, we overexpressed PC-1 in 3T3-L1 adipocytes using an adenovirus transfection system. PC-1 expression was markedly increased to a level 16-fold greater than that in normal human adipose tissue, which is higher than the previously reported levels in diabetic patients. However, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1, activation of phosphatidylinositol 3-kinase, and glucose uptake were not affected by PC-1 overexpression. These results strongly suggest that increased PC-1 expression is not causally related to insulin resistance.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Sakoda",
      "authorRank" : 1,
      "name" : "Sakoda H",
      "referenceId" : "RGD:A6461"
    }, {
      "firstName" : "T",
      "lastName" : "Ogihara",
      "authorRank" : 2,
      "name" : "Ogihara T",
      "referenceId" : "RGD:A5048"
    }, {
      "firstName" : "M",
      "lastName" : "Anai",
      "authorRank" : 3,
      "name" : "Anai M",
      "referenceId" : "RGD:A33326"
    }, {
      "firstName" : "M",
      "lastName" : "Funaki",
      "authorRank" : 4,
      "name" : "Funaki M",
      "referenceId" : "RGD:A5046"
    }, {
      "firstName" : "K",
      "lastName" : "Inukai",
      "authorRank" : 5,
      "name" : "Inukai K",
      "referenceId" : "RGD:A161879"
    }, {
      "firstName" : "H",
      "lastName" : "Katagiri",
      "authorRank" : 6,
      "name" : "Katagiri H",
      "referenceId" : "RGD:A114681"
    }, {
      "firstName" : "Y",
      "lastName" : "Fukushima",
      "authorRank" : 7,
      "name" : "Fukushima Y",
      "referenceId" : "RGD:A148039"
    }, {
      "firstName" : "Y",
      "lastName" : "Onishi",
      "authorRank" : 8,
      "name" : "Onishi Y",
      "referenceId" : "RGD:A6462"
    }, {
      "firstName" : "H",
      "lastName" : "Ono",
      "authorRank" : 9,
      "name" : "Ono H",
      "referenceId" : "RGD:A6464"
    }, {
      "firstName" : "Y",
      "lastName" : "Yazaki",
      "authorRank" : 10,
      "name" : "Yazaki Y",
      "referenceId" : "RGD:A161904"
    }, {
      "firstName" : "M",
      "lastName" : "Kikuchi",
      "authorRank" : 11,
      "name" : "Kikuchi M",
      "referenceId" : "RGD:A5166"
    }, {
      "firstName" : "Y",
      "lastName" : "Oka",
      "authorRank" : 12,
      "name" : "Oka Y",
      "referenceId" : "RGD:A115971"
    }, {
      "firstName" : "T",
      "lastName" : "Asano",
      "authorRank" : 13,
      "name" : "Asano T",
      "referenceId" : "RGD:A161880"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:728456"
    } ]
  }, {
    "primaryId" : "PMID:10389856",
    "title" : "The 3'-untranslated region polymorphism of the gene for skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 in the type 2 diabetic Japanese population.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Maegawa H, etal., Diabetes. 1999 Jul;48(7):1469-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-07-22T15:54:31.000-05:00",
    "volume" : "48",
    "pages" : "1469-72",
    "abstract" : "A newly identified 3'-untranslated region (UTR) polymorphism of the gene for skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PPP1R3) was associated with insulin resistance and type 2 diabetes in Pima Indians (Xia J, Scherers W, Cohen PTW, Majer M, Xi T, Norman RA, Knowler WC, Bogardus C, Prochazka M: A common variant in PP1R3 associated with insulin resistance and type 2 diabetes. Diabetes 47:1519-1524, 1998). Thus, we investigated the frequency of polymorphism of the adenine- and thymine-rich element (ARE-1 and its variant ARE-2) in 426 Japanese type 2 diabetic and 380 nondiabetic subjects using a polymerase chain reaction (PCR)-restriction enzyme fragment length polymorphism (RFLP) method. The allele frequency of the ARE-2 variant in diabetic subjects was higher than that in nondiabetic subjects (0.34 vs. 0.29; P < 0.05), even though its frequency in Japanese subjects was lower (P < 0.001) than the reported value in Pima Indians (0.56). An aspartate polymorphism at codon 905 was 100% coupled to the ARE-2 allele, and its allele frequency was higher also in diabetic subjects. Although a serine substitution at codon 883 was partially linked with the ARE-2 allele, there was no difference between diabetic and nondiabetic subjects. These results indicate that the frequency of polymorphism of the PPP1R3 gene (ARE-2 and Asp905) is different between two ethnic groups and is increased in Japanese people with type 2 diabetes, suggesting that these variants may be a possible marker for searching for diabetogenic genes.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Maegawa",
      "authorRank" : 1,
      "name" : "Maegawa H",
      "referenceId" : "RGD:A13196"
    }, {
      "firstName" : "K",
      "lastName" : "Shi",
      "authorRank" : 2,
      "name" : "Shi K",
      "referenceId" : "RGD:A83443"
    }, {
      "firstName" : "H",
      "lastName" : "Hidaka",
      "authorRank" : 3,
      "name" : "Hidaka H",
      "referenceId" : "RGD:A5692"
    }, {
      "firstName" : "N",
      "lastName" : "Iwai",
      "authorRank" : 4,
      "name" : "Iwai N",
      "referenceId" : "RGD:A109702"
    }, {
      "firstName" : "Y",
      "lastName" : "Nishio",
      "authorRank" : 5,
      "name" : "Nishio Y",
      "referenceId" : "RGD:A13194"
    }, {
      "firstName" : "K",
      "lastName" : "Egawa",
      "authorRank" : 6,
      "name" : "Egawa K",
      "referenceId" : "RGD:A27662"
    }, {
      "firstName" : "H",
      "lastName" : "Kojima",
      "authorRank" : 7,
      "name" : "Kojima H",
      "referenceId" : "RGD:A15945"
    }, {
      "firstName" : "M",
      "lastName" : "Haneda",
      "authorRank" : 8,
      "name" : "Haneda M",
      "referenceId" : "RGD:A10300"
    }, {
      "firstName" : "H",
      "lastName" : "Yasuda",
      "authorRank" : 9,
      "name" : "Yasuda H",
      "referenceId" : "RGD:A8224"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakamura",
      "authorRank" : 10,
      "name" : "Nakamura Y",
      "referenceId" : "RGD:A161073"
    }, {
      "firstName" : "M",
      "lastName" : "Kinoshita",
      "authorRank" : 11,
      "name" : "Kinoshita M",
      "referenceId" : "RGD:A10840"
    }, {
      "firstName" : "R",
      "lastName" : "Kikkawa",
      "authorRank" : 12,
      "name" : "Kikkawa R",
      "referenceId" : "RGD:A10302"
    }, {
      "firstName" : "A",
      "lastName" : "Kashiwagi",
      "authorRank" : 13,
      "name" : "Kashiwagi A",
      "referenceId" : "RGD:A13197"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311532"
    } ]
  }, {
    "primaryId" : "PMID:10389888",
    "title" : "Immunosuppression for neural xenografts: a comparison of cyclosporin and anti-CD25 monoclonal antibody.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Honey CR and Shen H, J Neurosurg. 1999 Jul;91(1):109-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-28T16:15:23.000-06:00",
    "volume" : "91",
    "pages" : "109-13",
    "abstract" : "OBJECT: The goal of this study was to compare the effects of short- and long-term immunosuppression induced by cyclosporin with those of immunosuppression induced by a monoclonal antibody against the rat interleukin-2 receptor (anti-CD25 mAb) in rats with xenografts. METHODS: The authors compared the in vivo function and final histological characteristics of fetal mouse mesencephalon xenografts in hemiparkinsonian rats in which immunosuppression was induced by: 1) a short course (2 weeks) of cyclosporin; 2) a long course (8 weeks) of cyclosporin; or 3) a short course of treatment with anti-CD25 mAb. Adult Wistar rats were unilaterally lesioned with 6-hydroxydopamine in their medial forebrain bundle, after which their rotational behavior in response to methamphetamine was quantified. Four groups of 20 rats with rotations numbering greater than six turns per minute received fetal mouse mesencephalon transplants to their dopamine-denervated striatum. Group 1 received no immunosuppression therapy; Group 2 received daily intraperitoneal injections of 10 mg/kg cyclosporin for 2 weeks; Group 3 received daily intraperitoneal injections of 10 mg/kg cyclosporin for 8 weeks; and Group 4 received daily intraperitoneal injections of 1 mg/kg anti-CD25 mAb for 2 weeks. The rats were tested for rotational behavior every 4 weeks and killed after 16 weeks. Surviving xenografts were assessed using immunohistochemical staining for a mouse neuronal marker (Thy-1.2). Sixteen weeks after transplant, there were significantly more surviving xenografts in Groups 3 (p < 0.001) and 4 (p < 0.001) compared with control Group 1 (Fisher's exact test) and significantly better functioning xenografts in Groups 3 (p < 0.01) and 4 (p < 0.05) compared with control Group 1 (contrasts of groups following analysis of variance with Bonferroni correction). CONCLUSIONS: A short course of anti-CD25 mAb-induced immunosuppression was as effective as a long course of cyclosporin-induced immunosuppression in this model.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CR",
      "lastName" : "Honey",
      "authorRank" : 1,
      "name" : "Honey CR",
      "referenceId" : "RGD:A76329"
    }, {
      "firstName" : "H",
      "lastName" : "Shen",
      "authorRank" : 2,
      "name" : "Shen H",
      "referenceId" : "RGD:A33600"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600145"
    } ]
  }, {
    "primaryId" : "PMID:10389944",
    "title" : "Combination surgery and nonviral interleukin 2 gene therapy for head and neck cancer.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Li D, etal., Clin Cancer Res. 1999 Jun;5(6):1551-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-30T11:39:46.000-05:00",
    "volume" : "5",
    "pages" : "1551-6",
    "abstract" : "We have developed a novel nonviral interleukin 2 (IL-2) gene therapy that demonstrates significant treatment-specific, antitumor efficacy in combination with subtotal surgical resection in a head and neck cancer murine model. Treatment of established head and neck tumors in immunocompetent mice was performed via direct injection with a cationic liposome composed of DOTMA and cholesterol formulation carrying DNA plasmid for human IL-2 (hIL-2) gene expression. ELISA assays of tumor extracts 24 h after treatment of hIL-2 gene therapy revealed increased local hIL-2 production as well as a formulation-specific secondary induction of murine IFN-gamma and IL-12. We hypothesize that the paracrine production of multiple cytokines after IL-2 single gene transfer is important for generating a therapeutic effect, and that this strategy will be well tolerated and effective in combination with surgery for head and neck cancer. In animal experiments where surgery was performed in conjunction with an operative site injection of hIL-2 plasmid formulation, no pre-, intra-, or postoperative toxicity or compromise to wound healing was identified. In murine experiments combining partial surgical resection with the nonviral gene therapy, significant antitumor efficacy was demonstrated in the hIL-2 plasmid formulation group compared with empty plasmid formulation and lactose-injected controls. In a separate experiment using smaller tumor sizes, we also demonstrated that treatment outcomes were dependent on the technical aspect  of the actual treatment injection as well as visualization with surgical access.  The hIL-2 plasmid formulation gene therapy induces local expression of multiple cytokines, results in treatment-specific antitumor effects, and circumvents many  of the concerns and toxicity encountered with viral gene transfer. These data support the need for continued preclinical investigation and the consideration of human clinical trials for combination nonviral hIL-2 gene therapy and surgery for head and neck cancer.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li D",
      "referenceId" : "RGD:A11822"
    }, {
      "firstName" : "W",
      "lastName" : "Jiang",
      "authorRank" : 2,
      "name" : "Jiang W",
      "referenceId" : "RGD:A51614"
    }, {
      "firstName" : "JS",
      "lastName" : "Bishop",
      "authorRank" : 3,
      "name" : "Bishop",
      "referenceId" : "RGD:A190708"
    }, {
      "firstName" : "R",
      "lastName" : "Ralston",
      "authorRank" : 4,
      "name" : "Ralston",
      "referenceId" : "RGD:A190709"
    }, {
      "firstName" : "JR",
      "lastName" : "O'Malley BW",
      "authorRank" : 5,
      "name" : "O'Malley BW",
      "referenceId" : "RGD:A190710"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662949"
    } ]
  }, {
    "primaryId" : "PMID:10389971",
    "title" : "Microsatellite instability and mismatch repair gene inactivation in sporadic pancreatic and colon tumours.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ghimenti C, etal., Br J Cancer. 1999 Apr;80(1-2):11-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:34:12.000-05:00",
    "volume" : "80",
    "pages" : "11-6",
    "abstract" : "Genomic instability has been proposed as a new mechanism of carcinogenesis involved in hereditary non-polyposis colorectal cancer (HNPCC) and in a large number of sporadic cancers like pancreatic and colon tumours. Mutations in human  mismatch repair genes have been found in HNPCC patients, but their involvement in sporadic cancer has not been clarified yet. In this study we screened 21 pancreatic and 23 colorectal sporadic cancers for microsatellite instability by ten and six different microsatellite markers respectively. Microsatellite alterations were observed at one or more loci in 66.6% (14/21) of pancreatic cancers and in 26% (6/23) colon tumours, but all the pancreatic and half of the colon samples showed a low rate of microsatellite instability. All the unstable samples were further analysed for mutations in the hMLH1 and hMSH2 genes and for  hypermethylation of the hMLH1 promoter region. Alterations in the hMLH1 gene were found only in colorectal tumours with a large presence of microsatellite instability. None of the pancreatic tumours showed any alteration in the two genes analysed. Our results demonstrate that microsatellite instability is unlikely to play a role in the tumorigenesis of sporadic pancreatic cancers and confirm the presence of mismatch repair gene alterations only in sporadic colon tumours with a highly unstable phenotype.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Ghimenti",
      "authorRank" : 1,
      "name" : "Ghimenti",
      "referenceId" : "RGD:A258583"
    }, {
      "firstName" : "P",
      "lastName" : "Tannergard",
      "authorRank" : 2,
      "name" : "Tannergard P",
      "referenceId" : "RGD:A83179"
    }, {
      "firstName" : "S",
      "lastName" : "Wahlberg",
      "authorRank" : 3,
      "name" : "Wahlberg",
      "referenceId" : "RGD:A258584"
    }, {
      "firstName" : "T",
      "lastName" : "Liu",
      "authorRank" : 4,
      "name" : "Liu T",
      "referenceId" : "RGD:A43376"
    }, {
      "firstName" : "PG",
      "lastName" : "Giulianotti",
      "authorRank" : 5,
      "name" : "Giulianotti",
      "referenceId" : "RGD:A258585"
    }, {
      "firstName" : "F",
      "lastName" : "Mosca",
      "authorRank" : 6,
      "name" : "Mosca F",
      "referenceId" : "RGD:A109046"
    }, {
      "firstName" : "G",
      "lastName" : "Fornaciari",
      "authorRank" : 7,
      "name" : "Fornaciari",
      "referenceId" : "RGD:A258586"
    }, {
      "firstName" : "G",
      "lastName" : "Bevilacqua",
      "authorRank" : 8,
      "name" : "Bevilacqua G",
      "referenceId" : "RGD:A92045"
    }, {
      "firstName" : "A",
      "lastName" : "Lindblom",
      "authorRank" : 9,
      "name" : "Lindblom A",
      "referenceId" : "RGD:A83185"
    }, {
      "firstName" : "MA",
      "lastName" : "Caligo",
      "authorRank" : 10,
      "name" : "Caligo MA",
      "referenceId" : "RGD:A98924"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064428"
    } ]
  }, {
    "primaryId" : "PMID:10390012",
    "title" : "Expression of MUC1 mucins inversely correlated with post-surgical survival of renal cell carcinoma patients.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Fujita K, etal., Br J Cancer. 1999 Apr;80(1-2):301-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-06-17T15:20:46.000-05:00",
    "volume" : "80",
    "pages" : "301-8",
    "abstract" : "Surgical specimens of the normal kidney and of renal cell carcinoma (RCC) tissues at different stages of progression and of various histological grades were examined for the expression of MUC1 mucins with sialylated carbohydrates (sialylated MUC1 mucins) using a monoclonal antibody MY.1E12. Immunohistochemical studies revealed that the binding sites for this antibody were localized to the apical side of the epithelial cells of the distal convoluted tubules, Henle's loops and collecting ducts. However, proximal convoluted tubules, where RCC is considered to originate, were not stained. This antibody also bound strongly to RCC at advanced stages of progression and at metastatic sites, and to RCC of histologically high grades (undifferentiated). The epitope, presumably sialylated MUC1 mucin, was detected not only along the surface of the cell membranes but also in the cytoplasm. The level of expression of sialylated MUC1 mucins was inversely correlated with the survival of the patients with RCC and the disease-free survival period after curative surgery. Western blot analysis demonstrated that the electrophoretic mobility of sialylated MUC1 mucins of RCC was greater than that from the normal kidney. It is suggested that high levels of expression of sialylated MUC1 mucins in certain human RCC populations correlate with the aggressiveness of the disease, such as the tendency to form metastasis.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Fujita",
      "authorRank" : 1,
      "name" : "Fujita K",
      "referenceId" : "RGD:A25057"
    }, {
      "firstName" : "K",
      "lastName" : "Denda",
      "authorRank" : 2,
      "name" : "Denda",
      "referenceId" : "RGD:A170783"
    }, {
      "firstName" : "M",
      "lastName" : "Yamamoto",
      "authorRank" : 3,
      "name" : "Yamamoto M",
      "referenceId" : "RGD:A5108"
    }, {
      "firstName" : "T",
      "lastName" : "Matsumoto",
      "authorRank" : 4,
      "name" : "Matsumoto T",
      "referenceId" : "RGD:A12200"
    }, {
      "firstName" : "M",
      "lastName" : "Fujime",
      "authorRank" : 5,
      "name" : "Fujime M",
      "referenceId" : "RGD:A68323"
    }, {
      "firstName" : "T",
      "lastName" : "Irimura",
      "authorRank" : 6,
      "name" : "Irimura T",
      "referenceId" : "RGD:A10348"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7245968"
    } ]
  }, {
    "primaryId" : "PMID:10390159",
    "title" : "Cloning and characterization of rat BAT3 cDNA.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Ozaki T, etal., DNA Cell Biol 1999 Jun;18(6):503-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-13T12:37:45.000-05:00",
    "volume" : "18",
    "pages" : "503-12",
    "abstract" : "HLA-B-associated transcript 3 (BAT3) was originally identified as one of the genes located within human major histocompatibility complex. It encodes a large proline-rich protein with unknown function. In this study, we found that a fragment of the BAT3 gene product interacts with a candidate tumor suppressor, DAN, in the yeast-based two-hybrid system. We cloned the full-length rat BAT3 cDNA from a fibroblast 3Y1 cDNA library. Our sequence analysis has demonstrated that rat BAT3 cDNA is 3617 nucleotides in length and encodes a full-length BAT3 (1098 amino acids) with an estimated molecular mass of 114,801 daltons, which displays an 87.4% identity with human BAT3. The deletion experiment revealed that the N-terminal region (amino acid residues 1-80) of DAN was required for the interaction with BAT3. Green fluorescent protein-tagged BAT3 was largely localized in the cytoplasm of COS cells. Northern hybridization showed that BAT3 mRNA was expressed in all the adult rat tissues examined but predominantly in testis. In addition, the level of BAT3 mRNA expression was more downregulated in some of the transformed cells, including v-mos- and v-Ha-ras-transformed 3Y1 cells, than in the parental cells.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Ozaki",
      "authorRank" : 1,
      "name" : "Ozaki T",
      "referenceId" : "RGD:A9679"
    }, {
      "firstName" : "E",
      "lastName" : "Hanaoka",
      "authorRank" : 2,
      "name" : "Hanaoka E",
      "referenceId" : "RGD:A9680"
    }, {
      "firstName" : "M",
      "lastName" : "Naka",
      "authorRank" : 3,
      "name" : "Naka M",
      "referenceId" : "RGD:A9681"
    }, {
      "firstName" : "A",
      "lastName" : "Nakagawara",
      "authorRank" : 4,
      "name" : "Nakagawara A",
      "referenceId" : "RGD:A9682"
    }, {
      "firstName" : "S",
      "lastName" : "Sakiyama",
      "authorRank" : 5,
      "name" : "Sakiyama S",
      "referenceId" : "RGD:A120861"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70664"
    } ]
  }, {
    "primaryId" : "PMID:10390358",
    "title" : "Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Simon DB, etal., Science. 1999 Jul 2;285(5424):103-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-08T15:21:13.000-06:00",
    "volume" : "285",
    "pages" : "103-6",
    "abstract" : "Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.",
    "issueName" : "5424",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DB",
      "lastName" : "Simon",
      "authorRank" : 1,
      "name" : "Simon DB",
      "referenceId" : "RGD:A53637"
    }, {
      "firstName" : "Y",
      "lastName" : "Lu",
      "authorRank" : 2,
      "name" : "Lu Y",
      "referenceId" : "RGD:A37000"
    }, {
      "firstName" : "KA",
      "lastName" : "Choate",
      "authorRank" : 3,
      "name" : "Choate KA",
      "referenceId" : "RGD:A64241"
    }, {
      "firstName" : "H",
      "lastName" : "Velazquez",
      "authorRank" : 4,
      "name" : "Velazquez H",
      "referenceId" : "RGD:A74530"
    }, {
      "firstName" : "E",
      "lastName" : "Al-Sabban",
      "authorRank" : 5,
      "name" : "Al-Sabban E",
      "referenceId" : "RGD:A74531"
    }, {
      "firstName" : "M",
      "lastName" : "Praga",
      "authorRank" : 6,
      "name" : "Praga M",
      "referenceId" : "RGD:A74532"
    }, {
      "firstName" : "G",
      "lastName" : "Casari",
      "authorRank" : 7,
      "name" : "Casari G",
      "referenceId" : "RGD:A15104"
    }, {
      "firstName" : "A",
      "lastName" : "Bettinelli",
      "authorRank" : 8,
      "name" : "Bettinelli A",
      "referenceId" : "RGD:A74533"
    }, {
      "firstName" : "G",
      "lastName" : "Colussi",
      "authorRank" : 9,
      "name" : "Colussi G",
      "referenceId" : "RGD:A74534"
    }, {
      "firstName" : "J",
      "lastName" : "Rodriguez-Soriano",
      "authorRank" : 10,
      "name" : "Rodriguez-Soriano J",
      "referenceId" : "RGD:A53645"
    }, {
      "firstName" : "D",
      "lastName" : "McCredie",
      "authorRank" : 11,
      "name" : "McCredie D",
      "referenceId" : "RGD:A74535"
    }, {
      "firstName" : "D",
      "lastName" : "Milford",
      "authorRank" : 12,
      "name" : "Milford D",
      "referenceId" : "RGD:A74536"
    }, {
      "firstName" : "S",
      "lastName" : "Sanjad",
      "authorRank" : 13,
      "name" : "Sanjad S",
      "referenceId" : "RGD:A74537"
    }, {
      "firstName" : "RP",
      "lastName" : "Lifton",
      "authorRank" : 14,
      "name" : "Lifton RP",
      "referenceId" : "RGD:A34798"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599615"
    } ]
  }, {
    "primaryId" : "PMID:10391136",
    "title" : "Mitochondrial creatine kinase functional development in post-natal rat skeletal muscle. A combined polarographic/31P NMR study.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Kernec F, etal., Mol Cell Biochem. 1999 Apr;194(1-2):165-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-11-18T16:00:10.000-06:00",
    "volume" : "194",
    "pages" : "165-71",
    "abstract" : "Mitochondrial creatine kinase (Mi-CK) function in viable mitochondria from developing rat skeletal muscle was assessed both by polarographic measurements of creatine-induced respiration and 31P NMR spectroscopy measurements of phosphocreatine (PCr) synthesis. Creatine-induced respiration was observed in very young rats and increased by 50% to 35 days of age. PCr synthesis was present in 7 day old animals and increased by 300% reaching levels measured in 35 day and adult muscle. Unlike reports showing Mi-CK enzymatic activities but no mitochondrial function in several situations, a concomitant progression of enzymatic activity and mitochondrial function was evidenced during the developmental stages of skeletal muscle Mi-CK in altricious animals. These results correlated with the progressive pattern of muscle differentiation during  development of motricity in such animals. The observation that Mi-CK is functional in skeletal muscle mitochondria very early after birth, strongly favors the notion that adaptations in skeletal muscle of Mi-CK knock-out mice occur early.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Kernec",
      "authorRank" : 1,
      "name" : "Kernec",
      "referenceId" : "RGD:A412703"
    }, {
      "firstName" : "L",
      "lastName" : "Nadal",
      "authorRank" : 2,
      "name" : "Nadal",
      "referenceId" : "RGD:A347433"
    }, {
      "firstName" : "C",
      "lastName" : "Rocher",
      "authorRank" : 3,
      "name" : "Rocher C",
      "referenceId" : "RGD:A155491"
    }, {
      "firstName" : "P",
      "lastName" : "Mateo",
      "authorRank" : 4,
      "name" : "Mateo P",
      "referenceId" : "RGD:A35055"
    }, {
      "firstName" : "J",
      "lastName" : "De Certaines",
      "authorRank" : 5,
      "name" : "De Certaines",
      "referenceId" : "RGD:A412704"
    }, {
      "firstName" : "E",
      "lastName" : "Le Rumeur",
      "authorRank" : 6,
      "name" : "Le Rumeur",
      "referenceId" : "RGD:A222804"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11565092"
    } ]
  }, {
    "primaryId" : "PMID:10391208",
    "title" : "Absence of Cd36 mutation in the original spontaneously hypertensive rats with insulin resistance.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Gotoda T, etal., Nat Genet 1999 Jul;22(3):226-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-03-28T10:52:28.000-06:00",
    "volume" : "22",
    "pages" : "226-8",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Gotoda",
      "authorRank" : 1,
      "name" : "Gotoda T",
      "referenceId" : "RGD:A65263"
    }, {
      "firstName" : "Y",
      "lastName" : "Iizuka",
      "authorRank" : 2,
      "name" : "Iizuka Y",
      "referenceId" : "RGD:A14299"
    }, {
      "firstName" : "N",
      "lastName" : "Kato",
      "authorRank" : 3,
      "name" : "Kato N",
      "referenceId" : "RGD:A159893"
    }, {
      "firstName" : "J",
      "lastName" : "Osuga",
      "authorRank" : 4,
      "name" : "Osuga J",
      "referenceId" : "RGD:A14301"
    }, {
      "firstName" : "MT",
      "lastName" : "Bihoreau",
      "authorRank" : 5,
      "name" : "Bihoreau MT",
      "referenceId" : "RGD:A156487"
    }, {
      "firstName" : "T",
      "lastName" : "Murakami",
      "authorRank" : 6,
      "name" : "Murakami T",
      "referenceId" : "RGD:A13788"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamori",
      "authorRank" : 7,
      "name" : "Yamori Y",
      "referenceId" : "RGD:A7348"
    }, {
      "firstName" : "H",
      "lastName" : "Shimano",
      "authorRank" : 8,
      "name" : "Shimano H",
      "referenceId" : "RGD:A14303"
    }, {
      "firstName" : "S",
      "lastName" : "Ishibashi",
      "authorRank" : 9,
      "name" : "Ishibashi S",
      "referenceId" : "RGD:A13076"
    }, {
      "firstName" : "N",
      "lastName" : "Yamada",
      "authorRank" : 10,
      "name" : "Yamada N",
      "referenceId" : "RGD:A14304"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:629460"
    } ]
  }, {
    "primaryId" : "PMID:10391211",
    "title" : "Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Pierce EA, etal., Nat Genet. 1999 Jul;22(3):248-54. doi: 10.1038/10305.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:26:31.000-05:00",
    "volume" : "22",
    "pages" : "248-54",
    "abstract" : "The autosomal dominant retinitis pigmentosa (RP) locus, designated RP1, has been mapped through linkage studies to a 4-cM interval at 8q11-13. Here we describe a new photoreceptor-specific gene that maps in this interval and whose expression is modulated by retinal oxygen levels in vivo. This gene consists of at least 4 exons that encode a predicted protein of 2,156 amino acids. A nonsense mutation at codon 677 of this gene is present in approximately 3% of cases of dominant RP in North America. We also detected two deletion mutations that cause frameshifts and introduce premature termination codons in three other families with dominant RP. Our data suggest that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E A",
      "lastName" : "Pierce",
      "authorRank" : 1,
      "name" : "Pierce EA",
      "referenceId" : "RGD:A592201"
    }, {
      "firstName" : "T",
      "lastName" : "Quinn",
      "authorRank" : 2,
      "name" : "Quinn T",
      "referenceId" : "RGD:A592202"
    }, {
      "firstName" : "T",
      "lastName" : "Meehan",
      "authorRank" : 3,
      "name" : "Meehan T",
      "referenceId" : "RGD:A16914"
    }, {
      "firstName" : "T L",
      "lastName" : "McGee",
      "authorRank" : 4,
      "name" : "McGee TL",
      "referenceId" : "RGD:A592203"
    }, {
      "firstName" : "E L",
      "lastName" : "Berson",
      "authorRank" : 5,
      "name" : "Berson EL",
      "referenceId" : "RGD:A583081"
    }, {
      "firstName" : "T P",
      "lastName" : "Dryja",
      "authorRank" : 6,
      "name" : "Dryja TP",
      "referenceId" : "RGD:A583082"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118101"
    } ]
  }, {
    "primaryId" : "PMID:10391218",
    "title" : "Mutations in a delta 8-delta 7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. jderry@immunex.com.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Derry JM, etal., Nat Genet 1999 Jul;22(3):286-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T16:10:10.000-06:00",
    "volume" : "22",
    "pages" : "286-90",
    "abstract" : "Tattered (Td) is an X-linked, semi-dominant mouse mutation associated with prenatal male lethality. Heterozygous females are small and at 4-5 days of age develop patches of hyperkeratotic skin where no hair grows, resulting in a striping of the coat in adults. Craniofacial anomalies and twisted toes have also been observed in some affected females. A potential second allele of Td has also been described. The phenotype of Td is similar to that seen in heterozygous females with human X-linked dominant chondrodysplasia punctata (CDPX2, alternatively known as X-linked dominant Conradi-Hunermann-Happle syndrome) as well as another X-linked, semi-dominant mouse mutation, bare patches (Bpa). The Bpa gene has recently been identified and encodes a protein with homology to 3beta-hydroxysteroid dehydrogenases that functions in one of the later steps of cholesterol biosynthesis. CDPX2 patients display skin defects including linear or whorled atrophic and pigmentary lesions, striated hyperkeratosis, coarse lusterless hair and alopecia, cataracts and skeletal abnormalities including short stature, rhizomelic shortening of the limbs, epiphyseal stippling and craniofacial defects (MIM 302960). We have now identified the defect in Td mice as a single amino acid substitution in the delta8-delta7 sterol isomerase emopamil binding protein (Ebp; encoded by Ebp in mouse) and identified alterations in human EBP in seven unrelated CDPX2 patients.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Derry",
      "authorRank" : 1,
      "name" : "Derry JM",
      "referenceId" : "RGD:A38024"
    }, {
      "firstName" : "E",
      "lastName" : "Gormally",
      "authorRank" : 2,
      "name" : "Gormally E",
      "referenceId" : "RGD:A38025"
    }, {
      "firstName" : "GD",
      "lastName" : "Means",
      "authorRank" : 3,
      "name" : "Means GD",
      "referenceId" : "RGD:A38026"
    }, {
      "firstName" : "W",
      "lastName" : "Zhao",
      "authorRank" : 4,
      "name" : "Zhao W",
      "referenceId" : "RGD:A403995"
    }, {
      "firstName" : "A",
      "lastName" : "Meindl",
      "authorRank" : 5,
      "name" : "Meindl A",
      "referenceId" : "RGD:A36610"
    }, {
      "firstName" : "RI",
      "lastName" : "Kelley",
      "authorRank" : 6,
      "name" : "Kelley RI",
      "referenceId" : "RGD:A37883"
    }, {
      "firstName" : "Y",
      "lastName" : "Boyd",
      "authorRank" : 7,
      "name" : "Boyd Y",
      "referenceId" : "RGD:A38028"
    }, {
      "firstName" : "GE",
      "lastName" : "Herman",
      "authorRank" : 8,
      "name" : "Herman GE",
      "referenceId" : "RGD:A38029"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734908"
    } ]
  }, {
    "primaryId" : "PMID:10391221",
    "title" : "Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Labay V, etal., Nat Genet. 1999 Jul;22(3):300-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-30T13:44:36.000-06:00",
    "volume" : "22",
    "pages" : "300-4",
    "abstract" : "Thiamine-responsive megaloblastic anaemia (TRMA), also known as Rogers syndrome, is an early onset, autosomal recessive disorder defined by the occurrence of megaloblastic anaemia, diabetes mellitus and sensorineural deafness, responding in varying degrees to thiamine treatment (MIM 249270). We have previously narrowed the TRMA locus from a 16-cM to a 4-cM interval on chromosomal region 1q23.3 (refs 3,4) and this region has been further refined to a 1.4-cM interval. Previous studies have suggested that deficiency in a high-affinity thiamine transporter may cause this disorder. Here we identify the TRMA gene by positional cloning. We assembled a P1-derived artificial chromosome (PAC) contig spanning the TRMA candidate region. This clarified the order of genetic markers across the TRMA locus, provided 9 new polymorphic markers and narrowed the locus to an approximately 400-kb region. Mutations in a new gene, SLC19A2, encoding a putative transmembrane protein homologous to the reduced folate carrier proteins, were found in all affected individuals in six TRMA families, suggesting that a defective thiamine transporter protein (THTR-1) may underlie the TRMA syndrome.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Labay",
      "authorRank" : 1,
      "name" : "Labay V",
      "referenceId" : "RGD:A73350"
    }, {
      "firstName" : "T",
      "lastName" : "Raz",
      "authorRank" : 2,
      "name" : "Raz T",
      "referenceId" : "RGD:A73351"
    }, {
      "firstName" : "D",
      "lastName" : "Baron",
      "authorRank" : 3,
      "name" : "Baron D",
      "referenceId" : "RGD:A73352"
    }, {
      "firstName" : "H",
      "lastName" : "Mandel",
      "authorRank" : 4,
      "name" : "Mandel H",
      "referenceId" : "RGD:A36148"
    }, {
      "firstName" : "H",
      "lastName" : "Williams",
      "authorRank" : 5,
      "name" : "Williams H",
      "referenceId" : "RGD:A73353"
    }, {
      "firstName" : "T",
      "lastName" : "Barrett",
      "authorRank" : 6,
      "name" : "Barrett T",
      "referenceId" : "RGD:A35434"
    }, {
      "firstName" : "R",
      "lastName" : "Szargel",
      "authorRank" : 7,
      "name" : "Szargel R",
      "referenceId" : "RGD:A73354"
    }, {
      "firstName" : "L",
      "lastName" : "McDonald",
      "authorRank" : 8,
      "name" : "McDonald L",
      "referenceId" : "RGD:A73355"
    }, {
      "firstName" : "A",
      "lastName" : "Shalata",
      "authorRank" : 9,
      "name" : "Shalata A",
      "referenceId" : "RGD:A73356"
    }, {
      "firstName" : "K",
      "lastName" : "Nosaka",
      "authorRank" : 10,
      "name" : "Nosaka K",
      "referenceId" : "RGD:A73357"
    }, {
      "firstName" : "S",
      "lastName" : "Gregory",
      "authorRank" : 11,
      "name" : "Gregory S",
      "referenceId" : "RGD:A73264"
    }, {
      "firstName" : "N",
      "lastName" : "Cohen",
      "authorRank" : 12,
      "name" : "Cohen N",
      "referenceId" : "RGD:A56331"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599325"
    } ]
  }, {
    "primaryId" : "PMID:10391689",
    "title" : "High incidence of allelic loss on chromosome 5 and inactivation of p15INK4B and p16INK4A tumor suppressor genes in oxystress-induced renal cell carcinoma of rats.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Tanaka T, etal., Oncogene. 1999 Jun 24;18(25):3793-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-08-16T17:13:27.000-05:00",
    "volume" : "18",
    "pages" : "3793-7",
    "abstract" : "Ferric nitrilotriacetate induces oxidative damage in renal proximal tubules, a consequence of Fenton-like reaction, that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. In order to find common genetic alterations in this oxystress-induced carcinogenesis model, RCCs were produced in F1 hybrid rats between Wistar and Long-Evans strains and genomes were screened for loss of  heterozygosity (LOH) with microsatellite polymorphic markers by PCR. Five consecutive markers on chromosome 5 (D5Mgh5, D5Mit9, D5Mgh6, D5Mit11 and D5Mit6)  showed LOH in >40% of the RCCs. As possible candidate tumor suppressor genes on chromosome 5, p15INK4B and p16INK4A were investigated for genetic alteration and  aberrant methylation by Southern blot, PCR/SSCP/ sequencing and methylation-specific PCR. Genetic alteration (homozygous or hemizygous deletion with or without point mutation) or aberrant methylation were found in 30.7 and 53.8% of the RCC cases, respectively, which was proportionally associated with the histological nuclear grade and metastatic activity. Our data suggest that inactivation of p15 and p16 genes could be one of the major pathways responsible  for oxystress-induced carcinogenesis.",
    "issueName" : "25",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Tanaka",
      "authorRank" : 1,
      "name" : "Tanaka",
      "referenceId" : "RGD:A416765"
    }, {
      "firstName" : "Y",
      "lastName" : "Iwasa",
      "authorRank" : 2,
      "name" : "Iwasa Y",
      "referenceId" : "RGD:A86448"
    }, {
      "firstName" : "S",
      "lastName" : "Kondo",
      "authorRank" : 3,
      "name" : "Kondo",
      "referenceId" : "RGD:A413966"
    }, {
      "firstName" : "H",
      "lastName" : "Hiai",
      "authorRank" : 4,
      "name" : "Hiai H",
      "referenceId" : "RGD:A7203"
    }, {
      "firstName" : "S",
      "lastName" : "Toyokuni",
      "authorRank" : 5,
      "name" : "Toyokuni S",
      "referenceId" : "RGD:A7204"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7248758"
    } ]
  }, {
    "primaryId" : "PMID:10391909",
    "title" : "The colonic H+,K+-ATPase functions as a Na+-dependent K+(NH4+)-ATPase in apical membranes from rat distal colon.",
    "datePublished" : "1999-07-09T00:00:00.000-05:00",
    "citation" : "Codina J, etal., J Biol Chem. 1999 Jul 9;274(28):19693-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-01-08T16:33:55.000-06:00",
    "volume" : "274",
    "pages" : "19693-8",
    "abstract" : "Recent studies have suggested that the colonic H+,K+-ATPase (HKalpha2) can secrete either Na+ or H+ in exchange for K+. If correct, this view would indicate that the transporter could function as either a Na+ or a H+ pump. To investigate this possibility a series of experiments was performed using apical membranes from rat colon which were enriched in colonic H+,K+-ATPase protein. An antibody specific for HKalpha2 was employed to determine whether HKalpha2 functions under physiological conditions as a Na+-dependent or Na+-independent K+-ATPase in this same membrane fraction. K+-ATPase activity was measured as [gamma-32P]ATP hydrolysis. The Na+-dependent K+-ATPase accounted for approximately 80% of overall K+-ATPase activity and was characterized by insensitivity to Sch-28080 but partial sensitivity to ouabain. The Na+-independent K+-ATPase activity was insensitive to both Sch-28080 and ouabain. Both types of K+-ATPase activity substituted NH4+ for K+ in a similar manner. Furthermore, our results demonstrate that when incubated with native distal colon membranes, the blocking antibody inhibited dramatically Na+-dependent K+-ATPase activity. Therefore, these data demonstrate that HKalpha2 can function in native distal colon apical membranes as a Na+-dependent K+-ATPase. Elucidation of the role of the pump as a transporter of Na+ versus H+ or NH4+ versus K+ in vivo will require additional studies.",
    "issueName" : "28",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Codina",
      "authorRank" : 1,
      "name" : "Codina J",
      "referenceId" : "RGD:A14996"
    }, {
      "firstName" : "T A",
      "lastName" : "Pressley",
      "authorRank" : 2,
      "name" : "Pressley TA",
      "referenceId" : "RGD:A467180"
    }, {
      "firstName" : "T D",
      "lastName" : "DuBose",
      "authorRank" : 3,
      "name" : "DuBose TD",
      "referenceId" : "RGD:A467158"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13838666"
    } ]
  }, {
    "primaryId" : "PMID:10391916",
    "title" : "Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Segawa H, etal., J Biol Chem 1999 Jul 9;274(28):19745-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:16:17.000-05:00",
    "volume" : "274",
    "pages" : "19745-51",
    "abstract" : "We have isolated a cDNA from rat small intestine that encodes a novel Na+-independent neutral amino acid transporter with distinctive characteristics in substrate selectivity and transport property. The encoded protein, designated L-type amino acid transporter-2 (LAT-2), shows amino acid sequence similarity to the system L Na+-independent neutral amino acid transporter LAT-1 (Kanai, Y., Segawa, H., Miyamoto, K., Uchino, H., Takeda, E., and Endou, H. (1998) J. Biol. Chem. 273, 23629-23632) (50% identity) and the system y+L transporters y+LAT-1 (47%) and KIAA0245/y+LAT-2 (45%) (Torrents, D., Estevez, R., Pineda, M., Fernandez, E., Lloberas, J., Shi, Y.-B., Zorzano, A., and Palacin, M. (1998) J. Biol. Chem. 273, 32437-32445). LAT-2 is a nonglycosylated membrane protein. It requires 4F2 heavy chain, a type II membrane glycoprotein, for its functional expression in Xenopus oocytes. LAT-2-mediated transport is not dependent on Na+ or Cl- and is inhibited by a system L-specific inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), indicating that LAT-2 is a second isoform of the system L transporter. Compared with LAT-1, which prefers large neutral amino acids with branched or aromatic side chains, LAT-2 exhibits remarkably broad substrate selectivity. It transports all of the L-isomers of neutral alpha-amino acids. LAT-2 exhibits higher affinity (Km = 30-50 microM) to Tyr, Phe, Trp, Thr, Asn, Ile, Cys, Ser, Leu, Val, and Gln and relatively lower affinity (Km = 180-300 microM) to His, Ala, Met, and Gly. In addition, LAT-2 mediates facilitated diffusion of substrate amino acids, as distinct from LAT-1, which mediates amino acid exchange. LAT-2-mediated transport is increased by lowering the pH level, with peak activity at pH 6.25, because of the decrease in the Km value without changing the Vmax value. Because of these functional properties and a high level of expression of LAT-2 in the small intestine, kidney, placenta, and brain, it is suggested that the heterodimeric complex of LAT-2 and 4F2 heavy chain is involved in the trans-cellular transport of neutral amino acids in epithelia and blood-tissue barriers.",
    "issueName" : "28",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Segawa",
      "authorRank" : 1,
      "name" : "Segawa H",
      "referenceId" : "RGD:A21707"
    }, {
      "firstName" : "Y",
      "lastName" : "Fukasawa",
      "authorRank" : 2,
      "name" : "Fukasawa Y",
      "referenceId" : "RGD:A23079"
    }, {
      "firstName" : "K",
      "lastName" : "Miyamoto",
      "authorRank" : 3,
      "name" : "Miyamoto K",
      "referenceId" : "RGD:A11191"
    }, {
      "firstName" : "E",
      "lastName" : "Takeda",
      "authorRank" : 4,
      "name" : "Takeda E",
      "referenceId" : "RGD:A21714"
    }, {
      "firstName" : "H",
      "lastName" : "Endou",
      "authorRank" : 5,
      "name" : "Endou H",
      "referenceId" : "RGD:A121444"
    }, {
      "firstName" : "Y",
      "lastName" : "Kanai",
      "authorRank" : 6,
      "name" : "Kanai Y",
      "referenceId" : "RGD:A122459"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634080"
    } ]
  }, {
    "primaryId" : "PMID:10391919",
    "title" : "Cloning and characterization of a novel RING finger protein that interacts with class V myosins.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "El-Husseini AE and Vincent SR, J Biol Chem 1999 Jul 9;274(28):19771-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-15T17:17:05.000-05:00",
    "volume" : "274",
    "pages" : "19771-7",
    "abstract" : "We have identified a novel protein (BERP) that is a specific partner for the tail domain of myosin V. Class V myosins are a family of molecular motors thought to interact via their unique C-terminal tails with specific proteins for the targeted transport of organelles. BERP is highly expressed in brain and contains an N-terminal RING finger, followed by a B-box zinc finger, a coiled-coil (RBCC domain), and a unique C-terminal beta-propeller domain. A yeast two-hybrid screening indicated that the C-terminal beta-propeller domain mediates binding to the tail of the class V myosin myr6 (myosin Vb). This interaction was confirmed by immunoprecipitation, which also demonstrated that BERP could associate with myosin Va, the product of the dilute gene. Like myosin Va, BERP is expressed in a punctate pattern in the cytoplasm as well as in the neurites and growth cones of PC12 cells. We also found that the RBCC domain of BERP is involved in protein dimerization. Stable expression of a mutant form of BERP lacking the myosin-binding domain but containing the dimerization domain resulted in defective PC12 cell spreading and prevented neurite outgrowth in response to nerve growth factor. Our studies present a novel interaction for the beta-propeller domain and provide evidence for a role for BERP in myosin V-mediated cargo transport.",
    "issueName" : "28",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AE",
      "lastName" : "El-Husseini",
      "authorRank" : 1,
      "name" : "El-Husseini AE",
      "referenceId" : "RGD:A24199"
    }, {
      "firstName" : "SR",
      "lastName" : "Vincent",
      "authorRank" : 2,
      "name" : "Vincent SR",
      "referenceId" : "RGD:A43745"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68906"
    } ]
  }, {
    "primaryId" : "PMID:10391935",
    "title" : "Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Smith FD, etal., J Biol Chem 1999 Jul 9;274(28):19894-900.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-17T16:59:46.000-05:00",
    "volume" : "274",
    "pages" : "19894-900",
    "abstract" : "Signaling through D2 class dopamine receptors is crucial to correct brain development and function, and dysfunction of this system is implicated in major neurological disorders such as Parkinson's disease and schizophrenia. To investigate potential novel mechanisms of D2 receptor regulation, the third cytoplasmic loop of the D2 dopamine receptor was used to screen a rat hippocampal yeast two-hybrid library. Spinophilin, a recently characterized F-actin and protein phosphatase-1-binding protein with a single PDZ domain was identified as a protein that specifically associates with this region of D2 receptors. A direct interaction between spinophilin and the D2 receptor was confirmed in vitro using recombinant fusion proteins. The portion of spinophilin responsible for interacting with the D2 third cytoplasmic loop was narrowed to a region that does not include the actin-binding domain, the PDZ domain, or the coiled-coil. This region is distinct from the site of interaction with protein phosphatase-1, and both D2 receptors and protein phosphatase-1 may bind spinophilin at the same time. The interaction is not mediated via the unique 29-amino acid insert in D2long; both D2long and D2short third cytoplasmic loops interact with spinophilin in vitro and in yeast two-hybrid assays. Expression of D2 receptors containing an extracellular hemagglutinin epitope in Madin-Darby canine kidney cells results in co-localization of receptor and endogenous spinophilin as determined by immunocytochemistry using antibodies directed against spinophilin and the HA tag. We hypothesize that spinophilin is important for establishing a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors to downstream signaling molecules and the actin cytoskeleton.",
    "issueName" : "28",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FD",
      "lastName" : "Smith",
      "authorRank" : 1,
      "name" : "Smith FD",
      "referenceId" : "RGD:A12217"
    }, {
      "firstName" : "GS",
      "lastName" : "Oxford",
      "authorRank" : 2,
      "name" : "Oxford GS",
      "referenceId" : "RGD:A53249"
    }, {
      "firstName" : "SL",
      "lastName" : "Milgram",
      "authorRank" : 3,
      "name" : "Milgram SL",
      "referenceId" : "RGD:A12218"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358601"
    } ]
  }, {
    "primaryId" : "PMID:10391944",
    "title" : "Ig-hepta, a novel member of the G protein-coupled hepta-helical receptor (GPCR) family that has immunoglobulin-like repeats in a long N-terminal extracellular domain and defines a new subfamily of GPCRs.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Abe J, etal., J Biol Chem 1999 Jul 9;274(28):19957-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-21T15:00:11.000-05:00",
    "volume" : "274",
    "pages" : "19957-64",
    "abstract" : "A novel member of the G protein-coupled receptor (GPCR) family was cloned and characterized, which is unique, among the members, in its long extracellular domain comprising Ig-like repeats and in its high expression predominantly in the lung. The clone (Ig-Hepta) was first identified as a polymerase chain reaction product generated with primers designed to amplify secretin receptor family members including the parathyroid hormone-related peptide receptors. Analysis of the open reading frame of cDNAs isolated from a rat lung cDNA library indicated that Ig-Hepta is a protein of 1389 amino acid residues and has two Ig-like repeats in the N-terminal extracellular domain (exodomain) of 1053 amino acid residues and 7 transmembrane spans in the C-terminal region. Northern blot analysis revealed very high expression of its mRNA in the lung and low but detectable levels in the kidney and heart. The mRNA expression in the lung was found to be strongly induced postnatally. Biochemical analysis indicated that Ig-Hepta is a highly glycosylated protein and exists as a disulfide-linked dimer. Immunohistochemistry on rat lung and kidney sections revealed dense localization of Ig-Hepta in alveolar walls and intercalated cells in the collecting duct, respectively, suggesting a role in the regulation of acid-base balance. Ig-Hepta defines a new subfamily of GPCRs.",
    "issueName" : "28",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Abe",
      "authorRank" : 1,
      "name" : "Abe J",
      "referenceId" : "RGD:A11535"
    }, {
      "firstName" : "H",
      "lastName" : "Suzuki",
      "authorRank" : 2,
      "name" : "Suzuki H",
      "referenceId" : "RGD:A299780"
    }, {
      "firstName" : "M",
      "lastName" : "Notoya",
      "authorRank" : 3,
      "name" : "Notoya M",
      "referenceId" : "RGD:A11536"
    }, {
      "firstName" : "T",
      "lastName" : "Yamamoto",
      "authorRank" : 4,
      "name" : "Yamamoto T",
      "referenceId" : "RGD:A161440"
    }, {
      "firstName" : "S",
      "lastName" : "Hirose",
      "authorRank" : 5,
      "name" : "Hirose S",
      "referenceId" : "RGD:A123061"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:625424"
    } ]
  }, {
    "primaryId" : "PMID:10393062",
    "title" : "Frequency of mutations in the gene encoding the alpha subunit of rod cGMP-phosphodiesterase in autosomal recessive retinitis pigmentosa.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Dryja TP, etal., Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1859-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:35:31.000-05:00",
    "volume" : "40",
    "pages" : "1859-65",
    "abstract" : "PURPOSE: To determine the mutation spectrum of the PDE6A gene encoding the alpha  subunit of rod cyclic guanosine monophosphate (cGMP)phosphodiesterase and the proportion of patients with recessive retinitis pigmentosa (RP) due to mutations  in this gene. METHODS: The single-strand conformation polymorphism (SSCP) technique and a direct genomic sequencing technique were used to screen all 22 exons of this gene for mutations in 164 unrelated patients with recessive or isolate RP. Variant DNA fragments revealed by SSCP analysis were subsequently sequenced. Selected alleles that altered the coding region or intron splice sites were evaluated further through segregation analysis in the families of the index  cases. RESULTS: Four new families were identified with five novel mutations in this gene that cosegregated with disease. Combining the data presented here with  those published earlier by the authors, eight different mutations in six families have been discovered to be pathogenic. Two of the mutations are nonsense, five are missense, and one affects a canonical splice-donor site. CONCLUSIONS: The PDE6A gene appears to account for roughly 3% to 4% of families with recessive RP  in North America. A compilation of the pathogenic mutations in PDE6A and those reported in the homologous gene PDE6B encoding the beta subunit of rod cGMP-phosphodiesterase shows that the cGMP-binding and catalytic domains are frequently affected.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TP",
      "lastName" : "Dryja",
      "authorRank" : 1,
      "name" : "Dryja TP",
      "referenceId" : "RGD:A44923"
    }, {
      "firstName" : "DE",
      "lastName" : "Rucinski",
      "authorRank" : 2,
      "name" : "Rucinski",
      "referenceId" : "RGD:A264325"
    }, {
      "firstName" : "SH",
      "lastName" : "Chen",
      "authorRank" : 3,
      "name" : "Chen SH",
      "referenceId" : "RGD:A46828"
    }, {
      "firstName" : "EL",
      "lastName" : "Berson",
      "authorRank" : 4,
      "name" : "Berson EL",
      "referenceId" : "RGD:A44927"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066253"
    } ]
  }, {
    "primaryId" : "PMID:10393098",
    "title" : "Histidine-193 of rat glucosylceramide synthase resides in a UDP-glucose- and inhibitor (D-threo-1-phenyl-2-decanoylamino-3-morpholinopropan-1-ol)-binding region: a biochemical and mutational study.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wu K, etal., Biochem J 1999 Jul 15;341 ( Pt 2):395-400.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:34.000-05:00",
    "volume" : "341 ( Pt 2)",
    "pages" : "395-400",
    "abstract" : "Glucosylceramide synthase (GCS) catalyses the transfer of glucose from UDP-glucose (UDP-Glc) to ceramide to form glucosylceramide, the common precursor of most higher-order glycosphingolipids. Inhibition of GCS activity has been proposed as a possible target of chemotherapeutic agents for a number of diseases, including cancer. Design of new GCS inhibitors with desirable pharmaceutical properties is hampered by lack of knowledge of the secondary structure or catalytic mechanism of the GCS protein. Thus we cloned the rat homologue of GCS to begin studies to identify its catalytic regions. The histidine-modifying agent diethyl pyrocarbonate (DEPC) inhibited recombinant rat GCS expressed in bacteria; this inhibition was rapidly reversible by hydroxylamine and could be diminished by preincubation of GCS with UDP-Glc. These data suggest that DEPC acts on histidine residues within or near the UDP-Glc-binding site of GCS. Mutant proteins were expressed in which the eight histidine residues in GCS were individually replaced by other amino acids. H193A (His193-->Ala) and H193N (His193-->Asn) mutants were unaffected by 0.1 mM DEPC, a concentration that inhibited other histidine mutants and the wild-type enzyme by at least 60%. These results indicate that His193 is the primary target of DEPC and is at, or near, the UDP-Glc-binding site of GCS. His193 mutants were also insensitive to the GCS inhibitor d-threo-1-phenyl-2- decanoylamino-3-morpholinopropan-1-ol, at concentrations which inhibited the wild-type enzyme by >80%. These results have significance for both an understanding of the GCS active site and also for the possible design of new and specific inhibitors of GCS.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Wu",
      "authorRank" : 1,
      "name" : "Wu K",
      "referenceId" : "RGD:A20870"
    }, {
      "firstName" : "DL",
      "lastName" : "Marks",
      "authorRank" : 2,
      "name" : "Marks DL",
      "referenceId" : "RGD:A23655"
    }, {
      "firstName" : "R",
      "lastName" : "Watanabe",
      "authorRank" : 3,
      "name" : "Watanabe R",
      "referenceId" : "RGD:A7309"
    }, {
      "firstName" : "P",
      "lastName" : "Paul",
      "authorRank" : 4,
      "name" : "Paul P",
      "referenceId" : "RGD:A23656"
    }, {
      "firstName" : "N",
      "lastName" : "Rajan",
      "authorRank" : 5,
      "name" : "Rajan N",
      "referenceId" : "RGD:A23657"
    }, {
      "firstName" : "RE",
      "lastName" : "Pagano",
      "authorRank" : 6,
      "name" : "Pagano RE",
      "referenceId" : "RGD:A23658"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634250"
    } ]
  }, {
    "primaryId" : "PMID:10393181",
    "title" : "Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Chevet E, etal., EMBO J. 1999 Jul 1;18(13):3655-66.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-11T11:39:38.000-05:00",
    "volume" : "18",
    "pages" : "3655-66",
    "abstract" : "Calnexin was initially identified as an endoplasmic reticulum (ER) type I integral membrane protein, phosphorylated on its cytosolic domain by ER-associated protein kinases. Although the role of the ER luminal domain of calnexin has been established as a constituent of the molecular chaperone machinery of the ER, less is known about the role of the cytosolic phosphorylation of calnexin. Analysis by two-dimensional phosphopeptide maps revealed that calnexin was in vitro phosphorylated in isolated microsomes by casein kinase 2 (CK2) and extracellular-signal regulated kinase-1 (ERK-1) at sites corresponding to those for in vivo phosphorylation. In canine pancreatic microsomes, synergistic phosphorylation by CK2 and ERK-1 led to increased association of calnexin with membrane-bound ribosomes. In vivo, calnexin-associated ERK-1 activity was identified by co-immunoprecipitation. This activity was abolished in cells expressing a dominant-negative MEK-1. Activation of ERK-1 in cells by addition of serum led to a 4-fold increase in ribosome-associated calnexin over unstimulated cells. Taken together with studies revealing calnexin association with CK2 and ERK-1, a model is proposed whereby phosphorylation of calnexin leads to a potential increase in glycoprotein folding close to the translocon.",
    "issueName" : "13",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Chevet",
      "authorRank" : 1,
      "name" : "Chevet E",
      "referenceId" : "RGD:A36671"
    }, {
      "firstName" : "HN",
      "lastName" : "Wong",
      "authorRank" : 2,
      "name" : "Wong HN",
      "referenceId" : "RGD:A111887"
    }, {
      "firstName" : "D",
      "lastName" : "Gerber",
      "authorRank" : 3,
      "name" : "Gerber D",
      "referenceId" : "RGD:A111888"
    }, {
      "firstName" : "C",
      "lastName" : "Cochet",
      "authorRank" : 4,
      "name" : "Cochet C",
      "referenceId" : "RGD:A111889"
    }, {
      "firstName" : "A",
      "lastName" : "Fazel",
      "authorRank" : 5,
      "name" : "Fazel A",
      "referenceId" : "RGD:A57756"
    }, {
      "firstName" : "PH",
      "lastName" : "Cameron",
      "authorRank" : 6,
      "name" : "Cameron PH",
      "referenceId" : "RGD:A111890"
    }, {
      "firstName" : "JN",
      "lastName" : "Gushue",
      "authorRank" : 7,
      "name" : "Gushue JN",
      "referenceId" : "RGD:A57757"
    }, {
      "firstName" : "DY",
      "lastName" : "Thomas",
      "authorRank" : 8,
      "name" : "Thomas DY",
      "referenceId" : "RGD:A24022"
    }, {
      "firstName" : "JJ",
      "lastName" : "Bergeron",
      "authorRank" : 9,
      "name" : "Bergeron JJ",
      "referenceId" : "RGD:A24021"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313159"
    } ]
  }, {
    "primaryId" : "PMID:10393239",
    "title" : "Interaction between the two ubiquitously expressed transcription factors NF-Y and Sp1.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Roder K, etal., Gene. 1999 Jun 24;234(1):61-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:37:03.000-05:00",
    "volume" : "234",
    "pages" : "61-9",
    "abstract" : "The regulation of the rat fatty acid synthase gene by mediators such as diet, hormones, cAMP, sterols or retinoic acid is controlled by three NF-Y binding sites. All three sites have a neighbouring Sp1-binding GC-box. This NF-Y/Sp1 motif is conserved in the FAS promoters of rat, human, goose and chicken. We have previously shown cooperative binding of NF-Y and Sp1 to the promoter region at -500 coincident with a diet-induced DNAse I-hypersensitive site. Here, we show an in-vivo interaction of NF-YA with Sp1 using the yeast two-hybrid system. The interacting domains are located between amino acids 55 and 139 of the NF-Y subunit NF-YA and between amino acids 139 and 344 of Sp1. In addition, we show by co-immunoprecipitation direct interaction of NF-Y subunit NF-YA with Sp1 in extracts of rat hepatoma cells H4IIE. Furthermore, we demonstrate by the GST pull-down assay that NF-YA interacts physically with Sp1 in-vitro in the absence  of DNA. Therefore, NF-Y can be added to the list of transcription factors interacting with Sp1.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Roder",
      "authorRank" : 1,
      "name" : "Roder",
      "referenceId" : "RGD:A184954"
    }, {
      "firstName" : "SS",
      "lastName" : "Wolf",
      "authorRank" : 2,
      "name" : "Wolf SS",
      "referenceId" : "RGD:A114559"
    }, {
      "firstName" : "KJ",
      "lastName" : "Larkin",
      "authorRank" : 3,
      "name" : "Larkin",
      "referenceId" : "RGD:A184955"
    }, {
      "firstName" : "M",
      "lastName" : "Schweizer",
      "authorRank" : 4,
      "name" : "Schweizer M",
      "referenceId" : "RGD:A16106"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553812"
    } ]
  }, {
    "primaryId" : "PMID:10393248",
    "title" : "A serine residue in the N-terminal acidic region of rat RPB6, one of the common subunits of RNA polymerases, is exclusively phosphorylated by casein kinase II in vitro.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kayukawa K, etal., Gene 1999 Jun 24;234(1):139-47.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:53.000-05:00",
    "volume" : "234",
    "pages" : "139-47",
    "abstract" : "RPB6 is one of the common subunits of all eukaryotic RNA polymerases and is indispensable for the enzyme function. Here, we isolated a rat cDNA encoding RPB6. It contained 127 amino acid (a.a.) residues. From alignment of RPB6 homologues of various eukaryotes, we defined two conserved regions, i.e. an N-terminal acidic region and a C-terminal core. In this study, we investigated in vitro phosphorylation of rat RPB6 by casein kinase II (CKII), a pleiotropic regulator of numerous cellular proteins. Three putative CKII-phosphorylated a.a. within rat RPB6 were assigned. We found that serines were phosphorylated by CKII in vitro. Mutagenesis studies provided evidence that a serine at a.a. position 2 was exclusively phosphorylated. Finally, an RPB6-engaged in-gel kinase assay clarified that CKII was a prominent protein kinase in rat liver nuclear extract that phosphorylates RPB6. Therefore, RPB6 was implied to be phosphorylated by CKII in the nucleus. We postulate that the N-terminal acidic region of the RPB6 subunit has some phosphorylation-coupled regulatory functions.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Kayukawa",
      "authorRank" : 1,
      "name" : "Kayukawa K",
      "referenceId" : "RGD:A24114"
    }, {
      "firstName" : "Y",
      "lastName" : "Makino",
      "authorRank" : 2,
      "name" : "Makino Y",
      "referenceId" : "RGD:A5103"
    }, {
      "firstName" : "S",
      "lastName" : "Yogosawa",
      "authorRank" : 3,
      "name" : "Yogosawa S",
      "referenceId" : "RGD:A24110"
    }, {
      "firstName" : "T",
      "lastName" : "Tamura",
      "authorRank" : 4,
      "name" : "Tamura T",
      "referenceId" : "RGD:A156706"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299534"
    } ]
  }, {
    "primaryId" : "PMID:10393316",
    "title" : "Structure, evolution, and liver-specific expression of sterol 12alpha-hydroxylase P450 (CYP8B).",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Ishida H, etal., J Biochem (Tokyo) 1999 Jul;126(1):19-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:17:15.000-05:00",
    "volume" : "126",
    "pages" : "19-25",
    "abstract" : "The rat CYP8B cDNA encoding sterol 12alpha-hydroxylase was cloned and sequenced. The amino acid sequence of the heme-binding region of CYP8B was close to those of CYP7A (cholesterol 7alpha-hydroxylase) and CYP7B (oxysterol 7alpha-hydroxylase). Molecular phylogenetic analysis suggests that CYP8B and the CYP7 family derive from a common ancestor. The P450s of the CYP7 and CYP8 families, except for CYP8A (prostacyclin synthase), catalyze the oxygenation of sterols from an alpha surface in the middle of the steroid skeleton. These facts suggest that CYP8B is a P450 closely linked to those of the CYP7 family. CYP8B was expressed specifically in liver. Hepatic CYP8B mRNA level and the 12alpha-hydroxylase activity were altered by cholestyramine feeding, starvation, streptozotocin-induced diabetes mellitus, and administration of clofibrate, dexamethasone or thyroxin, indicating the pretranslational regulation of CYP8B expression. The enhanced CYP8B mRNA expression in streptozotocin-induced diabetic rats was significantly decreased by insulin within 3 h of its administration. These facts demonstrate a regulatory role of insulin in CYP8B expression as a suppressor.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Ishida",
      "authorRank" : 1,
      "name" : "Ishida H",
      "referenceId" : "RGD:A6129"
    }, {
      "firstName" : "Y",
      "lastName" : "Kuruta",
      "authorRank" : 2,
      "name" : "Kuruta Y",
      "referenceId" : "RGD:A9869"
    }, {
      "firstName" : "O",
      "lastName" : "Gotoh",
      "authorRank" : 3,
      "name" : "Gotoh O",
      "referenceId" : "RGD:A9870"
    }, {
      "firstName" : "C",
      "lastName" : "Yamashita",
      "authorRank" : 4,
      "name" : "Yamashita C",
      "referenceId" : "RGD:A9871"
    }, {
      "firstName" : "Y",
      "lastName" : "Yoshida",
      "authorRank" : 5,
      "name" : "Yoshida Y",
      "referenceId" : "RGD:A6909"
    }, {
      "firstName" : "M",
      "lastName" : "Noshiro",
      "authorRank" : 6,
      "name" : "Noshiro M",
      "referenceId" : "RGD:A9872"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70706"
    } ]
  }, {
    "primaryId" : "PMID:10393337",
    "title" : "A brain region-specific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kimura N, etal., J Biochem (Tokyo) 1999 Jul;126(1):180-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-14T14:11:17.000-05:00",
    "volume" : "126",
    "pages" : "180-7",
    "abstract" : "LIM-homeodomain (LHX) transcription factors play critical roles in cell fate determination during development, in particular, in CNS. The transcriptional activity of several LHX proteins is postulated to be regulated by interaction with an LIM-domain binding protein, Ldb1. We have now identified a novel LHX molecule, termed Lhx6.1, that is closely related to a recently reported Lhx6 molecule. The Lhx6.1 transcript is found in several restricted regions in the developing CNS, mostly within the embryonic forebrain. We further show that Lhx6.1 interacts with Ldb1 through tandem LIM-domains, implying transcriptional regulation of Lhx6.1 by Ldb1.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Kimura",
      "authorRank" : 1,
      "name" : "Kimura N",
      "referenceId" : "RGD:A161499"
    }, {
      "firstName" : "M",
      "lastName" : "Ueno",
      "authorRank" : 2,
      "name" : "Ueno M",
      "referenceId" : "RGD:A52700"
    }, {
      "firstName" : "K",
      "lastName" : "Nakashima",
      "authorRank" : 3,
      "name" : "Nakashima K",
      "referenceId" : "RGD:A149907"
    }, {
      "firstName" : "T",
      "lastName" : "Taga",
      "authorRank" : 4,
      "name" : "Taga T",
      "referenceId" : "RGD:A50151"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358487"
    } ]
  }, {
    "primaryId" : "PMID:10393355",
    "title" : "Roles of vasopressin and hypertonicity in basolateral Na/K/2Cl cotransporter expression in rat kidney inner medullary collecting duct cells.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Anzai N, etal., Jpn J Physiol 1999 Apr;49(2):201-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:14:08.000-05:00",
    "volume" : "49",
    "pages" : "201-6",
    "abstract" : "The basolateral Na/K/2Cl cotransporter mRNA (rNKCC1) increased when the cultured kidney inner medullary collecting duct (IMCD) cells of rats were exposed to vasopressin (10(-8) M) and/or hypertonicity (500 mOsm/kgH2O). However, only hypertonicity was effective in increasing the expression of rNKCC1 protein.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Anzai",
      "authorRank" : 1,
      "name" : "Anzai N",
      "referenceId" : "RGD:A22990"
    }, {
      "firstName" : "I",
      "lastName" : "Izumida",
      "authorRank" : 2,
      "name" : "Izumida I",
      "referenceId" : "RGD:A22991"
    }, {
      "firstName" : "Y",
      "lastName" : "Kobayashi",
      "authorRank" : 3,
      "name" : "Kobayashi Y",
      "referenceId" : "RGD:A8337"
    }, {
      "firstName" : "K",
      "lastName" : "Kawahara",
      "authorRank" : 4,
      "name" : "Kawahara K",
      "referenceId" : "RGD:A22992"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634054"
    } ]
  }, {
    "primaryId" : "PMID:10393385",
    "title" : "Decreased glomerular proteinase activity in the streptozotocin diabetic rat.",
    "datePublished" : "1000-01-01T00:00:00.000-06:00",
    "citation" : "Song RH, etal., Am J Nephrol. 1999;19(3):441-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-01-04T09:46:10.000-06:00",
    "volume" : "19",
    "pages" : "441-6",
    "abstract" : "Decreased glomerular proteinase activity may contribute to matrix accumulation in diabetes. Male Sprague-Dawley rats were rendered diabetic by injection of streptozotocin (STZ) 65 mg/kg i.v.; age-matched, sham-injected rats served as controls. Glomeruli from diabetic rats 1 month after STZ injection demonstrated significant decreases in collagenase and cathepsin B activities compared to control glomeruli. Treatment with insulin resulted in a slight (but not significant) increase in collagenase activity and normalized cathepsin B activity. We conclude that decreased glomerular collagenase and cathepsin B activities are present in STZ diabetes. These alterations may contribute to mesangial matrix accumulation.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RH",
      "lastName" : "Song",
      "authorRank" : 1,
      "name" : "Song RH",
      "referenceId" : "RGD:A116879"
    }, {
      "firstName" : "AK",
      "lastName" : "Singh",
      "authorRank" : 2,
      "name" : "Singh AK",
      "referenceId" : "RGD:A28644"
    }, {
      "firstName" : "DJ",
      "lastName" : "Leehey",
      "authorRank" : 3,
      "name" : "Leehey DJ",
      "referenceId" : "RGD:A116880"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2315531"
    } ]
  }, {
    "primaryId" : "PMID:10393431",
    "title" : "Human and mouse GPAA1 (Glycosylphosphatidylinositol anchor attachment 1) genes: genomic structures, chromosome loci and the presence of a minor class intron.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Inoue N, etal., Cytogenet Cell Genet 1999;84(3-4):199-205.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-01-17T16:45:41.000-06:00",
    "volume" : "84",
    "pages" : "199-205",
    "abstract" : "Many eukaryotic cell surface proteins are anchored to the membrane with glycosylphosphatidylinositol (GPI) that is covalently linked to the carboxyl-terminus. A Saccharomyces cerevisiae gaa1 mutant is defective in posttranslational attachment of GPI to proteins. A recent report demonstrated that the GPAA1 gene encodes a component of a transamidase that mediates GPI-anchor attachment. Here, we report structures and chromosome loci of human and mouse GPAA1 genes. Both genes consist of twelve exons that span about 4 kb. Human and mouse GPAA1s are located at 8q24.3 and 15E, respectively. There is a human pseudo GPAA1 gene (GPAA1P1) that is located at 2q12-->q14. Introns 8 of human and mouse GPAA1s were minor class introns bearing AT at the 5' splice sites and AC and AT at the 3' splice sites, respectively. The 3' splice sites of corresponding introns of African green monkey, Chinese hamster, dog and rat were AC, AT, AT and AA, respectively. The mouse GPAA1 gene (Gpaa1) bearing AG at the 3' splice site prepared by site-directed mutagenesis was functional, indicating that any nucleotide is allowed at the 3' end of a minor class intron.",
    "issueName" : "3-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Inoue",
      "authorRank" : 1,
      "name" : "Inoue N",
      "referenceId" : "RGD:A32809"
    }, {
      "firstName" : "K",
      "lastName" : "Ohishi",
      "authorRank" : 2,
      "name" : "Ohishi K",
      "referenceId" : "RGD:A7310"
    }, {
      "firstName" : "Y",
      "lastName" : "Endo",
      "authorRank" : 3,
      "name" : "Endo Y",
      "referenceId" : "RGD:A20549"
    }, {
      "firstName" : "T",
      "lastName" : "Fujita",
      "authorRank" : 4,
      "name" : "Fujita T",
      "referenceId" : "RGD:A6425"
    }, {
      "firstName" : "J",
      "lastName" : "Takeda",
      "authorRank" : 5,
      "name" : "Takeda J",
      "referenceId" : "RGD:A13883"
    }, {
      "firstName" : "T",
      "lastName" : "Kinoshita",
      "authorRank" : 6,
      "name" : "Kinoshita T",
      "referenceId" : "RGD:A7311"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1331365"
    } ]
  }, {
    "primaryId" : "PMID:10393695",
    "title" : "Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-adrenergic receptor gene delivery.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Maurice JP, etal., J Clin Invest 1999 Jul;104(1):21-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T12:09:18.000-05:00",
    "volume" : "104",
    "pages" : "21-9",
    "abstract" : "Exogenous gene delivery to alter the function of the heart is a potential novel therapeutic strategy for treatment of cardiovascular diseases such as heart failure (HF). Before gene therapy approaches to alter cardiac function can be realized, efficient and reproducible in vivo gene techniques must be established to efficiently transfer transgenes globally to the myocardium. We have been testing the hypothesis that genetic manipulation of the myocardial beta-adrenergic receptor (beta-AR) system, which is impaired in HF, can enhance cardiac function. We have delivered adenoviral transgenes, including the human beta2-AR (Adeno-beta2AR), to the myocardium of rabbits using an intracoronary approach. Catheter-mediated Adeno-beta2AR delivery produced diffuse multichamber myocardial expression, peaking 1 week after gene transfer. A total of 5 x 10(11) viral particles of Adeno-beta2AR reproducibly produced 5- to 10-fold beta-AR overexpression in the heart, which, at 7 and 21 days after delivery, resulted in increased in vivo hemodynamic function compared with control rabbits that received an empty adenovirus. Several physiological parameters, including dP/dtmax as a measure of contractility, were significantly enhanced basally and showed increased responsiveness to the beta-agonist isoproterenol. Our results demonstrate that global myocardial in vivo gene delivery is possible and that genetic manipulation of beta-AR density can result in enhanced cardiac performance. Thus, replacement of lost receptors seen in HF may represent novel inotropic therapy.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JP",
      "lastName" : "Maurice",
      "authorRank" : 1,
      "name" : "Maurice JP",
      "referenceId" : "RGD:A44318"
    }, {
      "firstName" : "JA",
      "lastName" : "Hata",
      "authorRank" : 2,
      "name" : "Hata JA",
      "referenceId" : "RGD:A44319"
    }, {
      "firstName" : "AS",
      "lastName" : "Shah",
      "authorRank" : 3,
      "name" : "Shah AS",
      "referenceId" : "RGD:A44320"
    }, {
      "firstName" : "DC",
      "lastName" : "White",
      "authorRank" : 4,
      "name" : "White DC",
      "referenceId" : "RGD:A44321"
    }, {
      "firstName" : "PH",
      "lastName" : "McDonald",
      "authorRank" : 5,
      "name" : "McDonald PH",
      "referenceId" : "RGD:A44322"
    }, {
      "firstName" : "PC",
      "lastName" : "Dolber",
      "authorRank" : 6,
      "name" : "Dolber PC",
      "referenceId" : "RGD:A44323"
    }, {
      "firstName" : "KH",
      "lastName" : "Wilson",
      "authorRank" : 7,
      "name" : "Wilson KH",
      "referenceId" : "RGD:A44324"
    }, {
      "firstName" : "RJ",
      "lastName" : "Lefkowitz",
      "authorRank" : 8,
      "name" : "Lefkowitz RJ",
      "referenceId" : "RGD:A151578"
    }, {
      "firstName" : "DD",
      "lastName" : "Glower",
      "authorRank" : 9,
      "name" : "Glower DD",
      "referenceId" : "RGD:A44326"
    }, {
      "firstName" : "WJ",
      "lastName" : "Koch",
      "authorRank" : 10,
      "name" : "Koch WJ",
      "referenceId" : "RGD:A11839"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300266"
    } ]
  }, {
    "primaryId" : "PMID:10393804",
    "title" : "LAP2 binding protein 1 (L2BP1/BAF) is a candidate mediator of LAP2-chromatin interaction.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Furukawa K J Cell Sci. 1999 Aug;112 ( Pt 15):2485-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-07-22T15:29:30.000-05:00",
    "volume" : "112 ( Pt 15)",
    "pages" : "2485-92",
    "abstract" : "Lamina-associated polypeptide (LAP) 2, which directly interacts with B-type lamins and chromosomes, is an integral membrane protein specifically distributed  along the inner nuclear membrane of the nuclear envelope. The chromatin- and lamin-binding activity of LAP2 suggests that LAP2 plays an important role in targeting mitotic vesicles to chromosomes and reorganizing the nuclear structure  at the end of mitosis. Here I identified a LAP2 interacting protein, termed L2BP1 (LAP2 binding protein 1). The rat L2BP1 cDNA sequence is predicted to encode a protein of 89 amino acids which turns out to be a rat homolog of mouse and human  BAF (Barrier-to-Autointegration Factor). L2BP1 is distributed diffusely throughout the nucleus in interphase cells. It is, however, highly concentrated at the chromosomes during the M-phase. Further, the L2BP1 binding domain of LAP2  overlaps its chromosome-binding region. These findings suggest that L2BP1 is a candidate mediator of LAP2-chromosome interaction at the end of mitosis.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Furukawa",
      "authorRank" : 1,
      "name" : "Furukawa",
      "referenceId" : "RGD:A412398"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10054037"
    } ]
  }, {
    "primaryId" : "PMID:10393810",
    "title" : "A novel zymogen granule protein (ZG29p) and the nuclear protein MTA1p are differentially expressed by alternative transcription initiation in pancreatic acinar cells of the rat.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Kleene R, etal., J Cell Sci 1999 Aug;112 ( Pt 15):2539-48.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-11-25T10:40:08.000-06:00",
    "volume" : "112 ( Pt 15)",
    "pages" : "2539-48",
    "abstract" : "Using a polyclonal antibody against purified zymogen granule membrane components from rat pancreas a cDNA coding for the 29 kDa protein (ZG29p) was identified by immunoscreening of a hormonally stimulated pancreas cDNA library. Western blot analysis suggests that ZG29p is a pancreas-specific protein and immunofluorescence shows that ZG29p is mainly associated with zymogen granules. Analysis of subcellular fraction applying immunoblotting revealed that ZG29p was localized mainly in the soluble fraction of zymogen granules and in a Golgi- and RER-enriched fraction, but was absent from the cytosol. In isolated zymogen granule content ZG29p was associated with protein complexes containing amylase as main constituent. The cDNA coding for ZG29p is homologous to the C-terminal region of the candidate metastasis-associated gene mta1. Northern blot analysis and RT-PCR showed that no MTA1 mRNA is present in pancreas from fasted rats and in the rat pancreas carcinoma cell line AR4-2J in its protodifferentiated state. Although no ZG29p specific mRNA was seen in the northern blot analysis, RT-PCR showed that ZG29p was expressed under both non-stimulated and stimulated conditions. The expression of MTA1 was up-regulated in the pancreas by endogenous cholecystokinin release and in AR4-2J after induction of cellular differentiation by dexamethasone. Western blotting and immunofluorescense studies indicated that MTA1p is localized in the nucleus in all tissues studied. Using genomic DNA in PCR analysis it was shown that two short introns are present flanking the sequences of the 5'end of ZG29p cDNA. One intron contains consensus elements required for pancreas specific transcription initiation, suggesting that MTA1 and ZG29 are differentially expressed by alternative transcription initiation in the pancreas. The localisation of MTA1p in the nucleus of most cell types could signify a general role in gene regulation, while the cell type specific and exclusive expression of ZG29p in pancreatic acinar cells could indicate a role in granule formation.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Kleene",
      "authorRank" : 1,
      "name" : "Kleene R",
      "referenceId" : "RGD:A31885"
    }, {
      "firstName" : "J",
      "lastName" : "Zdzieblo",
      "authorRank" : 2,
      "name" : "Zdzieblo J",
      "referenceId" : "RGD:A31886"
    }, {
      "firstName" : "K",
      "lastName" : "Wege",
      "authorRank" : 3,
      "name" : "Wege K",
      "referenceId" : "RGD:A26044"
    }, {
      "firstName" : "HF",
      "lastName" : "Kern",
      "authorRank" : 4,
      "name" : "Kern HF",
      "referenceId" : "RGD:A31887"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:729214"
    } ]
  }, {
    "primaryId" : "PMID:10393934",
    "title" : "Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Robertson KM, etal., Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7986-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-12-15T16:12:20.000-06:00",
    "volume" : "96",
    "pages" : "7986-91",
    "abstract" : "It is well established that spermatogenesis is controlled by gonadotrophins and testosterone. However, a role for estrogens in male reproduction recently was suggested in adult mice deficient in estrogen receptor alpha. These mice became infertile primarily because of an interruption of fluid reabsorption by the efferent ductules of the epididymis, thus leading to a disruption of the seminiferous epithelium [Hess, R. A., Bunick, D., Lee, K. H., Bahr, J., Taylor, J. A., Korach, K. S., and Lubahn, D. B. (1997) Nature (London) 390, 509-512]. Despite the demonstration of the aromatase enzyme, which converts androgens to estrogens, and estrogen receptors within the rodent seminiferous epithelium, the role of aromatase and estrogen in germ cell development is unknown. We have investigated spermatogenesis in mice that lack aromatase because of the targeted disruption of the cyp19 gene (ArKO). Male mice deficient in aromatase were initially fertile but developed progressive infertility, until their ability to sire pups was severely impaired. The mice deficient in aromatase developed disruptions to spermatogenesis between 4.5 months and 1 year, despite no decreases in gonadotrophins or androgens. Spermatogenesis primarily was arrested at early spermiogenic stages, as characterized by an increase in apoptosis and the appearance of multinucleated cells, and there was a significant reduction in round and elongated spermatids, but no changes in Sertoli cells and earlier germ cells. In addition, Leydig cell hyperplasia/hypertrophy was evident, presumably as a consequence of increased circulating luteinizing hormone. Our findings indicate that local expression of aromatase is essential for spermatogenesis and provide evidence for a direct action of estrogen on male germ cell development and thus fertility.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KM",
      "lastName" : "Robertson",
      "authorRank" : 1,
      "name" : "Robertson KM",
      "referenceId" : "RGD:A132654"
    }, {
      "firstName" : "L",
      "lastName" : "O'Donnell",
      "authorRank" : 2,
      "name" : "O'Donnell L",
      "referenceId" : "RGD:A76085"
    }, {
      "firstName" : "ME",
      "lastName" : "Jones",
      "authorRank" : 3,
      "name" : "Jones ME",
      "referenceId" : "RGD:A132655"
    }, {
      "firstName" : "SJ",
      "lastName" : "Meachem",
      "authorRank" : 4,
      "name" : "Meachem SJ",
      "referenceId" : "RGD:A117083"
    }, {
      "firstName" : "WC",
      "lastName" : "Boon",
      "authorRank" : 5,
      "name" : "Boon WC",
      "referenceId" : "RGD:A13624"
    }, {
      "firstName" : "CR",
      "lastName" : "Fisher",
      "authorRank" : 6,
      "name" : "Fisher CR",
      "referenceId" : "RGD:A39459"
    }, {
      "firstName" : "KH",
      "lastName" : "Graves",
      "authorRank" : 7,
      "name" : "Graves KH",
      "referenceId" : "RGD:A132656"
    }, {
      "firstName" : "RI",
      "lastName" : "McLachlan",
      "authorRank" : 8,
      "name" : "McLachlan RI",
      "referenceId" : "RGD:A76087"
    }, {
      "firstName" : "ER",
      "lastName" : "Simpson",
      "authorRank" : 9,
      "name" : "Simpson ER",
      "referenceId" : "RGD:A37782"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4890384"
    } ]
  }, {
    "primaryId" : "PMID:10393981",
    "title" : "Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D3-1alpha-hydroxylase gene in normocalcemic rats.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Shinki T, etal., Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8253-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-05-27T14:22:21.000-05:00",
    "volume" : "96",
    "pages" : "8253-8",
    "abstract" : "Regulation of vitamin D metabolism has long been examined by using vitamin D-deficient hypocalcemic animals. We previously reported that, in a rat model of chronic hyperparathyroidism, expression of 25-hydroxyvitamin D3-1alpha-hydroxylase (CYP27B1) mRNA was markedly increased in renal proximal convoluted tubules. It is believed that the major regulator for the expression of renal CYP27B1 is parathyroid hormone (PTH). However, in the normocalcemic state, the mechanism to regulate the renal CYP27B1 gene could be different, since plasma levels of PTH are very low. In the present study, the effect of PTH and calcitonin (CT) on the expression of renal CYP27B1 mRNA was investigated in normocalcemic sham-operated rats and normocalcemic thyroparathyroidectomized (TPTX) rats generated by either PTH or CaCl2 infusion. A single injection of CT dose-dependently decreased the expression of vitamin D receptor mRNA in the kidney of normocalcemic sham-TPTX rats. Concomitantly, CT greatly increased the expression of CYP27B1 mRNA in the kidney of normocalcemic sham-TPTX rats. CT also increased the expression of CYP27B1 mRNA in the kidney of normocalcemic TPTX rats. Conversion of serum [3H]1alpha,25(OH)2D3 from 25-hydroxy[3H]vitamin D3 in vivo was also greatly increased by the injection of CT into sham-TPTX rats and normocalcemic TPTX rats, but not into hypocalcemic TPTX rats. In contrast, administration of PTH did not induce the expression of CYP27B1 mRNA in the kidney of vitamin D-replete sham-TPTX rats and hypocalcemic TPTX rats. PTH increased the expression of renal CYP27B1 mRNA only in vitamin D-deficient hypocalcemic TPTX rats. These results suggest that CT plays an important role in the maintenance of serum 1alpha,25(OH)2D3 under normocalcemic physiological conditions, at least in rats.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Shinki",
      "authorRank" : 1,
      "name" : "Shinki T",
      "referenceId" : "RGD:A6498"
    }, {
      "firstName" : "Y",
      "lastName" : "Ueno",
      "authorRank" : 2,
      "name" : "Ueno Y",
      "referenceId" : "RGD:A21547"
    }, {
      "firstName" : "HF",
      "lastName" : "DeLuca",
      "authorRank" : 3,
      "name" : "DeLuca HF",
      "referenceId" : "RGD:A6502"
    }, {
      "firstName" : "T",
      "lastName" : "Suda",
      "authorRank" : 4,
      "name" : "Suda T",
      "referenceId" : "RGD:A114503"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2307327"
    } ]
  }, {
    "primaryId" : "PMID:103940",
    "title" : "Development of the diencephalon in the rat. II. Correlation of the embryonic development of the hypothalamus with the time of origin of its neurons.",
    "datePublished" : "1978-09-01T00:00:00.000-05:00",
    "citation" : "Altman J and Bayer SA, J Comp Neurol 1978 Dec 15;182(4 Pt 2):973-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-06T13:26:31.000-05:00",
    "volume" : "182",
    "pages" : "973-93",
    "abstract" : "The development of the nuclei of the hypothalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The diencephalic neuroepithelium was subdivided into three lobes (dorsal, medial, and ventral) and two lobules (superior and inferior). The hypothalamus is derived from the ventral lobe and the inferior lobule. The ventral neuroepithelial lobe generates the neurons of most of the early arising hypothalamic structures, including those of the lateral tier nuclei associated with the medial forebrain bundle, and the heterogeneous intermediate tier nuclei. A specialized neuroepithelial region lining the diamond shaped ventricle produces the early neurohypophysial magnocellular neurons; the neurons of the paraventricular nucleus remain at this site, whereas the neurons of the supraoptic nucleus could be traced migrating laterally. The neurons of the late arising hypophysiotropic area of the posterior hypothalamus are derived from components of the inferior neuroepithelial lobule: the dorsomedial and ventromedial nuclei apparently from a shared matrix in the main portion of the inferior lobule; the tuberomammillary-arcuate complex from its posteroventral recess. The triple-decked and sequentially produced components of the mammillary system may arise from separate neuroepithelial sites. The autoradiographic results of the previous study (Altman and Bayer, '78a) showed that the structural and functional heterogeneity of the mature hypothalamus is paralleled by cytogenetic heterochronicity; the present embryonic observations indicate that many of the distinguishable components of the hypothalamus arise from a mosaic of heterogeneous neuroepithelial sites.",
    "issueName" : "4 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Altman",
      "authorRank" : 1,
      "name" : "Altman J",
      "referenceId" : "RGD:A55736"
    }, {
      "firstName" : "SA",
      "lastName" : "Bayer",
      "authorRank" : 2,
      "name" : "Bayer SA",
      "referenceId" : "RGD:A55737"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549648"
    } ]
  }, {
    "primaryId" : "PMID:10394193",
    "title" : "[Biotinidase deficiency: importance of its neonatal diagnosis and early treatment].",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Couce Pico ML, etal., An Esp Pediatr. 1999 May;50(5):504-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:06:03.000-05:00",
    "volume" : "50",
    "pages" : "504-6",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ML",
      "lastName" : "Couce Pico",
      "authorRank" : 1,
      "name" : "Couce Pico",
      "referenceId" : "RGD:A255113"
    }, {
      "firstName" : "F",
      "lastName" : "Martinon-Torres",
      "authorRank" : 2,
      "name" : "Martinon-Torres",
      "referenceId" : "RGD:A255114"
    }, {
      "firstName" : "DE",
      "lastName" : "Castineiras",
      "authorRank" : 3,
      "name" : "Castineiras",
      "referenceId" : "RGD:A255115"
    }, {
      "firstName" : "JR",
      "lastName" : "Alonso-Fernandez",
      "authorRank" : 4,
      "name" : "Alonso-Fernandez",
      "referenceId" : "RGD:A255116"
    }, {
      "firstName" : "JM",
      "lastName" : "Fraga",
      "authorRank" : 5,
      "name" : "Fraga",
      "referenceId" : "RGD:A251649"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063433"
    } ]
  }, {
    "primaryId" : "PMID:10394368",
    "title" : "Loss-of-function mutations in PPAR gamma associated with human colon cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Sarraf P, etal., Mol Cell. 1999 Jun;3(6):799-804.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-20T14:24:06.000-05:00",
    "volume" : "3",
    "pages" : "799-804",
    "abstract" : "The gamma isoform of the peroxisome proliferator-activated receptor, PPAR gamma, regulates adipocyte differentiation and has recently been shown to be expressed in neoplasia of the colon and other tissues. We have found four somatic PPAR gamma mutations among 55 sporadic colon cancers: one nonsense, one frameshift, and two missense mutations. Each greatly impaired the function of the protein. c.472delA results in deletion of the entire ligand binding domain. Q286P and K319X retain a total or partial ligand binding domain but lose the ability to activate transcription through a failure to bind to ligands. R288H showed a normal response to synthetic ligands but greatly decreased transcription and binding when exposed to natural ligands. These data indicate that colon cancer in humans is associated with loss-of-function mutations in PPAR gamma.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Sarraf",
      "authorRank" : 1,
      "name" : "Sarraf P",
      "referenceId" : "RGD:A80999"
    }, {
      "firstName" : "E",
      "lastName" : "Mueller",
      "authorRank" : 2,
      "name" : "Mueller E",
      "referenceId" : "RGD:A81000"
    }, {
      "firstName" : "WM",
      "lastName" : "Smith",
      "authorRank" : 3,
      "name" : "Smith WM",
      "referenceId" : "RGD:A81001"
    }, {
      "firstName" : "HM",
      "lastName" : "Wright",
      "authorRank" : 4,
      "name" : "Wright HM",
      "referenceId" : "RGD:A81002"
    }, {
      "firstName" : "JB",
      "lastName" : "Kum",
      "authorRank" : 5,
      "name" : "Kum JB",
      "referenceId" : "RGD:A81003"
    }, {
      "firstName" : "LA",
      "lastName" : "Aaltonen",
      "authorRank" : 6,
      "name" : "Aaltonen LA",
      "referenceId" : "RGD:A36425"
    }, {
      "firstName" : "A",
      "lastName" : "De la Chapelle",
      "authorRank" : 7,
      "name" : "De la Chapelle A",
      "referenceId" : "RGD:A4151"
    }, {
      "firstName" : "BM",
      "lastName" : "Spiegelman",
      "authorRank" : 8,
      "name" : "Spiegelman BM",
      "referenceId" : "RGD:A39228"
    }, {
      "firstName" : "C",
      "lastName" : "Eng",
      "authorRank" : 9,
      "name" : "Eng C",
      "referenceId" : "RGD:A164779"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601444"
    } ]
  }, {
    "primaryId" : "PMID:10394930",
    "title" : "Phenylketonuria mutations in Germany.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Zschocke J and Hoffmann GF, Hum Genet. 1999 May;104(5):390-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:08:02.000-05:00",
    "volume" : "104",
    "pages" : "390-8",
    "abstract" : "We report the spectrum of mutations and associated modified haplotypes in patients with phenylketonuria living in Germany. A total of 546 independent alleles was investigated, including 411 of German and 65 of Turkish descent. Mutations were identified for 535 PKU alleles (98%) and there were 91 different mutations. The most common mutation was R408W on 22% of alleles. Two mutations, IVS12+1G-->A and IVS10-11G-->A accounted for just under 10% of alleles, whereas the remaining mutations were found at relative frequencies of 6% or less; 43 mutations were observed once only. IVS10-11G-->A was the most common mutation (38% of alleles) in the subgroup of patients of Turkish descent. Modified haplotypes were determined from the analysis of four silent mutations, three diallelic restriction fragment length polymorphisms, a variable number of tandem  repeats minisatellite and a short tandem repeat microsatellite in the phenylalanine hydroxylase gene, showing that a considerable proportion of mutations must have recurred in independent founders; other mutations may have changed chromosomal haplotype backgrounds by gene conversion. The spectrum of PKU mutations in Germany reflects the history of a heterogenous Central European population living at the crossroads of migration throughout the centuries.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Zschocke",
      "authorRank" : 1,
      "name" : "Zschocke J",
      "referenceId" : "RGD:A68505"
    }, {
      "firstName" : "GF",
      "lastName" : "Hoffmann",
      "authorRank" : 2,
      "name" : "Hoffmann GF",
      "referenceId" : "RGD:A60766"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063503"
    } ]
  }, {
    "primaryId" : "PMID:10394936",
    "title" : "Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Cornejo-Roldan LR, etal., Hum Genet. 1999 May;104(5):425-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-12T20:18:50.000-05:00",
    "volume" : "104",
    "pages" : "425-31",
    "abstract" : "Pfeiffer syndrome (PS) is one of the classical craniosynostosis syndromes correlated with specific mutations in the human fibroblast growth factor receptor (FGFR) genes, FGFR1 and FGFR2. In this study, we set out to examine the exons in  FGFR2 most commonly associated with mutations in PS, exons IIIa and IIIc, in a panel of 78 unrelated individuals with PS by the most sensitive method (direct DNA sequencing). We have identified a total of 18 different mutations among 40 patients; eight of these mutations have not been previously described. The mutational spectrum displays a non-random character with the frequent involvement of cysteine codons.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LR",
      "lastName" : "Cornejo-Roldan",
      "authorRank" : 1,
      "name" : "Cornejo-Roldan",
      "referenceId" : "RGD:A396945"
    }, {
      "firstName" : "E",
      "lastName" : "Roessler",
      "authorRank" : 2,
      "name" : "Roessler E",
      "referenceId" : "RGD:A73403"
    }, {
      "firstName" : "M",
      "lastName" : "Muenke",
      "authorRank" : 3,
      "name" : "Muenke M",
      "referenceId" : "RGD:A36395"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11553503"
    } ]
  }, {
    "primaryId" : "PMID:10394939",
    "title" : "Gene symbol: AGXT. Disease: primary hyperoxaluria type I.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Amoroso A, etal., Hum Genet. 1999 May;104(5):441.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:44:11.000-05:00",
    "volume" : "104",
    "pages" : "441",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Amoroso",
      "authorRank" : 1,
      "name" : "Amoroso A",
      "referenceId" : "RGD:A66898"
    }, {
      "firstName" : "D",
      "lastName" : "Pirulli",
      "authorRank" : 2,
      "name" : "Pirulli",
      "referenceId" : "RGD:A258032"
    }, {
      "firstName" : "D",
      "lastName" : "Puzzer",
      "authorRank" : 3,
      "name" : "Puzzer",
      "referenceId" : "RGD:A258033"
    }, {
      "firstName" : "L",
      "lastName" : "Ferri",
      "authorRank" : 4,
      "name" : "Ferri",
      "referenceId" : "RGD:A256383"
    }, {
      "firstName" : "S",
      "lastName" : "Crovella",
      "authorRank" : 5,
      "name" : "Crovella S",
      "referenceId" : "RGD:A134745"
    }, {
      "firstName" : "C",
      "lastName" : "Ferrettini",
      "authorRank" : 6,
      "name" : "Ferrettini",
      "referenceId" : "RGD:A258034"
    }, {
      "firstName" : "M",
      "lastName" : "Marangella",
      "authorRank" : 7,
      "name" : "Marangella",
      "referenceId" : "RGD:A258035"
    }, {
      "firstName" : "G",
      "lastName" : "Mazzola",
      "authorRank" : 8,
      "name" : "Mazzola",
      "referenceId" : "RGD:A209683"
    }, {
      "firstName" : "F",
      "lastName" : "Florian",
      "authorRank" : 9,
      "name" : "Florian",
      "referenceId" : "RGD:A258036"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067849"
    } ]
  }, {
    "primaryId" : "PMID:10395190",
    "title" : "Genes involved in animal models of obesity and anorexia.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Schalling M, etal., J Intern Med 1999 Jun;245(6):613-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-07-02T15:22:50.000-05:00",
    "volume" : "245",
    "pages" : "613-9",
    "abstract" : "Pathological deviations in bodyweight is a major increasing health problem in industrialized societies. It is currently unclear what genetic mechanisms are involved in the long-term control of human body-weight and to what extent these genes are involved in pathological deviations of bodyweight control such as anorexia and obesity. Major support for the concept of genetic control of bodyweight has recently emerged from different animal models. A number of new genes have been found during recent years that, when mutated, have a negative effect on bodyweight in animals and sometimes also in man. Although available evidence points toward a multifactorial nature of weight disorders in most human subjects, the single genes isolated in animal models may become powerful tools to elucidate the genetics also in man. In addition, these genes may serve to promote the development of targeted small-drug pharmaceuticals aimed at novel biochemical pathways. Finally, the uncovering of several quantitative trait loci (QTL) influencing body mass, body fat or fat topography in the mouse and rat has now also made it possible to perform studies of polygenically caused obesity in rodents. The role of the Genome Project in developing a complete gene map will greatly facilitate transforming these OTLs to actual molecules involved in the biology of bodyweight.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Schalling",
      "authorRank" : 1,
      "name" : "Schalling M",
      "referenceId" : "RGD:A10487"
    }, {
      "firstName" : "J",
      "lastName" : "Johansen",
      "authorRank" : 2,
      "name" : "Johansen J",
      "referenceId" : "RGD:A10488"
    }, {
      "firstName" : "L",
      "lastName" : "Nordfors",
      "authorRank" : 3,
      "name" : "Nordfors L",
      "referenceId" : "RGD:A10489"
    }, {
      "firstName" : "F",
      "lastName" : "Lonnqvist",
      "authorRank" : 4,
      "name" : "Lonnqvist F",
      "referenceId" : "RGD:A10490"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70863"
    } ]
  }, {
    "primaryId" : "PMID:10395222",
    "title" : "Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Tiihonen J, etal., Mol Psychiatry. 1999 May;4(3):286-9. doi: 10.1038/sj.mp.4000509.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-12-28T15:33:51.000-06:00",
    "volume" : "4",
    "pages" : "286-9",
    "abstract" : "Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity, may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism. Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. The aim of this study was to test this hypothesis among type 1 (late-onset) alcoholics. The COMT polymorphism was determined in two independent male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuopio (n = 56). The high (H) and low (L) activity COMT genotype and allele frequencies were compared with previously published data from 3140 Finnish blood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the patients both in Turku (P = 0.023) and in Kuopio (P = 0.005) when compared with the general population. When all patients were compared with the general population (blood donors), the difference was even more significant (P = 0.0004). When genotypes of all alcoholics (n = 123) were compared with genotypes of matched controls, the odds ratio (OR) for alcoholism for those subjects having the LL genotype vs those with HH genotype was 2.51, 95% CI 1.22-5.19, P = 0.006. Also, L allele frequency was significantly higher among alcoholics when compared with controls (P = 0.009). The estimate for population etiological (attributable) fraction for the LL genotype in alcoholism was 13.3% (95% CI 2.3-25.7%). The results indicate that the COMT polymorphism contributes significantly to the development of late-onset alcoholism.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Tiihonen",
      "authorRank" : 1,
      "name" : "Tiihonen J",
      "referenceId" : "RGD:A537077"
    }, {
      "firstName" : "T",
      "lastName" : "Hallikainen",
      "authorRank" : 2,
      "name" : "Hallikainen T",
      "referenceId" : "RGD:A537078"
    }, {
      "firstName" : "H",
      "lastName" : "Lachman",
      "authorRank" : 3,
      "name" : "Lachman H",
      "referenceId" : "RGD:A537079"
    }, {
      "firstName" : "T",
      "lastName" : "Saito",
      "authorRank" : 4,
      "name" : "Saito T",
      "referenceId" : "RGD:A161595"
    }, {
      "firstName" : "J",
      "lastName" : "Volavka",
      "authorRank" : 5,
      "name" : "Volavka J",
      "referenceId" : "RGD:A537080"
    }, {
      "firstName" : "J",
      "lastName" : "Kauhanen",
      "authorRank" : 6,
      "name" : "Kauhanen J",
      "referenceId" : "RGD:A61460"
    }, {
      "firstName" : "J T",
      "lastName" : "Salonen",
      "authorRank" : 7,
      "name" : "Salonen JT",
      "referenceId" : "RGD:A537081"
    }, {
      "firstName" : "O P",
      "lastName" : "Ryynänen",
      "authorRank" : 8,
      "name" : "Ryynänen OP",
      "referenceId" : "RGD:A537082"
    }, {
      "firstName" : "M",
      "lastName" : "Koulu",
      "authorRank" : 9,
      "name" : "Koulu M",
      "referenceId" : "RGD:A44310"
    }, {
      "firstName" : "M K",
      "lastName" : "Karvonen",
      "authorRank" : 10,
      "name" : "Karvonen MK",
      "referenceId" : "RGD:A537083"
    }, {
      "firstName" : "T",
      "lastName" : "Pohjalainen",
      "authorRank" : 11,
      "name" : "Pohjalainen T",
      "referenceId" : "RGD:A537084"
    }, {
      "firstName" : "E",
      "lastName" : "Syvälahti",
      "authorRank" : 12,
      "name" : "Syvälahti E",
      "referenceId" : "RGD:A537085"
    }, {
      "firstName" : "J",
      "lastName" : "Hietala",
      "authorRank" : 13,
      "name" : "Hietala J",
      "referenceId" : "RGD:A537086"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401940114"
    } ]
  }, {
    "primaryId" : "PMID:10395228",
    "title" : "Establishment of two substrains, diabetes-prone and non-diabetic, from Long-Evans Tokushima Lean (LETL) rats.",
    "datePublished" : "1998-12-01T00:00:00.000-06:00",
    "citation" : "Komeda K, etal., Endocr J. 1998 Dec;45(6):737-44. doi: 10.1507/endocrj.45.737.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-02-18T10:47:51.000-06:00",
    "volume" : "45",
    "pages" : "737-44",
    "abstract" : "Diabetes mellitus in Long-Evans Tokushima Lean (LETL) rats closely resembles type 1 diabetes in human beings, e.g., no gender differences in the incidence of diabetes and no T lymphopenia. Although the LETL rats have been established as an inbred strain, the incidence of diabetes is only approximately 20%. In the present study, we established two substrains, one a diabetes-prone (KDP) and the other a non-diabetic (KND) from the original inbred LETL rats. The features of KDP rats are a high incidence of diabetes (over all approximately 70%) without lymphopenia and 100% development of mild to severe insulitis at 120-220 days of age. In contrast, the KND substrain is characterized by the complete absence of diabetes incidence. Among 165 SSLP marker loci throughout all rat chromosomes, no loci showed variation among KDP and KND substrains and their parental LETL rats. In this regard, the genetic background of these two substrains, KDP and KND, appears to be uniform except for the major gene(s) that is responsible for the diabetes. In this context, these two substrains of LETL rats should serve as useful tools for research on the pathogenesis and for the genetic analysis of type 1 diabetes. In this report, we have not only established, but also characterized these two substrains, and provided their fundamental data.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Komeda",
      "authorRank" : 1,
      "name" : "Komeda K",
      "referenceId" : "RGD:A11722"
    }, {
      "firstName" : "M",
      "lastName" : "Noda",
      "authorRank" : 2,
      "name" : "Noda M",
      "referenceId" : "RGD:A6115"
    }, {
      "firstName" : "K",
      "lastName" : "Terao",
      "authorRank" : 3,
      "name" : "Terao K",
      "referenceId" : "RGD:A56434"
    }, {
      "firstName" : "N",
      "lastName" : "Kuzuya",
      "authorRank" : 4,
      "name" : "Kuzuya N",
      "referenceId" : "RGD:A107078"
    }, {
      "firstName" : "M",
      "lastName" : "Kanazawa",
      "authorRank" : 5,
      "name" : "Kanazawa M",
      "referenceId" : "RGD:A14701"
    }, {
      "firstName" : "Y",
      "lastName" : "Kanazawa",
      "authorRank" : 6,
      "name" : "Kanazawa Y",
      "referenceId" : "RGD:A13851"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:41412159"
    } ]
  }, {
    "primaryId" : "PMID:10395295",
    "title" : "Differential activation of some transcription factors during rat liver ischemia, reperfusion, and heat shock.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Tacchini L, etal., J Cell Physiol. 1999 Aug;180(2):255-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-15T12:04:14.000-06:00",
    "volume" : "180",
    "pages" : "255-62",
    "abstract" : "Cells respond to external stimuli by changes in gene expression that are largely dependent on transcription factors (TFs). We studied the behavior of some TFs in rat liver during ischemia, postischemic reperfusion, and heat shock. Knowledge of the conditions at the end of ischemia is essential to understand changes occurring at reperfusion. The TFs investigated are known to be typically responsive to heat shock (HSF), hypoxia (HIF-1), pro- and antioxidant conditions (AP-1), or to various environmental changes (HNF-1 and ATF/CREB family). The most relevant new information includes the following: 1) Liver ischemia activates extremely rapidly the DNA binding capacity of HSF, soon followed by analogous activation of HIF-1 and AP-1. 2) After a certain lag time from the activation of HIF-1, mRNAs accumulate for two glycolytic enzymes, in particular Aldolase A and Heme Oxygenase 1, which contain HIF-1 sequences in their promoters. 3) Reperfusion, which is known to further increase the binding of HSF and to induce NFkappaB binding, abrogates or decreases the binding of HIF-1 and AP-1, stimulated by ischemia, and activates the binding of ATF/CREB. Later on, a second peak of AP-1 binding is induced. 4) Heat shock activates both ischemia-responsive and reperfusion-responsive TFs. 5) Preliminary experiments of supergelshift reveal that the activation of AP-1 at reperfusion or upon heat shock may result from the different involvement of the component subunits.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Tacchini",
      "authorRank" : 1,
      "name" : "Tacchini L",
      "referenceId" : "RGD:A42460"
    }, {
      "firstName" : "L",
      "lastName" : "Radice",
      "authorRank" : 2,
      "name" : "Radice L",
      "referenceId" : "RGD:A72334"
    }, {
      "firstName" : "A",
      "lastName" : "Bernelli-Zazzera",
      "authorRank" : 3,
      "name" : "Bernelli-Zazzera A",
      "referenceId" : "RGD:A42462"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599061"
    } ]
  }, {
    "primaryId" : "PMID:10395320",
    "title" : "Induction of the p16INK4a senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Taniguchi K, etal., Nat Med. 1999 Jul;5(7):760-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-04-25T11:16:08.000-05:00",
    "volume" : "5",
    "pages" : "760-7",
    "abstract" : "Synovial tissue affected by rheumatoid arthritis is characterized by proliferation, which leads to irreversible cartilage and bone destruction. Current and experimental treatments have been aimed mainly at correcting the underlying immune abnormalities, but these treatments often prove ineffective in  preventing the invasive destruction. We studied the expression of cyclin-dependent kinase inhibitors in rheumatoid synovial cells as a means of suppressing synovial cell proliferation. Synovial cells derived from hypertrophic synovial tissue readily expressed p16INK4a when they were growth-inhibited. This  was not seen in other fibroblasts, including those derived from normal and osteoarthritis-affected synovial tissues. In vivo adenoviral gene therapy with the p16INK4a gene efficiently inhibited the pathology in an animal model of rheumatoid arthritis. Thus, the induction of p16INK4a may provide a new approach  to the effective treatment of rheumatoid arthritis.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Taniguchi",
      "authorRank" : 1,
      "name" : "Taniguchi K",
      "referenceId" : "RGD:A14702"
    }, {
      "firstName" : "H",
      "lastName" : "Kohsaka",
      "authorRank" : 2,
      "name" : "Kohsaka",
      "referenceId" : "RGD:A182849"
    }, {
      "firstName" : "N",
      "lastName" : "Inoue",
      "authorRank" : 3,
      "name" : "Inoue N",
      "referenceId" : "RGD:A32809"
    }, {
      "firstName" : "Y",
      "lastName" : "Terada",
      "authorRank" : 4,
      "name" : "Terada Y",
      "referenceId" : "RGD:A27066"
    }, {
      "firstName" : "H",
      "lastName" : "Ito",
      "authorRank" : 5,
      "name" : "Ito",
      "referenceId" : "RGD:A416960"
    }, {
      "firstName" : "K",
      "lastName" : "Hirokawa",
      "authorRank" : 6,
      "name" : "Hirokawa K",
      "referenceId" : "RGD:A24793"
    }, {
      "firstName" : "N",
      "lastName" : "Miyasaka",
      "authorRank" : 7,
      "name" : "Miyasaka N",
      "referenceId" : "RGD:A20176"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8552686"
    } ]
  }, {
    "primaryId" : "PMID:10395379",
    "title" : "Liposomal encapsulation of ganciclovir enhances the efficacy of herpes simplex virus type 1 thymidine kinase suicide gene therapy against hepatic tumors in rats.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Engelmann C, etal., Hum Gene Ther. 1999 Jun 10;10(9):1545-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-09-21T18:12:08.000-05:00",
    "volume" : "10",
    "pages" : "1545-51",
    "abstract" : "Suicide gene therapy based on ganciclovir (GCV) metabolism by transgene herpes simplex thymidine kinase (HSV-1 TK) has been used to selectively kill proliferating cells in clinical settings such as cancer, vascular restenosis, and immunological disorders. We investigated whether encapsulation of ganciclovir (GCV) into liposomes would improve its efficacy, especially against hepatic tumors. Large unilamellar liposomes containing GCV were prepared by reversed-phase evaporation. Pharmacokinetic studies in rats showed that, compared with free GCV, the intravenous injection of liposome-encapsulated GCV (lip-GCV) led to a faster decrease in GCV plasma concentrations, but higher liver-blood ratios. After treatment of syngeneic HSV-1 TK+ liver metastases in rats, histologically active tumors were found in 95% of the transplanted lesions when physiological saline had been given and in 50% when free GCV had been given at 90.2 microM/kg twice daily. This dose is known to be insufficient for the eradication of HSV-1 TK+ tumors. In contrast, only 5% viable tumors were found in rats receiving lip-GCV at this same concentration. Average tumor volumes were 19  +/- 15, 7 +/- 9, and <1 mm3 for the control, free GCV, and lip-GCV groups, respectively. GCV-related toxicity was no longer observed. The results demonstrate that liposomal encapsulation of GCV is feasible and significantly enhances its efficacy against HSV-1 TK+ hepatic tumors.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Engelmann",
      "authorRank" : 1,
      "name" : "Engelmann",
      "referenceId" : "RGD:A206148"
    }, {
      "firstName" : "Y",
      "lastName" : "Panis",
      "authorRank" : 2,
      "name" : "Panis",
      "referenceId" : "RGD:A206149"
    }, {
      "firstName" : "J",
      "lastName" : "Bolard",
      "authorRank" : 3,
      "name" : "Bolard",
      "referenceId" : "RGD:A206150"
    }, {
      "firstName" : "B",
      "lastName" : "Diquet",
      "authorRank" : 4,
      "name" : "Diquet",
      "referenceId" : "RGD:A206151"
    }, {
      "firstName" : "M",
      "lastName" : "Fabre",
      "authorRank" : 5,
      "name" : "Fabre",
      "referenceId" : "RGD:A206152"
    }, {
      "firstName" : "H",
      "lastName" : "Nagy",
      "authorRank" : 6,
      "name" : "Nagy",
      "referenceId" : "RGD:A206153"
    }, {
      "firstName" : "O",
      "lastName" : "Soubrane",
      "authorRank" : 7,
      "name" : "Soubrane",
      "referenceId" : "RGD:A198168"
    }, {
      "firstName" : "D",
      "lastName" : "Houssin",
      "authorRank" : 8,
      "name" : "Houssin",
      "referenceId" : "RGD:A206154"
    }, {
      "firstName" : "D",
      "lastName" : "Klatzmann",
      "authorRank" : 9,
      "name" : "Klatzmann D",
      "referenceId" : "RGD:A157193"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10400881"
    } ]
  }, {
    "primaryId" : "PMID:10395404",
    "title" : "The AT2 receptor: fact, fancy and fantasy.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "de Gasparo M and Siragy HM, Regul Pept. 1999 May 31;81(1-3):11-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-06-22T13:32:54.000-05:00",
    "volume" : "81",
    "pages" : "11-24",
    "abstract" : "The angiotensin AT2 receptor subtype was recently cloned and pharmacologically characterized but its function still remains elusive and controversial. It is a member of the G-protein coupled receptor superfamily with a minimal sequence homology with the AT1 receptor, responsible for the known effect of angiotensin II. The AT2 receptor displays a totally different signaling mechanisms from the AT1 receptor and involves various phosphatases. It is expressed at low density in adult tissues but up-regulated in pathological circumstances. Clearly, the AT2 receptor has antiproliferative properties and therefore opposes the growth promoting effect linked to the AT1 receptor stimulation. It is also reported that the AT2 receptor regulates ionic fluxes, affects differentiation and nerve regeneration, has anti-angiogenic and anti-fibrotic properties and stimulates apoptosis. However, the results, although suggestive, are sometimes equivocal. Obviously, the AT2 receptor plays a role in the pathogenesis and remodeling of cardiovascular and renal diseases. A more extensive knowledge of the AT2 receptor could therefore contribute to the understanding of the clincial beneficial effects of the AT1 receptor antagonists.",
    "issueName" : "1-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "De Gasparo",
      "authorRank" : 1,
      "name" : "De Gasparo M",
      "referenceId" : "RGD:A67559"
    }, {
      "firstName" : "HM",
      "lastName" : "Siragy",
      "authorRank" : 2,
      "name" : "Siragy HM",
      "referenceId" : "RGD:A61942"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5133661"
    } ]
  }, {
    "primaryId" : "PMID:10395649",
    "title" : "IgG-mediated enhancement of antibody responses is low in Fc receptor gamma chain-deficient mice and increased in Fc gamma RII-deficient mice.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wernersson S, etal., J Immunol. 1999 Jul 15;163(2):618-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:00:51.000-05:00",
    "volume" : "163",
    "pages" : "618-22",
    "abstract" : "Immunization with IgG/Ag or IgE/Ag complexes leads to a higher production of specific Abs than immunization with Ag alone. The enhancing effect of IgE is exclusively dependent upon the low-affinity receptor for IgE, Fc epsilon RII, whereas the mechanism behind IgG-mediated enhancement is unknown. We have investigated whether receptors for the Fc part of IgG are required for responses  to IgG/Ag. Mice lacking the gamma subunit of Fc receptors (FcRs) (FcR gamma-/-),  Fc gamma RII (Fc gamma RII-/-), or Fc gamma RIII (Fc gamma RIII-/-) were immunized with BSA-2,4,6-trinitrophenyl (TNP) alone or BSA-TNP complexed to monoclonal TNP-specific IgG1, IgG2a, or IgG2b. As expected, all subclasses enhanced the Ab-response to BSA in wild-type mice. Enhancement was in the same order of magnitude in Fc gamma RIII-/- mice (</=177-fold of controls administered Ag alone), whereas it was abrogated in FcR gamma-/- mice and augmented in Fc gamma RII-/- mice (</=5147-fold of controls). The response to IgE/Ag complexes in FcR gamma-/- and Fc gamma RII-/- mice was similar to that se for wild-type mice,  demonstrating that non-Fc gamma R-dependent responses were normal. Our observations suggest that IgG/Ag complexes enhance Ab responses via Fc gamma Rs.  Moreover, they reveal a strong negative regulation of Ab responses to IgG/Ag exerted by Fc gamma RII.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Wernersson",
      "authorRank" : 1,
      "name" : "Wernersson",
      "referenceId" : "RGD:A228898"
    }, {
      "firstName" : "MC",
      "lastName" : "Karlsson",
      "authorRank" : 2,
      "name" : "Karlsson",
      "referenceId" : "RGD:A167468"
    }, {
      "firstName" : "J",
      "lastName" : "Dahlstrom",
      "authorRank" : 3,
      "name" : "Dahlstrom",
      "referenceId" : "RGD:A228899"
    }, {
      "firstName" : "R",
      "lastName" : "Mattsson",
      "authorRank" : 4,
      "name" : "Mattsson",
      "referenceId" : "RGD:A228900"
    }, {
      "firstName" : "JS",
      "lastName" : "Verbeek",
      "authorRank" : 5,
      "name" : "Verbeek JS",
      "referenceId" : "RGD:A145866"
    }, {
      "firstName" : "B",
      "lastName" : "Heyman",
      "authorRank" : 6,
      "name" : "Heyman",
      "referenceId" : "RGD:A228901"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11055024"
    } ]
  }, {
    "primaryId" : "PMID:10395673",
    "title" : "Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Song JS, etal., J Immunol 1999 Jul 15;163(2):802-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:54:46.000-06:00",
    "volume" : "163",
    "pages" : "802-10",
    "abstract" : "This study investigates whether the guanine nucleotide exchange activity of Vav is linked to cytokine production in mast cells. Overexpression of Vav in the RBL-2H3 mast cell line resulted in the constitutive tyrosine phosphorylation and activation of Vav. We analyzed the functional effect of Vav overexpression on cytokine production. IL-2 and IL-6 mRNA levels were dramatically increased in Vav-overexpressing cells and correlated with increased NF-AT activity. Little or no effect was observed on the mRNA levels of IL-3, IL-4, GM-CSF, TNF-alpha, and TGF-beta. FcepsilonRI engagement did not further enhance IL-2 and IL-6 mRNA levels and only slightly enhanced NF-AT activity, but dramatically increased the mRNA levels of other tested cytokines. To understand the signal transduction required, we focused primarily on IL-6 induction by measuring mitogen-activated protein kinase activity and analyzing the effects of mutant or dominant negative forms of Vav, Rac1, and c-Jun N-terminal kinase-1 (JNK1). Vav overexpression resulted in the constitutive activation of JNK1 with little or no effect on p38 mitogen-activated protein kinase and ERK2. This was dependent on Vav-mediated activation of Rac1 as a Dbl domain-mutated Vav, inactive Rac N17, and inactive JNK1 down-regulated the Vav-induced JNK1 or IL-6 responses. Vav expression, but not expression of domain-mutated Vav, increased IL-6 secretion from nonimmortalized bone marrow-derived mast cells upon FcepsilonRI engagement. We conclude that Vav phosphorylation contributes to IL-6 induction in mast cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JS",
      "lastName" : "Song",
      "authorRank" : 1,
      "name" : "Song JS",
      "referenceId" : "RGD:A27193"
    }, {
      "firstName" : "H",
      "lastName" : "Haleem-Smith",
      "authorRank" : 2,
      "name" : "Haleem-Smith H",
      "referenceId" : "RGD:A18253"
    }, {
      "firstName" : "R",
      "lastName" : "Arudchandran",
      "authorRank" : 3,
      "name" : "Arudchandran R",
      "referenceId" : "RGD:A27194"
    }, {
      "firstName" : "J",
      "lastName" : "Gomez",
      "authorRank" : 4,
      "name" : "Gomez J",
      "referenceId" : "RGD:A27195"
    }, {
      "firstName" : "PM",
      "lastName" : "Scott",
      "authorRank" : 5,
      "name" : "Scott PM",
      "referenceId" : "RGD:A27196"
    }, {
      "firstName" : "JF",
      "lastName" : "Mill",
      "authorRank" : 6,
      "name" : "Mill JF",
      "referenceId" : "RGD:A18250"
    }, {
      "firstName" : "TH",
      "lastName" : "Tan",
      "authorRank" : 7,
      "name" : "Tan TH",
      "referenceId" : "RGD:A7522"
    }, {
      "firstName" : "J",
      "lastName" : "Rivera",
      "authorRank" : 8,
      "name" : "Rivera J",
      "referenceId" : "RGD:A27197"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727273"
    } ]
  }, {
    "primaryId" : "PMID:10395706",
    "title" : "Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases.",
    "datePublished" : "1999-07-15T00:00:00.000-05:00",
    "citation" : "Tan FK, etal., J Immunol. 1999 Jul 15;163(2):1066-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-06-14T16:50:39.000-05:00",
    "volume" : "163",
    "pages" : "1066-72",
    "abstract" : "A duplication in the fibrillin-1 gene has been implicated as the cause of the tight skin 1 (tsk1) phenotype, an animal model of scleroderma or systemic sclerosis (SSc). In addition to the production of abnormal fibrillin-1 protein, the tsk1 mouse also produces autoantibodies to fibrillin-1. Among a population of Choctaw Native Americans with the highest prevalence of SSc yet described, a chromosome 15q haplotype containing the fibrillin-1 gene has been strongly associated with SSc. With a recombinant human fibrillin-1 protein, autoantibodies to fibrillin-1 were detected in the sera of Native American SSc patients that correlated significantly with disease. Abs to fibrillin-1 also were detected in sera from Japanese, Caucasian, and African-American SSc patients. Compared with other ethnic groups, Japanese and Native American SSc patients had significantly higher frequencies of anti-fibrillin-1 Abs. Sera from patients with diffuse SSc, calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, and telangiectasias syndrome and mixed connective tissue disease also had significantly higher frequencies of anti-fibrillin-1 Abs than sera from controls or patients with other non-SSc connective tissue diseases (lupus, rheumatoid arthritis, and Sjögren's syndrome). Ab specificity for fibrillin-1 was demonstrated by the lack of binding to a panel of other purified autoantigens. The results presented demonstrate for the first time the presence of high levels of anti-fibrillin-1 Abs in a significant portion of patients with SSc.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F K",
      "lastName" : "Tan",
      "authorRank" : 1,
      "name" : "Tan FK",
      "referenceId" : "RGD:A445186"
    }, {
      "firstName" : "F C",
      "lastName" : "Arnett",
      "authorRank" : 2,
      "name" : "Arnett FC",
      "referenceId" : "RGD:A445187"
    }, {
      "firstName" : "S",
      "lastName" : "Antohi",
      "authorRank" : 3,
      "name" : "Antohi S",
      "referenceId" : "RGD:A445188"
    }, {
      "firstName" : "S",
      "lastName" : "Saito",
      "authorRank" : 4,
      "name" : "Saito S",
      "referenceId" : "RGD:A4941"
    }, {
      "firstName" : "A",
      "lastName" : "Mirarchi",
      "authorRank" : 5,
      "name" : "Mirarchi A",
      "referenceId" : "RGD:A445189"
    }, {
      "firstName" : "H",
      "lastName" : "Spiera",
      "authorRank" : 6,
      "name" : "Spiera H",
      "referenceId" : "RGD:A445190"
    }, {
      "firstName" : "T",
      "lastName" : "Sasaki",
      "authorRank" : 7,
      "name" : "Sasaki T",
      "referenceId" : "RGD:A8065"
    }, {
      "firstName" : "O",
      "lastName" : "Shoichi",
      "authorRank" : 8,
      "name" : "Shoichi O",
      "referenceId" : "RGD:A445191"
    }, {
      "firstName" : "K",
      "lastName" : "Takeuchi",
      "authorRank" : 9,
      "name" : "Takeuchi K",
      "referenceId" : "RGD:A5272"
    }, {
      "firstName" : "J P",
      "lastName" : "Pandey",
      "authorRank" : 10,
      "name" : "Pandey JP",
      "referenceId" : "RGD:A445192"
    }, {
      "firstName" : "R M",
      "lastName" : "Silver",
      "authorRank" : 11,
      "name" : "Silver RM",
      "referenceId" : "RGD:A445193"
    }, {
      "firstName" : "C",
      "lastName" : "LeRoy",
      "authorRank" : 12,
      "name" : "LeRoy C",
      "referenceId" : "RGD:A445194"
    }, {
      "firstName" : "A E",
      "lastName" : "Postlethwaite",
      "authorRank" : 13,
      "name" : "Postlethwaite AE",
      "referenceId" : "RGD:A445195"
    }, {
      "firstName" : "C A",
      "lastName" : "Bona",
      "authorRank" : 14,
      "name" : "Bona CA",
      "referenceId" : "RGD:A445196"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12910471"
    } ]
  }, {
    "primaryId" : "PMID:10395892",
    "title" : "Initiation of translation in prokaryotes and eukaryotes.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kozak M Gene. 1999 Jul 8;234(2):187-208.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:50:03.000-05:00",
    "volume" : "234",
    "pages" : "187-208",
    "abstract" : "The mechanisms whereby ribosomes engage a messenger RNA and select the start site for translation differ between prokaryotes and eukaryotes. Initiation sites in polycistronic prokaryotic mRNAs are usually selected via base pairing with ribosomal RNA. That straightforward mechanism is made complicated and interesting by cis- and trans-acting elements employed to regulate translation. Initiation sites in eukaryotic mRNAs are reached via a scanning mechanism which predicts that translation should start at the AUG codon nearest the 5' end of the mRNA. Interest has focused on mechanisms that occasionally allow escape from this first-AUG rule. With natural mRNAs, three escape mechanisms - context-dependent leaky scanning, reinitiation, and possibly direct internal initiation - allow access to AUG codons which, although not first, are still close to the 5' end of  the mRNA. This constraint on the initiation step of translation in eukaryotes dictates the location of transcriptional promoters and may have contributed to the evolution of splicing.The binding of Met-tRNA to ribosomes is mediated by a GTP-binding protein in both prokaryotes and eukaryotes, but the more complex structure of the eukaryotic factor (eIF-2) and its association with other proteins underlie some aspects of initiation unique to eukaryotes. Modulation of  GTP hydrolysis by eIF-2 is important during the scanning phase of initiation, while modulating the release of GDP from eIF-2 is a key mechanism for regulating  translation in eukaryotes. Our understanding of how some other protein factors participate in the initiation phase of translation is in flux. Genetic tests suggest that some proteins conventionally counted as eukaryotic initiation factors may not be required for translation, while other tests have uncovered interesting new candidates. Some popular ideas about the initiation pathway are predicated on static interactions between isolated factors and mRNA. The need for functional testing of these complexes is discussed. Interspersed with these theoretical topics are some practical points concerning the interpretation of cDNA sequences and the use of in vitro translation systems. Some human diseases resulting from defects in the initiation step of translation are also discussed.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kozak",
      "authorRank" : 1,
      "name" : "Kozak M",
      "referenceId" : "RGD:A31744"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072731"
    } ]
  }, {
    "primaryId" : "PMID:10395902",
    "title" : "Molecular cloning and characterization of the rat inducible nitric oxide synthase (iNOS) gene.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Keinanen R, etal., Gene. 1999 Jul 8;234(2):297-305.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-03T20:34:08.000-05:00",
    "volume" : "234",
    "pages" : "297-305",
    "abstract" : "We have cloned and characterized the rat inducible nitric oxide synthase (iNOS) gene. It spans approx. 36kb and is divided into 27 exons and 26 introns. The distribution and length of exons are similar to those in the human iNOS gene. In  the 5' flanking regulatory region of the rat iNOS gene, there are a number of putative transcription factor binding sites (>20), many of them probably indispensable for the gene's nuclear factor kappaB (NFkappaB)-dependent induction, but also many which may have a role in its NFkappaB-independent induction pathway. These include cyclic adenosine 3', 5'-monophosphate (cAMP) response elements (CRE), hypoxia responsive element (HRE) and GATA-core elements. Rat models are powerful tools in studies of neurological diseases. Because iNOS is most likely responsible for the harmful consequences of nitric oxide (NO) in general, the cloned rat iNOS gene will further reveal the mechanisms of iNOS inducibility in different cell types during development and disease, including brain diseases, and to promote studies of pharmacological intervention in cases where extensive NO production plays a critical role.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Keinanen",
      "authorRank" : 1,
      "name" : "Keinanen",
      "referenceId" : "RGD:A358148"
    }, {
      "firstName" : "N",
      "lastName" : "Vartiainen",
      "authorRank" : 2,
      "name" : "Vartiainen",
      "referenceId" : "RGD:A358149"
    }, {
      "firstName" : "J",
      "lastName" : "Koistinaho",
      "authorRank" : 3,
      "name" : "Koistinaho J",
      "referenceId" : "RGD:A27256"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11522263"
    } ]
  }, {
    "primaryId" : "PMID:10395927",
    "title" : "Interferon regulatory factor 1 tryptophan 11 to arginine point mutation abolishes DNA binding.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Eason DD, etal., Biochim Biophys Acta. 1999 Jul 7;1446(1-2):140-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-26T08:46:16.000-06:00",
    "volume" : "1446",
    "pages" : "140-4",
    "abstract" : "Interferon regulatory factor-1 (IRF-1) is a transcriptional activator of genes induced by a variety of cytokines and growth factors. Defects in IRF-1 occur frequently in human cancers and may contribute to tumorigenesis. The IRF family of transcription factors share invariant tryptophan residues that have been proposed to function by orienting the DNA contacting residues of IRF-1 with the DNA core sequence of the IRF element. Here we describe a point mutation in IRF-1 that converts the tryptophan at codon 11 to arginine (W11R). The IRF-1 (W11R) mutation abolishes IRF-1 DNA binding and transactivating activities demonstrating the critical role of this invariant tryptophan in IRF-1 function.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DD",
      "lastName" : "Eason",
      "authorRank" : 1,
      "name" : "Eason DD",
      "referenceId" : "RGD:A75885"
    }, {
      "firstName" : "AT",
      "lastName" : "Shepherd",
      "authorRank" : 2,
      "name" : "Shepherd AT",
      "referenceId" : "RGD:A75886"
    }, {
      "firstName" : "G",
      "lastName" : "Blanck",
      "authorRank" : 3,
      "name" : "Blanck G",
      "referenceId" : "RGD:A75887"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600014"
    } ]
  }, {
    "primaryId" : "PMID:10395931",
    "title" : "Identification, cloning and analysis of expression of a new alternatively spliced form of the metabotropic glutamate receptor mGluR1 mRNA1.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Soloviev MM, etal., Biochim Biophys Acta 1999 Jul 7;1446(1-2):161-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:41.000-05:00",
    "volume" : "1446",
    "pages" : "161-6",
    "abstract" : "We have applied quantitative RT-PCR analysis to characterise relative levels of expression of the alternatively spliced mGluR1 mRNAs. This has also allowed us to identify and clone a new alternatively spliced form of the mGluR1 mRNA. The newly identified mGluR1f mRNA is expressed at moderate levels in rat brain, reaching its maximum in cortex. mGluR1f differs from the mGluR1a mRNA by deletion of a 35-bp fragment of the mGluR1a/alpha coding sequence and insertion of an 85-bp fragment, found only in mGluR1b/beta mRNA.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Soloviev",
      "authorRank" : 1,
      "name" : "Soloviev MM",
      "referenceId" : "RGD:A27198"
    }, {
      "firstName" : "F",
      "lastName" : "Ciruela",
      "authorRank" : 2,
      "name" : "Ciruela F",
      "referenceId" : "RGD:A12347"
    }, {
      "firstName" : "WY",
      "lastName" : "Chan",
      "authorRank" : 3,
      "name" : "Chan WY",
      "referenceId" : "RGD:A16895"
    }, {
      "firstName" : "RA",
      "lastName" : "McIlhinney",
      "authorRank" : 4,
      "name" : "McIlhinney RA",
      "referenceId" : "RGD:A27199"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727274"
    } ]
  }, {
    "primaryId" : "PMID:10395942",
    "title" : "Retinoic acid repressed the expression of c-fos and c-jun and induced apoptosis in regenerating rat liver after partial hepatectomy.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Ozeki A and Tsukamoto I, Biochim Biophys Acta. 1999 Jul 8;1450(3):308-19.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-06-21T14:36:58.000-05:00",
    "volume" : "1450",
    "pages" : "308-19",
    "abstract" : "Retinoic acid (RA), which was injected within 4 h after partial hepatectomy (PH), inhibited DNA synthesis in regenerating liver. The inhibition was accompanied by apoptosis, evidenced by in situ end labeling and gel electrophoresis of DNA fragmentation. Characteristic DNA fragmentation was obvious at 4 h and reached a maximum at 8 h after injection. Northern blot analysis revealed that RA repressed the expression of c-fos and c-jun at 15 and 30 min with the up-regulation of retinoic acid receptor gamma (RARgamma) and RARbeta at 2 h after PH. The transglutaminase II mRNA level and activity were increased by RA injection at 4 h and 8 h after PH, respectively. The mRNA levels of thymidylate synthase and thymidine kinase, which are rate determining enzymes of DNA synthesis, decreased in RA injected rats. No change was seen in the expression of p53 and p21WAF1/CIP1 which have been suggested to participate in the apoptosis process. These results suggest that RA exerts the antiproliferative activity only on the early stage of liver regeneration accompanied by the repression of c-fos and c-jun expression and induction of apoptosis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Ozeki",
      "authorRank" : 1,
      "name" : "Ozeki A",
      "referenceId" : "RGD:A140850"
    }, {
      "firstName" : "I",
      "lastName" : "Tsukamoto",
      "authorRank" : 2,
      "name" : "Tsukamoto I",
      "referenceId" : "RGD:A10332"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5133444"
    } ]
  }, {
    "primaryId" : "PMID:10395949",
    "title" : "Possible mechanism for the decrease of mitochondrial aspartate aminotransferase activity in ischemic and hypoxic rat retinas.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Endo S, etal., Biochim Biophys Acta. 1999 Jul 8;1450(3):385-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-01-31T16:42:18.000-06:00",
    "volume" : "1450",
    "pages" : "385-96",
    "abstract" : "Glutamate is believed to be an excitatory amino acid neurotransmitter in the retina. Enzymes for glutamate metabolism, such as glutamate dehydrogenase, ornithine aminotransferase, glutaminase, and aspartate aminotransferase (AAT), exist mainly in the mitochondria. The abnormal increase of intracellular calcium ions in ischemic retinal cells may cause an influx of calcium ions into the mitochondria, subsequently affecting various mitochondrial enzyme activities through the activity of mitochondrial calpain. As AAT has the highest level of activity among enzymes involved in glutamate metabolism, we investigated the change of AAT activity in ischemic and hypoxic rat retinas and the protection against such activity by calpain inhibitors. We used normal RCS (rdy+/rdy+) rats. For the in vivo studies, we clamped the optic nerve of anesthetized rats to induce ischemia. In the in vitro studies, the eye cups were incubated with Locke's solution saturated with 95% N2/5% CO2. The activity of cytosolic AAT (cAAT) was about 20% of total activity, whereas mitochondrial AAT (mAAT) was about 75% in rat retina. Ninety minutes of ischemia or hypoxia caused a 20% decrease in mAAT activity, whereas cAAT activity remained unchanged. To examine the contribution of intracellular calcium ions to the degradation of mAAT, we used Ca2+-free Locke's solution containing 1 mM EGTA, ryanodine (Ca2+ channel blocker), and thapsigargin (Ca2+-ATPase inhibitor). In the present study, thapsigargin in Ca2+-free Locke's solution, but not ryanodine in this solution, was found to prevent AAT degradation. AAT degradation was also prevented by calpain inhibitors (Ca2+-dependent protease inhibitor) such as calpeptin at 1 nM, 10 nM, 0.1 microM, 1 microM and 10 microM, and by calpain inhibitor peptide, but not by other protease inhibitors (10 microM leupeptin, pepstatin, chymostatin). Additionally, we determined the subcellular localization of calpain activity and examined the change of calpain activity in ischemic rat retinas. Our results suggest that decreased activity of mAAT in ischemic and hypoxic rat retinas might be evoked by the degradation by calpain-catalyzed proteolysis in mitochondria.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Endo",
      "authorRank" : 1,
      "name" : "Endo S",
      "referenceId" : "RGD:A18754"
    }, {
      "firstName" : "S",
      "lastName" : "Ishiguro",
      "authorRank" : 2,
      "name" : "Ishiguro S",
      "referenceId" : "RGD:A67379"
    }, {
      "firstName" : "M",
      "lastName" : "Tamai",
      "authorRank" : 3,
      "name" : "Tamai M",
      "referenceId" : "RGD:A25202"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289395"
    } ]
  }, {
    "primaryId" : "PMID:10396627",
    "title" : "Photoreceptor function of retinal transplants implicated by light-dark shift of S-antigen and rod transducin.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Seiler MJ, etal., Vision Res. 1999 Jul;39(15):2589-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-09-12T15:54:20.000-05:00",
    "volume" : "39",
    "pages" : "2589-96",
    "abstract" : "The aim was to demonstrate functional properties of transplanted histologically normal photoreceptors. Subretinal intact-sheet transplants of fetal E17-E20 rat retinas to light-damaged albino rat eyes were fixed in light or dark, 2 to 42 weeks after transplantation, and stained immunohistochemically for certain phototransduction proteins. In light adapted transplants, transducin was predominantly found in inner segments of parallel-organized photoreceptors. Transducin shifted to the outer segments with dark-adaptation. S-antigen distribution was opposite to transducin. Rhodopsin distribution did not change. The shift of signal transduction proteins correlated to the light conditions indicates that normal phototransduction processes were established in photoreceptors of transplanted retinal sheets.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MJ",
      "lastName" : "Seiler",
      "authorRank" : 1,
      "name" : "Seiler MJ",
      "referenceId" : "RGD:A158011"
    }, {
      "firstName" : "RB",
      "lastName" : "Aramant",
      "authorRank" : 2,
      "name" : "Aramant RB",
      "referenceId" : "RGD:A158012"
    }, {
      "firstName" : "SL",
      "lastName" : "Ball",
      "authorRank" : 3,
      "name" : "Ball SL",
      "referenceId" : "RGD:A144284"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6893629"
    } ]
  }, {
    "primaryId" : "PMID:10397680",
    "title" : "Versican/PG-M isoforms in vascular smooth muscle cells.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Lemire JM, etal., Arterioscler Thromb Vasc Biol 1999 Jul;19(7):1630-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:51:34.000-05:00",
    "volume" : "19",
    "pages" : "1630-9",
    "abstract" : "The expression of increased amounts of proteoglycans in the extracellular matrix may play a role in vascular stenosis and lipid retention. The large chondroitin sulfate proteoglycan versican is synthesized by vascular smooth muscle cells (SMCs), accumulates during human atherosclerosis and restenosis, and has been shown to bind LDLs. We recently demonstrated that adult rat aortic SMCs express several versican mRNAs. Four versican splice variants, V0, V1, V2, and V3, have recently been described, which differ dramatically in length. These variants differ in the extent of modification by glycosaminoglycan chains, and V3 may lack glycosaminoglycan chains. In this study, we characterized versican RNAs from rat SMCs by cloning, sequencing, and hybridization with domain-specific probes. DNA sequence was obtained for the V3 isoform, and for a truncated V0 isoform. By hybridization of polyadenylated RNA with domain-specific probes, we determined that the V0, V1, and V3 isoforms are present in vascular SMCs. We confirmed the presence of the V3 isoform in polyadenylated RNA and in RT-PCR products by hybridization with an oligonucleotide that spans the splice junction between the hyaluronan-binding domain and the epidermal growth factor-like domain. In addition, a novel splice variant was cloned by PCR amplification from both rat and human SMC RNA. This appears to be an incompletely spliced variant, retaining the final intron. PCR analysis shows that this intron can be retained in both V1 and V3 isoforms. The predicted translation product of this variant would have a different carboxy-terminus than previously described versican isoforms.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Lemire",
      "authorRank" : 1,
      "name" : "Lemire JM",
      "referenceId" : "RGD:A15823"
    }, {
      "firstName" : "KR",
      "lastName" : "Braun",
      "authorRank" : 2,
      "name" : "Braun KR",
      "referenceId" : "RGD:A17904"
    }, {
      "firstName" : "P",
      "lastName" : "Maurel",
      "authorRank" : 3,
      "name" : "Maurel P",
      "referenceId" : "RGD:A105329"
    }, {
      "firstName" : "ED",
      "lastName" : "Kaplan",
      "authorRank" : 4,
      "name" : "Kaplan ED",
      "referenceId" : "RGD:A17906"
    }, {
      "firstName" : "SM",
      "lastName" : "Schwartz",
      "authorRank" : 5,
      "name" : "Schwartz SM",
      "referenceId" : "RGD:A15824"
    }, {
      "firstName" : "TN",
      "lastName" : "Wight",
      "authorRank" : 6,
      "name" : "Wight TN",
      "referenceId" : "RGD:A17907"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632588"
    } ]
  }, {
    "primaryId" : "PMID:10397765",
    "title" : "Functional and biochemical analysis of the C2 domains of synaptotagmin IV.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Thomas DM, etal., Mol Biol Cell. 1999 Jul;10(7):2285-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-09-21T00:02:06.000-05:00",
    "volume" : "10",
    "pages" : "2285-95",
    "abstract" : "Synaptotagmins (Syts) are a family of vesicle proteins that have been implicated  in both regulated neurosecretion and general membrane trafficking. Calcium-dependent interactions mediated through their C2 domains are proposed to  contribute to the mechanism by which Syts trigger calcium-dependent neurotransmitter release. Syt IV is a novel member of the Syt family that is induced by cell depolarization and has a rapid rate of synthesis and a short half-life. Moreover, the C2A domain of Syt IV does not bind calcium. We have examined the biochemical and functional properties of the C2 domains of Syt IV. Consistent with its non-calcium binding properties, the C2A domain of Syt IV binds syntaxin isoforms in a calcium-independent manner. In neuroendocrine pheochromocytoma (PC12) cells, Syt IV colocalizes with Syt I in the tips of the neurites. Microinjection of the C2A domain reveals that calcium-independent interactions mediated through this domain of Syt IV inhibit calcium-mediated neurotransmitter release from PC12 cells. Conversely, the C2B domain of Syt IV contains calcium binding properties, which permit homo-oligomerization as well as hetero-oligomerization with Syt I. Our observation that different combinatorial interactions exist between Syt and syntaxin isoforms, coupled with the calcium stimulated hetero-oligomerization of Syt isoforms, suggests that the secretory machinery contains a vast repertoire of biochemical properties for sensing calcium and regulating neurotransmitter release accordingly.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DM",
      "lastName" : "Thomas",
      "authorRank" : 1,
      "name" : "Thomas",
      "referenceId" : "RGD:A320094"
    }, {
      "firstName" : "GD",
      "lastName" : "Ferguson",
      "authorRank" : 2,
      "name" : "Ferguson",
      "referenceId" : "RGD:A384534"
    }, {
      "firstName" : "HR",
      "lastName" : "Herschman",
      "authorRank" : 3,
      "name" : "Herschman",
      "referenceId" : "RGD:A384573"
    }, {
      "firstName" : "LA",
      "lastName" : "Elferink",
      "authorRank" : 4,
      "name" : "Elferink LA",
      "referenceId" : "RGD:A5179"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11535116"
    } ]
  }, {
    "primaryId" : "PMID:10398137",
    "title" : "Expression of MUC1 and MUC2 mucin core proteins and their messenger RNA in gall bladder carcinoma: an immunohistochemical and in situ hybridization study.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Yamato T, etal., J Pathol. 1999 May;188(1):30-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-05-13T14:30:42.000-05:00",
    "volume" : "188",
    "pages" : "30-7",
    "abstract" : "Expression of mucin core protein MUC1 and MUC2 was examined at the protein and mRNA level in 55 cases of carcinoma and 20 of dysplasia, and in 15 non-dysplastic epithelia of the gall bladder. In non-dysplastic epithelium, MUC1 protein was not expressed, while in dysplasia, MUC1 was focally expressed in ten cases, particularly in those associated with carcinoma. In carcinoma, MUC1 was expressed heterogeneously, and the frequency and extent of MUC1 expression increased with histological dedifferentiation. MUC1 was found on the apical cell surface and also in the cytoplasm in well- and moderately-differentiated carcinoma, and on the cell border in poorly-differentiated cases. In infiltrative regions, MUC1 expression was more predominant and MUC1 frequently leaked outside the foci of carcinoma. By contrast, MUC2 was focally expressed in non-dysplastic as well as in dysplastic epithelia and more frequently in well-differentiated adenocarcinoma. MUC2-positive cells resembled goblet cells, whether in non-dysplastic epithelium, dysplasia or carcinoma. Cell proliferative activity was higher in MUC1-positive than in MUC1-negative carcinoma cells. Distributions of MUC1 and MUC2 mRNA signals and of MUC1 and MUC2 proteins were similar in carcinoma and dysplasia. These results suggest that MUC1 expression by gall bladder carcinoma may reflect histological dedifferentiation, increased proliferative activity, and invasiveness, while MUC2 expression is related to lower proliferative activity and reflects some differentiation towards goblet cells; and that MUC1 expression in gall bladder dysplasia reflects malignant transformation.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Yamato",
      "authorRank" : 1,
      "name" : "Yamato T",
      "referenceId" : "RGD:A123089"
    }, {
      "firstName" : "M",
      "lastName" : "Sasaki",
      "authorRank" : 2,
      "name" : "Sasaki M",
      "referenceId" : "RGD:A135678"
    }, {
      "firstName" : "Y",
      "lastName" : "Watanabe",
      "authorRank" : 3,
      "name" : "Watanabe Y",
      "referenceId" : "RGD:A162467"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakanuma",
      "authorRank" : 4,
      "name" : "Nakanuma Y",
      "referenceId" : "RGD:A68288"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2324857"
    } ]
  }, {
    "primaryId" : "PMID:10398147",
    "title" : "L-selectin and its ligands mediate infiltration of mononuclear cells into kidney interstitium after ureteric obstruction.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Shikata K, etal., J Pathol. 1999 May;188(1):93-9. doi: 10.1002/(SICI)1096-9896(199905)188:1<93::AID-PATH305>3.0.CO;2-#.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-01-16T14:53:06.000-06:00",
    "volume" : "188",
    "pages" : "93-9",
    "abstract" : "It was previously reported that the L-selectin ligands detected by a rat L-selectin and human IgG chimeric molecule (rLEC-IgG) are expressed in the distal tubules of the kidney, where no leukocyte traffic is seen under physiological conditions. In the present study, the role of L-selectin ligands in leukocyte infiltration into the kidney interstitium was investigated using a rat ureteric obstruction model. After ligation of the ureter, ligands for L-selectin rapidly disappeared from tubular epithelial cells and were relocated to the interstitium and peritubular capillary walls, where infiltration of monocytes and CD8(+) T cells subsequently occurred. Mononuclear cell infiltration was significantly inhibited by intravenous injection of a neutralizing monoclonal antibody (MAb) against L-selectin, indicating the possible involvement of an L-selectin-mediated pathway. Interestingly, immunohistochemical studies with a MAb against sulphatide showed that the distribution of sulphatide, known to be one of the candidates of L-selectin ligand, was almost indistinguishable from the staining pattern of rLEC-IgG in both normal and ureteric obstructed kidneys, suggesting that sulphatide and/or related molecule(s) relocated to the renal interstitium were recognized by leukocyte L-selectin, leading to interstitial leukocyte infiltration. In line with this notion, intravenous injection of sulphatide markedly inhibited leukocyte infiltration, suggesting that L-selectin-sulphatide interaction may play a pivotal role in interstitial leukocyte infiltration in the kidney following ureteric obstruction.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Shikata",
      "authorRank" : 1,
      "name" : "Shikata K",
      "referenceId" : "RGD:A34042"
    }, {
      "firstName" : "Y",
      "lastName" : "Suzuki",
      "authorRank" : 2,
      "name" : "Suzuki Y",
      "referenceId" : "RGD:A161488"
    }, {
      "firstName" : "J",
      "lastName" : "Wada",
      "authorRank" : 3,
      "name" : "Wada J",
      "referenceId" : "RGD:A15598"
    }, {
      "firstName" : "K",
      "lastName" : "Hirata",
      "authorRank" : 4,
      "name" : "Hirata K",
      "referenceId" : "RGD:A32364"
    }, {
      "firstName" : "M",
      "lastName" : "Matsuda",
      "authorRank" : 5,
      "name" : "Matsuda M",
      "referenceId" : "RGD:A17185"
    }, {
      "firstName" : "H",
      "lastName" : "Kawashima",
      "authorRank" : 6,
      "name" : "Kawashima H",
      "referenceId" : "RGD:A14272"
    }, {
      "firstName" : "T",
      "lastName" : "Suzuki",
      "authorRank" : 7,
      "name" : "Suzuki T",
      "referenceId" : "RGD:A4733"
    }, {
      "firstName" : "M",
      "lastName" : "Iizuka",
      "authorRank" : 8,
      "name" : "Iizuka M",
      "referenceId" : "RGD:A31368"
    }, {
      "firstName" : "H",
      "lastName" : "Makino",
      "authorRank" : 9,
      "name" : "Makino H",
      "referenceId" : "RGD:A160891"
    }, {
      "firstName" : "M",
      "lastName" : "Miyasaka",
      "authorRank" : 10,
      "name" : "Miyasaka M",
      "referenceId" : "RGD:A159147"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:597015755"
    } ]
  }, {
    "primaryId" : "PMID:10398149",
    "title" : "Effects of in vivo administration of anti-B7-1/B7-2 monoclonal antibodies on the survival of mice with chronic ongoing myocarditis caused by Coxsackievirus B3.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Seko Y, etal., J Pathol. 1999 May;188(1):107-12. doi: 10.1002/(SICI)1096-9896(199905)188:1<107::AID-PATH319>3.0.CO;2-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-23T16:54:53.000-05:00",
    "volume" : "188",
    "pages" : "107-12",
    "abstract" : "In acute myocarditis and dilated cardiomyopathy, it has previously been reported that antigen-specific T-cells infiltrate the heart and play an important role in the myocardial damage involved. For antigen-specific T-cell activation to occur, it is necessary for the T-cell to receive co-stimulatory signals provided by co-stimulatory molecules expressed on the antigen-presenting cell (APC), as well as the main signal provided by binding of the T-cell receptor (TCR) to the antigen. To investigate the roles for the co-stimulatory molecules B7-1 and B7-2 in the development of chronic ongoing viral myocarditis, firstly the expression of B7-1/B7-2 was analysed in the hearts of A/J mice with myocarditis induced by Coxsackievirus B3 (CVB3). Secondly the induction of B7-1/B7-2 on cultured cardiac myocytes treated with interferon (IFN)-gamma was evaluated. Thirdly the effects of the in vivo administration of anti-B7-1/B7-2 monoclonal antibodies (MAbs) on the survival of mice with viral myocarditis were examined. CVB3-induced myocarditis resulted in enhanced expression of B7-1/B7-2 on cardiac myocytes. The expression of B7-1/B7-2 on cardiac myocytes could be induced by IFN-gamma in vitro. In vivo anti-B7-1 MAb treatment significantly prolonged the survival of mice with myocarditis, whereas anti-B7-2 MAb treatment abrogated the protective effect of anti-B7-1. These findings indicate that distinct roles for B7-1 and B7-2 antigens are involved in the development of viral myocarditis and raise the possibility of immunotherapy with anti-B7-1 MAb to prevent T-cell-mediated cardiac myocyte injury and to improve the prognosis of viral myocarditis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Seko",
      "authorRank" : 1,
      "name" : "Seko Y",
      "referenceId" : "RGD:A63525"
    }, {
      "firstName" : "N",
      "lastName" : "Takahashi",
      "authorRank" : 2,
      "name" : "Takahashi N",
      "referenceId" : "RGD:A16701"
    }, {
      "firstName" : "H",
      "lastName" : "Yagita",
      "authorRank" : 3,
      "name" : "Yagita H",
      "referenceId" : "RGD:A17485"
    }, {
      "firstName" : "K",
      "lastName" : "Okumura",
      "authorRank" : 4,
      "name" : "Okumura K",
      "referenceId" : "RGD:A11657"
    }, {
      "firstName" : "M",
      "lastName" : "Azuma",
      "authorRank" : 5,
      "name" : "Azuma M",
      "referenceId" : "RGD:A5699"
    }, {
      "firstName" : "Y",
      "lastName" : "Yazaki",
      "authorRank" : 6,
      "name" : "Yazaki Y",
      "referenceId" : "RGD:A161904"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702899"
    } ]
  }, {
    "primaryId" : "PMID:10398166",
    "title" : "In vivo expression of soluble Fas and FAP-1: possible mechanisms of Fas resistance in human hepatoblastomas.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Lee SH, etal., J Pathol. 1999 Jun;188(2):207-12. doi: 10.1002/(SICI)1096-9896(199906)188:2<207::AID-PATH337>3.0.CO;2-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-08-12T10:57:49.000-05:00",
    "volume" : "188",
    "pages" : "207-12",
    "abstract" : "Many tumour cells express both Fas and its ligand (FasL) on their surface and it has remained a mystery why such cells do not simply kill themselves. It remains to be determined whether Fas and FasL are expressed in human hepatoblastomas and if so, what is responsible for the possible Fas resistance of these tumours. In this study, the expression of Fas and FasL was examined in 23 cases of human hepatoblastoma by immunohistochemical staining. To elucidate possible Fas resistance in hepatoblastomas, Fas-resistance pathways including the expression of bcl-2 and Fas-associated phosphatase-1 (FAP-1), and the expression of soluble Fas (sFas) mRNA, were analysed by immunohistochemistry and in situ reverse transcription-polymerase chain reaction (in situ RT-PCR). Fas gene mutation in the death domain was also examined. Fas and FasL were expressed in all hepatoblastomas analysed. Twenty (87 per cent) and 18 (78 per cent) cases of hepatoblastoma were positive for sFas mRNA and FAP-1, respectively, but none of the hepatoblastomas expressed bcl-2. Mutation in the death domain of the Fas gene was not found in hepatoblastomas. Taken together, these findings demonstrated that Fas, a death receptor, and its ligand are co-expressed in hepatoblastomas in vivo, but some inhibitors of Fas-mediated apoptosis are also expressed in these tumours. These results suggest that it is probably due to the action of inhibitory molecules of the Fas pathway that the tumour cells of hepatoblastomas do not kill themselves in an autocrine-driven cycle and that in this manner hepatoblastomas avoid apoptosis.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S H",
      "lastName" : "Lee",
      "authorRank" : 1,
      "name" : "Lee SH",
      "referenceId" : "RGD:A449607"
    }, {
      "firstName" : "M S",
      "lastName" : "Shin",
      "authorRank" : 2,
      "name" : "Shin MS",
      "referenceId" : "RGD:A472484"
    }, {
      "firstName" : "J Y",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee JY",
      "referenceId" : "RGD:A472497"
    }, {
      "firstName" : "W S",
      "lastName" : "Park",
      "authorRank" : 4,
      "name" : "Park WS",
      "referenceId" : "RGD:A472493"
    }, {
      "firstName" : "S Y",
      "lastName" : "Kim",
      "authorRank" : 5,
      "name" : "Kim SY",
      "referenceId" : "RGD:A472489"
    }, {
      "firstName" : "J J",
      "lastName" : "Jang",
      "authorRank" : 6,
      "name" : "Jang JJ",
      "referenceId" : "RGD:A472490"
    }, {
      "firstName" : "S M",
      "lastName" : "Dong",
      "authorRank" : 7,
      "name" : "Dong SM",
      "referenceId" : "RGD:A472540"
    }, {
      "firstName" : "E Y",
      "lastName" : "Na",
      "authorRank" : 8,
      "name" : "Na EY",
      "referenceId" : "RGD:A472541"
    }, {
      "firstName" : "C S",
      "lastName" : "Kim",
      "authorRank" : 9,
      "name" : "Kim CS",
      "referenceId" : "RGD:A472542"
    }, {
      "firstName" : "S H",
      "lastName" : "Kim",
      "authorRank" : 10,
      "name" : "Kim SH",
      "referenceId" : "RGD:A466968"
    }, {
      "firstName" : "N J",
      "lastName" : "Yoo",
      "authorRank" : 11,
      "name" : "Yoo NJ",
      "referenceId" : "RGD:A449606"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14700699"
    } ]
  }, {
    "primaryId" : "PMID:10398235",
    "title" : "X-linked mental retardation syndrome with short stature, small hands and feet, seizures, cleft palate, and glaucoma is linked to Xq28.",
    "datePublished" : "1999-07-30T00:00:00.000-05:00",
    "citation" : "Armfield K, etal., Am J Med Genet. 1999 Jul 30;85(3):236-42. doi: 10.1002/(sici)1096-8628(19990730)85:3<236::aid-ajmg10>3.0.co;2-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:25:05.000-05:00",
    "volume" : "85",
    "pages" : "236-42",
    "abstract" : "Of the gene-rich regions of the human genome, Xq28 is the most densely mapped. Mutations of genes in this band are responsible for 10 syndromal forms of mental retardation and 5 nonsyndromal forms. Clinical and molecular studies reported here add an additional syndromic form of X-linked mental retardation (XLMR) to this region. The condition comprises short stature, small hands and feet, seizures, cleft palate, and glaucoma. One affected male died at age 19 years in status epilepticus, but others have survived to old age. Carrier females do not have somatic anomalies or mental impairment. The gene is localized to the terminal 8 Mb of Xq28 with markers distal to DXS8011 showing linkage to the disorder with a lod score of 2.11 at zero recombination.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Armfield",
      "authorRank" : 1,
      "name" : "Armfield K",
      "referenceId" : "RGD:A602323"
    }, {
      "firstName" : "R",
      "lastName" : "Nelson",
      "authorRank" : 2,
      "name" : "Nelson R",
      "referenceId" : "RGD:A146561"
    }, {
      "firstName" : "H A",
      "lastName" : "Lubs",
      "authorRank" : 3,
      "name" : "Lubs HA",
      "referenceId" : "RGD:A573904"
    }, {
      "firstName" : "B",
      "lastName" : "Häne",
      "authorRank" : 4,
      "name" : "Häne B",
      "referenceId" : "RGD:A602324"
    }, {
      "firstName" : "R J",
      "lastName" : "Schroer",
      "authorRank" : 5,
      "name" : "Schroer RJ",
      "referenceId" : "RGD:A602325"
    }, {
      "firstName" : "F",
      "lastName" : "Arena",
      "authorRank" : 6,
      "name" : "Arena F",
      "referenceId" : "RGD:A595704"
    }, {
      "firstName" : "C E",
      "lastName" : "Schwartz",
      "authorRank" : 7,
      "name" : "Schwartz CE",
      "referenceId" : "RGD:A498389"
    }, {
      "firstName" : "R E",
      "lastName" : "Stevenson",
      "authorRank" : 8,
      "name" : "Stevenson RE",
      "referenceId" : "RGD:A573905"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119830"
    } ]
  }, {
    "primaryId" : "PMID:10398271",
    "title" : "Ventricular noncompaction and distal chromosome 5q deletion.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Pauli RM, etal., Am J Med Genet 1999 Aug 6;85(4):419-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T16:08:31.000-06:00",
    "volume" : "85",
    "pages" : "419-23",
    "abstract" : "We describe a 7 1/2-year-old girl with mildly unusual phenotype and complex heart disease including ventricular myocardial noncompaction. She was found to have a distal 5q deletion, del(5)(q35.1q35.3). Fluorescent in situ hybridization showed that this deletion included the locus for the cardiac specific homeobox gene, CSX. This suggests that some instances of ventricular myocardial noncompaction may be caused by haploinsufficiency of CSX.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RM",
      "lastName" : "Pauli",
      "authorRank" : 1,
      "name" : "Pauli RM",
      "referenceId" : "RGD:A37627"
    }, {
      "firstName" : "S",
      "lastName" : "Scheib-Wixted",
      "authorRank" : 2,
      "name" : "Scheib-Wixted S",
      "referenceId" : "RGD:A37628"
    }, {
      "firstName" : "L",
      "lastName" : "Cripe",
      "authorRank" : 3,
      "name" : "Cripe L",
      "referenceId" : "RGD:A37629"
    }, {
      "firstName" : "S",
      "lastName" : "Izumo",
      "authorRank" : 4,
      "name" : "Izumo S",
      "referenceId" : "RGD:A14245"
    }, {
      "firstName" : "GS",
      "lastName" : "Sekhon",
      "authorRank" : 5,
      "name" : "Sekhon GS",
      "referenceId" : "RGD:A37630"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734845"
    } ]
  }, {
    "primaryId" : "PMID:10398279",
    "title" : "Common mutations in BRCA1 and BRCA2 do not contribute to early prostate cancer in Jewish men.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Nastiuk KL, etal., Prostate 1999 Aug 1;40(3):172-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:44:51.000-06:00",
    "volume" : "40",
    "pages" : "172-7",
    "abstract" : "BACKGROUND: Families with a high incidence of hereditary breast cancer, and subsequently shown to have terminating mutations in BRCA1 or BRCA2, appear to have a higher incidence of prostate cancer among male relatives. We aimed to determine whether the common germline mutations of BRCA1 or BRCA2 in Ashkenazi Jewish men predisposed them to prostate cancer. METHODS: We examined genomic DNA from 83 (for BRCA1 185delAG) or 82 (for BRCA2 6174delT) Ashkenazi Jewish prostate cancer patients, most of whom were treated at a relatively young age, for the most common germline mutation in each gene seen in the Ashkenazi population. RESULTS: Our study should have been able to detect a 4-5-fold increase in the risk of prostate cancer due to mutation of BRCA1 or BRCA2. However, only one (1.15%; 95% confidence interval, 0-3.6%) of the patients was heterozygous for the BRCA1 mutant allele, and only two were heterozygous for the BRCA2 mutation (2.4%; 95% confidence interval, 0-6.2%). CONCLUSIONS: The incidence of each of the germline mutations in these prostate cancer patients closely matched their incidence (about 1%) in the general Ashkenazi Jewish population. This suggests that unlike cases of breast and ovarian cancers, mutations in BRCA1 or BRCA2 do not significantly predispose men to prostate cancer.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KL",
      "lastName" : "Nastiuk",
      "authorRank" : 1,
      "name" : "Nastiuk KL",
      "referenceId" : "RGD:A36508"
    }, {
      "firstName" : "M",
      "lastName" : "Mansukhani",
      "authorRank" : 2,
      "name" : "Mansukhani M",
      "referenceId" : "RGD:A36509"
    }, {
      "firstName" : "MB",
      "lastName" : "Terry",
      "authorRank" : 3,
      "name" : "Terry MB",
      "referenceId" : "RGD:A36510"
    }, {
      "firstName" : "P",
      "lastName" : "Kularatne",
      "authorRank" : 4,
      "name" : "Kularatne P",
      "referenceId" : "RGD:A36511"
    }, {
      "firstName" : "MA",
      "lastName" : "Rubin",
      "authorRank" : 5,
      "name" : "Rubin MA",
      "referenceId" : "RGD:A36512"
    }, {
      "firstName" : "J",
      "lastName" : "Melamed",
      "authorRank" : 6,
      "name" : "Melamed J",
      "referenceId" : "RGD:A36513"
    }, {
      "firstName" : "MD",
      "lastName" : "Gammon",
      "authorRank" : 7,
      "name" : "Gammon MD",
      "referenceId" : "RGD:A36514"
    }, {
      "firstName" : "M",
      "lastName" : "Ittmann",
      "authorRank" : 8,
      "name" : "Ittmann M",
      "referenceId" : "RGD:A36515"
    }, {
      "firstName" : "JJ",
      "lastName" : "Krolewski",
      "authorRank" : 9,
      "name" : "Krolewski JJ",
      "referenceId" : "RGD:A36516"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734657"
    } ]
  }, {
    "primaryId" : "PMID:10398295",
    "title" : "Platelet-activating factor (PAF) acetylhydrolase activity, LIS1 expression, and seizures.",
    "datePublished" : "1999-07-15T00:00:00.000-05:00",
    "citation" : "Shmueli O, etal., J Neurosci Res. 1999 Jul 15;57(2):176-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-02-23T09:38:40.000-06:00",
    "volume" : "57",
    "pages" : "176-84",
    "abstract" : "Lissencephaly patients are born with severe brain malformations and suffer from recurrent seizures. LIS1, the gene mutated in isolated lissencephaly patients, is a subunit of the heterotrimeric cytosolic enzyme platelet-activating factor acetylhydrolase (PAF-AH), interacts with tubulin, and affects microtubule dynamics. In order to gain molecular insights into the possible involvement of LIS1 in seizures in lissencephaly patients, we induced seizures in rats by injection of kainate. PAF-AH activity was markedly reduced as early as 30 min following initiation of seizures, making this parameter a sensitive indicator of seizure events. PAF-AH activity returned to and surpassed control values 1 week following initiation of seizures. Expression of LIS1 in the dentate gyrus changed significantly in a manner similar to that of PAF-AH enzymatic activity. This is the first correlation found between LIS1 expression and PAF-AH activity. Furthermore, the expression of the alpha2 catalytic subunit, which is the major PAF-AH catalytic subunit in rat adult brain, changed in a dramatic fashion. An additional higher-mobility LIS1 cross-reactive band was detected in samples isolated a week following seizure occurrence. This LIS1 isoform was enriched in the microtubule-associated fraction. We propose that LIS1 expression is an important factor in regulation of PAF-AH activity. We postulate that reductions in LIS1 protein levels found in lissencephaly patients may render them more susceptible to seizures.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Shmueli",
      "authorRank" : 1,
      "name" : "Shmueli O",
      "referenceId" : "RGD:A439516"
    }, {
      "firstName" : "A",
      "lastName" : "Cahana",
      "authorRank" : 2,
      "name" : "Cahana A",
      "referenceId" : "RGD:A439517"
    }, {
      "firstName" : "O",
      "lastName" : "Reiner",
      "authorRank" : 3,
      "name" : "Reiner O",
      "referenceId" : "RGD:A125860"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12790965"
    } ]
  }, {
    "primaryId" : "PMID:10398436",
    "title" : "Beta-catenin accumulation and mutation of the CTNNB1 gene in hepatoblastoma.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Bläker H, etal., Genes Chromosomes Cancer. 1999 Aug;25(4):399-402.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-05-28T11:01:20.000-05:00",
    "volume" : "25",
    "pages" : "399-402",
    "abstract" : "Hepatoblastoma is a rare malignant tumor of the liver that occurs in children at an average age of 2 to 3 years. Epidemiologic studies have shown an increased frequency of this tumor type in families affected by adenomatous polyposis coli. In addition to the epidemiologic data, molecular genetic studies suggest that inactivation of the APC tumor suppressor may be involved in hepatoblastoma tumorigenesis. A major function of APC is the downregulation of beta-catenin, a transcription-activating protein with oncogenic potential. In an ongoing immunohistochemical study of beta-catenin expression in sporadic cases of tumor types that are associated with adenomatous polyposis coli, we observed increased beta-catenin levels in the cytoplasm and in the nuclei of three investigated hepatoblastomas. Sequencing of exon 3 of the beta-catenin gene (CTNNB1) revealed an activating mutation in one of the tumor samples. Our data indicate for the first time that beta-catenin accumulation may play a role in the development of hepatoblastoma and that activating mutations of the beta-catenin gene may substitute biallelic APC inactivation in this tumor type. Genes Chromosomes Cancer 25:399-402, 1999.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Bläker",
      "authorRank" : 1,
      "name" : "Bläker H",
      "referenceId" : "RGD:A470277"
    }, {
      "firstName" : "W J",
      "lastName" : "Hofmann",
      "authorRank" : 2,
      "name" : "Hofmann WJ",
      "referenceId" : "RGD:A470278"
    }, {
      "firstName" : "R J",
      "lastName" : "Rieker",
      "authorRank" : 3,
      "name" : "Rieker RJ",
      "referenceId" : "RGD:A470279"
    }, {
      "firstName" : "R",
      "lastName" : "Penzel",
      "authorRank" : 4,
      "name" : "Penzel R",
      "referenceId" : "RGD:A124454"
    }, {
      "firstName" : "M",
      "lastName" : "Graf",
      "authorRank" : 5,
      "name" : "Graf M",
      "referenceId" : "RGD:A51008"
    }, {
      "firstName" : "H F",
      "lastName" : "Otto",
      "authorRank" : 6,
      "name" : "Otto HF",
      "referenceId" : "RGD:A470280"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14402054"
    } ]
  }, {
    "primaryId" : "PMID:10398437",
    "title" : "Frequent 4-bp deletion in exon 9 of the SMAD4/MADH4 gene in familial juvenile polyposis patients.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Friedl W, etal., Genes Chromosomes Cancer. 1999 Aug;25(4):403-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:18:51.000-05:00",
    "volume" : "25",
    "pages" : "403-6",
    "abstract" : "Familial juvenile polyposis (FJP) is a hamartomatous polyposis syndrome characterized by the appearance of juvenile polyps in the gastrointestinal tract. Patients with this syndrome are at an increased risk for cancer of the colon, stomach, and pancreas. Recently, germline mutations in the SMAD4/DPC4 gene (official symbol MADH4) have been found in the majority of patients suffering from FJP. We have examined 11 unrelated patients with FJP for MADH4 germline mutations by direct sequencing of genomic DNA encompassing all 11 exons of the gene. Besides a novel mutation (959-960delAC at codon 277, exon 6) in one patient, we observed a 4-bp deletion (1372-1375delACAG) in exon 9 in two unrelated patients. Examination with microsatellite markers flanking MADH4 supports an independent origin of the mutation in these two families. The same 4-bp deletion in exon 9 has previously been described in three out of nine patients examined for MADH4 mutations. Our results combined with these previous data demonstrate that a unique 4-bp deletion in exon 9 of MADH4 accounts for about 25% of all FJP cases and that other MADH4 mutations occur in an additional  15% of patients. Genes Chromosomes Cancer 25:403-406, 1999.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Friedl",
      "authorRank" : 1,
      "name" : "Friedl W",
      "referenceId" : "RGD:A94211"
    }, {
      "firstName" : "R",
      "lastName" : "Kruse",
      "authorRank" : 2,
      "name" : "Kruse R",
      "referenceId" : "RGD:A74370"
    }, {
      "firstName" : "S",
      "lastName" : "Uhlhaas",
      "authorRank" : 3,
      "name" : "Uhlhaas",
      "referenceId" : "RGD:A251599"
    }, {
      "firstName" : "M",
      "lastName" : "Stolte",
      "authorRank" : 4,
      "name" : "Stolte",
      "referenceId" : "RGD:A251834"
    }, {
      "firstName" : "B",
      "lastName" : "Schartmann",
      "authorRank" : 5,
      "name" : "Schartmann",
      "referenceId" : "RGD:A278456"
    }, {
      "firstName" : "KM",
      "lastName" : "Keller",
      "authorRank" : 6,
      "name" : "Keller KM",
      "referenceId" : "RGD:A126605"
    }, {
      "firstName" : "M",
      "lastName" : "Jungck",
      "authorRank" : 7,
      "name" : "Jungck",
      "referenceId" : "RGD:A251601"
    }, {
      "firstName" : "M",
      "lastName" : "Stern",
      "authorRank" : 8,
      "name" : "Stern M",
      "referenceId" : "RGD:A155988"
    }, {
      "firstName" : "S",
      "lastName" : "Loff",
      "authorRank" : 9,
      "name" : "Loff",
      "referenceId" : "RGD:A251835"
    }, {
      "firstName" : "W",
      "lastName" : "Back",
      "authorRank" : 10,
      "name" : "Back",
      "referenceId" : "RGD:A251836"
    }, {
      "firstName" : "P",
      "lastName" : "Propping",
      "authorRank" : 11,
      "name" : "Propping P",
      "referenceId" : "RGD:A52842"
    }, {
      "firstName" : "DE",
      "lastName" : "Jenne",
      "authorRank" : 12,
      "name" : "Jenne DE",
      "referenceId" : "RGD:A37222"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071021"
    } ]
  }, {
    "primaryId" : "PMID:10398805",
    "title" : "Identification of a new quantitative trait locus on chromosome 7 controlling disease severity of collagen-induced arthritis in rats.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Dracheva SV, etal., Immunogenetics 1999 Aug;49(9):787-91",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-08-29T15:43:32.000-05:00",
    "volume" : "49",
    "pages" : "787-91",
    "abstract" : "Autoimmune diseases, such as rheumatoid arthritis, Crohn's disease, and multiple sclerosis, are regulated by multiple genes. Major histocompatibility complex (MHC) genes have the strongest effects, but non-MHC genes also contribute to disease susceptibility/severity. In this paper, we describe a new non-MHC quantitative trait locus, Cia8, on rat Chromosome (Chr) 7 that controls collagen-induced arthritis severity in F2 progeny of DA and F344 inbred rats, and present an updated localization of Cia4 on the same chromosome. We also describe the location of mouse and human genes, orthologous to the genes in the genomic intervals containing Cia4 and Cia8, and provide evidence that the segment of rat Chr 7 containing Cia4 and Cia8 is homologous to segments of mouse Chr 10 and 15 and human Chr 8, 12, and 19.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SV",
      "lastName" : "Dracheva",
      "authorRank" : 1,
      "name" : "Dracheva SV",
      "referenceId" : "RGD:A30281"
    }, {
      "firstName" : "EF",
      "lastName" : "Remmers",
      "authorRank" : 2,
      "name" : "Remmers EF",
      "referenceId" : "RGD:A153565"
    }, {
      "firstName" : "PS",
      "lastName" : "Gulko",
      "authorRank" : 3,
      "name" : "Gulko PS",
      "referenceId" : "RGD:A148715"
    }, {
      "firstName" : "Y",
      "lastName" : "Kawahito",
      "authorRank" : 4,
      "name" : "Kawahito Y",
      "referenceId" : "RGD:A147123"
    }, {
      "firstName" : "RE",
      "lastName" : "Longman",
      "authorRank" : 5,
      "name" : "Longman RE",
      "referenceId" : "RGD:A30287"
    }, {
      "firstName" : "VR",
      "lastName" : "Reese",
      "authorRank" : 6,
      "name" : "Reese VR",
      "referenceId" : "RGD:A863"
    }, {
      "firstName" : "GW",
      "lastName" : "Cannon",
      "authorRank" : 7,
      "name" : "Cannon GW",
      "referenceId" : "RGD:A51675"
    }, {
      "firstName" : "MM",
      "lastName" : "Griffiths",
      "authorRank" : 8,
      "name" : "Griffiths MM",
      "referenceId" : "RGD:A54317"
    }, {
      "firstName" : "RL",
      "lastName" : "Wilder",
      "authorRank" : 9,
      "name" : "Wilder RL",
      "referenceId" : "RGD:A153568"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61069"
    } ]
  }, {
    "primaryId" : "PMID:10398810",
    "title" : "A rat gene homologous to human granule membrane protein 17 is expressed by natural killer cells, CD8(+) T cells, and a mast cell line.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Berg SF, etal., Immunogenetics 1999 Aug;49(9):815-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:10.000-05:00",
    "volume" : "49",
    "pages" : "815-8",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SF",
      "lastName" : "Berg",
      "authorRank" : 1,
      "name" : "Berg SF",
      "referenceId" : "RGD:A54401"
    }, {
      "firstName" : "IH",
      "lastName" : "Westgaard",
      "authorRank" : 2,
      "name" : "Westgaard IH",
      "referenceId" : "RGD:A54436"
    }, {
      "firstName" : "S",
      "lastName" : "Fossum",
      "authorRank" : 3,
      "name" : "Fossum S",
      "referenceId" : "RGD:A88266"
    }, {
      "firstName" : "E",
      "lastName" : "Dissen",
      "authorRank" : 4,
      "name" : "Dissen E",
      "referenceId" : "RGD:A88263"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633487"
    } ]
  }, {
    "primaryId" : "PMID:10399107",
    "title" : "Molecular characterization of Polish patients with classical galactosaemia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Zekanowski C, etal., J Inherit Metab Dis. 1999 Jun;22(5):679-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:43:55.000-05:00",
    "volume" : "22",
    "pages" : "679-82",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Zekanowski",
      "authorRank" : 1,
      "name" : "Zekanowski C",
      "referenceId" : "RGD:A156509"
    }, {
      "firstName" : "B",
      "lastName" : "Radomyska",
      "authorRank" : 2,
      "name" : "Radomyska",
      "referenceId" : "RGD:A260369"
    }, {
      "firstName" : "J",
      "lastName" : "Bal",
      "authorRank" : 3,
      "name" : "Bal J",
      "referenceId" : "RGD:A141700"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066452"
    } ]
  }, {
    "primaryId" : "PMID:10399108",
    "title" : "A novel exonic mutation in the aspartylglucosaminidase gene causes exon skipping.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Coulter-Mackie MB J Inherit Metab Dis. 1999 Jun;22(5):682-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:13:06.000-05:00",
    "volume" : "22",
    "pages" : "682-3",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MB",
      "lastName" : "Coulter-Mackie",
      "authorRank" : 1,
      "name" : "Coulter-Mackie",
      "referenceId" : "RGD:A250282"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069881"
    } ]
  }, {
    "primaryId" : "PMID:10399751",
    "title" : "Immunolocalization of tumor necrosis factor-alpha and its receptors in inflammatory myopathies.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "De Bleecker JL, etal., Neuromuscul Disord. 1999 Jun;9(4):239-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-11-07T12:14:44.000-06:00",
    "volume" : "9",
    "pages" : "239-46",
    "abstract" : "Adhesion molecule upregulation occurs in inflammatory myopathies, and is one of the myriad functions of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha acts via two different receptors of 55 (TNF-R55) and 75 kD (TNF-R75). We immunolocalized TNF-alpha and its receptors in polymyositis, inclusion body myositis and dermatomyositis. In each myopathy, TNF-alpha was detected in macrophages, in myonuclei in regenerating muscle fibers, and freely dispersed in  endomysial or perimysial connective tissue. Many endothelial cells in dermatomyositis expressed TNF-alpha. TNF-R55 was strongly expressed on myonuclei  of regenerating muscle fibers. TNF-R75 was increased on endothelial cells in the  midst of inflammatory infiltrates in each myopathy, and on perifascicular and perimysial endothelia, remote from inflammatory foci in dermatomyositis. Possible TNF-alpha-mediated effects include: increased transendothelial cell trafficking,  activation of T/B cells and macrophages, induction of MHC-I gene products, and focal muscle fiber atrophy. In dermatomyositis, the upregulated TNF-R75, via its  consensus elements for transcription factors, may be involved in endothelial cell degeneration. Strong TNF-R55 expression on regenerating myonuclei is consistent with a role of TNF-alpha and TNF-R55 in muscle regeneration.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JL",
      "lastName" : "De Bleecker",
      "authorRank" : 1,
      "name" : "De Bleecker JL",
      "referenceId" : "RGD:A153301"
    }, {
      "firstName" : "VI",
      "lastName" : "Meire",
      "authorRank" : 2,
      "name" : "Meire",
      "referenceId" : "RGD:A175258"
    }, {
      "firstName" : "W",
      "lastName" : "Declercq",
      "authorRank" : 3,
      "name" : "Declercq",
      "referenceId" : "RGD:A175259"
    }, {
      "firstName" : "EH",
      "lastName" : "Van Aken",
      "authorRank" : 4,
      "name" : "Van Aken",
      "referenceId" : "RGD:A175260"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7401187"
    } ]
  }, {
    "primaryId" : "PMID:10399770",
    "title" : "Chronic intermittent stress does not differentially alter brain corticosteroid receptor densities in rats prenatally exposed to ethanol.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kim CK, etal., Psychoneuroendocrinology. 1999 Aug;24(6):585-611. doi: 10.1016/s0306-4530(99)00015-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-02-20T16:52:45.000-06:00",
    "volume" : "24",
    "pages" : "585-611",
    "abstract" : "Prenatal ethanol exposure produces hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors. The present study tested the hypothesis that decreased corticosteroid receptor densities at HPA feedback sites may play a role in deficient feedback inhibition and the resultant HPA hyperresponsiveness that is observed following prenatal ethanol exposure. Brains of adult Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF) and ad libitum-fed control (C) treatment groups were examined for both mineralocorticoid receptor (MR; Type I) and glucocorticoid receptor (GR; Type II) densities using a cytosolic binding assay. Experiment 1 compared the effects of chronic intermittent stress (Stress Regimen I) and corticosterone (CORT) pellet implants on hippocampal corticosteroid receptor densities in control rats. Experiment 2 determined whether exposure to Stress Regimen I would differentially downregulate and whether adrenalectomy (ADX) would differentially upregulate hippocampal corticosteroid receptors in E compared with PF and C animals. Experiment 3 examined the effects of a modified chronic intermittent stress regimen (Stress Regimen II) on corticosteroid receptor densities at several HPA feedback sites (hippocampus, prefrontal cortex, hypothalamus, and anterior pituitary) in E compared with PF and C animals. CORT pellet implants significantly downregulated hippocampal GR and MR densities in control males and females. Exposure to Stress Regimen I produced downregulation of hippocampal GRs and MRs in males comparable with that produced with CORT pellet implants, and significant downregulation of hippocampal GRs in females across all prenatal treatment groups. This stress regimen also elevated basal plasma CORT levels without concurrent changes in plasma CBG levels, and increased relative adrenal weights in both males and females. In addition, upregulation of hippocampal GRs occurred at 7 days compared with 24 h following ADX in females that had previously been exposed to this stress regimen. Following exposure to Stress Regimen II, both the downregulation of hippocampal corticosteroid receptors and the increase in basal CORT levels in males and females appear to have been abolished by the changes in housing condition during the period of chronic stress. Importantly, prenatal ethanol exposure did not differentially alter GR or MR densities at any feedback site under non-stressed conditions. Exposure to Stress Regimen II, revealed subtle effects of prenatal treatments on hippocampal GRs however it is unlikely that these changes in corticosteroid receptor densities mediated the feedback inhibition deficits observed in E animals. Together, these data demonstrate that: (1) a relatively mild intermittent stress regimen can increase basal CORT levels and downregulate hippocampal corticosteroid receptor densities (2) a seemingly small change in housing conditions during stress appears to eliminate both receptor downregulation and increase in basal CORT levels and (3) decreased corticosteroid receptor densities at HPA feedback sites in the brain do not appear to underlie the HPA hyperresponsiveness observed in E animals.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C K",
      "lastName" : "Kim",
      "authorRank" : 1,
      "name" : "Kim CK",
      "referenceId" : "RGD:A538939"
    }, {
      "firstName" : "W",
      "lastName" : "Yu",
      "authorRank" : 2,
      "name" : "Yu W",
      "referenceId" : "RGD:A17108"
    }, {
      "firstName" : "G",
      "lastName" : "Edin",
      "authorRank" : 3,
      "name" : "Edin G",
      "referenceId" : "RGD:A538940"
    }, {
      "firstName" : "L",
      "lastName" : "Ellis",
      "authorRank" : 4,
      "name" : "Ellis L",
      "referenceId" : "RGD:A21194"
    }, {
      "firstName" : "J A",
      "lastName" : "Osborn",
      "authorRank" : 5,
      "name" : "Osborn JA",
      "referenceId" : "RGD:A538941"
    }, {
      "firstName" : "J",
      "lastName" : "Weinberg",
      "authorRank" : 6,
      "name" : "Weinberg J",
      "referenceId" : "RGD:A538794"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401976290"
    } ]
  }, {
    "primaryId" : "PMID:10399774",
    "title" : "Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer's disease: results of a placebo-controlled, double-blind, pilot study.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Asthana S, etal., Psychoneuroendocrinology. 1999 Aug;24(6):657-77.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-10-27T15:18:52.000-05:00",
    "volume" : "24",
    "pages" : "657-77",
    "abstract" : "Preliminary evidence from clinical studies indicates that treatment with estrogen augments cognitive function for women with Alzheimer's disease (AD). The neurobiology of estrogen, particularly its neuromodulatory and neuroprotective actions, provide a viable basis to support such cognition-enhancing effects. We conducted a placebo-controlled, double-blind, parallel-group design pilot clinical study to evaluate the cognitive and neuroendocrine response to estrogen  administration for postmenopausal women with AD. Twelve women with probably AD of mild-moderate severity completed the study. During an eight week treatment period, six women received 0.05 mg/day dosage of 17 beta-estradiol via a skin patch and the remaining six wore a placebo skin patch. Subjects were randomized to equal distribution, and evaluated at baseline, at weeks 1, 3, 5, and 8 on treatment, and at weeks 9, 10, 11, and 13 off treatment. On each day of evaluation, cognition was assessed using a battery of neuropsychological tests, and blood samples were collected to measure plasma concentrations of estradiol and estrone. In addition, several neuroendocrine markers were measured in plasma  to evaluate the relationship between estrogen-induced cognitive effects and fluctuations in the catecholaminergic and insulin-like growth factor systems. Significant effects of estrogen treatment were observed on attention (i.e. Stroop: number of self-corrections in the Interference condition, F[1,8] = 8.22,  P < 0.03) and verbal memory (i.e., Buschke: delayed cued recall, F[3,30] = 4.31,  P < 0.02). The salutary effects of estrogen on cognition were observed after the  first week of treatment, and started to diminish when treatment was terminated. For women treated with estrogen, enhancement in verbal memory was positively correlated with plasma levels of estradiol (r = 0.96, P < 0.02) and negatively correlated with concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) in plasma (r = -0.92, P < 0.03). Furthermore, a trend in the data was evident to suggest a negative relationship between plasma levels of insulin-like  growth factor-1 (IGF-1) and verbal memory (r = -0.86, P = 0.06). Estrogen administration suppressed peripheral markers of the IGF system, as evidenced by a negative correlation between plasma concentration of estradiol and IGF-1 (r = -0.93, P < 0.03), and a trend for a similar relationship between plasma levels of estradiol and IGFBP-3 (r = -0.86, P = 0.06). With respect to the catecholamines assayed, norepinephrine was positively correlated with verbal memory (r = 0.95, P < 0.02) for women who were treated with estrogen. Furthermore, there was a trend  to suggest a negative relationship between plasma epinephrine levels and the number of errors committed on a test of attention (r = -0.84, P = 0.07). In the placebo group, no significant effects of estrogen replacement were evident either on measures of cognition or on any of the neuroendocrine markers. The results of  this study suggest that estrogen replacement may enhance cognition for postmenopausal women with AD. Furthermore, several markers of neuroendocrine activity may serve to index the magnitude of estrogen-induced facilitation on cognition. In addition, research findings from the present study will provide important information for the design of larger prospective clinical studies that  are essential to definitively establish the therapeutic role of estrogen replacement for postmenopausal women with AD.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Asthana",
      "authorRank" : 1,
      "name" : "Asthana",
      "referenceId" : "RGD:A207739"
    }, {
      "firstName" : "S",
      "lastName" : "Craft",
      "authorRank" : 2,
      "name" : "Craft S",
      "referenceId" : "RGD:A107445"
    }, {
      "firstName" : "LD",
      "lastName" : "Baker",
      "authorRank" : 3,
      "name" : "Baker",
      "referenceId" : "RGD:A206598"
    }, {
      "firstName" : "MA",
      "lastName" : "Raskind",
      "authorRank" : 4,
      "name" : "Raskind MA",
      "referenceId" : "RGD:A145929"
    }, {
      "firstName" : "RS",
      "lastName" : "Birnbaum",
      "authorRank" : 5,
      "name" : "Birnbaum",
      "referenceId" : "RGD:A207740"
    }, {
      "firstName" : "CP",
      "lastName" : "Lofgreen",
      "authorRank" : 6,
      "name" : "Lofgreen",
      "referenceId" : "RGD:A207741"
    }, {
      "firstName" : "RC",
      "lastName" : "Veith",
      "authorRank" : 7,
      "name" : "Veith",
      "referenceId" : "RGD:A207742"
    }, {
      "firstName" : "SR",
      "lastName" : "Plymate",
      "authorRank" : 8,
      "name" : "Plymate",
      "referenceId" : "RGD:A207743"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10402576"
    } ]
  }, {
    "primaryId" : "PMID:10399916",
    "title" : "Rhodopsin's carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Tai AW, etal., Cell. 1999 Jun 25;97(7):877-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:39:14.000-05:00",
    "volume" : "97",
    "pages" : "877-87",
    "abstract" : "The interaction of cytoplasmic dynein with its cargoes is thought to be indirectly mediated by dynactin, a complex that binds to the dynein intermediate  chain. However, the roles of other dynein subunits in cargo binding have been unknown. Here we demonstrate that dynein translocates rhodopsin-bearing vesicles  along microtubules. This interaction occurs directly between the C-terminal cytoplasmic tail of rhodopsin and Tctex-1, a dynein light chain. C-terminal rhodopsin mutations responsible for retinitis pigmentosa inhibit this interaction. Our results point to an alternative docking mechanism for cytoplasmic dynein, provide novel insights into the role of motor proteins in the polarized transport of post-Golgi vesicles, and shed light on the molecular basis of retinitis pigmentosa.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AW",
      "lastName" : "Tai",
      "authorRank" : 1,
      "name" : "Tai",
      "referenceId" : "RGD:A185479"
    }, {
      "firstName" : "JZ",
      "lastName" : "Chuang",
      "authorRank" : 2,
      "name" : "Chuang JZ",
      "referenceId" : "RGD:A158314"
    }, {
      "firstName" : "C",
      "lastName" : "Bode",
      "authorRank" : 3,
      "name" : "Bode C",
      "referenceId" : "RGD:A40237"
    }, {
      "firstName" : "U",
      "lastName" : "Wolfrum",
      "authorRank" : 4,
      "name" : "Wolfrum U",
      "referenceId" : "RGD:A39209"
    }, {
      "firstName" : "CH",
      "lastName" : "Sung",
      "authorRank" : 5,
      "name" : "Sung CH",
      "referenceId" : "RGD:A158313"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554023"
    } ]
  }, {
    "primaryId" : "PMID:10399937",
    "title" : "Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "O'Brien RJ, etal., Neuron. 1999 Jun;23(2):309-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T01:58:56.000-05:00",
    "volume" : "23",
    "pages" : "309-23",
    "abstract" : "Narp (neuronal activity-regulated pentraxin) is a secreted immediate-early gene (IEG) regulated by synaptic activity in brain. In this study, we demonstrate that Narp possesses several properties that make it likely to play a key role in excitatory synaptogenesis. Narp is shown to be selectively enriched at excitatory synapses on neurons from both the hippocampus and spinal cord. Overexpression of recombinant Narp increases the number of excitatory but not inhibitory synapses in cultured spinal neurons. In transfected HEK 293T cells, Narp interacts with itself, forming large surface clusters that coaggregate AMPA receptor subunits. Moreover, Narp-expressing HEK 293T cells can induce the aggregation of neuronal AMPA receptors. These studies support a model in which Narp functions as an extracellular aggregating factor for AMPA receptors.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R J",
      "lastName" : "O'Brien",
      "authorRank" : 1,
      "name" : "O'Brien RJ",
      "referenceId" : "RGD:A460276"
    }, {
      "firstName" : "D",
      "lastName" : "Xu",
      "authorRank" : 2,
      "name" : "Xu D",
      "referenceId" : "RGD:A10982"
    }, {
      "firstName" : "R S",
      "lastName" : "Petralia",
      "authorRank" : 3,
      "name" : "Petralia RS",
      "referenceId" : "RGD:A460277"
    }, {
      "firstName" : "O",
      "lastName" : "Steward",
      "authorRank" : 4,
      "name" : "Steward O",
      "referenceId" : "RGD:A460278"
    }, {
      "firstName" : "R L",
      "lastName" : "Huganir",
      "authorRank" : 5,
      "name" : "Huganir RL",
      "referenceId" : "RGD:A460279"
    }, {
      "firstName" : "P",
      "lastName" : "Worley",
      "authorRank" : 6,
      "name" : "Worley P",
      "referenceId" : "RGD:A4908"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702159"
    } ]
  }, {
    "primaryId" : "PMID:10399947",
    "title" : "Germline brca2 sequence variants in patients with ocular melanoma.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Sinilnikova OM, etal., Int J Cancer. 1999 Jul 30;82(3):325-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:51:01.000-05:00",
    "volume" : "82",
    "pages" : "325-8",
    "abstract" : "On the basis, chiefly, of anecdotal reports of cases of ocular melanoma (OM) occurring in families with inherited susceptibility to breast cancer due to brca2 germline mutations, we examined the frequency of brca2 alterations in a series of 62 ocular melanoma cases. These cases were preferentially selected on the basis of reported family history of breast or ovarian cancer, or OM, although the series also included a randomly selected set of cases without family history of cancer. A total of 7 germline alterations were found, of which 3 were likely to be associated with disease. While all 3 deleterious mutations were found in patients who also had a personal history of breast cancer, only 1 of the 3 families had a family history of breast/ovarian cancer or OM. Although germline brca2 mutations may account for a small proportion of all OM cases, there may be  additional loci that contribute to familial aggregation of OM and to the familial association between OM and breast cancer.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "OM",
      "lastName" : "Sinilnikova",
      "authorRank" : 1,
      "name" : "Sinilnikova OM",
      "referenceId" : "RGD:A95510"
    }, {
      "firstName" : "KM",
      "lastName" : "Egan",
      "authorRank" : 2,
      "name" : "Egan",
      "referenceId" : "RGD:A181073"
    }, {
      "firstName" : "JL",
      "lastName" : "Quinn",
      "authorRank" : 3,
      "name" : "Quinn",
      "referenceId" : "RGD:A260470"
    }, {
      "firstName" : "L",
      "lastName" : "Boutrand",
      "authorRank" : 4,
      "name" : "Boutrand L",
      "referenceId" : "RGD:A52935"
    }, {
      "firstName" : "GM",
      "lastName" : "Lenoir",
      "authorRank" : 5,
      "name" : "Lenoir GM",
      "referenceId" : "RGD:A96075"
    }, {
      "firstName" : "D",
      "lastName" : "Stoppa-Lyonnet",
      "authorRank" : 6,
      "name" : "Stoppa-Lyonnet D",
      "referenceId" : "RGD:A77748"
    }, {
      "firstName" : "L",
      "lastName" : "Desjardins",
      "authorRank" : 7,
      "name" : "Desjardins",
      "referenceId" : "RGD:A180486"
    }, {
      "firstName" : "C",
      "lastName" : "Levy",
      "authorRank" : 8,
      "name" : "Levy C",
      "referenceId" : "RGD:A160589"
    }, {
      "firstName" : "D",
      "lastName" : "Goldgar",
      "authorRank" : 9,
      "name" : "Goldgar D",
      "referenceId" : "RGD:A74481"
    }, {
      "firstName" : "ES",
      "lastName" : "Gragoudas",
      "authorRank" : 10,
      "name" : "Gragoudas ES",
      "referenceId" : "RGD:A63052"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065001"
    } ]
  }, {
    "primaryId" : "PMID:10400082",
    "title" : "Distribution of neurons expressing alpha 1G subunit mRNA of T-type voltage-dependent calcium channel in adult rat central nervous system.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Kase M, etal., Neurosci Lett. 1999 Jun 18;268(2):77-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-12-06T13:41:48.000-06:00",
    "volume" : "268",
    "pages" : "77-80",
    "abstract" : "T-type voltage-dependent calcium channel has central roles in neuronal burst firing. The alpha1G subunit of T-type channel has been recently cloned and we here reported a cellular distribution of the alpha1G by in situ hybridization in  adult rat brain and spinal cord. The cells expressing alpha1G were widely distributed in the central nervous system. The distribution seemed to be restricted to neurons, and exhibited a specific pattern in the cerebellum, thalamus, hippocampus and cerebral cortex.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kase",
      "authorRank" : 1,
      "name" : "Kase M",
      "referenceId" : "RGD:A160175"
    }, {
      "firstName" : "S",
      "lastName" : "Kakimoto",
      "authorRank" : 2,
      "name" : "Kakimoto S",
      "referenceId" : "RGD:A160176"
    }, {
      "firstName" : "S",
      "lastName" : "Sakuma",
      "authorRank" : 3,
      "name" : "Sakuma S",
      "referenceId" : "RGD:A42360"
    }, {
      "firstName" : "T",
      "lastName" : "Houtani",
      "authorRank" : 4,
      "name" : "Houtani T",
      "referenceId" : "RGD:A26540"
    }, {
      "firstName" : "H",
      "lastName" : "Ohishi",
      "authorRank" : 5,
      "name" : "Ohishi H",
      "referenceId" : "RGD:A88151"
    }, {
      "firstName" : "T",
      "lastName" : "Ueyama",
      "authorRank" : 6,
      "name" : "Ueyama T",
      "referenceId" : "RGD:A105306"
    }, {
      "firstName" : "T",
      "lastName" : "Sugimoto",
      "authorRank" : 7,
      "name" : "Sugimoto T",
      "referenceId" : "RGD:A9607"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7175537"
    } ]
  }, {
    "primaryId" : "PMID:10400129",
    "title" : "Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Norrgard KJ, etal., Pediatr Res. 1999 Jul;46(1):20-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:35:11.000-05:00",
    "volume" : "46",
    "pages" : "20-7",
    "abstract" : "Biotinidase deficiency is an autosomal recessive disorder of biotin metabolism that can lead to varying degrees of neurologic and cutaneous symptoms when untreated. Because this disorder meets the criteria for newborn screening, many states and countries perform this testing. Because newborn screening should result in complete ascertainment of mutations causing profound biotinidase deficiency (less than 10% of mean normal serum activity), we compared the mutations in a group of 59 children with profound biotinidase deficiency who were identified by newborn screening in the United States with 33 children ascertained by exhibiting symptoms. Of the 40 total mutations identified among the two populations, four mutations comprise 59% of the disease alleles studied. Two of these mutations occur in both populations, but in the symptomatic group at a significantly greater frequency. The other two common mutations occur only in the newborn screening group. Because two common mutations do not occur in the symptomatic population, it is possible that individuals with these mutations either develop mild or no symptoms if left untreated. However, inasmuch as biotin treatment is inexpensive and innocuous, it is still recommended that all children with profound biotinidase deficiency be treated.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KJ",
      "lastName" : "Norrgard",
      "authorRank" : 1,
      "name" : "Norrgard",
      "referenceId" : "RGD:A252834"
    }, {
      "firstName" : "RJ",
      "lastName" : "Pomponio",
      "authorRank" : 2,
      "name" : "Pomponio",
      "referenceId" : "RGD:A252835"
    }, {
      "firstName" : "J",
      "lastName" : "Hymes",
      "authorRank" : 3,
      "name" : "Hymes",
      "referenceId" : "RGD:A252837"
    }, {
      "firstName" : "B",
      "lastName" : "Wolf",
      "authorRank" : 4,
      "name" : "Wolf B",
      "referenceId" : "RGD:A47421"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064460"
    } ]
  }, {
    "primaryId" : "PMID:10400139",
    "title" : "Chemokine receptor CCR2 and CCR5 polymorphisms in children with insulin-dependent diabetes mellitus.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Szalai C, etal., Pediatr Res. 1999 Jul;46(1):82-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-10-01T16:50:27.000-05:00",
    "volume" : "46",
    "pages" : "82-4",
    "abstract" : "Studies have shown the important roles of several regulatory and proinflammatory cytokines in insulin-dependent diabetes mellitus (IDDM). CC-chemokine receptors CCR2 and CCR5 bind chemokines that are involved in the trafficking of leukocytes in both basal and inflammatory states. A common 32-bp deletion mutation in the CCR5 gene (CCR5delta32) and a G-to-A nucleotide substitution in the CCR2 at position 190 (CCR2-64I) have recently been described. In the present study, we have determined the frequency of the CCR5delta32 and CCR2-64I alleles in children with IDDM [n = 115; age 1-14 (9.3+/-4.3) y] and in nondiabetic subjects [n = 280; age 1-14 (8.5+/-4.5) y]. The CCR5delta32 allele frequencies were 0.117 in children with IDDM and 0.111 in nondiabetic subjects, indicating that the deletion allele has no association with IDDM. The CCR2-64I allele frequency in children with IDDM was 0.226, which differed significantly from the allele frequency in controls (0.114, p = 0.001). The role of this mutation in IDDM cannot be explained yet, but, because CCR2 mediates the chemotaxis of CD4+ and CD8+ T cells to areas of inflammation and because these cells play important roles in insulitis, a mutation in the CCR2 gene may contribute to the susceptibility to the disease. Alternatively, the 64I allele could be a marker of a linked mutation through linkage disequilibrium. According to these results, the CCR2 gene may be a new candidate for the susceptibility locus of IDDM. However, because no IDDM locus has been identified near 3p21 until now, further investigations are needed to confirm this statement.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Szalai",
      "authorRank" : 1,
      "name" : "Szalai C",
      "referenceId" : "RGD:A84120"
    }, {
      "firstName" : "A",
      "lastName" : "Csaszar",
      "authorRank" : 2,
      "name" : "Csaszar A",
      "referenceId" : "RGD:A59187"
    }, {
      "firstName" : "A",
      "lastName" : "Czinner",
      "authorRank" : 3,
      "name" : "Czinner A",
      "referenceId" : "RGD:A112366"
    }, {
      "firstName" : "T",
      "lastName" : "Szabo",
      "authorRank" : 4,
      "name" : "Szabo T",
      "referenceId" : "RGD:A112954"
    }, {
      "firstName" : "P",
      "lastName" : "Panczel",
      "authorRank" : 5,
      "name" : "Panczel P",
      "referenceId" : "RGD:A112955"
    }, {
      "firstName" : "L",
      "lastName" : "Madacsy",
      "authorRank" : 6,
      "name" : "Madacsy L",
      "referenceId" : "RGD:A109902"
    }, {
      "firstName" : "A",
      "lastName" : "Falus",
      "authorRank" : 7,
      "name" : "Falus A",
      "referenceId" : "RGD:A84122"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313564"
    } ]
  }, {
    "primaryId" : "PMID:10400640",
    "title" : "The linkage of Kennedy's neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hsiao PW, etal., J Biol Chem. 1999 Jul 16;274(29):20229-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-13T16:24:12.000-05:00",
    "volume" : "274",
    "pages" : "20229-34",
    "abstract" : "Although the linkage of polyglutamine (poly-Q) repeat expansion in the androgen receptor (AR) to Kennedy's disease (X-linked spinal and bulbar muscular atrophy) was a major step forward, the detailed molecular mechanism of how the change in poly-Q length contributes to the disease remains unclear. Here we report the identification of a nuclear G-protein, Ras-related nuclear protein/ARA24, as the first AR coactivator that can bind differentially with different lengths of poly-Q within AR. In the yeast and mammalian reciprocal interacting assays, our data suggested the interaction of AR N-terminal domain with ARA24 diminishes as the poly-Q length increases. The coactivation of ARA24 also diminishes with the poly-Q expansion within AR. Deletion of the acidic hexapeptide (DEDDDL) at the C terminus of ARA24 further enhances its AR coactivation. Together, our data suggest that poor interaction and weaker coactivation of ARA24 to the longer poly-Q AR in the X-linked spinal and bulbar muscular atrophied AR could contribute to the weaker transactivation of AR. The consequence of poor interaction and weak coactivation may eventually lead to the partial androgen insensitivity during the development of Kennedy's disease.",
    "issueName" : "29",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PW",
      "lastName" : "Hsiao",
      "authorRank" : 1,
      "name" : "Hsiao PW",
      "referenceId" : "RGD:A26933"
    }, {
      "firstName" : "DL",
      "lastName" : "Lin",
      "authorRank" : 2,
      "name" : "Lin DL",
      "referenceId" : "RGD:A59521"
    }, {
      "firstName" : "R",
      "lastName" : "Nakao",
      "authorRank" : 3,
      "name" : "Nakao R",
      "referenceId" : "RGD:A59522"
    }, {
      "firstName" : "C",
      "lastName" : "Chang",
      "authorRank" : 4,
      "name" : "Chang C",
      "referenceId" : "RGD:A23824"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578680"
    } ]
  }, {
    "primaryId" : "PMID:10400672",
    "title" : "Neonatal lethality in mice deficient in XCE, a novel member of the endothelin-converting enzyme and neutral endopeptidase family.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Schweizer A, etal., J Biol Chem 1999 Jul 16;274(29):20450-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T16:10:14.000-06:00",
    "volume" : "274",
    "pages" : "20450-6",
    "abstract" : "XCE, a new member of the endothelin-converting enzyme and neutral endopeptidase family, is preferentially expressed in specific areas of the central nervous system including spinal chord and medulla. To elucidate the importance and function of XCE, we disrupted its gene in mouse embryonic stem cells by homologous recombination and created mice deficient in XCE. The resulting phenotype is characterized by neonatal lethality. All XCE -/- homozygous mice died of respiratory failure shortly after birth, and in most cases their lungs were never ventilated. Apart from the atelectasis, anatomical and histological examinations of embryonic day 18.5 XCE -/- embryos and newborn homozygotes did not reveal any obvious abnormalities in organs and tissues. Malformations that are related to the knock-out were also not found in the skeletons of XCE -/- mice. In addition, XCE knock-out animals showed no deficiency of pulmonary surfactant proteins and had normal heart beat frequencies. Taken together, our results demonstrate that XCE is an essential gene. The phenotype of the XCE-deficient mice together with the central nervous system-specific expression further suggest that XCE may play a vital role in the control of respiration.",
    "issueName" : "29",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Schweizer",
      "authorRank" : 1,
      "name" : "Schweizer A",
      "referenceId" : "RGD:A17788"
    }, {
      "firstName" : "O",
      "lastName" : "Valdenaire",
      "authorRank" : 2,
      "name" : "Valdenaire O",
      "referenceId" : "RGD:A17785"
    }, {
      "firstName" : "A",
      "lastName" : "Koster",
      "authorRank" : 3,
      "name" : "Koster A",
      "referenceId" : "RGD:A38038"
    }, {
      "firstName" : "Y",
      "lastName" : "Lang",
      "authorRank" : 4,
      "name" : "Lang Y",
      "referenceId" : "RGD:A38039"
    }, {
      "firstName" : "G",
      "lastName" : "Schmitt",
      "authorRank" : 5,
      "name" : "Schmitt G",
      "referenceId" : "RGD:A38040"
    }, {
      "firstName" : "B",
      "lastName" : "Lenz",
      "authorRank" : 6,
      "name" : "Lenz B",
      "referenceId" : "RGD:A38041"
    }, {
      "firstName" : "H",
      "lastName" : "Bluethmann",
      "authorRank" : 7,
      "name" : "Bluethmann H",
      "referenceId" : "RGD:A38042"
    }, {
      "firstName" : "J",
      "lastName" : "Rohrer",
      "authorRank" : 8,
      "name" : "Rohrer J",
      "referenceId" : "RGD:A38043"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734911"
    } ]
  }, {
    "primaryId" : "PMID:10400692",
    "title" : "Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen  synthase and phosphorylation of 4E-BP1 (PHAS-1).",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Takata M, etal., J Biol Chem. 1999 Jul 16;274(29):20611-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:37:29.000-05:00",
    "volume" : "274",
    "pages" : "20611-8",
    "abstract" : "The roles of Akt (protein kinase B) and the atypical lambda isoform of protein kinase C (PKClambda), both of which act downstream of phosphoinositide 3-kinase,  in the activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1) in  response to insulin were investigated. A mutant Akt (Akt-AA) in which the phosphorylation sites targeted by growth factors are replaced by alanine was shown to inhibit insulin-induced activation of both Akt and glycogen synthase in  L6 myotubes. Expression of a mutant Akt in which Lys179 in the kinase domain was  replaced by aspartate also inhibited insulin-induced activation of glycogen synthase but had no effect on insulin activation of endogenous Akt. A kinase-defective mutant of PKClambda (lambdaDeltaNKD), which prevents insulin-induced activation of PKClambda, did not affect the activation of glycogen synthase by insulin. Insulin-induced phosphorylation of 4E-BP1 was inhibited by Akt-AA in Chinese hamster ovary cells. However, lambdaDeltaNKD had no effect on 4E-BP1 phosphorylation induced by insulin. These data suggest that Akt, but not PKClambda, is required for insulin activation of glycogen synthase and for insulin-induced phosphorylation of 4E-BP1.",
    "issueName" : "29",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Takata",
      "authorRank" : 1,
      "name" : "Takata M",
      "referenceId" : "RGD:A50158"
    }, {
      "firstName" : "W",
      "lastName" : "Ogawa",
      "authorRank" : 2,
      "name" : "Ogawa",
      "referenceId" : "RGD:A368568"
    }, {
      "firstName" : "T",
      "lastName" : "Kitamura",
      "authorRank" : 3,
      "name" : "Kitamura",
      "referenceId" : "RGD:A392568"
    }, {
      "firstName" : "Y",
      "lastName" : "Hino",
      "authorRank" : 4,
      "name" : "Hino Y",
      "referenceId" : "RGD:A87191"
    }, {
      "firstName" : "S",
      "lastName" : "Kuroda",
      "authorRank" : 5,
      "name" : "Kuroda S",
      "referenceId" : "RGD:A4186"
    }, {
      "firstName" : "K",
      "lastName" : "Kotani",
      "authorRank" : 6,
      "name" : "Kotani K",
      "referenceId" : "RGD:A84922"
    }, {
      "firstName" : "A",
      "lastName" : "Klip",
      "authorRank" : 7,
      "name" : "Klip A",
      "referenceId" : "RGD:A14804"
    }, {
      "firstName" : "AC",
      "lastName" : "Gingras",
      "authorRank" : 8,
      "name" : "Gingras",
      "referenceId" : "RGD:A185076"
    }, {
      "firstName" : "N",
      "lastName" : "Sonenberg",
      "authorRank" : 9,
      "name" : "Sonenberg N",
      "referenceId" : "RGD:A13932"
    }, {
      "firstName" : "M",
      "lastName" : "Kasuga",
      "authorRank" : 10,
      "name" : "Kasuga",
      "referenceId" : "RGD:A329486"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553850"
    } ]
  }, {
    "primaryId" : "PMID:10400702",
    "title" : "Ribonuclease activity of rat liver perchloric acid-soluble protein, a potent inhibitor of protein synthesis.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Morishita R, etal., J Biol Chem. 1999 Jul 16;274(29):20688-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-19T10:36:29.000-06:00",
    "volume" : "274",
    "pages" : "20688-92",
    "abstract" : "Rat liver perchloric acid-soluble protein (L-PSP) is a potent inhibitor of cell-free protein synthesis; however, its mechanism of action is not known. Here  we show that the protein is a unique ribonuclease and that this activity is responsible for the inhibition of translation. The addition of perchloric acid-soluble protein to a rabbit reticulocyte cell-free system at a concentration of 6.2 microM led to an almost complete inhibition of protein synthesis. The kinetics are unlike those of hemin-controlled inhibitor, a protein that acts at the initiation step. The inhibition appears to be due to an endoribonucleolytic activity of perchloric acid-soluble protein because L-PSP directly affects mRNA template activity and induces disaggregation of the reticulocyte polysomes into 80 S ribosomes, even in the presence of cycloheximide. These effects were observed with authentic as well as recombinant L-PSP. Analysis by thin-layer chromatography of [alpha-32P]UTP-labeled mRNA incubated with the protein showed production of the ribonucleoside 3'-monophosphates Ap, Gp, Up, and Cp, providing  direct evidence that the protein is an endoribonuclease. When either 5'- or 3'-32P-labeled 5 S rRNA was the substrate, L-PSP cleaved phosphodiester bonds only in the single-stranded regions of the molecule.",
    "issueName" : "29",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Morishita",
      "authorRank" : 1,
      "name" : "Morishita R",
      "referenceId" : "RGD:A65526"
    }, {
      "firstName" : "A",
      "lastName" : "Kawagoshi",
      "authorRank" : 2,
      "name" : "Kawagoshi",
      "referenceId" : "RGD:A198428"
    }, {
      "firstName" : "T",
      "lastName" : "Sawasaki",
      "authorRank" : 3,
      "name" : "Sawasaki",
      "referenceId" : "RGD:A198429"
    }, {
      "firstName" : "K",
      "lastName" : "Madin",
      "authorRank" : 4,
      "name" : "Madin",
      "referenceId" : "RGD:A198430"
    }, {
      "firstName" : "T",
      "lastName" : "Ogasawara",
      "authorRank" : 5,
      "name" : "Ogasawara",
      "referenceId" : "RGD:A198431"
    }, {
      "firstName" : "T",
      "lastName" : "Oka",
      "authorRank" : 6,
      "name" : "Oka T",
      "referenceId" : "RGD:A9885"
    }, {
      "firstName" : "Y",
      "lastName" : "Endo",
      "authorRank" : 7,
      "name" : "Endo Y",
      "referenceId" : "RGD:A20549"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685547"
    } ]
  }, {
    "primaryId" : "PMID:10400910",
    "title" : "Mouse model of a familial hypertrophic cardiomyopathy mutation in alpha-tropomyosin manifests cardiac dysfunction.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Muthuchamy M, etal., Circ Res. 1999 Jul 9;85(1):47-56.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:28:13.000-05:00",
    "volume" : "85",
    "pages" : "47-56",
    "abstract" : "To investigate the functional consequences of a tropomyosin (TM) mutation associated with familial hypertrophic cardiomyopathy (FHC), we generated transgenic mice that express mutant alpha-TM in the adult heart. The missense mutation, which results in the substitution of asparagine for aspartic acid at amino acid position 175, occurs in a troponin T binding region of TM. S1 nuclease mapping and Western blot analyses demonstrate that increased expression of the alpha-TM 175 transgene in different lines causes a concomitant decrease in levels of endogenous alpha-TM mRNA and protein expression. In vivo physiological analyses show a severe impairment of both contractility and relaxation in hearts  of the FHC mice, with a significant change in left ventricular fractional shortening. Myofilaments that contain alpha-TM 175 demonstrate an increased activation of the thin filament through enhanced Ca2+ sensitivity of steady-state force. Histological analyses show patchy areas of mild ventricular myocyte disorganization and hypertrophy, with occasional thrombi formation in the left atria. Thus, the FHC alpha-TM transgenic mouse can serve as a model system for the examination of pathological and physiological alterations imparted through aberrant TM isoforms.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Muthuchamy",
      "authorRank" : 1,
      "name" : "Muthuchamy",
      "referenceId" : "RGD:A263797"
    }, {
      "firstName" : "K",
      "lastName" : "Pieples",
      "authorRank" : 2,
      "name" : "Pieples",
      "referenceId" : "RGD:A263798"
    }, {
      "firstName" : "P",
      "lastName" : "Rethinasamy",
      "authorRank" : 3,
      "name" : "Rethinasamy",
      "referenceId" : "RGD:A263799"
    }, {
      "firstName" : "B",
      "lastName" : "Hoit",
      "authorRank" : 4,
      "name" : "Hoit",
      "referenceId" : "RGD:A203713"
    }, {
      "firstName" : "IL",
      "lastName" : "Grupp",
      "authorRank" : 5,
      "name" : "Grupp IL",
      "referenceId" : "RGD:A36189"
    }, {
      "firstName" : "GP",
      "lastName" : "Boivin",
      "authorRank" : 6,
      "name" : "Boivin GP",
      "referenceId" : "RGD:A57808"
    }, {
      "firstName" : "B",
      "lastName" : "Wolska",
      "authorRank" : 7,
      "name" : "Wolska",
      "referenceId" : "RGD:A263800"
    }, {
      "firstName" : "C",
      "lastName" : "Evans",
      "authorRank" : 8,
      "name" : "Evans C",
      "referenceId" : "RGD:A93580"
    }, {
      "firstName" : "RJ",
      "lastName" : "Solaro",
      "authorRank" : 9,
      "name" : "Solaro RJ",
      "referenceId" : "RGD:A11896"
    }, {
      "firstName" : "DF",
      "lastName" : "Wieczorek",
      "authorRank" : 10,
      "name" : "Wieczorek DF",
      "referenceId" : "RGD:A31130"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066061"
    } ]
  }, {
    "primaryId" : "PMID:10400919",
    "title" : "Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Shi W, etal., Circ Res 1999 Jul 9;85(1):e1-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:51.000-05:00",
    "volume" : "85",
    "pages" : "e1-6",
    "abstract" : "HCN cation channel mRNA expression was determined in the rabbit heart and neonatal and adult rat ventricle using RNase protection assays. In the rabbit SA node, the dominant HCN transcript is HCN4, representing >81% of the total HCN message. HCN1 is also expressed, representing >18% of the total HCN mRNA. Rabbit Purkinje fibers contained almost equal amounts of HCN1 and HCN4 transcripts with low levels of HCN2, whereas rabbit ventricle contained predominantly HCN2. The SA node contained 25 times the total HCN message of Purkinje fibers and 140 times the total HCN message of ventricle. No reports of hyperpolarization-activated current (If) exist in rabbit Purkinje fibers, and we could not record If in rabbit ventricular myocytes. To investigate the possible role of isoform switching in determining the voltage dependence of If, we determined the prevalence of HCN isoforms in neonatal and adult rat ventricle. We had previously determined the threshold for activation of If to be approximately -70 mV in neonatal rat ventricle and -113 mV in adult rat ventricle. In both neonatal and adult rat ventricle, only HCN2 and HCN4 transcripts are present. The ratio of HCN2 to HCN4 is approximately 5:1 in the neonate and 13:1 in the adult. Taken together, these results suggest that different cardiac regions express different isoforms of the HCN family. The HCN1 and HCN4 isoforms are most closely associated with a depolarized threshold for If activation, whereas the HCN2 isoform is associated with a more negative activation curve.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Shi",
      "authorRank" : 1,
      "name" : "Shi W",
      "referenceId" : "RGD:A5939"
    }, {
      "firstName" : "R",
      "lastName" : "Wymore",
      "authorRank" : 2,
      "name" : "Wymore R",
      "referenceId" : "RGD:A19159"
    }, {
      "firstName" : "H",
      "lastName" : "Yu",
      "authorRank" : 3,
      "name" : "Yu H",
      "referenceId" : "RGD:A11701"
    }, {
      "firstName" : "J",
      "lastName" : "Wu",
      "authorRank" : 4,
      "name" : "Wu J",
      "referenceId" : "RGD:A160329"
    }, {
      "firstName" : "RT",
      "lastName" : "Wymore",
      "authorRank" : 5,
      "name" : "Wymore RT",
      "referenceId" : "RGD:A19161"
    }, {
      "firstName" : "Z",
      "lastName" : "Pan",
      "authorRank" : 6,
      "name" : "Pan Z",
      "referenceId" : "RGD:A5938"
    }, {
      "firstName" : "RB",
      "lastName" : "Robinson",
      "authorRank" : 7,
      "name" : "Robinson RB",
      "referenceId" : "RGD:A19162"
    }, {
      "firstName" : "JE",
      "lastName" : "Dixon",
      "authorRank" : 8,
      "name" : "Dixon JE",
      "referenceId" : "RGD:A104481"
    }, {
      "firstName" : "D",
      "lastName" : "McKinnon",
      "authorRank" : 9,
      "name" : "McKinnon D",
      "referenceId" : "RGD:A5943"
    }, {
      "firstName" : "IS",
      "lastName" : "Cohen",
      "authorRank" : 10,
      "name" : "Cohen IS",
      "referenceId" : "RGD:A5942"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632926"
    } ]
  }, {
    "primaryId" : "PMID:10400928",
    "title" : "A high density integrated genetic linkage and radiation hybrid map of the laboratory rat",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Steen RG, Kwitek-Black AE, etal., Genome Research, 1999, 6:1-8",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-12-19T14:36:40.000-06:00",
    "volume" : "6",
    "pages" : "1-8",
    "abstract" : "The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP W BN and FHH W ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod  3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http://www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RG",
      "lastName" : "Steen",
      "authorRank" : 1,
      "name" : "Steen RG",
      "referenceId" : "RGD:A95444"
    }, {
      "firstName" : "AE",
      "lastName" : "Kwitek-Black",
      "authorRank" : 2,
      "name" : "Kwitek-Black AE",
      "referenceId" : "RGD:A51102"
    }, {
      "firstName" : "C",
      "lastName" : "Glenn",
      "authorRank" : 3,
      "name" : "Glenn C",
      "referenceId" : "RGD:A6724"
    }, {
      "firstName" : "J",
      "lastName" : "Gullings-Handley",
      "authorRank" : 4,
      "name" : "Gullings-Handley J",
      "referenceId" : "RGD:A48066"
    }, {
      "firstName" : "W",
      "lastName" : "Van Etten",
      "authorRank" : 5,
      "name" : "Van Etten W",
      "referenceId" : "RGD:A6726"
    }, {
      "firstName" : "OS",
      "lastName" : "Atkinson",
      "authorRank" : 6,
      "name" : "Atkinson OS",
      "referenceId" : "RGD:A6727"
    }, {
      "firstName" : "D",
      "lastName" : "Appel",
      "authorRank" : 7,
      "name" : "Appel D",
      "referenceId" : "RGD:A6728"
    }, {
      "firstName" : "S",
      "lastName" : "Twigger",
      "authorRank" : 8,
      "name" : "Twigger S",
      "referenceId" : "RGD:A48068"
    }, {
      "firstName" : "M",
      "lastName" : "Muir",
      "authorRank" : 9,
      "name" : "Muir M",
      "referenceId" : "RGD:A6729"
    }, {
      "firstName" : "T",
      "lastName" : "Mull",
      "authorRank" : 10,
      "name" : "Mull T",
      "referenceId" : "RGD:A6730"
    }, {
      "firstName" : "M",
      "lastName" : "Granados",
      "authorRank" : 11,
      "name" : "Granados M",
      "referenceId" : "RGD:A6731"
    }, {
      "firstName" : "M",
      "lastName" : "Kissegah",
      "authorRank" : 12,
      "name" : "Kissegah M",
      "referenceId" : "RGD:A6732"
    }, {
      "firstName" : "K",
      "lastName" : "Russo",
      "authorRank" : 13,
      "name" : "Russo K",
      "referenceId" : "RGD:A6733"
    }, {
      "firstName" : "R",
      "lastName" : "Crane",
      "authorRank" : 14,
      "name" : "Crane R",
      "referenceId" : "RGD:A6734"
    }, {
      "firstName" : "M",
      "lastName" : "Popp",
      "authorRank" : 15,
      "name" : "Popp M",
      "referenceId" : "RGD:A6735"
    }, {
      "firstName" : "M",
      "lastName" : "Peden",
      "authorRank" : 16,
      "name" : "Peden M",
      "referenceId" : "RGD:A6736"
    }, {
      "firstName" : "DM",
      "lastName" : "Brown",
      "authorRank" : 17,
      "name" : "Brown DM",
      "referenceId" : "RGD:A45881"
    }, {
      "firstName" : "T",
      "lastName" : "Matise",
      "authorRank" : 18,
      "name" : "Matise T",
      "referenceId" : "RGD:A6737"
    }, {
      "firstName" : "J",
      "lastName" : "Lu",
      "authorRank" : 19,
      "name" : "Lu J",
      "referenceId" : "RGD:A158093"
    }, {
      "firstName" : "S",
      "lastName" : "Kingsmore",
      "authorRank" : 20,
      "name" : "Kingsmore S",
      "referenceId" : "RGD:A6739"
    }, {
      "firstName" : "PJ",
      "lastName" : "Tonellato",
      "authorRank" : 21,
      "name" : "Tonellato PJ",
      "referenceId" : "RGD:A130134"
    }, {
      "firstName" : "S",
      "lastName" : "Rozen",
      "authorRank" : 22,
      "name" : "Rozen S",
      "referenceId" : "RGD:A6740"
    }, {
      "firstName" : "D",
      "lastName" : "Slonim",
      "authorRank" : 23,
      "name" : "Slonim D",
      "referenceId" : "RGD:A6741"
    }, {
      "firstName" : "P",
      "lastName" : "Young",
      "authorRank" : 24,
      "name" : "Young P",
      "referenceId" : "RGD:A91866"
    }, {
      "firstName" : "M",
      "lastName" : "Knoblauch",
      "authorRank" : 25,
      "name" : "Knoblauch M",
      "referenceId" : "RGD:A48994"
    }, {
      "firstName" : "A",
      "lastName" : "Provoost",
      "authorRank" : 26,
      "name" : "Provoost A",
      "referenceId" : "RGD:A6743"
    }, {
      "firstName" : "D",
      "lastName" : "Ganten",
      "authorRank" : 27,
      "name" : "Ganten D",
      "referenceId" : "RGD:A119738"
    }, {
      "firstName" : "SD",
      "lastName" : "Colman",
      "authorRank" : 28,
      "name" : "Colman SD",
      "referenceId" : "RGD:A44912"
    }, {
      "firstName" : "J",
      "lastName" : "Rothberg",
      "authorRank" : 29,
      "name" : "Rothberg J",
      "referenceId" : "RGD:A6745"
    }, {
      "firstName" : "ES",
      "lastName" : "Lander",
      "authorRank" : 30,
      "name" : "Lander ES",
      "referenceId" : "RGD:A144400"
    }, {
      "firstName" : "HJ",
      "lastName" : "Jacob",
      "authorRank" : 31,
      "name" : "Jacob HJ",
      "referenceId" : "RGD:A160476"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1016"
    } ]
  }, {
    "primaryId" : "PMID:10400993",
    "title" : "PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Marsh DJ, etal., Hum Mol Genet. 1999 Aug;8(8):1461-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:36:13.000-05:00",
    "volume" : "8",
    "pages" : "1461-72",
    "abstract" : "Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and  Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway.  CS is characterized by multiple hamartomas and an increased risk of benign and malignant disease of the breast, thyroid and central nervous system, whilst the presence of cancer has not been formally documented in BRR. The partial clinical  overlap in these two syndromes is exemplified by the hallmark features of BRR: macrocephaly and multiple lipomas, the latter of which occur in a minority of individuals with CS. Additional features observed in BRR, which may also occur in a minority of CS patients, include Hashimoto's thyroiditis, vascular malformations and mental retardation. Pigmented macules of the glans penis, delayed motor development and neonatal or infant onset are noted only in BRR. In  this study, constitutive DNA samples from 43 BRR individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both CS and BRR, were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) BRR cases. Genotype-phenotype analyses within the BRR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, BRR or BRR/CS overlap family ( P = 0.014), and, in  particular, truncating mutations were associated with the presence of cancer and  breast fibroadenoma in a given family ( P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRR patients ( P = 0.028). In contrast to a prior report, no significant difference in mutation status was found in familial versus sporadic cases of BRR ( P = 0.113). Comparisons between BRR and a previously studied group of 37 CS families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CS alone or both CS and BRR when compared with BRR alone ( P = 0.002). Among CS, BRR and BRR/CS overlap families that are PTEN mutation positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS and BRR may be different presentations of a single syndrome and, hence, both should receive equal attention with respect to cancer surveillance.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Marsh",
      "authorRank" : 1,
      "name" : "Marsh",
      "referenceId" : "RGD:A252775"
    }, {
      "firstName" : "JB",
      "lastName" : "Kum",
      "authorRank" : 2,
      "name" : "Kum JB",
      "referenceId" : "RGD:A81003"
    }, {
      "firstName" : "KL",
      "lastName" : "Lunetta",
      "authorRank" : 3,
      "name" : "Lunetta KL",
      "referenceId" : "RGD:A147695"
    }, {
      "firstName" : "MJ",
      "lastName" : "Bennett",
      "authorRank" : 4,
      "name" : "Bennett MJ",
      "referenceId" : "RGD:A37422"
    }, {
      "firstName" : "RJ",
      "lastName" : "Gorlin",
      "authorRank" : 5,
      "name" : "Gorlin RJ",
      "referenceId" : "RGD:A37729"
    }, {
      "firstName" : "SF",
      "lastName" : "Ahmed",
      "authorRank" : 6,
      "name" : "Ahmed",
      "referenceId" : "RGD:A258812"
    }, {
      "firstName" : "J",
      "lastName" : "Bodurtha",
      "authorRank" : 7,
      "name" : "Bodurtha",
      "referenceId" : "RGD:A258813"
    }, {
      "firstName" : "C",
      "lastName" : "Crowe",
      "authorRank" : 8,
      "name" : "Crowe",
      "referenceId" : "RGD:A258814"
    }, {
      "firstName" : "MA",
      "lastName" : "Curtis",
      "authorRank" : 9,
      "name" : "Curtis",
      "referenceId" : "RGD:A204377"
    }, {
      "firstName" : "M",
      "lastName" : "Dasouki",
      "authorRank" : 10,
      "name" : "Dasouki",
      "referenceId" : "RGD:A258815"
    }, {
      "firstName" : "T",
      "lastName" : "Dunn",
      "authorRank" : 11,
      "name" : "Dunn T",
      "referenceId" : "RGD:A22660"
    }, {
      "firstName" : "H",
      "lastName" : "Feit",
      "authorRank" : 12,
      "name" : "Feit",
      "referenceId" : "RGD:A258816"
    }, {
      "firstName" : "MT",
      "lastName" : "Geraghty",
      "authorRank" : 13,
      "name" : "Geraghty",
      "referenceId" : "RGD:A255047"
    }, {
      "firstName" : "JR",
      "lastName" : "Graham JM",
      "authorRank" : 14,
      "name" : "Graham JM JR",
      "referenceId" : "RGD:A75297"
    }, {
      "firstName" : "SV",
      "lastName" : "Hodgson",
      "authorRank" : 15,
      "name" : "Hodgson SV",
      "referenceId" : "RGD:A36413"
    }, {
      "firstName" : "A",
      "lastName" : "Hunter",
      "authorRank" : 16,
      "name" : "Hunter",
      "referenceId" : "RGD:A258817"
    }, {
      "firstName" : "BR",
      "lastName" : "Korf",
      "authorRank" : 17,
      "name" : "Korf",
      "referenceId" : "RGD:A235727"
    }, {
      "firstName" : "D",
      "lastName" : "Manchester",
      "authorRank" : 18,
      "name" : "Manchester",
      "referenceId" : "RGD:A258818"
    }, {
      "firstName" : "S",
      "lastName" : "Miesfeldt",
      "authorRank" : 19,
      "name" : "Miesfeldt",
      "referenceId" : "RGD:A258819"
    }, {
      "firstName" : "VA",
      "lastName" : "Murday",
      "authorRank" : 20,
      "name" : "Murday VA",
      "referenceId" : "RGD:A80144"
    }, {
      "firstName" : "KL",
      "lastName" : "Nathanson",
      "authorRank" : 21,
      "name" : "Nathanson KL",
      "referenceId" : "RGD:A9660"
    }, {
      "firstName" : "M",
      "lastName" : "Parisi",
      "authorRank" : 22,
      "name" : "Parisi",
      "referenceId" : "RGD:A258820"
    }, {
      "firstName" : "B",
      "lastName" : "Pober",
      "authorRank" : 23,
      "name" : "Pober B",
      "referenceId" : "RGD:A63233"
    }, {
      "firstName" : "C",
      "lastName" : "Romano",
      "authorRank" : 24,
      "name" : "Romano C",
      "referenceId" : "RGD:A37352"
    }, {
      "firstName" : "C",
      "lastName" : "Eng",
      "authorRank" : 25,
      "name" : "Eng",
      "referenceId" : "RGD:A405865"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064501"
    } ]
  }, {
    "primaryId" : "PMID:10400996",
    "title" : "Linkage and association of atopic asthma to markers on chromosome 13 in the Japanese population.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Kimura K, etal., Hum Mol Genet 1999 Aug;8(8):1487-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-01-26T08:19:06.000-06:00",
    "volume" : "8",
    "pages" : "1487-90",
    "abstract" : "Chromosome 13 contains several candidate genes for asthma and atopy, and markers on this chromosome have been shown to be linked to phenotypes of atopy or asthma in two genome-wide searches. We conducted a linkage study for atopic asthma using markers spanning the whole of chromosome 13 in Japanese families ascertained through asthmatic children and examined associations of atopic asthma with markers where linkage was suggested. Data were analysed using MAPMAKER/SIBS for the multipoint lod score (MLS) analysis and SIB-PAIR for the transmission dis-equilibrium test (TDT). Three peaks which exceeded a lod score of 1.0 were observed (MLS 2.4 between D13S175 and D13S217, MLS 2.0 between D13S153 and D13S156, and MLS 1.4 between D13S285 and D13S293). The global TDT for atopic asthma was significant for the marker D13S153 ( P = 0.0065) and the 96 bp allele of D13S153 was preferentially transmitted to atopic asthma-affected children ( P = 0.0009, Bonferroni correction 5% = 0. 0037, 1% = 0.00072). These findings indicate that genes on chromosome 13 may play an important role in the development of atopy or asthma across various populations.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Kimura",
      "authorRank" : 1,
      "name" : "Kimura K",
      "referenceId" : "RGD:A8857"
    }, {
      "firstName" : "E",
      "lastName" : "Noguchi",
      "authorRank" : 2,
      "name" : "Noguchi E",
      "referenceId" : "RGD:A50436"
    }, {
      "firstName" : "M",
      "lastName" : "Shibasaki",
      "authorRank" : 3,
      "name" : "Shibasaki M",
      "referenceId" : "RGD:A50435"
    }, {
      "firstName" : "T",
      "lastName" : "Arinami",
      "authorRank" : 4,
      "name" : "Arinami T",
      "referenceId" : "RGD:A35984"
    }, {
      "firstName" : "Y",
      "lastName" : "Yokouchi",
      "authorRank" : 5,
      "name" : "Yokouchi Y",
      "referenceId" : "RGD:A50433"
    }, {
      "firstName" : "K",
      "lastName" : "Takeda",
      "authorRank" : 6,
      "name" : "Takeda K",
      "referenceId" : "RGD:A4193"
    }, {
      "firstName" : "K",
      "lastName" : "Yamakawa-Kobayashi",
      "authorRank" : 7,
      "name" : "Yamakawa-Kobayashi K",
      "referenceId" : "RGD:A35980"
    }, {
      "firstName" : "A",
      "lastName" : "Matsui",
      "authorRank" : 8,
      "name" : "Matsui A",
      "referenceId" : "RGD:A27427"
    }, {
      "firstName" : "H",
      "lastName" : "Hamaguchi",
      "authorRank" : 9,
      "name" : "Hamaguchi H",
      "referenceId" : "RGD:A35985"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1331589"
    } ]
  }, {
    "primaryId" : "PMID:10400998",
    "title" : "Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Bianchi L, etal., Hum Mol Genet. 1999 Aug;8(8):1499-507.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:38:02.000-05:00",
    "volume" : "8",
    "pages" : "1499-507",
    "abstract" : "Mutations in the minK gene KCNE1 have been linked to the LQT5 variant of human long QT syndrome. MinK assembles with KvLQT1 to produce the slow delayed rectifier K+ current IKs and may assemble with HERG to modulate the rapid delayed rectifier IKr. We used electrophysiological and immunocytochemical methods to compare the cellular phenotypes of wild-type minK and four LQT5 mutants co-expressed with KvLQT1 in Xenopus oocytes and HERG in HEK293 cells. We found that three mutants, V47F, W87R and D76N, were expressed at the cell surface, while one mutant, L51H, was not. Co-expression of V47F and W87R with KvLQT1 produced IKs currents having altered gating and reduced amplitudes compared with  WT-minK, co-expression with L51H produced KvLQT1 current rather than IKs and co-expression with D76N suppressed KvLQT1 current. V47F increased HERG current but to a lesser extent than WT-minK, while L51H and W87R had no effect and D76N suppressed HERG current markedly. Thus, V47F interacts with both KvLQT1 and HERG, W87R interacts functionally with KvLQT1 but not with HERG, D76N suppresses both KvLQT1 and HERG, and L51H is processed improperly and interacts with neither channel. We conclude that minK is a co-factor in the expression of both IKs and IKr and propose that clinical manifestations of LQT5 may be complicated by differing effects of minK mutations on KvLQT1 and HERG.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Bianchi",
      "authorRank" : 1,
      "name" : "Bianchi L",
      "referenceId" : "RGD:A154731"
    }, {
      "firstName" : "Z",
      "lastName" : "Shen",
      "authorRank" : 2,
      "name" : "Shen Z",
      "referenceId" : "RGD:A7212"
    }, {
      "firstName" : "AT",
      "lastName" : "Dennis",
      "authorRank" : 3,
      "name" : "Dennis",
      "referenceId" : "RGD:A259068"
    }, {
      "firstName" : "SG",
      "lastName" : "Priori",
      "authorRank" : 4,
      "name" : "Priori SG",
      "referenceId" : "RGD:A72524"
    }, {
      "firstName" : "C",
      "lastName" : "Napolitano",
      "authorRank" : 5,
      "name" : "Napolitano C",
      "referenceId" : "RGD:A72520"
    }, {
      "firstName" : "E",
      "lastName" : "Ronchetti",
      "authorRank" : 6,
      "name" : "Ronchetti",
      "referenceId" : "RGD:A219041"
    }, {
      "firstName" : "R",
      "lastName" : "Bryskin",
      "authorRank" : 7,
      "name" : "Bryskin",
      "referenceId" : "RGD:A259069"
    }, {
      "firstName" : "PJ",
      "lastName" : "Schwartz",
      "authorRank" : 8,
      "name" : "Schwartz",
      "referenceId" : "RGD:A250812"
    }, {
      "firstName" : "AM",
      "lastName" : "Brown",
      "authorRank" : 9,
      "name" : "Brown AM",
      "referenceId" : "RGD:A31063"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064571"
    } ]
  }, {
    "primaryId" : "PMID:10401760",
    "title" : "Inhibition of endothelin-converting enzyme attenuates transplant vasculopathy and rejection in rat cardiac allografts.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Simonson MS, etal., Transplantation. 1999 Jun 27;67(12):1542-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-23T13:37:17.000-05:00",
    "volume" : "67",
    "pages" : "1542-7",
    "abstract" : "BACKGROUND: Transplant vasculopathy in kidney and heart allografts is associated  with marked elevation of endothelin-1 (ET-1), but a role for ET-1 in the pathogenesis of transplant vasculopathy and chronic rejection has not been established. We, therefore, tested whether inhibition of ET-1-converting enzyme by phosphoramidon (PA) would attenuate rejection in a rat model of chronic cardiac allograft rejection (Lewis [LEW] to F344). METHODS: Donor LEW rats were pretreated 24 hr before transplantation with a bolus injection of vehicle (water) or PA. Twenty- four hour after transplantation, water or PA was continuously administered through an osmotic mini-pump. Plasma ET-1 levels in Fisher 344 (F344) recipients were 0.8+/-0.1 pg/ml in water-treated rats and 0.2+/-0.2 pg/ml  (P<0.01) in PA-treated rats, demonstrating that the PA treatment protocol effectively lowered ET-1 biosynthesis. RESULTS: LEW cardiac allografts treated with water survived (i.e., palpable heart beat) for 16.0+/-0.5 days (n=6). Inhibition of ET-1 secretion by PA improved allograft survival to 28.8+/-3.3 days (P<0.01, n=8). An analysis of cardiac arteries demonstrated that PA treatment attenuated transplant vasculopathy. A morphometric scale of neointima formation (0-5) was 1.4+/-0.2 and 3.6+/-0.2 in PA- or water-treated rats, respectively (P<0.01). The percent of luminal occlusion, as measured by microscopic image analysis, was 19+/-6% in PA-treated animals and 38+/-6% (P<0.01) in animals treated with water. PA treatment also reduced infiltration of ED-1-positive monocytes/macrophages into the vascular neointima. CONCLUSIONS: We conclude that, even in the absence of concomitant immunosuppression, inhibition of ET-1 biosynthesis significantly attenuates transplant vasculopathy and improves survival of LEW to F344 cardiac allografts.",
    "issueName" : "12",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MS",
      "lastName" : "Simonson",
      "authorRank" : 1,
      "name" : "Simonson",
      "referenceId" : "RGD:A170075"
    }, {
      "firstName" : "WH",
      "lastName" : "Herman",
      "authorRank" : 2,
      "name" : "Herman",
      "referenceId" : "RGD:A170076"
    }, {
      "firstName" : "A",
      "lastName" : "Robinson",
      "authorRank" : 3,
      "name" : "Robinson",
      "referenceId" : "RGD:A170077"
    }, {
      "firstName" : "J",
      "lastName" : "Schulak",
      "authorRank" : 4,
      "name" : "Schulak",
      "referenceId" : "RGD:A170078"
    }, {
      "firstName" : "DE",
      "lastName" : "Hricik",
      "authorRank" : 5,
      "name" : "Hricik",
      "referenceId" : "RGD:A170079"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7244165"
    } ]
  }, {
    "primaryId" : "PMID:10402458",
    "title" : "A visual screen of a GFP-fusion library identifies a new type of nuclear envelope membrane protein.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Rolls MM, etal., J Cell Biol 1999 Jul 12;146(1):29-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-12-28T08:43:30.000-06:00",
    "volume" : "146",
    "pages" : "29-44",
    "abstract" : "The nuclear envelope (NE) is a distinct subdomain of the ER, but few membrane components have been described that are specific to it. We performed a visual screen in tissue culture cells to identify proteins targeted to the NE. This approach does not require assumptions about the nature of the association with the NE or the physical separation of NE and ER. We confirmed that screening a library of fusions to the green fluorescent protein can be used to identify proteins targeted to various subcompartments of mammalian cells, including the NE. With this approach, we identified a new NE membrane protein, named nurim. Nurim is a multispanning membrane protein without large hydrophilic domains that is very tightly associated with the nucleus. Unlike the known NE membrane proteins, it is neither associated with nuclear pores, nor targeted like lamin-associated membrane proteins. Thus, nurim is a new type of NE membrane protein that is localized to the NE by a distinct mechanism.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Rolls",
      "authorRank" : 1,
      "name" : "Rolls MM",
      "referenceId" : "RGD:A49852"
    }, {
      "firstName" : "PA",
      "lastName" : "Stein",
      "authorRank" : 2,
      "name" : "Stein PA",
      "referenceId" : "RGD:A49853"
    }, {
      "firstName" : "SS",
      "lastName" : "Taylor",
      "authorRank" : 3,
      "name" : "Taylor SS",
      "referenceId" : "RGD:A6389"
    }, {
      "firstName" : "E",
      "lastName" : "Ha",
      "authorRank" : 4,
      "name" : "Ha E",
      "referenceId" : "RGD:A49854"
    }, {
      "firstName" : "F",
      "lastName" : "McKeon",
      "authorRank" : 5,
      "name" : "McKeon F",
      "referenceId" : "RGD:A49855"
    }, {
      "firstName" : "TA",
      "lastName" : "Rapoport",
      "authorRank" : 6,
      "name" : "Rapoport TA",
      "referenceId" : "RGD:A122893"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1304479"
    } ]
  }, {
    "primaryId" : "PMID:10402461",
    "title" : "GBF1: A novel Golgi-associated BFA-resistant guanine nucleotide exchange factor that displays specificity for ADP-ribosylation factor 5.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Claude A, etal., J Cell Biol. 1999 Jul 12;146(1):71-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-10T14:21:15.000-06:00",
    "volume" : "146",
    "pages" : "71-84",
    "abstract" : "Expression cloning from a cDNA library prepared from a mutant CHO cell line with Golgi-specific resistance to Brefeldin A (BFA) identified a novel 206-kD protein with a Sec7 domain termed GBF1 for Golgi BFA resistance factor 1. Overexpression of GBF1 allowed transfected cells to maintain normal Golgi morphology and grow in the presence of BFA. Golgi- enriched membrane fractions from such transfected cells displayed normal levels of ADP ribosylation factors (ARFs) activation and coat protein recruitment that were, however, BFA resistant. Hexahistidine-tagged-GBF1 exhibited BFA-resistant guanine nucleotide exchange activity that appears specific towards ARF5 at physiological Mg2+concentration. Characterization of cDNAs recovered from the mutant and wild-type parental lines established that transcripts in these cells had identical sequence and, therefore, that GBF1 was naturally BFA resistant. GBF1 was primarily cytosolic but a significant pool colocalized to a perinuclear structure with the beta-subunit of COPI. Immunogold labeling showed highest density of GBF1 over Golgi cisternae and significant labeling over pleiomorphic smooth vesiculotubular structures. The BFA-resistant nature of GBF1 suggests involvement in retrograde traffic.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Claude",
      "authorRank" : 1,
      "name" : "Claude A",
      "referenceId" : "RGD:A119018"
    }, {
      "firstName" : "BP",
      "lastName" : "Zhao",
      "authorRank" : 2,
      "name" : "Zhao BP",
      "referenceId" : "RGD:A119019"
    }, {
      "firstName" : "CE",
      "lastName" : "Kuziemsky",
      "authorRank" : 3,
      "name" : "Kuziemsky CE",
      "referenceId" : "RGD:A119020"
    }, {
      "firstName" : "S",
      "lastName" : "Dahan",
      "authorRank" : 4,
      "name" : "Dahan S",
      "referenceId" : "RGD:A85981"
    }, {
      "firstName" : "SJ",
      "lastName" : "Berger",
      "authorRank" : 5,
      "name" : "Berger SJ",
      "referenceId" : "RGD:A119021"
    }, {
      "firstName" : "JP",
      "lastName" : "Yan",
      "authorRank" : 6,
      "name" : "Yan JP",
      "referenceId" : "RGD:A119022"
    }, {
      "firstName" : "AD",
      "lastName" : "Armold",
      "authorRank" : 7,
      "name" : "Armold AD",
      "referenceId" : "RGD:A119023"
    }, {
      "firstName" : "EM",
      "lastName" : "Sullivan",
      "authorRank" : 8,
      "name" : "Sullivan EM",
      "referenceId" : "RGD:A119024"
    }, {
      "firstName" : "P",
      "lastName" : "Melancon",
      "authorRank" : 9,
      "name" : "Melancon P",
      "referenceId" : "RGD:A119017"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316367"
    } ]
  }, {
    "primaryId" : "PMID:10402475",
    "title" : "Glypican-3-deficient mice exhibit developmental overgrowth and some of the abnormalities typical of Simpson-Golabi-Behmel syndrome.",
    "datePublished" : "1999-07-12T00:00:00.000-05:00",
    "citation" : "Cano-Gauci DF, etal., J Cell Biol. 1999 Jul 12;146(1):255-64. doi: 10.1083/jcb.146.1.255.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-04-12T11:50:19.000-05:00",
    "volume" : "146",
    "pages" : "255-64",
    "abstract" : "Glypicans are a family of heparan sulfate proteoglycans that are linked to the cell surface through a glycosyl-phosphatidylinositol anchor. One member of this family, glypican-3 (Gpc3), is mutated in patients with the Simpson-Golabi-Behmel syndrome (SGBS). These patients display pre- and postnatal overgrowth, and a varying range of dysmorphisms. The clinical features of SGBS are very similar to the more extensively studied Beckwith-Wiedemann syndrome (BWS). Since BWS has been associated with biallelic expression of insulin-like growth factor II (IGF-II), it has been proposed that GPC3 is a negative regulator of IGF-II. However, there is still no biochemical evidence indicating that GPC3 plays such a role.Here, we report that GPC3-deficient mice exhibit several of the clinical features observed in SGBS patients, including developmental overgrowth, perinatal death, cystic and dyplastic kidneys, and abnormal lung development. A proportion of the mutant mice also display mandibular hypoplasia and an imperforate vagina. In the particular case of the kidney, we demonstrate that there is an early and persistent developmental abnormality of the ureteric bud/collecting system due to increased proliferation of cells in this tissue element. The degree of developmental overgrowth of the GPC3-deficient mice is similar to that of mice deficient in IGF receptor type 2 (IGF2R), a well characterized negative regulator of IGF-II. Unlike the IGF2R-deficient mice, however, the levels of IGF-II in GPC3 knockouts are similar to those of the normal littermates.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D F",
      "lastName" : "Cano-Gauci",
      "authorRank" : 1,
      "name" : "Cano-Gauci DF",
      "referenceId" : "RGD:A526379"
    }, {
      "firstName" : "H H",
      "lastName" : "Song",
      "authorRank" : 2,
      "name" : "Song HH",
      "referenceId" : "RGD:A526380"
    }, {
      "firstName" : "H",
      "lastName" : "Yang",
      "authorRank" : 3,
      "name" : "Yang H",
      "referenceId" : "RGD:A17044"
    }, {
      "firstName" : "C",
      "lastName" : "McKerlie",
      "authorRank" : 4,
      "name" : "McKerlie C",
      "referenceId" : "RGD:A44601"
    }, {
      "firstName" : "B",
      "lastName" : "Choo",
      "authorRank" : 5,
      "name" : "Choo B",
      "referenceId" : "RGD:A526381"
    }, {
      "firstName" : "W",
      "lastName" : "Shi",
      "authorRank" : 6,
      "name" : "Shi W",
      "referenceId" : "RGD:A5939"
    }, {
      "firstName" : "R",
      "lastName" : "Pullano",
      "authorRank" : 7,
      "name" : "Pullano R",
      "referenceId" : "RGD:A526382"
    }, {
      "firstName" : "T D",
      "lastName" : "Piscione",
      "authorRank" : 8,
      "name" : "Piscione TD",
      "referenceId" : "RGD:A526383"
    }, {
      "firstName" : "S",
      "lastName" : "Grisaru",
      "authorRank" : 9,
      "name" : "Grisaru S",
      "referenceId" : "RGD:A526384"
    }, {
      "firstName" : "S",
      "lastName" : "Soon",
      "authorRank" : 10,
      "name" : "Soon S",
      "referenceId" : "RGD:A526385"
    }, {
      "firstName" : "L",
      "lastName" : "Sedlackova",
      "authorRank" : 11,
      "name" : "Sedlackova L",
      "referenceId" : "RGD:A8544"
    }, {
      "firstName" : "A K",
      "lastName" : "Tanswell",
      "authorRank" : 12,
      "name" : "Tanswell AK",
      "referenceId" : "RGD:A526386"
    }, {
      "firstName" : "T W",
      "lastName" : "Mak",
      "authorRank" : 13,
      "name" : "Mak TW",
      "referenceId" : "RGD:A440664"
    }, {
      "firstName" : "H",
      "lastName" : "Yeger",
      "authorRank" : 14,
      "name" : "Yeger H",
      "referenceId" : "RGD:A87423"
    }, {
      "firstName" : "G A",
      "lastName" : "Lockwood",
      "authorRank" : 15,
      "name" : "Lockwood GA",
      "referenceId" : "RGD:A526387"
    }, {
      "firstName" : "N D",
      "lastName" : "Rosenblum",
      "authorRank" : 16,
      "name" : "Rosenblum ND",
      "referenceId" : "RGD:A526388"
    }, {
      "firstName" : "J",
      "lastName" : "Filmus",
      "authorRank" : 17,
      "name" : "Filmus J",
      "referenceId" : "RGD:A29967"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:243065142"
    } ]
  }, {
    "primaryId" : "PMID:10402503",
    "title" : "Studies of the 48 bp repeat polymorphism of the DRD4 gene in impulsive, compulsive, addictive behaviors: Tourette syndrome, ADHD, pathological gambling, and substance abuse.",
    "datePublished" : "1999-08-20T00:00:00.000-05:00",
    "citation" : "Comings DE, etal., Am J Med Genet. 1999 Aug 20;88(4):358-68.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-09-01T17:18:05.000-05:00",
    "volume" : "88",
    "pages" : "358-68",
    "abstract" : "Prior studies have reported an association between the presence of the 7 repeat allele of the 48 bp repeat polymorphism of the third cytoplasmic loop of the dopamine D4 receptor gene (DRD4) and novelty seeking behaviors, attention deficit hyperactivity disorder (ADHD), Tourette syndrome (TS), pathological gambling, and substance abuse. However, other studies have failed to replicate some of these observations. To determine whether we could replicate these associations we genotyped 737 individuals from four different groups of control subjects, and 707 index subjects from four different groups of impulsive, compulsive addictive behaviors including substance abuse, pathological gambling, TS, and ADHD. Chi-square analysis of those carrying the 7 allele versus non-7 allele carriers was not significant for any of the groups using a Bonferroni corrected alpha of.0125. However, chi-square analysis of those carrying any 5 to 8 allele versus noncarriers was significant for pathological gambling (p <.0001), ADHD (p </=.01) and the total index group (p </=.0004). When the comparison included all 7 alleles the results were significant for gamblers (p <.0001), TS (p </=.003), ADHD (p </=.003), and the total group (p </=.0002). There was a significant increase in the frequency of heterozygosity versus homozygosity for all alleles for pathological gamblers (p </=.0031) and the total index group (p </=.0015), suggesting that heterosis played a role. In the substance abuse subjects a quantitative summary variable for the severity of drug dependence, based on the Addiction Severity Index, showed that the scores varied by increasing severity across the following genotypes: 44 </= heterozygotes </= 77 </= 22. Studies of other quantitative traits indicated an important role for the 2 allele and the 22, 24, and 27 genotypes. All studies indicated that the role of the DRD4 gene in impulsive, compulsive, addictive behaviors is more complex than a sole focus on the 7 versus non-7 alleles.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D E",
      "lastName" : "Comings",
      "authorRank" : 1,
      "name" : "Comings DE",
      "referenceId" : "RGD:A438573"
    }, {
      "firstName" : "N",
      "lastName" : "Gonzalez",
      "authorRank" : 2,
      "name" : "Gonzalez N",
      "referenceId" : "RGD:A63407"
    }, {
      "firstName" : "S",
      "lastName" : "Wu",
      "authorRank" : 3,
      "name" : "Wu S",
      "referenceId" : "RGD:A5677"
    }, {
      "firstName" : "R",
      "lastName" : "Gade",
      "authorRank" : 4,
      "name" : "Gade R",
      "referenceId" : "RGD:A52526"
    }, {
      "firstName" : "D",
      "lastName" : "Muhleman",
      "authorRank" : 5,
      "name" : "Muhleman D",
      "referenceId" : "RGD:A52525"
    }, {
      "firstName" : "G",
      "lastName" : "Saucier",
      "authorRank" : 6,
      "name" : "Saucier G",
      "referenceId" : "RGD:A52206"
    }, {
      "firstName" : "P",
      "lastName" : "Johnson",
      "authorRank" : 7,
      "name" : "Johnson P",
      "referenceId" : "RGD:A28913"
    }, {
      "firstName" : "R",
      "lastName" : "Verde",
      "authorRank" : 8,
      "name" : "Verde R",
      "referenceId" : "RGD:A52527"
    }, {
      "firstName" : "R J",
      "lastName" : "Rosenthal",
      "authorRank" : 9,
      "name" : "Rosenthal RJ",
      "referenceId" : "RGD:A449781"
    }, {
      "firstName" : "H R",
      "lastName" : "Lesieur",
      "authorRank" : 10,
      "name" : "Lesieur HR",
      "referenceId" : "RGD:A449782"
    }, {
      "firstName" : "L J",
      "lastName" : "Rugle",
      "authorRank" : 11,
      "name" : "Rugle LJ",
      "referenceId" : "RGD:A449783"
    }, {
      "firstName" : "W B",
      "lastName" : "Miller",
      "authorRank" : 12,
      "name" : "Miller WB",
      "referenceId" : "RGD:A449784"
    }, {
      "firstName" : "J P",
      "lastName" : "MacMurray",
      "authorRank" : 13,
      "name" : "MacMurray JP",
      "referenceId" : "RGD:A449785"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13210523"
    } ]
  }, {
    "primaryId" : "PMID:10403029",
    "title" : "Modifications of HIV-1 retrovirus-like particles to enhance safety and immunogenicity.",
    "datePublished" : "1998-12-01T00:00:00.000-06:00",
    "citation" : "Persson RH, etal., Biologicals. 1998 Dec;26(4):255-65. doi: 10.1006/biol.1998.0142.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-04-19T10:09:29.000-05:00",
    "volume" : "26",
    "pages" : "255-65",
    "abstract" : "HIV-1 retrovirus-like particles can be produced in VERO cells that have been transfected with an expression construct encoding HIV-1 structural proteins. The particles are entirely non-infectious although structurally they resemble infectious virus particles. This makes them a promising candidate for use as an HIV-1 vaccine. In order to ensure their safety and enhance their immunogenicity, the retrovirus-like particles were modified in a number of ways. A large deletion in the HIV-1 pol gene has eliminated reverse transcriptase and integrase activities. Deletion of RNA packaging signals in the RNA untranslated leader sequence and in Gag reduced packaged RNA to 5% of that in HIV-1 virus. Replacement of the existing HIV-1LAI envelope protein with that of HIV-1MN has ensured that immune responses to the particles are relevant to those against the majority of HIV-1 clade B isolates. In addition to these changes in particle composition, yields of the modified particles were increased using a superior method of inducing the expression construct promoter, and an effective scheme for particle purification was developed. Immunization of non-human primates demonstrated that the particles were capable of generating anti-HIV-1 neutralizing antibodies. The technological refinements reported here will permit retrovirus-like particles to be tested safely in humans, and the change in envelope proteins should allow a more realistic evaluation of the immunogenicity of these particles. Experience gained in engineering these refinements will greatly facilitate other modifications that may be required to achieve maximum efficacy as a vaccine against HIV-1.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R H",
      "lastName" : "Persson",
      "authorRank" : 1,
      "name" : "Persson RH",
      "referenceId" : "RGD:A497381"
    }, {
      "firstName" : "S X",
      "lastName" : "Cao",
      "authorRank" : 2,
      "name" : "Cao SX",
      "referenceId" : "RGD:A497382"
    }, {
      "firstName" : "G",
      "lastName" : "Cates",
      "authorRank" : 3,
      "name" : "Cates G",
      "referenceId" : "RGD:A497383"
    }, {
      "firstName" : "F L",
      "lastName" : "Yao",
      "authorRank" : 4,
      "name" : "Yao FL",
      "referenceId" : "RGD:A497384"
    }, {
      "firstName" : "M H",
      "lastName" : "Klein",
      "authorRank" : 5,
      "name" : "Klein MH",
      "referenceId" : "RGD:A497385"
    }, {
      "firstName" : "B",
      "lastName" : "Rovinski",
      "authorRank" : 6,
      "name" : "Rovinski B",
      "referenceId" : "RGD:A497386"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:126781742"
    } ]
  }, {
    "primaryId" : "PMID:10403180",
    "title" : "Thyroglobulin binding and TSH regulation of the RHL-1 subunit of the asialoglycoprotein receptor in rat thyroid.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Pacifico F, etal., Biochimie. 1999 May;81(5):493-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-03-14T19:09:05.000-05:00",
    "volume" : "81",
    "pages" : "493-6",
    "abstract" : "The ability of asialo-thyroglobulin to bind the thyroid RHL-1 subunit of the asialoglycoprotein receptor has been investigated. Ligand blot assays show that the recombinant carbohydrate recognition domain of the thyroid RHL-1 subunit specifically interacts with rat desialated thyroglobulin. Moreover, RT-PCR and Western blot assays show that TSH deprivation decreases RHL-1 expression in PC C13 thyroid differentiated cells whereas insulin deprivation does not have any effect. The simultaneous absence of both TSH and insulin dramatically decreases the level of RHL-1 expression.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Pacifico",
      "authorRank" : 1,
      "name" : "Pacifico F",
      "referenceId" : "RGD:A160939"
    }, {
      "firstName" : "D",
      "lastName" : "Liguoro",
      "authorRank" : 2,
      "name" : "Liguoro",
      "referenceId" : "RGD:A180904"
    }, {
      "firstName" : "R",
      "lastName" : "Acquaviva",
      "authorRank" : 3,
      "name" : "Acquaviva R",
      "referenceId" : "RGD:A105262"
    }, {
      "firstName" : "S",
      "lastName" : "Formisano",
      "authorRank" : 4,
      "name" : "Formisano S",
      "referenceId" : "RGD:A105263"
    }, {
      "firstName" : "E",
      "lastName" : "Consiglio",
      "authorRank" : 5,
      "name" : "Consiglio E",
      "referenceId" : "RGD:A160940"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8548646"
    } ]
  }, {
    "primaryId" : "PMID:10403283",
    "title" : "Inhibitory effect of annexin I on synovial inflammation in rat adjuvant arthritis.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Yang Y, etal., Arthritis Rheum. 1999 Jul;42(7):1538-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-05-12T15:22:17.000-05:00",
    "volume" : "42",
    "pages" : "1538-44",
    "abstract" : "OBJECTIVE: Annexin I is an endogenous antiinflammatory mediator, expressed in rheumatoid arthritis (RA) synovium, the contribution of which to autoregulation of the synovial inflammatory response has not been examined in models of RA. We investigated the antiinflammatory role of annexin I in rat adjuvant arthritis. METHODS: Rats with adjuvant-induced arthritis (AIA) were treated with a specific anti-annexin I monoclonal antibody (mAb), isotype control IgG, and/or dexamethasone. Clinical outcomes and synovial synthesis of tumor necrosis factor alpha (TNFalpha), prostaglandin E2 (PGE2), and nitric oxide were examined, and annexin I expression was assessed by flow cytometry and reverse transcription-polymerase chain reaction. RESULTS: Anti-annexin I mAb reversed the effects of dexamethasone on the clinical features of AIA and exacerbated AIA in the absence of exogenous glucocorticoid. Clinical exacerbation of AIA by anti-annexin I mAb was accompanied by significantly increased synovial TNFalpha and PGE2, suggesting that annexin I tonically inhibits the production of these mediators. Anti-annexin I mAb treatment was associated with significantly reduced leukocyte intracellular annexin I, despite increased annexin I messenger RNA expression, consistent with a depletion effect of extracellular mAb via the cell surface. CONCLUSION: Annexin I is a key endogenous inhibitory mediator of arthritis via mechanisms that include inhibition of cytokine and effector molecule production. Moreover, a synthesis-independent depletion of intracellular annexin I by extracellular antibody supports the hypothesis that externalization of annexin I is involved in its mode of action.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang Y",
      "referenceId" : "RGD:A10922"
    }, {
      "firstName" : "P",
      "lastName" : "Hutchinson",
      "authorRank" : 2,
      "name" : "Hutchinson P",
      "referenceId" : "RGD:A106533"
    }, {
      "firstName" : "EF",
      "lastName" : "Morand",
      "authorRank" : 3,
      "name" : "Morand EF",
      "referenceId" : "RGD:A51358"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306928"
    } ]
  }, {
    "primaryId" : "PMID:10403390",
    "title" : "Cloning of a novel kinase (SIK) of the SNF1/AMPK family from high salt diet-treated rat adrenal.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Wang Z, etal., FEBS Lett 1999 Jun 18;453(1-2):135-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-11-26T12:12:49.000-06:00",
    "volume" : "453",
    "pages" : "135-9",
    "abstract" : "PCR-coupled cDNA subtraction hybridization was adapted to identify the genes expressed in the adrenocortical tissues from high salt diet-treated rat. A novel cDNA clone, termed salt-inducible kinase (SIK), encoding a polypeptide (776 amino acids) with significant similarity to protein serine/ threonine kinases in the SNF1/AMPK family was isolated. An in vitro kinase assay demonstrated that SIK protein had autophosphorylation activity. Northern blot revealed that SIK mRNA levels were markedly augmented by ACTH treatment both in rat adrenal glands and in Y1 cells. SIK may play an important role in the regulation of adrenocortical functions in response to high plasma salt and ACTH stimulation.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang Z",
      "referenceId" : "RGD:A161162"
    }, {
      "firstName" : "H",
      "lastName" : "Takemori",
      "authorRank" : 2,
      "name" : "Takemori H",
      "referenceId" : "RGD:A6547"
    }, {
      "firstName" : "SK",
      "lastName" : "Halder",
      "authorRank" : 3,
      "name" : "Halder SK",
      "referenceId" : "RGD:A6548"
    }, {
      "firstName" : "Y",
      "lastName" : "Nonaka",
      "authorRank" : 4,
      "name" : "Nonaka Y",
      "referenceId" : "RGD:A6549"
    }, {
      "firstName" : "M",
      "lastName" : "Okamoto",
      "authorRank" : 5,
      "name" : "Okamoto M",
      "referenceId" : "RGD:A159261"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69385"
    } ]
  }, {
    "primaryId" : "PMID:10403401",
    "title" : "Cytokine-inducible CD40 gene expression in vascular smooth muscle cells is mediated by nuclear factor kappaB and signal transducer and activation of transcription-1.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Krzesz R, etal., FEBS Lett 1999 Jun 18;453(1-2):191-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:31:41.000-05:00",
    "volume" : "453",
    "pages" : "191-6",
    "abstract" : "The interaction of T-lymphocytes expressing the CD40 ligand (CD154) and cells of the vessel wall expressing the corresponding receptor protein (CD40) may play an important role in chronic inflammation including arteriosclerosis. One way of interfering with CD40-CD154 signalling is to prevent CD40 expression, the regulation of which, however, has yet to be elucidated. Therefore, we studied CD40 expression in rat aortic cultured smooth muscle cells. Both CD40 mRNA and protein expression in these cells was markedly enhanced as early as 6 h after exposure to different pro-inflammatory cytokines. Experiments with actinomycin D and subsequent run-on analyses revealed that CD40 expression in response to these cytokines was regulated at the level of transcription. Moreover, electrophoretic mobility shift analyses along with the employment of transcription factor decoy oligodeoxynucleotides demonstrated that tumor necrosis factor alpha via nuclear kappaB and interferon-gamma via signal transducer and activator of transcription-1 up-regulate CD40 gene expression in rat aortic cultured smooth muscle cells.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Krzesz",
      "authorRank" : 1,
      "name" : "Krzesz R",
      "referenceId" : "RGD:A23659"
    }, {
      "firstName" : "AH",
      "lastName" : "Wagner",
      "authorRank" : 2,
      "name" : "Wagner AH",
      "referenceId" : "RGD:A23660"
    }, {
      "firstName" : "M",
      "lastName" : "Cattaruzza",
      "authorRank" : 3,
      "name" : "Cattaruzza M",
      "referenceId" : "RGD:A18116"
    }, {
      "firstName" : "M",
      "lastName" : "Hecker",
      "authorRank" : 4,
      "name" : "Hecker M",
      "referenceId" : "RGD:A18118"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634252"
    } ]
  }, {
    "primaryId" : "PMID:10403529",
    "title" : "Cellular localization of hepatic cytochrome 1B1 expression and its regulation by  aromatic hydrocarbons and inflammatory cytokines.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Piscaglia F, etal., Biochem Pharmacol. 1999 Jul 1;58(1):157-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-21T16:11:48.000-06:00",
    "volume" : "58",
    "pages" : "157-65",
    "abstract" : "Cytochrome P450 1B1 (CYP1B1) is an activator of several xenobiotics and is induced in the liver upon experimental exposure to aromatic hydrocarbons. Since its cellular localization and regulation are incompletely clarified, Cyp1B1 expression and inducibility by 9,10-dimethyl-1,2-benzanthracene (DMBA) and inflammatory cytokines were investigated in different rat liver cell populations  in vitro and in the liver during hepatocellular injury. Expression of Cyp1B1 was  studied by Northern blot analysis in hepatic stellate cells (HSCs), myofibroblasts (MFs), Kupffer cells (KCs), and hepatocytes at various time points of primary cultures and in acutely damaged rat liver (carbon tetrachloride model). Enzyme inducibility was assessed by incubation of cells with DMBA as well as, in the case of HSCs, with tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor beta1 (TGFbeta1). Cyp1B1 messengers were expressed at  high levels by HSCs and MFs, whereas constitutive expression was not detectable in KCs or in hepatocytes. Cyp1B1-specific mRNA were expressed at highest levels in HSCs at an early stage of activation (2 days after plating) and were diminished upon further activation. DMBA strongly enhanced Cyp1B1 gene expression in HSCs, MFs, and in hepatocytes at day 3 of primary cultures, but not in hepatocytes at day 1, or in KCs. The inflammatory cytokine TNF-alpha enhanced the Cyp1B1 gene expression in HSCs, either when administered alone or in addition to  DMBA, while TGFbeta1 did not affect Cyp1B1 expression, even after DMBA induction. We conclude that HSCs and MFs seem to be the major cellular sources of hepatic Cyp1B1 expression and that the constitutive expression of the Cyp1B1 gene and the responsiveness to DMBA stimulation differ between mesenchymal and parenchymal liver cells, indicating a cell-specific regulation of Cyp1B1 gene expression. Interestingly, TNF-alpha is a potent stimulator of the Cyp1B1 gene in HSCs and acts in concert with DMBA.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Piscaglia",
      "authorRank" : 1,
      "name" : "Piscaglia F",
      "referenceId" : "RGD:A122562"
    }, {
      "firstName" : "T",
      "lastName" : "Knittel",
      "authorRank" : 2,
      "name" : "Knittel T",
      "referenceId" : "RGD:A15131"
    }, {
      "firstName" : "D",
      "lastName" : "Kobold",
      "authorRank" : 3,
      "name" : "Kobold D",
      "referenceId" : "RGD:A122561"
    }, {
      "firstName" : "S",
      "lastName" : "Barnikol-Watanabe",
      "authorRank" : 4,
      "name" : "Barnikol-Watanabe",
      "referenceId" : "RGD:A178304"
    }, {
      "firstName" : "P",
      "lastName" : "Di Rocco",
      "authorRank" : 5,
      "name" : "Di Rocco",
      "referenceId" : "RGD:A178305"
    }, {
      "firstName" : "G",
      "lastName" : "Ramadori",
      "authorRank" : 6,
      "name" : "Ramadori G",
      "referenceId" : "RGD:A12547"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7815048"
    } ]
  }, {
    "primaryId" : "PMID:10403542",
    "title" : "Genetic properties for the suppression of development of putative preneoplastic glutathione S-transferase placental form-positive foci in the liver of carcinogen-resistant DRH strain rats.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Denda A, etal., Cancer Lett 1999 Jun 1;140(1-2):59-67.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T10:07:31.000-05:00",
    "volume" : "140",
    "pages" : "59-67",
    "abstract" : "The post-initiation stage of hepatocarcinogenesis was investigated in carcinogen-resistant inbred DRH rats and the parental strain, carcinogen-sensitive Donryu rats. Male rats at 5 weeks of age from both strains were treated with N-nitrosodiethylamine (200 mg/kg i.p.) followed by feeding with a diet containing 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) from 2 weeks later and were then subjected to partial hepatectomy at 1 week later. At 8 weeks after the start of treatment, the mean area occupied by glutathione S-transferase placental form (GST-P)-positive lesions was about 30% in Donryu rats but less than 4% in DRH rats despite the presence of comparable numbers of foci in the livers of both strains. These observations suggested that clonal expansion of GST-P-positive foci in DRH rat liver was significantly suppressed under these conditions. Furthermore, this genetic property was dominantly inherited in the F1 rats by crosses of DRH and carcinogen-sensitive inbred F344 rats; that is, the induction of GST-P mRNA in the livers of F344 x DRH F1 rats was dominantly suppressed after administration of 3'-Me-DAB for 8 weeks as compared with parental F344 rats under the same conditions. We compared the intrinsic properties related to growth potential of liver cells between adult DRH and Donryu rats. DRH rat liver showed retarded and/or reduced DNA synthesis after partial hepatectomy or a single i.v. injection of lead nitrate and lower activity of telomerase induced by 3'-Me-DAB administration for 1 week, as compared with the Donryu rat liver. The intrinsic properties observed in this study may be related, at least in part, to the low incidence of liver tumors induced by hepatocarcinogens in DRH rats.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Denda",
      "authorRank" : 1,
      "name" : "Denda A",
      "referenceId" : "RGD:A10802"
    }, {
      "firstName" : "W",
      "lastName" : "Kitayama",
      "authorRank" : 2,
      "name" : "Kitayama W",
      "referenceId" : "RGD:A10801"
    }, {
      "firstName" : "Y",
      "lastName" : "Konishi",
      "authorRank" : 3,
      "name" : "Konishi Y",
      "referenceId" : "RGD:A8646"
    }, {
      "firstName" : "Y",
      "lastName" : "Yan",
      "authorRank" : 4,
      "name" : "Yan Y",
      "referenceId" : "RGD:A10803"
    }, {
      "firstName" : "Y",
      "lastName" : "Fukamachi",
      "authorRank" : 5,
      "name" : "Fukamachi Y",
      "referenceId" : "RGD:A12642"
    }, {
      "firstName" : "M",
      "lastName" : "Miura",
      "authorRank" : 6,
      "name" : "Miura M",
      "referenceId" : "RGD:A12643"
    }, {
      "firstName" : "S",
      "lastName" : "Gotoh",
      "authorRank" : 7,
      "name" : "Gotoh S",
      "referenceId" : "RGD:A12644"
    }, {
      "firstName" : "K",
      "lastName" : "Ikemura",
      "authorRank" : 8,
      "name" : "Ikemura K",
      "referenceId" : "RGD:A12645"
    }, {
      "firstName" : "T",
      "lastName" : "Abe",
      "authorRank" : 9,
      "name" : "Abe T",
      "referenceId" : "RGD:A8476"
    }, {
      "firstName" : "T",
      "lastName" : "Higashi",
      "authorRank" : 10,
      "name" : "Higashi T",
      "referenceId" : "RGD:A12646"
    }, {
      "firstName" : "K",
      "lastName" : "Higashi",
      "authorRank" : 11,
      "name" : "Higashi K",
      "referenceId" : "RGD:A10805"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:625658"
    } ]
  }, {
    "primaryId" : "PMID:10403766",
    "title" : "BCR binds to the xeroderma pigmentosum group B protein.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Maru Y, etal., Biochem Biophys Res Commun. 1999 Jul 5;260(2):309-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-12T13:59:02.000-05:00",
    "volume" : "260",
    "pages" : "309-12",
    "abstract" : "The BCR gene is involved in the formation of the BCR-ABL oncogene responsible for the pathogenesis of Philadelphia chromosome-positive human leukemias. We have previously shown that P210 BCR-ABL binds to the xeroderma pigmentosum group B protein (XPB) through the portion of BCR that is homologous to the catalytic domain of GDP-GTP exchangers such as yeast CDC24 and Dbl. In the baculovirus overexpression system which facilitates binding of coexpressed proteins, we now show that XPB binds to the intact BCR protein efficiently but not to CDC24 or Dbl, suggesting specificity of this interaction. The binding of endogenous BCR and XPB proteins was also detected in Hela cells, and this was inhibited by a blocking peptide. Full-length (1-782) XPB and its truncated form (203-782), which does not contain the nuclear localization signal, were tagged with glutathione S-transferase (GST) and were expressed in Rat1 fibroblasts. GST-XPB(203-782) was localized predominantly in the cytoplasm and bound to BCR but not to p62, one of the other components in TFIIH. GST-XPB(1-782) was largely in the nucleus and bound to p62 and BCR. Although the biological significance of the binding remains to be uncovered, BCR binds to the XPB/p62 complex.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Maru",
      "authorRank" : 1,
      "name" : "Maru Y",
      "referenceId" : "RGD:A46317"
    }, {
      "firstName" : "T",
      "lastName" : "Kobayashi",
      "authorRank" : 2,
      "name" : "Kobayashi T",
      "referenceId" : "RGD:A5222"
    }, {
      "firstName" : "K",
      "lastName" : "Tanaka",
      "authorRank" : 3,
      "name" : "Tanaka K",
      "referenceId" : "RGD:A297697"
    }, {
      "firstName" : "M",
      "lastName" : "Shibuya",
      "authorRank" : 4,
      "name" : "Shibuya M",
      "referenceId" : "RGD:A6324"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600513"
    } ]
  }, {
    "primaryId" : "PMID:10403848",
    "title" : "Ontogeny and species differences in the pancreatic expression and localization of the CCK(A) receptors.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Bourassa J, etal., Biochem Biophys Res Commun. 1999 Jul 14;260(3):820-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-18T08:44:51.000-05:00",
    "volume" : "260",
    "pages" : "820-8",
    "abstract" : "We have evaluated the presence and localization of the CCK(A) receptor in rat, mouse, pig and human fetal pancreas by Northern, Western blots and immunofluorescence techniques. In the rat, parallelism exists between development of the CCK(A) receptor mRNA and protein with maximal peaks of expression during the suckling period. In the course of pancreatitis induction, CCK(A) receptor mRNA were maximally expressed and sustained during the gland's regeneration. In the rat and mouse pancreas, the CCK(A) receptor protein is localized around the acinar cells and beta cells of the islets of Langerhans. In the adult pig and fetal human pancreas, the CCK(A) receptor proteins were detected by Western blot. By immunofluorescence, its detection was possible only in the islet of Langerhans of the pig pancreas. These new findings support the views that CCK plays important and various roles in specific physiological systems of the pancreas of different species.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Bourassa",
      "authorRank" : 1,
      "name" : "Bourassa J",
      "referenceId" : "RGD:A99284"
    }, {
      "firstName" : "J",
      "lastName" : "Laine",
      "authorRank" : 2,
      "name" : "Laine J",
      "referenceId" : "RGD:A52538"
    }, {
      "firstName" : "ML",
      "lastName" : "Kruse",
      "authorRank" : 3,
      "name" : "Kruse ML",
      "referenceId" : "RGD:A112405"
    }, {
      "firstName" : "MC",
      "lastName" : "Gagnon",
      "authorRank" : 4,
      "name" : "Gagnon MC",
      "referenceId" : "RGD:A112406"
    }, {
      "firstName" : "E",
      "lastName" : "Calvo",
      "authorRank" : 5,
      "name" : "Calvo E",
      "referenceId" : "RGD:A112407"
    }, {
      "firstName" : "J",
      "lastName" : "Morisset",
      "authorRank" : 6,
      "name" : "Morisset J",
      "referenceId" : "RGD:A6035"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313336"
    } ]
  }, {
    "primaryId" : "PMID:10404008",
    "title" : "Mechanical tension-stress induces expression of bone morphogenetic protein (BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Sato M, etal., J Bone Miner Res. 1999 Jul;14(7):1084-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-01-15T12:15:56.000-06:00",
    "volume" : "14",
    "pages" : "1084-95",
    "abstract" : "Bone lengthening with osteotomy and gradual distraction was achieved in 57 rats, and the effect of mechanical tension-stress on gene expression of bone morphogenetic proteins (BMPs) was investigated by in situ hybridization and Northern blot analysis using probes of BMP-2, BMP-4, BMP-6, BMP-7, and growth/differentiation factor (GDF)-5. There was a lag phase for 7 days after femoral osteotomy until gradual distraction was carried out for 21 days at a rate of 0. 25 mm/12 h using a small external fixator. The signals of the above BMPs mRNA were not detected in the intact rat bone but they were induced after osteotomy except those for BMP-7. By 4 days after osteotomy, BMP-2 and BMP-4 mRNAs were detected in chondrogenic precursor cells in the subperiosteal immature callus. BMP-6 and GDF-5 mRNA were detected in more differentiated cells in chondroid bone. By 7 days after osteotomy, cartilaginous external callus and bony endosteal callus were formed. Meanwhile, the signals of BMP-2 and BMP-4 mRNAs declined to preoperative levels, whereas the signals of BMP-6 and GDF-5 mRNAs were rather elevated. As distraction was started, the callus elongated and eventually separated into proximal and distal segments forming a fibrous interzone in the middle. Expression of BMP-2 and BMP-4 mRNAs was markedly induced at this stage. Their signals were detected widely among chondrogenic and osteogenic cells and their precursor cells sustaining mechanical tension-stress at the fibrous interzone. BMP-6 and GDF-5 mRNAs were detected exclusively in chondrogenic cells at both ends of the fibrous interzone, where endochondral ossification occurred. But neither mRNA was detected in terminally differentiated hypertrophic chondrocytes. As distraction advanced, the cartilage was progressively resorbed from both ends and new bone was formed directly by intramembranous ossification. There was no new cartilage formation in the advanced stage of distraction. The signals of BMP-6 and GDF-5 mRNA declined by this stage, while those of BMP-2 and BMP-4 were maintained at high level for as long as distraction was continued. After completion of distraction, the fibrous interzone fused and the lengthened segment was consolidated. BMP-2, BMP-4, BMP-6, nor GDF-5 was expressed at this stage. The signals of BMP-7 were not detected throughout the experiment. The present results suggest that excellent and uninterrupted bone formation during distraction osteogenesis owes to enhanced expression of BMP-2 and BMP-4 genes by mechanical tension-stress. Abundant gene products of BMP-2 and BMP-4 could induce in situ bone formation by paracrine and autocrine mechanisms.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Sato",
      "authorRank" : 1,
      "name" : "Sato M",
      "referenceId" : "RGD:A154914"
    }, {
      "firstName" : "T",
      "lastName" : "Ochi",
      "authorRank" : 2,
      "name" : "Ochi T",
      "referenceId" : "RGD:A23067"
    }, {
      "firstName" : "T",
      "lastName" : "Nakase",
      "authorRank" : 3,
      "name" : "Nakase T",
      "referenceId" : "RGD:A69188"
    }, {
      "firstName" : "S",
      "lastName" : "Hirota",
      "authorRank" : 4,
      "name" : "Hirota S",
      "referenceId" : "RGD:A13881"
    }, {
      "firstName" : "Y",
      "lastName" : "Kitamura",
      "authorRank" : 5,
      "name" : "Kitamura Y",
      "referenceId" : "RGD:A142002"
    }, {
      "firstName" : "S",
      "lastName" : "Nomura",
      "authorRank" : 6,
      "name" : "Nomura S",
      "referenceId" : "RGD:A10331"
    }, {
      "firstName" : "N",
      "lastName" : "Yasui",
      "authorRank" : 7,
      "name" : "Yasui N",
      "referenceId" : "RGD:A51784"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289026"
    } ]
  }, {
    "primaryId" : "PMID:10404063",
    "title" : "Predominant germ-line mutation of the hMSH2 gene in Japanese hereditary non-polyposis colorectal cancer kindreds.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Bai YQ, etal., Int J Cancer. 1999 Aug 12;82(4):512-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:20:17.000-05:00",
    "volume" : "82",
    "pages" : "512-5",
    "abstract" : "By means of PCR-SSCP and direct sequencing, we detected 12 germ-line mutations of hMSH2 or hMLH1 in 37 Japanese hereditary non-polyposis colorectal cancer (HNPCC)  kindreds, of whom 15 satisfied the Amsterdam and 22 the Japanese criteria. The germ-line mutation detection rate of hMSH2 was much higher than that of hMLH1 (11/37 vs. 1/37). The total mutation detection rate of hMSH2 and hMLH1 in the Amsterdam criteria group was significantly higher than that in the Japanese criteria group (9/15 vs. 3/22). Furthermore, the mean age of the HNPCC patients in the mutation-positive group was lower than that in the mutation-negative one;  the rates of both vertical transmission and multiplicity of tumors in the mutation-positive group were higher than those in the mutation-negative one. In addition, the number of patients with microsatellite instability-positive cancers in the mutation-positive group was higher than that in the mutation-negative one. Our results suggest firstly that the hMSH2 gene plays a much more important role  than hMLH1 in the carcinogenesis of Japanese HNPCC patients, secondly that the rate of hMSH2 and hMLH1 mutations is high in the kindreds satisfying the Amsterdam criteria and thirdly that both the clinical phenotypes (early onset, vertical transmission and multiplicity of tumors) and the microsatellite instability status are important for the genetic screening of HNPCC.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YQ",
      "lastName" : "Bai",
      "authorRank" : 1,
      "name" : "Bai",
      "referenceId" : "RGD:A256904"
    }, {
      "firstName" : "Y",
      "lastName" : "Akiyama",
      "authorRank" : 2,
      "name" : "Akiyama Y",
      "referenceId" : "RGD:A60358"
    }, {
      "firstName" : "H",
      "lastName" : "Nagasaki",
      "authorRank" : 3,
      "name" : "Nagasaki H",
      "referenceId" : "RGD:A114798"
    }, {
      "firstName" : "SL",
      "lastName" : "Lu",
      "authorRank" : 4,
      "name" : "Lu SL",
      "referenceId" : "RGD:A42486"
    }, {
      "firstName" : "T",
      "lastName" : "Arai",
      "authorRank" : 5,
      "name" : "Arai T",
      "referenceId" : "RGD:A57955"
    }, {
      "firstName" : "T",
      "lastName" : "Morisaki",
      "authorRank" : 6,
      "name" : "Morisaki T",
      "referenceId" : "RGD:A7009"
    }, {
      "firstName" : "M",
      "lastName" : "Kitamura",
      "authorRank" : 7,
      "name" : "Kitamura M",
      "referenceId" : "RGD:A22277"
    }, {
      "firstName" : "A",
      "lastName" : "Muto",
      "authorRank" : 8,
      "name" : "Muto A",
      "referenceId" : "RGD:A98530"
    }, {
      "firstName" : "M",
      "lastName" : "Nagashima",
      "authorRank" : 9,
      "name" : "Nagashima M",
      "referenceId" : "RGD:A5629"
    }, {
      "firstName" : "T",
      "lastName" : "Nomizu",
      "authorRank" : 10,
      "name" : "Nomizu T",
      "referenceId" : "RGD:A60359"
    }, {
      "firstName" : "T",
      "lastName" : "Iwama",
      "authorRank" : 11,
      "name" : "Iwama T",
      "referenceId" : "RGD:A17034"
    }, {
      "firstName" : "H",
      "lastName" : "Itoh",
      "authorRank" : 12,
      "name" : "Itoh H",
      "referenceId" : "RGD:A7545"
    }, {
      "firstName" : "S",
      "lastName" : "Baba",
      "authorRank" : 13,
      "name" : "Baba S",
      "referenceId" : "RGD:A35966"
    }, {
      "firstName" : "T",
      "lastName" : "Iwai",
      "authorRank" : 14,
      "name" : "Iwai T",
      "referenceId" : "RGD:A13974"
    }, {
      "firstName" : "Y",
      "lastName" : "Yuasa",
      "authorRank" : 15,
      "name" : "Yuasa Y",
      "referenceId" : "RGD:A37841"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063948"
    } ]
  }, {
    "primaryId" : "PMID:10404069",
    "title" : "Acquired immunity in nude mice induced by expression of the IL-2 or IL-4 gene in human pancreatic carcinoma cells and anti-tumor effect generated by in vivo gene transfer using retrovirus.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kimura M, etal., Int J Cancer. 1999 Aug 12;82(4):549-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-24T17:00:02.000-05:00",
    "volume" : "82",
    "pages" : "549-55",
    "abstract" : "We have examined the anti-tumor effect in nude mice caused by human pancreatic cancer cells (AsPC-1) modified to secrete IL-2 or IL-4. Loss of tumorigenicity of cytokine-producing, but not wild-type, cells was observed despite their unaltered in vitro proliferation rates; and these anti-tumor effects were dependent on the amount of cytokine released. Wild-type cells inoculated into mice which had rejected IL-2- or IL-4-producer cells showed significant growth retardation, while no retardation was detected when unrelated human colon carcinoma cells were inoculated. Histological examination of regressing IL-2- or IL-4-producing AsPC-1 tumors in nude mice revealed infiltration by CD11b-, but not CD90-, positive cells around the tumors. Treatment of nude mice with anti-asialoGM(1) antibody did not affect loss of tumorigenicity. Mice injected i.p. with IL-2- or IL-4-producing AsPC-1 cells did not die, in contrast to mice inoculated with wild-type cells. Injection of retrovirus-bearing IL-2, but not beta-galactosidase, gene into mice which had wild-type cells in the peritoneal cavity also significantly prolonged survival. Thus, expression of the IL-2 or IL-4 gene in AsPC-1 cells may generate tumor-specific acquired immunity, even in mature T cell-deficient conditions. An anti-tumor response can be induced by in vivo transfer of the IL-2 gene.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kimura",
      "authorRank" : 1,
      "name" : "Kimura M",
      "referenceId" : "RGD:A14901"
    }, {
      "firstName" : "Y",
      "lastName" : "Yoshida",
      "authorRank" : 2,
      "name" : "Yoshida Y",
      "referenceId" : "RGD:A6909"
    }, {
      "firstName" : "M",
      "lastName" : "Narita",
      "authorRank" : 3,
      "name" : "Narita M",
      "referenceId" : "RGD:A5781"
    }, {
      "firstName" : "K",
      "lastName" : "Takenaga",
      "authorRank" : 4,
      "name" : "Takenaga K",
      "referenceId" : "RGD:A69558"
    }, {
      "firstName" : "T",
      "lastName" : "Takenouchi",
      "authorRank" : 5,
      "name" : "Takenouchi T",
      "referenceId" : "RGD:A120859"
    }, {
      "firstName" : "T",
      "lastName" : "Yamaguchi",
      "authorRank" : 6,
      "name" : "Yamaguchi T",
      "referenceId" : "RGD:A12815"
    }, {
      "firstName" : "H",
      "lastName" : "Saisho",
      "authorRank" : 7,
      "name" : "Saisho H",
      "referenceId" : "RGD:A120860"
    }, {
      "firstName" : "S",
      "lastName" : "Sakiyama",
      "authorRank" : 8,
      "name" : "Sakiyama S",
      "referenceId" : "RGD:A120861"
    }, {
      "firstName" : "M",
      "lastName" : "Tagawa",
      "authorRank" : 9,
      "name" : "Tagawa M",
      "referenceId" : "RGD:A120862"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317267"
    } ]
  }, {
    "primaryId" : "PMID:10404396",
    "title" : "Ethanol inhibits prolactin-induced activation of the JAK/STAT pathway in cultured astrocytes.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "DeVito WJ and Stone S, J Cell Biochem. 1999 Aug 1;74(2):278-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-01-22T14:45:02.000-06:00",
    "volume" : "74",
    "pages" : "278-91",
    "abstract" : "Alcohol consumption has multiple effects in the central nervous system (CNS). Whereas, alcohol is an immunosuppressive drug the effect of alcohol on the neuroimmune system, remains unclear. In cultured astrocytes, prolactin (PRL) induces mitogenesis and the expression of inflammatory cytokines, including tumor necrosis factor-alpha (TNF alpha). We have recently shown that whereas ethanol does not inhibit PRL receptor binding, it markedly inhibits PRL-induced mitogenesis and TNF alpha secretion in cultured astrocytes. It is clear that PRL activates the tyrosine phosphorylation of several proteins, including members of a novel family of protein tyrosine kinases, the Janus Kinases (JAKs). The aims of this study were to characterize PRL-induced activation of the JAK/STAT (signal transducers and activators of transcription) pathway, and to determine if ethanol affects JAK/STAT activation in cultured astrocytes. We found that PRL specifically increases the tyrosine phosphorylation of JAK2, but not JAK1, JAK3, or Tyk2, and the subsequent phosphorylation of STAT1 alpha, STAT5a, and STAT5b. Preincubation of astrocytes with ethanol markedly inhibited phosphorylation of JAK2, STAT1 alpha, STAT5a, and STAT5b. In PRL-stimulated astrocytes, ethanol inhibited binding of nuclear proteins to oligonucleotides corresponding to the gamma-interferon activated sequence (GAS). Further, ethanol blocked PRL-induced increases in interferon regulatory factor-1 (IRF-1) mRNA, a PRL/cytokine inducible transcription factor involved in the regulation of a number of cytokine inducible genes. The inhibition of tyrosine phosphorylation by ethanol was not a general effect, however, as we found that ethanol increased basal and NGF-induced tyrosine phosphorylation of extracellular signal-activated protein kinase-1 (ERK-1). These data indicate that ethanol inhibits PRL-induced tyrosine phosphorylation of the JAK/STAT pathway resulting in decreased nuclear GAS DNA binding and inhibition of the PRL inducible gene, IRF-1. Thus, suggesting that ethanol-induced inhibition of JAK2 phosphorylation may be one mechanism though which ethanol could after the brain's response to injury or infection.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W J",
      "lastName" : "DeVito",
      "authorRank" : 1,
      "name" : "DeVito WJ",
      "referenceId" : "RGD:A537787"
    }, {
      "firstName" : "S",
      "lastName" : "Stone",
      "authorRank" : 2,
      "name" : "Stone S",
      "referenceId" : "RGD:A39837"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401959328"
    } ]
  }, {
    "primaryId" : "PMID:10404802",
    "title" : "Plasma brain natriuretic peptide levels in normotensive noninsulin-dependent diabetic patients with microalbuminuria.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Yano Y, etal., J Clin Endocrinol Metab. 1999 Jul;84(7):2353-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-07-30T11:38:35.000-05:00",
    "volume" : "84",
    "pages" : "2353-6",
    "abstract" : "Brain natriuretic peptide (BNP), a member of the natriuretic peptide family, is produced and released from cardiac ventricles. BNP regulates the body fluid volume, blood pressure, and vascular tones through the A-type guanylate cyclase-coupled receptor. The presence of renal dysfunction in patients with diabetes affects the plasma levels of atrial natriuretic peptide (ANP). In the present study, we investigated the plasma levels of BNP and ANP and their relationship in normotensive diabetic patients with normoalbuminuria and microalbuminuria. Forty-seven normotensive lean noninsulin-dependent diabetic patients (31 with normoalbuminuria, 16 with microalbuminuria), with normal cardiac function, and 30 age-matched control subjects were enrolled in this study. The plasma levels of BNP in diabetic patients with microalbuminuria were significantly higher than those in diabetic patients with normoalbuminuria (16.7+/-2.4 vs. 9.6+/-1.3 pg/mL, P<0.01) or normal subjects (16.7+/-2.4 vs. 7.0+/-0.6 pg/mL, P<0.01). There was a significant positive correlation between plasma BNP levels and urinary albumin excretion rate in all diabetic patients (r  = 0.58, P<0.0001). There was also a significantly positive correlation between plasma BNP and ANP levels in diabetic patients (r = 0.62, P<0.0001). The increased plasma level of BNP in patients with microalbuminuria and its significant correlation with urinary albumin excretion rate suggest that the elevated circulating levels of BNP are caused by the presence of diabetic nephropathy. Down-regulation of A-type guanylate cyclase-coupled receptor of renal tubules may explain the increased plasma levels of both BNP and ANP in normotensive diabetic patients with microalbuminuria.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Yano",
      "authorRank" : 1,
      "name" : "Yano Y",
      "referenceId" : "RGD:A44371"
    }, {
      "firstName" : "A",
      "lastName" : "Katsuki",
      "authorRank" : 2,
      "name" : "Katsuki A",
      "referenceId" : "RGD:A44365"
    }, {
      "firstName" : "EC",
      "lastName" : "Gabazza",
      "authorRank" : 3,
      "name" : "Gabazza EC",
      "referenceId" : "RGD:A26829"
    }, {
      "firstName" : "K",
      "lastName" : "Ito",
      "authorRank" : 4,
      "name" : "Ito K",
      "referenceId" : "RGD:A4474"
    }, {
      "firstName" : "M",
      "lastName" : "Fujii",
      "authorRank" : 5,
      "name" : "Fujii M",
      "referenceId" : "RGD:A33844"
    }, {
      "firstName" : "M",
      "lastName" : "Furuta",
      "authorRank" : 6,
      "name" : "Furuta M",
      "referenceId" : "RGD:A44369"
    }, {
      "firstName" : "K",
      "lastName" : "Tuchihashi",
      "authorRank" : 7,
      "name" : "Tuchihashi",
      "referenceId" : "RGD:A171326"
    }, {
      "firstName" : "H",
      "lastName" : "Goto",
      "authorRank" : 8,
      "name" : "Goto H",
      "referenceId" : "RGD:A89401"
    }, {
      "firstName" : "K",
      "lastName" : "Nakatani",
      "authorRank" : 9,
      "name" : "Nakatani K",
      "referenceId" : "RGD:A5261"
    }, {
      "firstName" : "Y",
      "lastName" : "Hori",
      "authorRank" : 10,
      "name" : "Hori Y",
      "referenceId" : "RGD:A22209"
    }, {
      "firstName" : "Y",
      "lastName" : "Sumida",
      "authorRank" : 11,
      "name" : "Sumida Y",
      "referenceId" : "RGD:A44366"
    }, {
      "firstName" : "Y",
      "lastName" : "Adachi",
      "authorRank" : 12,
      "name" : "Adachi Y",
      "referenceId" : "RGD:A26833"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7247731"
    } ]
  }, {
    "primaryId" : "PMID:10404810",
    "title" : "The development of Graves' disease and the CTLA-4 gene on chromosome 2q33.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Heward JM, etal., J Clin Endocrinol Metab. 1999 Jul;84(7):2398-401.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-07-12T11:37:35.000-05:00",
    "volume" : "84",
    "pages" : "2398-401",
    "abstract" : "Case-control studies suggest that the CTLA-4 gene may be a susceptibility locus for Graves' disease. The previously reported A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene was, therefore, investigated in a case-control (n = 743) and family-based (n = 179) dataset of white Caucasian subjects with Graves'  disease. The relationship between CTLA-4 genotype and severity of thyroid dysfunction at diagnosis was also investigated. An increase in frequency of the G (alanine) allele was seen in Graves' patients compared with control subjects (42% vs. 31.5%, respectively; corrected P<0.0002; odds ratio = 1.58), and a significant difference in the distribution of GG, GA, and AA genotypes was observed between the groups (chi2 = 21.7; corrected P<0.00003). Increased transmission of the G allele was seen from heterozygous parents to affected offspring compared to unaffected offspring (chi2 = 5.7; P = 0.025). Circulating free T4 concentrations at diagnosis were significantly associated with CTLA-4 genotype (F = 3.26; P = 0.04). These results support the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders such as Graves' disease.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Heward",
      "authorRank" : 1,
      "name" : "Heward JM",
      "referenceId" : "RGD:A101827"
    }, {
      "firstName" : "A",
      "lastName" : "Allahabadia",
      "authorRank" : 2,
      "name" : "Allahabadia A",
      "referenceId" : "RGD:A101828"
    }, {
      "firstName" : "M",
      "lastName" : "Armitage",
      "authorRank" : 3,
      "name" : "Armitage",
      "referenceId" : "RGD:A344299"
    }, {
      "firstName" : "A",
      "lastName" : "Hattersley",
      "authorRank" : 4,
      "name" : "Hattersley",
      "referenceId" : "RGD:A237810"
    }, {
      "firstName" : "PM",
      "lastName" : "Dodson",
      "authorRank" : 5,
      "name" : "Dodson",
      "referenceId" : "RGD:A190929"
    }, {
      "firstName" : "K",
      "lastName" : "MacLeod",
      "authorRank" : 6,
      "name" : "MacLeod K",
      "referenceId" : "RGD:A94225"
    }, {
      "firstName" : "J",
      "lastName" : "Carr-Smith",
      "authorRank" : 7,
      "name" : "Carr-Smith J",
      "referenceId" : "RGD:A101829"
    }, {
      "firstName" : "J",
      "lastName" : "Daykin",
      "authorRank" : 8,
      "name" : "Daykin J",
      "referenceId" : "RGD:A101830"
    }, {
      "firstName" : "A",
      "lastName" : "Daly",
      "authorRank" : 9,
      "name" : "Daly",
      "referenceId" : "RGD:A171536"
    }, {
      "firstName" : "MC",
      "lastName" : "Sheppard",
      "authorRank" : 10,
      "name" : "Sheppard MC",
      "referenceId" : "RGD:A61124"
    }, {
      "firstName" : "RL",
      "lastName" : "Holder",
      "authorRank" : 11,
      "name" : "Holder",
      "referenceId" : "RGD:A344300"
    }, {
      "firstName" : "AH",
      "lastName" : "Barnett",
      "authorRank" : 12,
      "name" : "Barnett AH",
      "referenceId" : "RGD:A40326"
    }, {
      "firstName" : "JA",
      "lastName" : "Franklyn",
      "authorRank" : 13,
      "name" : "Franklyn JA",
      "referenceId" : "RGD:A61125"
    }, {
      "firstName" : "SC",
      "lastName" : "Gough",
      "authorRank" : 14,
      "name" : "Gough SC",
      "referenceId" : "RGD:A101831"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11352245"
    } ]
  }, {
    "primaryId" : "PMID:10404816",
    "title" : "Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Heinonen P, etal., J Clin Endocrinol Metab 1999 Jul;84(7):2429-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T12:09:16.000-05:00",
    "volume" : "84",
    "pages" : "2429-33",
    "abstract" : "The alpha2-adrenergic receptors mediate part of the actions of the catecholamines noradrenaline and adrenaline on the regulation of energy balance. As part of an ongoing study on the genetics of obesity, the entire coding sequence of the alpha2B-adrenoceptor gene was screened in 58 obese, nondiabetic Finns by PCR-single stranded conformational analysis (PCR-SSCA). A polymorphism that leads to a deletion of 3 glutamic acids from a glutamic acid repeat element (Glu x 12, amino acids 297-309) present in the third intracellular loop of the receptor protein was identified. This repeat element has previously been shown to be important for agonist-dependent receptor desensitization. Of 166 genotyped subjects, 47 (28%) had 2 normal (long) alleles (Glu12/Glu12), 90 (54%) were heterozygous (Glu12/Glu9), and 29 (17%) were homozygous for the short (Glu9/Glu9) form. The basal metabolic rate, determined by indirect calorimetry and adjusted for fat-free body mass, fat mass, sex, and age, was 94 Cal/day (5.6%) lower (95% confidence interval for difference, 32, 156) in subjects homozygous for the short allele than in subjects with two long alleles (F = 4.84; P = 0.009, by ANOVA). Thus, a genetic polymorphism of the alpha2B-adrenoceptor subtype can partly explain the variation in basal metabolic rate in an obese population and may therefore contribute to the pathogenesis of obesity.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Heinonen",
      "authorRank" : 1,
      "name" : "Heinonen P",
      "referenceId" : "RGD:A164167"
    }, {
      "firstName" : "M",
      "lastName" : "Koulu",
      "authorRank" : 2,
      "name" : "Koulu M",
      "referenceId" : "RGD:A44310"
    }, {
      "firstName" : "U",
      "lastName" : "Pesonen",
      "authorRank" : 3,
      "name" : "Pesonen U",
      "referenceId" : "RGD:A44311"
    }, {
      "firstName" : "MK",
      "lastName" : "Karvonen",
      "authorRank" : 4,
      "name" : "Karvonen MK",
      "referenceId" : "RGD:A44312"
    }, {
      "firstName" : "A",
      "lastName" : "Rissanen",
      "authorRank" : 5,
      "name" : "Rissanen A",
      "referenceId" : "RGD:A44313"
    }, {
      "firstName" : "M",
      "lastName" : "Laakso",
      "authorRank" : 6,
      "name" : "Laakso M",
      "referenceId" : "RGD:A164269"
    }, {
      "firstName" : "R",
      "lastName" : "Valve",
      "authorRank" : 7,
      "name" : "Valve R",
      "referenceId" : "RGD:A44315"
    }, {
      "firstName" : "M",
      "lastName" : "Uusitupa",
      "authorRank" : 8,
      "name" : "Uusitupa M",
      "referenceId" : "RGD:A163623"
    }, {
      "firstName" : "M",
      "lastName" : "Scheinin",
      "authorRank" : 9,
      "name" : "Scheinin M",
      "referenceId" : "RGD:A164171"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300265"
    } ]
  }, {
    "primaryId" : "PMID:10404822",
    "title" : "Serum antibodies against megalin (GP330) in patients with autoimmune thyroiditis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Marino M, etal., J Clin Endocrinol Metab. 1999 Jul;84(7):2468-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-08-23T15:18:11.000-05:00",
    "volume" : "84",
    "pages" : "2468-74",
    "abstract" : "Megalin (gp330) is a multiligand receptor found on the apical surface of selected epithelial cells, including thyroid cells. We recently showed that megalin is a high-affinity receptor for thyroglobulin. Megalin is capable of inducing autoantibodies, as shown in the rat model, Heymann nephritis. Based on this consideration and on the knowledge that autoantibodies against several thyroid antigens develop in patients with autoimmune thyroid diseases, we searched for antimegalin antibodies in 78 patients with autoimmune and nonautoimmune thyroid diseases. We developed an assay, based on flow cytometry, to measure binding of serum IgGs to L2 cells, a rat carcinoma cell line that expresses abundant megalin. After incubation of L2 cells with serum samples and then with fluorescein isothiocynate-conjugated antihuman IgG Fc-specific antibody, the mean fluorescence intensity (MFI) was determined. Using results obtained in sera from 32 normal subjects, we established a cutoff value for MFI (50.62), above which, tests were considered positive. Significantly elevated values were found in 18 patients, including 13 of 26 patients with autoimmune thyroiditis (50.0%) and in 2 of 19 patients with Graves' disease (10.5%). Furthermore, 2 of 19 patients with nontoxic goiter (10.5%) and 1 of 14 patients with differentiated thyroid cancer (7.14%) had MFI values greater than 50.62, associated with the presence of circulating antithyroid autoantibodies. As a control cell line, we used Chinese hamster ovary cells, which do not express megalin. We found that, among the 18 patients with positive tests for binding to L2 cells, only 1 patient with nontoxic goiter had significant binding of serum IgGs to Chinese hamster ovary cells. Binding of serum IgGs to L2 cells was significantly reduced by coincubation with purified megalin in 15 of 18 positive patients (83.33%) and by a rabbit antimegalin antibody in 11 patients (61.11%). Further and more conclusive evidence that positive tests (MFI >50.62) for binding to L2 cells were attributable to serum antimegalin antibodies was demonstrated by immunoprecipitation experiments. After incubation of serum samples with L2 cell extracts, incubation with antihuman IgG Fc-specific agarose beads resulted in immunoprecipitation of megalin in all the 18 positive patients, but not in normal subjects, as assessed by Western blotting using a monoclonal antibody against megalin. Furthermore, the intensity of the band corresponding to megalin precipitated by serum IgGs in the above 18 patients was significantly correlated with the L2 binding MFI. This is the first clear-cut demonstration of antibodies against megalin in humans. Further studies are needed to determine whether antimegalin antibodies have pathogenic significance or diagnostic value in autoimmune thyroid diseases.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Marino",
      "authorRank" : 1,
      "name" : "Marino M",
      "referenceId" : "RGD:A65567"
    }, {
      "firstName" : "L",
      "lastName" : "Chiovato",
      "authorRank" : 2,
      "name" : "Chiovato L",
      "referenceId" : "RGD:A76327"
    }, {
      "firstName" : "JA",
      "lastName" : "Friedlander",
      "authorRank" : 3,
      "name" : "Friedlander JA",
      "referenceId" : "RGD:A87073"
    }, {
      "firstName" : "F",
      "lastName" : "Latrofa",
      "authorRank" : 4,
      "name" : "Latrofa F",
      "referenceId" : "RGD:A87074"
    }, {
      "firstName" : "A",
      "lastName" : "Pinchera",
      "authorRank" : 5,
      "name" : "Pinchera A",
      "referenceId" : "RGD:A76326"
    }, {
      "firstName" : "RT",
      "lastName" : "McCluskey",
      "authorRank" : 6,
      "name" : "McCluskey RT",
      "referenceId" : "RGD:A25668"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1641847"
    } ]
  }, {
    "primaryId" : "PMID:10405153",
    "title" : "Differential expression of gap-junction gene connexin 31 in seminiferous epithelium of rat testes.",
    "datePublished" : "1999-06-25T00:00:00.000-05:00",
    "citation" : "Mok BW, etal., FEBS Lett. 1999 Jun 25;453(3):243-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-01-26T17:36:56.000-06:00",
    "volume" : "453",
    "pages" : "243-8",
    "abstract" : "Spermatogenesis, a tightly regulated developmental process of male germ cells in testis, is associated with temporal and spatial expression of certain gap-junction connexins. Our findings by RT-PCR indicate that the Cx31 gene is expressed in testis tissue of adult and postnatal rats. During the postnatal spermatogenic process, the Cx31-specific signal became detectable at 15 dpp and onward by in situ hybridization, and apparently localized in the basal compartment of seminiferous epithelium where active spermatogonia and early primary spermatocytes reside. No signal was found in the luminal region. In adult testes, spermatids of elongation phase were also Cx31 positive. Immunohistochemical analysis with mouse anti-Cx31 antibody gave a similar staining pattern, providing further evidence that the gap-junction protein is abundant in the basal seminiferous epithelium, in accordance with the cellular distribution of Cx31 mRNA. These results represent the first demonstration of Cx31 expression at both transcriptional and protein levels in the seminiferous epithelium of rat testes. Thus, Cx31 may play a role in cell-cell communication during spermatogenesis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B W",
      "lastName" : "Mok",
      "authorRank" : 1,
      "name" : "Mok BW",
      "referenceId" : "RGD:A438186"
    }, {
      "firstName" : "W S",
      "lastName" : "Yeung",
      "authorRank" : 2,
      "name" : "Yeung WS",
      "referenceId" : "RGD:A438187"
    }, {
      "firstName" : "J M",
      "lastName" : "Luk",
      "authorRank" : 3,
      "name" : "Luk JM",
      "referenceId" : "RGD:A438188"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12437073"
    } ]
  }, {
    "primaryId" : "PMID:10405196",
    "title" : "Distribution of the sodium/phosphate transporter during postnatal ontogeny of the rat kidney.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Traebert M, etal., J Am Soc Nephrol. 1999 Jul;10(7):1407-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-01T09:10:47.000-05:00",
    "volume" : "10",
    "pages" : "1407-15",
    "abstract" : "Renal phosphate reabsorption via the type II sodium/ phosphate cotransporter (NaPi-2) in the brush border membrane (BBM) of proximal tubules underlies alterations during aging. The ontogeny of NaPi-2 in kidneys from newborn to 6-wk-old rats was investigated. NaPi-2 protein distribution in the kidneys of neonatal, 13-d-old, 22-d-old, and 6-wk-old rats was immunohistochemically analyzed, and NaPi-2 mRNA distribution in neonatal and 6-wk-old rats was analyzed by in situ hybridization. In kidneys of newborn rats, the appearance of NaPi-2 protein and mRNA coincided with the development of the brush border (assessed by  actin staining) on proximal tubular cells. NaPi-2 was not detectable in the nephrogenic zone or in the outgrowing straight sections of proximal tubules, which lack a brush border. In 13-d-old suckling rats, strong NaPi-2 staining was  seen in the BBM of convoluted proximal tubules of all nephron generations. In contrast, in 22-d-old weaned rats, NaPi-2 staining in the BBM of superficial nephrons was weaker than that in the BBM of juxtamedullary nephrons. Western blotting demonstrated that the overall abundance of NaPi-2 protein in the BBM of  22-d-old rats was decreased to approximately 70% of that in 13-d-old rats. In kidneys of 6-wk-old rats, the internephron gradient for NaPi-2 abundance in the BBM corresponded to that in adult rats. The data suggest that the NaPi-2 system in the kidney is fully functional and possesses the capacity for regulation as soon as nephrogenesis is completed. The manifestation of NaPi-2 internephron heterogeneity immediately after weaning might be related to the change in dietary inorganic phosphate content.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Traebert",
      "authorRank" : 1,
      "name" : "Traebert",
      "referenceId" : "RGD:A169472"
    }, {
      "firstName" : "M",
      "lastName" : "Lotscher",
      "authorRank" : 2,
      "name" : "Lotscher",
      "referenceId" : "RGD:A169473"
    }, {
      "firstName" : "R",
      "lastName" : "Aschwanden",
      "authorRank" : 3,
      "name" : "Aschwanden",
      "referenceId" : "RGD:A169474"
    }, {
      "firstName" : "T",
      "lastName" : "Ritthaler",
      "authorRank" : 4,
      "name" : "Ritthaler",
      "referenceId" : "RGD:A169475"
    }, {
      "firstName" : "J",
      "lastName" : "Biber",
      "authorRank" : 5,
      "name" : "Biber",
      "referenceId" : "RGD:A403617"
    }, {
      "firstName" : "H",
      "lastName" : "Murer",
      "authorRank" : 6,
      "name" : "Murer",
      "referenceId" : "RGD:A341576"
    }, {
      "firstName" : "B",
      "lastName" : "Kaissling",
      "authorRank" : 7,
      "name" : "Kaissling B",
      "referenceId" : "RGD:A89473"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7243094"
    } ]
  }, {
    "primaryId" : "PMID:10405333",
    "title" : "cAMP-dependent positive control of cyclin A2 expression during G1/S transition in primary hepatocytes.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Desdouets C, etal., Biochem Biophys Res Commun. 1999 Jul 22;261(1):118-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-05-29T09:17:58.000-05:00",
    "volume" : "261",
    "pages" : "118-22",
    "abstract" : "cAMP positively and negatively regulates hepatocyte proliferation but its molecular targets are still unknown. Cyclin A2 is a major regulator of the cell cycle progression and its synthesis is required for progression to S phase. We have investigated whether cyclin A2 and cyclin A2-associated kinase might be one of the targets for the cAMP transduction pathway during progression of hepatocytes through G1 and G1/S. We show that stimulation of primary cultured hepatocytes by glucagon differentially modulated the expression of G1/S cyclins. Glucagon indeed upregulated cyclin A2 and cyclin A2-associated kinase while cyclin E-associated kinase was unmodified. In conclusion, our study identifies cyclin A2 as an important effector of the cAMP transduction network during hepatocyte proliferation.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Desdouets",
      "authorRank" : 1,
      "name" : "Desdouets C",
      "referenceId" : "RGD:A96401"
    }, {
      "firstName" : "GH",
      "lastName" : "Thoresen",
      "authorRank" : 2,
      "name" : "Thoresen GH",
      "referenceId" : "RGD:A96402"
    }, {
      "firstName" : "C",
      "lastName" : "Senamaud-Beaufort",
      "authorRank" : 3,
      "name" : "Senamaud-Beaufort C",
      "referenceId" : "RGD:A96403"
    }, {
      "firstName" : "T",
      "lastName" : "Christoffersen",
      "authorRank" : 4,
      "name" : "Christoffersen T",
      "referenceId" : "RGD:A29641"
    }, {
      "firstName" : "C",
      "lastName" : "Brechot",
      "authorRank" : 5,
      "name" : "Brechot C",
      "referenceId" : "RGD:A96404"
    }, {
      "firstName" : "J",
      "lastName" : "Sobczak-Thepot",
      "authorRank" : 6,
      "name" : "Sobczak-Thepot J",
      "referenceId" : "RGD:A96405"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2293352"
    } ]
  }, {
    "primaryId" : "PMID:10405344",
    "title" : "Pharbin, a novel inositol polyphosphate 5-phosphatase, induces dendritic appearances in fibroblasts.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Asano T, etal., Biochem Biophys Res Commun 1999 Jul 22;261(1):188-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:49:35.000-05:00",
    "volume" : "261",
    "pages" : "188-95",
    "abstract" : "We have cloned a cDNA encoding a novel protein pharbin with a homology to inositol polyphosphate 5-phosphatases. Pharbin contains relatively well-conserved catalytic motifs for 5-phosphatase, a proline-rich sequence corresponding to the SH3-binding motif, and a sequence consistent with the CaaX motif at the C-terminus. COS-7 cells transfected with pharbin exhibited elevated hydrolytic activity on the 5-phosphate group of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, and phosphatidylinositol 4, 5-bisphosphate. Thus, pharbin indeed serves as an inositol polyphosphate 5-phosphatase. When pharbin was transfected to C3H/10T1/2 fibroblasts, it was located to the plasma membrane-associated structures including membrane ruffles. The cells were converted to dendritic forms within 24 h. The protein with deleted or point-mutated CaaX motif hardly induced the dendritic forms but remained associated with the membranes. These results imply that the CaaX motif is required for the morphological alteration but that some other structural element is likely to also be responsible for the membrane localization.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Asano",
      "authorRank" : 1,
      "name" : "Asano T",
      "referenceId" : "RGD:A161880"
    }, {
      "firstName" : "Y",
      "lastName" : "Mochizuki",
      "authorRank" : 2,
      "name" : "Mochizuki Y",
      "referenceId" : "RGD:A21822"
    }, {
      "firstName" : "K",
      "lastName" : "Matsumoto",
      "authorRank" : 3,
      "name" : "Matsumoto K",
      "referenceId" : "RGD:A159245"
    }, {
      "firstName" : "T",
      "lastName" : "Takenawa",
      "authorRank" : 4,
      "name" : "Takenawa T",
      "referenceId" : "RGD:A7721"
    }, {
      "firstName" : "T",
      "lastName" : "Endo",
      "authorRank" : 5,
      "name" : "Endo T",
      "referenceId" : "RGD:A8527"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299274"
    } ]
  }, {
    "primaryId" : "PMID:10405781",
    "title" : "Physiological genetics: application to hypertension research.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Jacob HJ Clin Exp Pharmacol Physiol 1999 Jul;26(7):530-5",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-12-18T16:26:02.000-06:00",
    "volume" : "26",
    "pages" : "530-5",
    "abstract" : "1. The rapid advancement of the human genome within the next 5-7 years begins a new era for biological research. The structure of all approximately 100,000 genes will be known, but the function of the majority of these genes will remain unknown. This paper outlines a 'physiological genetics' strategy for determining the genetic basis of hypertension by combining a variety of techniques (e.g. genetics, molecular biology, bioinformatics and physiology), to help identify gene function and the pathways involved in the development of hypertension in the rat. 2. Using comparative gene mapping, these regions can be used to implicate susceptibility loci for hypertension in humans, resulting in rapid conversion of basic research in animal models to relevant clinical assessment. The present study outlines some new strategies (i.e. whole-animal physiological genetics) as a means to study disease aetiology in polygenic disorders and to facilitate gene identification in the ascent of functional genomics.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HJ",
      "lastName" : "Jacob",
      "authorRank" : 1,
      "name" : "Jacob HJ",
      "referenceId" : "RGD:A160476"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61026"
    } ]
  }, {
    "primaryId" : "PMID:10405783",
    "title" : "Genetic analysis in Dahl salt-sensitive rats.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kato N Clin Exp Pharmacol Physiol 1999 Jul;26(7):539-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-05T10:50:47.000-05:00",
    "volume" : "26",
    "pages" : "539-40",
    "abstract" : "1. To investigate predisposition to hypertension in Dahl salt-sensitive rats, genome-wide screens were performed in F2 populations. 2. Several quantitative trait loci (QTL) for blood pressure were detected, of which some were shown to confer susceptibility genes by the construction of congenic animals carrying relevant chromosome fragments. 3. Chromosome regions homologous to one QTL (on rat chromosome 10) were recently shown to be linked to hypertension in humans. Thus, there is a possibility that a 'common' susceptibility gene causes hypertension in both species.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Kato",
      "authorRank" : 1,
      "name" : "Kato N",
      "referenceId" : "RGD:A159893"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619630"
    } ]
  }, {
    "primaryId" : "PMID:10406239",
    "title" : "Epidemiological evaluation of recurrent stomatitis, nitrates in drinking water, and cytochrome b5 reductase activity.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Gupta SK, etal., Am J Gastroenterol. 1999 Jul;94(7):1808-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-07-15T12:54:39.000-05:00",
    "volume" : "94",
    "pages" : "1808-12",
    "abstract" : "OBJECTIVE: Our aim was to examine a possible correlation between drinking water nitrate concentration, recurrent stomatitis, and cytochrome b5 reductase activity. Dietary nitrate can form nitrite in vivo. This can cause methemoglobinemia in the red blood cells. Cytochrome b5 reductase is an enzyme in the red blood cells that reduces methemoglobin back to hemoglobin. METHODS: Five  areas were selected in the State of Rajasthan, India, having drinking water nitrate concentration (as nitrate) of 26, 45, 95, 222, and 459 mg of NO3/L. House schedules were prepared in these areas in accordance with a statistically designed protocol. We selected 193 age- and weight-matched persons, representing  10% of the total population in each of these areas. Detailed history was taken for recurrent stomatitis, medical examination was conducted, and blood samples were taken to ascertain cytochrome b5 reductase activity in the selected population. Collected data were statistically analyzed to ascertain a relationship between nitrate concentration, cytochrome b5 reductase activity, and percent stomatitis, using Microsoft Excel software. RESULTS: This study suggests  that there is a significant interdependence between drinking water nitrate concentration, cytochrome b5 reductase activity, and recurrent stomatitis. CONCLUSION: Increased cytochrome b5 reductase activity primarily induced by the presence of high nitrate concentration in drinking water could be the cause for recurrent stomatitis.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SK",
      "lastName" : "Gupta",
      "authorRank" : 1,
      "name" : "Gupta SK",
      "referenceId" : "RGD:A17607"
    }, {
      "firstName" : "RC",
      "lastName" : "Gupta",
      "authorRank" : 2,
      "name" : "Gupta",
      "referenceId" : "RGD:A346306"
    }, {
      "firstName" : "AK",
      "lastName" : "Seth",
      "authorRank" : 3,
      "name" : "Seth",
      "referenceId" : "RGD:A231383"
    }, {
      "firstName" : "AB",
      "lastName" : "Gupta",
      "authorRank" : 4,
      "name" : "Gupta",
      "referenceId" : "RGD:A346307"
    }, {
      "firstName" : "JK",
      "lastName" : "Bassin",
      "authorRank" : 5,
      "name" : "Bassin",
      "referenceId" : "RGD:A346308"
    }, {
      "firstName" : "DK",
      "lastName" : "Gupta",
      "authorRank" : 6,
      "name" : "Gupta DK",
      "referenceId" : "RGD:A63309"
    }, {
      "firstName" : "S",
      "lastName" : "Sharma",
      "authorRank" : 7,
      "name" : "Sharma S",
      "referenceId" : "RGD:A11943"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11352692"
    } ]
  }, {
    "primaryId" : "PMID:10406815",
    "title" : "Evidence for linkage between essential hypertension and a putative locus on human chromosome 17.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Baima J, etal., Hypertension 1999 Jul;34(1):4-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-05T10:31:41.000-05:00",
    "volume" : "34",
    "pages" : "4-7",
    "abstract" : "Several clinical and animal studies indicate that essential hypertension is inherited as a multifactorial trait with a significant genetic and environmental component. In the stroke-prone spontaneously hypertensive rat model, investigators have found evidence for linkage to blood pressure regulatory genes (quantitative trait loci) on rat chromosomes 2, 10, and X. In 1 human study of French and UK sib pairs, evidence for linkage has been reported to human chromosome 17q, the syntenic region of the rat chromosome 10 quantitative trait loci (QTL). Our study confirms this linkage (P=0.0005) and refines the location of the blood pressure QTL.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Baima",
      "authorRank" : 1,
      "name" : "Baima J",
      "referenceId" : "RGD:A10807"
    }, {
      "firstName" : "M",
      "lastName" : "Nicolaou",
      "authorRank" : 2,
      "name" : "Nicolaou M",
      "referenceId" : "RGD:A10808"
    }, {
      "firstName" : "F",
      "lastName" : "Schwartz",
      "authorRank" : 3,
      "name" : "Schwartz F",
      "referenceId" : "RGD:A10809"
    }, {
      "firstName" : "AL",
      "lastName" : "DeStefano",
      "authorRank" : 4,
      "name" : "DeStefano AL",
      "referenceId" : "RGD:A10810"
    }, {
      "firstName" : "A",
      "lastName" : "Manolis",
      "authorRank" : 5,
      "name" : "Manolis A",
      "referenceId" : "RGD:A10811"
    }, {
      "firstName" : "I",
      "lastName" : "Gavras",
      "authorRank" : 6,
      "name" : "Gavras I",
      "referenceId" : "RGD:A10812"
    }, {
      "firstName" : "C",
      "lastName" : "Laffer",
      "authorRank" : 7,
      "name" : "Laffer C",
      "referenceId" : "RGD:A10813"
    }, {
      "firstName" : "F",
      "lastName" : "Elijovich",
      "authorRank" : 8,
      "name" : "Elijovich F",
      "referenceId" : "RGD:A10814"
    }, {
      "firstName" : "L",
      "lastName" : "Farrer",
      "authorRank" : 9,
      "name" : "Farrer L",
      "referenceId" : "RGD:A10815"
    }, {
      "firstName" : "CT",
      "lastName" : "Baldwin",
      "authorRank" : 10,
      "name" : "Baldwin CT",
      "referenceId" : "RGD:A10816"
    }, {
      "firstName" : "H",
      "lastName" : "Gavras",
      "authorRank" : 11,
      "name" : "Gavras H",
      "referenceId" : "RGD:A10817"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619621"
    } ]
  }, {
    "primaryId" : "PMID:10406945",
    "title" : "Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Dussossoy D, etal., Eur J Biochem. 1999 Jul;263(2):377-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-07-13T19:45:06.000-05:00",
    "volume" : "263",
    "pages" : "377-86",
    "abstract" : "SR31747A is a sigma ligand previously described as having original immunosuppressive properties. Two SR31747A targets were recently identified and termed sigma(1) or SR-BP-1 (SR31747A-binding protein-1) and hSI (human sterol isomerase). In order to characterize these proteins further, we examined their expression and localization at the subcellular level. Based on the amino acid sequence deduced from the cloned hSI, anti-hSI polyclonal antibody was raised against the N-terminal fragment of the protein. Using this antibody, we performed Western-blot experiments to demonstrate the presence of hSI in various B and T cell lines, and hSI expression was quantified in these cell lines by flow cytometry and estimated at 15 000-30 000 sites per cell. Subcellular localization studies by both confocal and electron microscopy, performed on THP1 cells with anti-hSI antibody and with the previously described anti-(SR-BP-1) monoclonal antibody, demonstrated that: (a) hSI was colocalized with SR-BP-1; (b) hSI and SR-BP-1 were associated with the endoplasmic reticulum and with the outer and inner membranes of the nuclear envelope; (c) both proteins were delocalized during the cell cycle at the mitosis step when the nuclear membranes disappeared. Taken together our results suggest that both SR31747A-binding proteins not only play a role in sterol metabolism but indirectly affect lipoprotein functions.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Dussossoy",
      "authorRank" : 1,
      "name" : "Dussossoy",
      "referenceId" : "RGD:A346013"
    }, {
      "firstName" : "P",
      "lastName" : "Carayon",
      "authorRank" : 2,
      "name" : "Carayon P",
      "referenceId" : "RGD:A46328"
    }, {
      "firstName" : "S",
      "lastName" : "Belugou",
      "authorRank" : 3,
      "name" : "Belugou",
      "referenceId" : "RGD:A346014"
    }, {
      "firstName" : "D",
      "lastName" : "Feraut",
      "authorRank" : 4,
      "name" : "Feraut",
      "referenceId" : "RGD:A346015"
    }, {
      "firstName" : "A",
      "lastName" : "Bord",
      "authorRank" : 5,
      "name" : "Bord",
      "referenceId" : "RGD:A346016"
    }, {
      "firstName" : "C",
      "lastName" : "Goubet",
      "authorRank" : 6,
      "name" : "Goubet",
      "referenceId" : "RGD:A346017"
    }, {
      "firstName" : "C",
      "lastName" : "Roque",
      "authorRank" : 7,
      "name" : "Roque",
      "referenceId" : "RGD:A346018"
    }, {
      "firstName" : "H",
      "lastName" : "Vidal",
      "authorRank" : 8,
      "name" : "Vidal H",
      "referenceId" : "RGD:A80862"
    }, {
      "firstName" : "T",
      "lastName" : "Combes",
      "authorRank" : 9,
      "name" : "Combes T",
      "referenceId" : "RGD:A46326"
    }, {
      "firstName" : "G",
      "lastName" : "Loison",
      "authorRank" : 10,
      "name" : "Loison",
      "referenceId" : "RGD:A346019"
    }, {
      "firstName" : "P",
      "lastName" : "Casellas",
      "authorRank" : 11,
      "name" : "Casellas P",
      "referenceId" : "RGD:A46329"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11352571"
    } ]
  }, {
    "primaryId" : "PMID:10406962",
    "title" : "Cloning, expression and characterization of an A6-related protein.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Rohwer A, etal., Eur J Biochem. 1999 Jul;263(2):518-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:41:28.000-05:00",
    "volume" : "263",
    "pages" : "518-25",
    "abstract" : "By interaction cloning (yeast two-hybrid system) using the catalytic domain of protein kinase Czeta (PKCzeta) as bait, we cloned a human full-length cDNA with 62% nucleotide homology to the A6 protein recently cloned and characterized by Beeler et al. [Beeler, J.F., LaRochelle, W.J., Chedid, M., Tronick, S.R. & Aaronson, S. A. (1994) Mol. Cell. Biol. 14, 982-988]. The deduced amino acid sequence (349 amino acids) of the A6-related protein (A6rp) contained potential actin-binding sites and ATP-binding sites. We also cloned the murine homolog of A6rp. Human A6rp was expressed in an in-vitro transcriptional/translational system with an apparent molecular mass of 40 kDa and as a glutathione S-transferase (GST) fusion protein in bacteria. A polyclonal anti-(A6rp) was raised in rabbits and used for the identification of A6rp by immunoblotting. A6rp was found to be expressed at the mRNA and the protein levels in all cells and tissues investigated. GST-A6rp was phosphorylated by PKCzeta but not significantly by other PKC isoenzymes. Moreover, it was phosphorylated by casein  kinase 2 and most effectively by the tyrosine kinase Src. In contrast to GST-A6rp, GST-A6 was also phosphorylated by PKC isoforms other than PKCzeta and strongly by CK2, but just weakly by Src. In contrast to the results of Beeler et  al. on beta-galactosidase-A6, we were unable to demonstrate autokinase activity or tyrosine phosphorylation of either GST-A6 or GST-A6rp. In accordance with the  potential ATP-binding sites, both proteins were able to bind ATP.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Rohwer",
      "authorRank" : 1,
      "name" : "Rohwer",
      "referenceId" : "RGD:A186024"
    }, {
      "firstName" : "W",
      "lastName" : "Kittstein",
      "authorRank" : 2,
      "name" : "Kittstein",
      "referenceId" : "RGD:A186025"
    }, {
      "firstName" : "F",
      "lastName" : "Marks",
      "authorRank" : 3,
      "name" : "Marks F",
      "referenceId" : "RGD:A24289"
    }, {
      "firstName" : "M",
      "lastName" : "Gschwendt",
      "authorRank" : 4,
      "name" : "Gschwendt M",
      "referenceId" : "RGD:A88374"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554241"
    } ]
  }, {
    "primaryId" : "PMID:10407114",
    "title" : "Induction of glial cell line-derived neurotrophic factor receptor proteins in cerebral cortex and striatum after permanent middle cerebral artery occlusion in  rats.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kitagawa H, etal., Brain Res. 1999 Jul 10;834(1-2):190-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-03-07T16:45:57.000-06:00",
    "volume" : "834",
    "pages" : "190-5",
    "abstract" : "In an attempt to elucidate whether glial cell line-derived neurotrophic factor (GDNF) receptors are induced after ischemic brain injury, possible expression of  immunoreactive GDNF receptor-alpha1 (GFRalpha-1) and c-ret (RET) was examined at  3, 8, or 24 h after permanent middle cerebral artery occlusion (MCAO) in rats. Immunohistochemical study showed that both GFRalpha-1 and RET staining cells which were not detected in sham control brain, were present in the ipsilateral cortex and caudate at 3 to 8 h after permanent MCAO, and then decreased but remained to some extent at 24 h. Positive cells for both GDNF receptors were predominantly in cortical neurons of ischemic penumbral area. Western blot analysis confirmed the induction of those receptors after permanent MCAO. This rapid induction of GFRalpha-1 and RET, which correlates with the similar induction of GDNF under these conditions, may play a role in the early response to ischemic brain injury.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Kitagawa",
      "authorRank" : 1,
      "name" : "Kitagawa H",
      "referenceId" : "RGD:A7985"
    }, {
      "firstName" : "C",
      "lastName" : "Sasaki",
      "authorRank" : 2,
      "name" : "Sasaki C",
      "referenceId" : "RGD:A68500"
    }, {
      "firstName" : "WR",
      "lastName" : "Zhang",
      "authorRank" : 3,
      "name" : "Zhang WR",
      "referenceId" : "RGD:A7791"
    }, {
      "firstName" : "K",
      "lastName" : "Sakai",
      "authorRank" : 4,
      "name" : "Sakai K",
      "referenceId" : "RGD:A162498"
    }, {
      "firstName" : "Y",
      "lastName" : "Shiro",
      "authorRank" : 5,
      "name" : "Shiro Y",
      "referenceId" : "RGD:A151970"
    }, {
      "firstName" : "H",
      "lastName" : "Warita",
      "authorRank" : 6,
      "name" : "Warita H",
      "referenceId" : "RGD:A68501"
    }, {
      "firstName" : "Y",
      "lastName" : "Mitsumoto",
      "authorRank" : 7,
      "name" : "Mitsumoto Y",
      "referenceId" : "RGD:A151971"
    }, {
      "firstName" : "T",
      "lastName" : "Mori",
      "authorRank" : 8,
      "name" : "Mori T",
      "referenceId" : "RGD:A151972"
    }, {
      "firstName" : "K",
      "lastName" : "Abe",
      "authorRank" : 9,
      "name" : "Abe K",
      "referenceId" : "RGD:A9795"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6218981"
    } ]
  }, {
    "primaryId" : "PMID:10407135",
    "title" : "A novel mammalian T-box-containing gene, Tbr2, expressed in mouse developing brain.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Kimura N, etal., Brain Res Dev Brain Res 1999 Jun 2;115(2):183-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-07T13:10:39.000-06:00",
    "volume" : "115",
    "pages" : "183-93",
    "abstract" : "We have identified and characterized a new member of the mammalian brain-specific T-box gene family, Tbr2, which is closely related to mouse Tbr1, and to the Xenopus earliest mesodermal gene, Eomesodermin. As Tbr1, Tbr2 is predominantly expressed in some regions of the developing brain, but in a strikingly complementary manner. On embryonic day 14.5 (E14.5), Tbr2 mRNA expression was observed in the mesencephalon and rhombencephalon in contrast to Tbr1 which was expressed mostly in the telencephalon. At this stage, Tbr2 mRNA was readily detectable in the postmitotic and differentiating neurons located in various brain regions, i.e., oculomotor, red, trigeminal, vestibular, facial, and hypoglossal nuclei. However, expression of Tbr2 in these nuclei became undetectable on E18.5. In contrast, Tbr2 mRNA expression was detected in the hippocampus only from E18.5 onwards. Whereas Tbr2 expression disappeared in most parts of the mature adult brain, it remained detectable in the hippocampus and olfactory bulb, regions where some neuronal precursors retain their differentiation potential. These results suggest that Tbr2 may play a crucial role in differentiating neurons rather than in proliferating or already differentiated neurons. In addition, similarly to Xenopus Eomesodermin, mouse Tbr2 showed biphasic expression; a first peak around E6.5 and a second peak around E14.5, suggesting that Tbr2 may also be important at early stages of gastrulation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Kimura",
      "authorRank" : 1,
      "name" : "Kimura N",
      "referenceId" : "RGD:A161499"
    }, {
      "firstName" : "K",
      "lastName" : "Nakashima",
      "authorRank" : 2,
      "name" : "Nakashima K",
      "referenceId" : "RGD:A149907"
    }, {
      "firstName" : "M",
      "lastName" : "Ueno",
      "authorRank" : 3,
      "name" : "Ueno M",
      "referenceId" : "RGD:A52700"
    }, {
      "firstName" : "H",
      "lastName" : "Kiyama",
      "authorRank" : 4,
      "name" : "Kiyama H",
      "referenceId" : "RGD:A152812"
    }, {
      "firstName" : "T",
      "lastName" : "Taga",
      "authorRank" : 5,
      "name" : "Taga T",
      "referenceId" : "RGD:A50151"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556617"
    } ]
  }, {
    "primaryId" : "PMID:10407136",
    "title" : "Regulation of metallothionein-3 mRNA by thyroid hormone in developing rat brain and primary cultures of rat astrocytes and neurons.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Yeiser EC, etal., Brain Res Dev Brain Res. 1999 Jun 2;115(2):195-200.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-27T14:24:14.000-06:00",
    "volume" : "115",
    "pages" : "195-200",
    "abstract" : "Metallothionein-3 (MT-3) is a brain specific member of the MT family. Unlike other members of this family, MT-3 has been shown to act as a neuronal growth inhibitory factor. MT-3 mRNA abundance increases throughout the developmental period, reaching adult levels by postnatal day 21. The role of thyroid hormone in the developmental regulation of MT-3 mRNA was tested because thyroid hormone is known to regulate brain gene expression. Furthermore, gestational hypothyroidism  results in developmental brain abnormalities. Hypothyroidism was induced in pregnant dams by the administration of PTU from gestational day 7, resulting in a 4- to 6-fold increase in pup MT-3 mRNA abundance on the day of birth (day 0) and  on postnatal day 3. Normal pups did not reach this level of brain MT-3 mRNA until postnatal day 21. Administration of thyroxine (T(4), 2 microg/g) to pups on postnatal day 1 or day 20 resulted in a decrease in MT-3 mRNA abundance on postnatal day 21, regardless of when the injection was given. Furthermore, addition of T(4) to primary cultures of brain (olfactory bulb) astrocytes and neurons from 4-day-old rats resulted in a significant decrease in MT-3 mRNA in 24 h. Given the neuronal growth inhibitory function of MT-3, these data suggest that MT-3 may play a role in the CNS-related consequences of hypo- and hyperthyroidism during development.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EC",
      "lastName" : "Yeiser",
      "authorRank" : 1,
      "name" : "Yeiser EC",
      "referenceId" : "RGD:A98742"
    }, {
      "firstName" : "CA",
      "lastName" : "Fitch",
      "authorRank" : 2,
      "name" : "Fitch CA",
      "referenceId" : "RGD:A98741"
    }, {
      "firstName" : "MS",
      "lastName" : "Horning",
      "authorRank" : 3,
      "name" : "Horning",
      "referenceId" : "RGD:A198608"
    }, {
      "firstName" : "N",
      "lastName" : "Rutkoski",
      "authorRank" : 4,
      "name" : "Rutkoski",
      "referenceId" : "RGD:A198609"
    }, {
      "firstName" : "CW",
      "lastName" : "Levenson",
      "authorRank" : 5,
      "name" : "Levenson CW",
      "referenceId" : "RGD:A7272"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685800"
    } ]
  }, {
    "primaryId" : "PMID:10407168",
    "title" : "Molecular characterization of a new member of the protein 4.1 family (brain 4.1) in rat brain.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Yamakawa H, etal., Brain Res Mol Brain Res 1999 Jul 5;70(2):197-209.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:27:20.000-05:00",
    "volume" : "70",
    "pages" : "197-209",
    "abstract" : "In addition to the well-known erythroid 4.1 gene, two human genes (KIAA0338 and 4.1G) have recently been identified as members of the protein 4.1 family of genes. We compared the expression levels of these three genes and found that the KIAA0338 gene was predominantly expressed in human brain. To further characterize this novel protein 4.1, called brain 4.1, we isolated rat brain 4.1 cDNA and analyzed its gene products in rat brain. The results indicated that the mRNA and protein products of the brain 4.1 gene were more abundant in brain compared to any other tissues examined. The brain 4.1 mRNA appeared as multiple bands with estimated sizes of 3.9 kb, 6.2 kb and 8.7 kb on RNA blotting analysis, and was found to consist of various alternative forms as reported previously for the erythroid 4. 1 gene. As for the brain 4.1 gene product, many isoforms discernible by immunoblotting analysis were also observed depending on the tissue type and the brain region. The existence of multiple forms of the brain 4.1 implies that it has multiple and diverse functions like the erythroid 4.1 gene product.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Yamakawa",
      "authorRank" : 1,
      "name" : "Yamakawa H",
      "referenceId" : "RGD:A8060"
    }, {
      "firstName" : "R",
      "lastName" : "Ohara",
      "authorRank" : 2,
      "name" : "Ohara R",
      "referenceId" : "RGD:A8059"
    }, {
      "firstName" : "D",
      "lastName" : "Nakajima",
      "authorRank" : 3,
      "name" : "Nakajima D",
      "referenceId" : "RGD:A5748"
    }, {
      "firstName" : "M",
      "lastName" : "Nakayama",
      "authorRank" : 4,
      "name" : "Nakayama M",
      "referenceId" : "RGD:A5747"
    }, {
      "firstName" : "O",
      "lastName" : "Ohara",
      "authorRank" : 5,
      "name" : "Ohara O",
      "referenceId" : "RGD:A299726"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70731"
    } ]
  }, {
    "primaryId" : "PMID:10407179",
    "title" : "Discordant expression of c-Ret and glial cell line-derived neurotrophic factor receptor alpha-1 mRNAs in response to motor nerve injury in neonate rats.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Tsujino H, etal., Brain Res Mol Brain Res. 1999 Jul 5;70(2):298-303.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-03-07T16:30:22.000-06:00",
    "volume" : "70",
    "pages" : "298-303",
    "abstract" : "Adult motoneurons can survive following axotomy, whereas neonate motoneurons result in cell death. Following hypoglossal nerve axotomy in neonate rat, Glial cell line-Derived Neurotrophic Factor (GDNF) receptor alpha-1 (GFRalpha-1) mRNA expression was dramatically suppressed in the injured motoneurons, while a slight increase of c-Ret mRNA expression was observed. In adult, both GFRalpha-1 and c-Ret mRNAs increased substantially after axotomy. The present result suggests that the difference of motoneuron fate after axotomy may be partly due to the coordinate or discordant responses of GFRalpha-1 and c-Ret expression to nerve injury.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Tsujino",
      "authorRank" : 1,
      "name" : "Tsujino H",
      "referenceId" : "RGD:A151963"
    }, {
      "firstName" : "K",
      "lastName" : "Mansur",
      "authorRank" : 2,
      "name" : "Mansur K",
      "referenceId" : "RGD:A151964"
    }, {
      "firstName" : "S",
      "lastName" : "Kiryu-Seo",
      "authorRank" : 3,
      "name" : "Kiryu-Seo S",
      "referenceId" : "RGD:A151965"
    }, {
      "firstName" : "K",
      "lastName" : "Namikawa",
      "authorRank" : 4,
      "name" : "Namikawa K",
      "referenceId" : "RGD:A151966"
    }, {
      "firstName" : "T",
      "lastName" : "Kitahara",
      "authorRank" : 5,
      "name" : "Kitahara T",
      "referenceId" : "RGD:A43633"
    }, {
      "firstName" : "K",
      "lastName" : "Tanabe",
      "authorRank" : 6,
      "name" : "Tanabe K",
      "referenceId" : "RGD:A6071"
    }, {
      "firstName" : "T",
      "lastName" : "Ochi",
      "authorRank" : 7,
      "name" : "Ochi T",
      "referenceId" : "RGD:A23067"
    }, {
      "firstName" : "H",
      "lastName" : "Kiyama",
      "authorRank" : 8,
      "name" : "Kiyama H",
      "referenceId" : "RGD:A152812"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6218979"
    } ]
  }, {
    "primaryId" : "PMID:10407183",
    "title" : "Downregulation of DNA (cytosine-5-)methyltransferase is a late event in NGF-induced PC12 cell differentiation.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Deng J and Szyf M, Brain Res Mol Brain Res. 1999 Jul 23;71(1):23-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-10-31T13:45:51.000-05:00",
    "volume" : "71",
    "pages" : "23-31",
    "abstract" : "DNA methylation patterns are a critical component of the epigenetic machinery that controls the expression of genetic programs in vertebrates. DNA methyltransferase gene (dnmt1) encodes the enzyme catalyzing the methylation of DNA during replication. We tested the hypothesis that the expression of dnmt1 is  regulated with the developmental state of neuronal cells. We show that DNA methyltransferase (Dnmt1) activity is sharply reduced 4 days after induction of differentiation of PC12 cells with NGF. Similarly, the adult brain expresses reduced levels of Dnmt1 activity. We propose that the level of Dnmt1 is downregulated to adjust the activity of the DNA methyltransferase to a different  role in mature post-mitotic neurons. Both the abundance of dnmt1 mRNA as well as  the Dnmt1 polypeptide are downregulated. Downregulation of dnmt1 parallels other  indicators of withdrawal from the cell cycle such as induction of p21, and downregulation of the S phase maker PCNA (proliferating cell nuclear antigen). The temporal pattern of downregulation of dnmt1 in nerve growth factor (NGF)-induced PC12 cells is different from myotube differentiation where downregulation of DNA methyltransferase and demethylation is an early event and was proposed to play a causal role in differentiation. We propose that NGF differentiation of PC12 cells represents a different paradigm of involvement of DNA methylation in terminal differentiation.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Deng",
      "authorRank" : 1,
      "name" : "Deng J",
      "referenceId" : "RGD:A43374"
    }, {
      "firstName" : "M",
      "lastName" : "Szyf",
      "authorRank" : 2,
      "name" : "Szyf M",
      "referenceId" : "RGD:A122431"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9588607"
    } ]
  }, {
    "primaryId" : "PMID:10407194",
    "title" : "Molecular cloning, expression and characterization of a bovine serotonin transporter.",
    "datePublished" : "1999-07-23T00:00:00.000-05:00",
    "citation" : "Mortensen OV, etal., Brain Res Mol Brain Res. 1999 Jul 23;71(1):120-6. doi: 10.1016/s0169-328x(99)00178-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-11-23T01:58:25.000-06:00",
    "volume" : "71",
    "pages" : "120-6",
    "abstract" : "The serotonin transporter (SERT) is a member of a highly homologous family of sodium/chloride dependent neurotransmitter transporters responsible for reuptake of biogenic amines from the extracellular fluid. SERT constitutes the pharmacological target of several clinically important antidepressants. Here we report the molecular cloning of SERT from the bovine species. Translation of the nucleotide sequence revealed 44 amino acid differences compared to human SERT. When transiently expressed in HeLa cells and compared with rat and human SERTs the K(m) value for uptake was increased 2-fold. V(max) and B(max) were both increased about 4-fold indicating the turnover number is conserved. The pharmacological profile revealed a decreased sensitivity towards imipramine, desipramine, citalopram, fluoxetine and paroxetine compared with human SERT, while the sensitivity towards 3, 4-methylenedioxymethamphetamine (MDMA) was mainly unchanged. RT-PCR amplification of RNA from different tissues demonstrated expression of SERT in placenta, brain stem, bone marrow, kidney, lung, heart, adrenal gland, liver, parathyroid gland, thyroid gland, small intestine and pancreas.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O V",
      "lastName" : "Mortensen",
      "authorRank" : 1,
      "name" : "Mortensen OV",
      "referenceId" : "RGD:A523310"
    }, {
      "firstName" : "A S",
      "lastName" : "Kristensen",
      "authorRank" : 2,
      "name" : "Kristensen AS",
      "referenceId" : "RGD:A523311"
    }, {
      "firstName" : "G",
      "lastName" : "Rudnick",
      "authorRank" : 3,
      "name" : "Rudnick G",
      "referenceId" : "RGD:A63391"
    }, {
      "firstName" : "O",
      "lastName" : "Wiborg",
      "authorRank" : 4,
      "name" : "Wiborg O",
      "referenceId" : "RGD:A131760"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:155663546"
    } ]
  }, {
    "primaryId" : "PMID:10407778",
    "title" : "4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Medina-Kauwe LK, etal., J Inherit Metab Dis. 1999 Jun;22(4):414-27. doi: 10.1023/a:1005500122231.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:15:48.000-05:00",
    "volume" : "22",
    "pages" : "414-27",
    "abstract" : "4-Aminobutyrate aminotransferase (GABA-transaminase, GABA-T, EC 2.6.1.19) deficiency (McKusick 137150), an inborn error of GABA degradation, has until now been documented in only a single Flemish child. Compared to the other defects of GABA degradation, succinic semialdehyde dehydrogenase (SSADH, EC 1.2.1.24) deficiency with > 150 patients (McKusick 271980) and pyridoxine-dependent seizures with > 100 patients ('putative' glutamic acid decarboxylase (GAD, EC 4.1.1.15) deficiency; McKusick 266100), GABA-T deficiency is very rare. We present a summary of the clinical, biochemical, enzymatic and molecular findings on the index proband, and a recently identified second patient, with GABA-T deficiency. The phenotype in both included psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures and electroencephalographic abnormalities. In an effort to elucidate the molecular basis of GABA-T deficiency, we isolated and characterized a 1.5 kb cDNA encoding human GABA-T, in addition to a 41 kb genomic clone which encompassed the GABA-T coding region. Standard methods of cloning and sequencing revealed an A-to-G transition at nucleotide 754 of the coding region in lymphoblast cDNAs derived from the index proband. This mutation resulted in substitution of an invariant arginine at amino acid 220 by lysine. Expression of the mutant in E. coli, followed by isolation and enzymatic characterization of the recombinant protein, revealed an enzyme whose Vmax was reduced to 25% of wild-type activity. The patient and father were heterozygous for this allele; the second allele in the patient remains unidentified. Genomic Southern analysis revealed that the second proband most likely harbours a deletion in the 3' region of the GABA-T gene.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L K",
      "lastName" : "Medina-Kauwe",
      "authorRank" : 1,
      "name" : "Medina-Kauwe LK",
      "referenceId" : "RGD:A577162"
    }, {
      "firstName" : "A J",
      "lastName" : "Tobin",
      "authorRank" : 2,
      "name" : "Tobin AJ",
      "referenceId" : "RGD:A521073"
    }, {
      "firstName" : "L",
      "lastName" : "De Meirleir",
      "authorRank" : 3,
      "name" : "De Meirleir L",
      "referenceId" : "RGD:A35368"
    }, {
      "firstName" : "J",
      "lastName" : "Jaeken",
      "authorRank" : 4,
      "name" : "Jaeken J",
      "referenceId" : "RGD:A52148"
    }, {
      "firstName" : "C",
      "lastName" : "Jakobs",
      "authorRank" : 5,
      "name" : "Jakobs C",
      "referenceId" : "RGD:A16901"
    }, {
      "firstName" : "W L",
      "lastName" : "Nyhan",
      "authorRank" : 6,
      "name" : "Nyhan WL",
      "referenceId" : "RGD:A571472"
    }, {
      "firstName" : "K M",
      "lastName" : "Gibson",
      "authorRank" : 7,
      "name" : "Gibson KM",
      "referenceId" : "RGD:A571470"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598116013"
    } ]
  }, {
    "primaryId" : "PMID:10407784",
    "title" : "The spectrum of mutations of the aspartoacylase gene in Canavan disease in non-Jewish patients.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Elpeleg ON and Shaag A, J Inherit Metab Dis. 1999 Jun;22(4):531-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:17:52.000-05:00",
    "volume" : "22",
    "pages" : "531-4",
    "abstract" : "Canavan disease is an infantile neurodegenerative disease that is caused by mutations in the gene encoding the enzyme aspartoacylase. It has mainly been reported in Jewish families. Genotyping of newly diagnosed patients is essential  for the carrier identification and prenatal diagnosis. The sequence of the coding region was determined in 15 non-Jewish patients and 9 new mutations were identified: Y109X, P183H, V186F, M195R, P280L, P280S, A287T, 245insA, and a tentative missplicing mutation which leads to skipping of exon 5. The common pan-European mutation, A305E, was identified in 40% of the alleles and the overall detection rate was 93%.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ON",
      "lastName" : "Elpeleg",
      "authorRank" : 1,
      "name" : "Elpeleg",
      "referenceId" : "RGD:A263807"
    }, {
      "firstName" : "A",
      "lastName" : "Shaag",
      "authorRank" : 2,
      "name" : "Shaag",
      "referenceId" : "RGD:A230793"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067156"
    } ]
  }, {
    "primaryId" : "PMID:10408532",
    "title" : "Genetic heterogeneity in Italian families with familial hemiplegic migraine.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Carrera P, etal., Neurology. 1999 Jul 13;53(1):26-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-05T15:27:00.000-05:00",
    "volume" : "53",
    "pages" : "26-33",
    "abstract" : "OBJECTIVE: To verify linkage to chromosome 19p13, to detect mutations in the CACNA1A gene, and to correlate genetic results to their clinical phenotypes in Italian families with familial hemiplegic migraine (FHM). BACKGROUND: FHM is an autosomal dominant disease, classified as a subtype of migraine with aura. Only a proportion of FHM patients have been associated with chromosome 19p13. Among these, four missense mutations within the CACNA1A gene in five unrelated families have been described. METHODS: A linkage study was performed in 19 patients affected by FHM from five families by studying microsatellite markers associated  with the 19p13 region. All familial and seven additional sporadic patients with FHM were analyzed to search for mutations within the CACNA1A gene by applying the double gradient-denaturant gradient electrophoresis technique. RESULTS: Lod score values did not establish significantly linkage to chromosome 19. However, seven new genetic variants were detected: six were new polymorphisms. The seventh was a missense mutation present in family 1, and it was associated with a hemiplegic migraine phenotype without unconsciousness and cerebellar ataxia. Because this missense mutation is absent in the general population and cosegregates with the disease, it may be a pathologic mutation. CONCLUSIONS: Genetic heterogeneity of FHM has been shown in familial and sporadic FHM patients of Italian origin. The new missense mutation-G4644T-is associated with milder clinical features compared with typical FHM.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Carrera",
      "authorRank" : 1,
      "name" : "Carrera P",
      "referenceId" : "RGD:A29966"
    }, {
      "firstName" : "M",
      "lastName" : "Piatti",
      "authorRank" : 2,
      "name" : "Piatti",
      "referenceId" : "RGD:A205028"
    }, {
      "firstName" : "S",
      "lastName" : "Stenirri",
      "authorRank" : 3,
      "name" : "Stenirri",
      "referenceId" : "RGD:A205029"
    }, {
      "firstName" : "LM",
      "lastName" : "Grimaldi",
      "authorRank" : 4,
      "name" : "Grimaldi LM",
      "referenceId" : "RGD:A53942"
    }, {
      "firstName" : "E",
      "lastName" : "Marchioni",
      "authorRank" : 5,
      "name" : "Marchioni E",
      "referenceId" : "RGD:A92547"
    }, {
      "firstName" : "M",
      "lastName" : "Curcio",
      "authorRank" : 6,
      "name" : "Curcio",
      "referenceId" : "RGD:A205030"
    }, {
      "firstName" : "PG",
      "lastName" : "Righetti",
      "authorRank" : 7,
      "name" : "Righetti",
      "referenceId" : "RGD:A205031"
    }, {
      "firstName" : "M",
      "lastName" : "Ferrari",
      "authorRank" : 8,
      "name" : "Ferrari M",
      "referenceId" : "RGD:A117726"
    }, {
      "firstName" : "C",
      "lastName" : "Gelfi",
      "authorRank" : 9,
      "name" : "Gelfi",
      "referenceId" : "RGD:A205032"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10054422"
    } ]
  }, {
    "primaryId" : "PMID:10408538",
    "title" : "Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy.",
    "datePublished" : "1999-07-13T00:00:00.000-05:00",
    "citation" : "Leppert D, etal., Neurology. 1999 Jul 13;53(1):62-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-07-24T12:32:14.000-05:00",
    "volume" : "53",
    "pages" : "62-70",
    "abstract" : "<br><b>OBJECTIVE: </b>To determine the expression pattern and cellular source of matrix metalloproteinases (MMPs) in chronic inflammatory demyelinating polyneuropathy (CIDP) and nonsystemic vasculitic neuropathy (NSVN).<br><b>BACKGROUND: </b>MMPs are endopeptidases involved in tissue destruction and infiltration by immune cells in multiple sclerosis and Guillain-Barré syndrome. Enzyme inhibitors of MMPs attenuate clinical symptoms in corresponding animal models of these diseases. MMP inhibition may therefore be a novel approach for the treatment of CIDP and NSVN. However, the spectrum of MMPs expressed in chronic inflammatory neuropathies has not been established.<br><b>METHODS: </b>The expression of MMP-2, MMP-3, MMP-7, and MMP-9 in T cells, macrophages, and stromal cells in CIDP, NSVN, and noninflammatory neuropathies (NIN) was quantitated by immunohistochemistry. Results were correlated with clinical and electrophysiologic findings.<br><b>RESULTS: </b>The production of MMP-2 and MMP-9 is increased in nerve tissue in CIDP and NSVN compared with NIN. T cells are the predominant source of MMP-2 and MMP-9 in CIDP and NSVN, whereas macrophages contribute only to a minor extent. Stromal cells of the perineurium/epineurium are an additional source of MMP-2 in NSVN, but not in CIDP. Expression of MMP-3 and MMP-7 was not detectable in CIDP or NSVN. Expression of MMP-2 and MMP-9 did not correlate with clinical disease activity and electrophysiologic measurements.<br><b>CONCLUSIONS: </b>The upregulation of MMP-2 and MMP-9 is a specific feature of CIDP and NSVN, and selective inhibitors of these enzymes could be used to prevent inflammatory tissue damage. The similar increase of MMP-2 and MMP-9 in both demyelinating (CIDP) and nondemyelinating (NSVN) neuropathies raises doubts about whether MMPs play a primary role in demyelination.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Leppert",
      "authorRank" : 1,
      "name" : "Leppert D",
      "referenceId" : "RGD:A89348"
    }, {
      "firstName" : "P",
      "lastName" : "Hughes",
      "authorRank" : 2,
      "name" : "Hughes P",
      "referenceId" : "RGD:A447961"
    }, {
      "firstName" : "S",
      "lastName" : "Huber",
      "authorRank" : 3,
      "name" : "Huber S",
      "referenceId" : "RGD:A447962"
    }, {
      "firstName" : "B",
      "lastName" : "Erne",
      "authorRank" : 4,
      "name" : "Erne B",
      "referenceId" : "RGD:A12466"
    }, {
      "firstName" : "C",
      "lastName" : "Grygar",
      "authorRank" : 5,
      "name" : "Grygar C",
      "referenceId" : "RGD:A447963"
    }, {
      "firstName" : "G",
      "lastName" : "Said",
      "authorRank" : 6,
      "name" : "Said G",
      "referenceId" : "RGD:A447964"
    }, {
      "firstName" : "K M",
      "lastName" : "Miller",
      "authorRank" : 7,
      "name" : "Miller KM",
      "referenceId" : "RGD:A447965"
    }, {
      "firstName" : "A J",
      "lastName" : "Steck",
      "authorRank" : 8,
      "name" : "Steck AJ",
      "referenceId" : "RGD:A447966"
    }, {
      "firstName" : "A",
      "lastName" : "Probst",
      "authorRank" : 9,
      "name" : "Probst A",
      "referenceId" : "RGD:A73743"
    }, {
      "firstName" : "P",
      "lastName" : "Fuhr",
      "authorRank" : 10,
      "name" : "Fuhr P",
      "referenceId" : "RGD:A447967"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13204856"
    } ]
  }, {
    "primaryId" : "PMID:10408612",
    "title" : "Immunohistochemical distribution of the prohormone convertase PC5-A in rat brain.",
    "datePublished" : "1000-10-01T00:00:00.000-06:00",
    "citation" : "Villeneuve P, etal., Neuroscience. 1999;92(2):641-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-31T15:23:39.000-05:00",
    "volume" : "92",
    "pages" : "641-54",
    "abstract" : "Prohormone convertase 5 is an endoprotease of the kexin/subtilisin-like family, which has been postulated to play a role in the proteolytic maturation of a variety of pro-peptides in the mammalian brain. In order to gain insight into the functional role of prohormone convertase 5 in the central nervous system, the regional, cellular and subcellular distributions of the enzyme were investigated  by immunohistochemistry in rat brain using an N-terminal-directed specific antibody shown previously to recognize both the mature and unprocessed forms of the enzyme. Throughout the brain, prohormone convertase 5 immunoreactivity was concentrated within nerve cell bodies and proximal dendrites. No prohormone convertase 5 immunoreactivity was associated with astrocytes, as confirmed by the absence of prohormone convertase 5 immunolabeling in cells immunopositive for the glial protein S-100alpha. Within neurons, prohormone convertase 5 immunoreactivity was concentrated within the Golgi apparatus, as revealed immunohistochemically within the same sections using antibodies against the medial cisternae protein MG-160. It was also present within small vesicular-like  elements distributed throughout the cytoplasm of perikarya and dendrites, but not of axons, as confirmed by its lack of co-localization with the synaptic terminal  marker Dynamin-1. These results suggest that prohormone convertase 5 is active within early compartments of the neuronal regulated secretory pathway and that it is unlikely to be released with its processed substrates. At the regional level,  prohormone convertase 5-immunoreactive perikarya were distributed extensively throughout the forebrain. The most numerous and intensely labeled were detected in the olfactory bulb, cerebral cortex, globus pallidus, endopeduncular and subthalamic nuclei, septum, diagonal band of Broca, magnocellular and medial preoptic areas, supraoptic and arcuate nuclei of the hypothalamus, and anterodorsal, laterodorsal, paraventricular and reticular nuclei of the thalamus. Moderate to dense neuronal labeling was also evident in the olfactory tubercle, caudate-putamen, claustrum, bed nucleus of the stria terminalis, substantia innominata, hippocampus, amygdala, and remaining thalamic and hypothalamic nuclei. This widespread distribution suggests that prohormone convertase 5 is involved in the processing of a variety of neuropeptide and/or neurotrophin precursors in mammalian brain.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Villeneuve",
      "authorRank" : 1,
      "name" : "Villeneuve",
      "referenceId" : "RGD:A199241"
    }, {
      "firstName" : "NG",
      "lastName" : "Seidah",
      "authorRank" : 2,
      "name" : "Seidah NG",
      "referenceId" : "RGD:A7673"
    }, {
      "firstName" : "A",
      "lastName" : "Beaudet",
      "authorRank" : 3,
      "name" : "Beaudet A",
      "referenceId" : "RGD:A27607"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11556235"
    } ]
  }, {
    "primaryId" : "PMID:10408625",
    "title" : "Differential subcellular immunolocalization of voltage-gated calcium channel alpha1 subunits in the chinchilla cristae ampullaris.",
    "datePublished" : "1000-10-01T00:00:00.000-06:00",
    "citation" : "Lopez I, etal., Neuroscience. 1999;92(2):773-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-28T16:31:51.000-05:00",
    "volume" : "92",
    "pages" : "773-82",
    "abstract" : "The immunohistochemical localization of alpha1A, alpha1B, alpha1C, alpha1D and alpha1E voltage-gated calcium channel subunits was investigated in the chinchilla cristae ampullaris and Scarpa's ganglia at the light and electron microscopy level with the use of specific antipeptide antibodies directed against these subunits. The stereocilia membrane of type I and type II hair cells was immunoreactive for alpha1B along its entire length. The basolateral membrane of both types of hair cells was alpha1B, alpha1C and alpha1D immunoreactive. Neurons in the Scarpa's ganglia and afferent nerve terminals in the cristae were immunoreactive for alpha1C and alpha1B. No specific immunoreactivity to alpha1A or alpha1E was seen in the sensory epithelia or ganglia. These findings are consistent with the presence of alpha1B (N-type channel), alpha1C and alpha1D (L-type channels) in the vestibular hair cells, and alpha1B (N-type channel) and  alpha1C (L-type channel) in primary vestibular neurons.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Lopez",
      "authorRank" : 1,
      "name" : "Lopez I",
      "referenceId" : "RGD:A65439"
    }, {
      "firstName" : "G",
      "lastName" : "Ishiyama",
      "authorRank" : 2,
      "name" : "Ishiyama",
      "referenceId" : "RGD:A192719"
    }, {
      "firstName" : "A",
      "lastName" : "Ishiyama",
      "authorRank" : 3,
      "name" : "Ishiyama",
      "referenceId" : "RGD:A192720"
    }, {
      "firstName" : "JC",
      "lastName" : "Jen",
      "authorRank" : 4,
      "name" : "Jen",
      "referenceId" : "RGD:A403871"
    }, {
      "firstName" : "F",
      "lastName" : "Liu",
      "authorRank" : 5,
      "name" : "Liu F",
      "referenceId" : "RGD:A13887"
    }, {
      "firstName" : "RW",
      "lastName" : "Baloh",
      "authorRank" : 6,
      "name" : "Baloh",
      "referenceId" : "RGD:A265665"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11556226"
    } ]
  }, {
    "primaryId" : "PMID:10408771",
    "title" : "Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Tyfield L, etal., Hum Mutat. 1999;13(6):417-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:01:50.000-05:00",
    "volume" : "13",
    "pages" : "417-30",
    "abstract" : "Classical galactosemia is caused by a deficiency in activity of the enzyme galactose-1-phosphate uridyl transferase (GALT), which, in turn, is caused by mutations at the GALT gene. The disorder exhibits considerable allelic heterogeneity and, at the end of 1998, more than 150 different base changes were  recorded in 24 different populations and ethnic groups in 15 countries worldwide. The mutations most frequently cited are Q188R, K285N, S135L, and N314D. Q188R is  the most common mutation in European populations or in those predominantly of European descent. Overall, it accounts for 60-70% of mutant chromosomes, but there are significant differences in its relative frequency in individual populations. Individuals homoallelic for Q188R tend to have a severe phenotype and this is in keeping with the virtually complete loss of enzyme activity observed in in vitro expression systems. Globally, K285N is rarer, but in many European populations it can be found on 25-40% of mutant chromosomes. It is invariably associated with a severe phenotype. S135L is found almost exclusively  in African Americans. In vitro expression results are discrepant, but some individuals carrying S135L appear to exhibit GALT activity in some tissues. Duarte 1 (or Los Angeles) and Duarte 2 (or Duarte) variants carry the same amino  acid substitution, N314D, even though D1 is associated with increased erythrocyte GALT activity and D2 with reduced activity. N314D is in linkage disequilibrium with other base changes that differ on the D1 and D2 alleles. N314D does not impair GALT activity in in vitro expression systems. However, there are differences in the abundance of GALT protein in lymphoblastoid cells lines from D2 and D1 individuals. It is unclear whether the specific molecular changes that  distinguish the D1 and D2 alleles account for the different activities. The considerable genetic heterogeneity documented to date undoubtedly contributes to  the phenotypic heterogeneity that is observed in galactosemia. The additional effects of nonallelic variation and other constitutional factors on phenotypic variability remain to be elucidated.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Tyfield",
      "authorRank" : 1,
      "name" : "Tyfield",
      "referenceId" : "RGD:A254377"
    }, {
      "firstName" : "J",
      "lastName" : "Reichardt",
      "authorRank" : 2,
      "name" : "Reichardt",
      "referenceId" : "RGD:A254378"
    }, {
      "firstName" : "J",
      "lastName" : "Fridovich-Keil",
      "authorRank" : 3,
      "name" : "Fridovich-Keil",
      "referenceId" : "RGD:A254379"
    }, {
      "firstName" : "DT",
      "lastName" : "Croke",
      "authorRank" : 4,
      "name" : "Croke",
      "referenceId" : "RGD:A254380"
    }, {
      "firstName" : "2ND",
      "lastName" : "Elsas LJ",
      "authorRank" : 5,
      "name" : "Elsas LJ 2ND",
      "referenceId" : "RGD:A65329"
    }, {
      "firstName" : "W",
      "lastName" : "Strobl",
      "authorRank" : 6,
      "name" : "Strobl W",
      "referenceId" : "RGD:A72709"
    }, {
      "firstName" : "L",
      "lastName" : "Kozak",
      "authorRank" : 7,
      "name" : "Kozak",
      "referenceId" : "RGD:A252489"
    }, {
      "firstName" : "T",
      "lastName" : "Coskun",
      "authorRank" : 8,
      "name" : "Coskun T",
      "referenceId" : "RGD:A36145"
    }, {
      "firstName" : "G",
      "lastName" : "Novelli",
      "authorRank" : 9,
      "name" : "Novelli G",
      "referenceId" : "RGD:A37187"
    }, {
      "firstName" : "Y",
      "lastName" : "Okano",
      "authorRank" : 10,
      "name" : "Okano Y",
      "referenceId" : "RGD:A22194"
    }, {
      "firstName" : "C",
      "lastName" : "Zekanowski",
      "authorRank" : 11,
      "name" : "Zekanowski C",
      "referenceId" : "RGD:A156509"
    }, {
      "firstName" : "Y",
      "lastName" : "Shin",
      "authorRank" : 12,
      "name" : "Shin Y",
      "referenceId" : "RGD:A18836"
    }, {
      "firstName" : "MD",
      "lastName" : "Boleda",
      "authorRank" : 13,
      "name" : "Boleda MD",
      "referenceId" : "RGD:A51311"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063254"
    } ]
  }, {
    "primaryId" : "PMID:10408774",
    "title" : "Four novel mutations in the cystathionine beta-synthase gene: effect of a second  linked mutation on the severity of the homocystinuric phenotype.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "de Franchis R, etal., Hum Mutat. 1999;13(6):453-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:53:28.000-05:00",
    "volume" : "13",
    "pages" : "453-7",
    "abstract" : "Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is frequently  caused by missense mutations. In this article, we report four novel missense mutations in the CBS gene: 172C-->T (R58W) linked in cis with A114V; 376A-->G (M126V); 904G-->A (E302K); and 1006C-->T (R336C). The CBS activity of the corresponding mutant enzymes expressed in Escherichia coli was greatly diminished, confirming the pathogenicity of these mutations. Western analysis showed that the R58W+A114V and M126V mutant enzymes were unstable in E. coli, while the E302K subunits were partially degraded to shorter products. Using site-directed mutagenesis we found that CBS containing either the R58W or A114V as the only mutations demonstrated 18% and 46% of normal activity, respectively.  Both mutant forms of CBS were stable in E. coli. When these two mutations were expressed in cis, the resultant mutant protein exhibited activity 1.3% that of a  control. All these in vitro results were in good agreement with the clinical manifestation in these patients. The Italian patient 2241, an A114V+R58W/M126V compound heterozygote, exhibited severe pyridoxine nonresponsive homocystinuria,  while another Italian patient 2242, with an A114V/E302K genotype, responded to pyridoxine treatment and had a much milder phenotype. The third patient 3064, an  English compound heterozygote for two severe mutations R336C and G307S, was B6 nonresponsive. This report of a ninth homocystinuric allele carrying two mutations in cis raises the possibility that double mutant alleles may be underestimated in homocystinuric patients. In this context, a search for additional mutations in cis may sometimes be necessary to establish a good genotype-phenotype relationship.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "De Franchis",
      "authorRank" : 1,
      "name" : "De Franchis",
      "referenceId" : "RGD:A253531"
    }, {
      "firstName" : "E",
      "lastName" : "Kraus",
      "authorRank" : 2,
      "name" : "Kraus",
      "referenceId" : "RGD:A271618"
    }, {
      "firstName" : "V",
      "lastName" : "Kozich",
      "authorRank" : 3,
      "name" : "Kozich V",
      "referenceId" : "RGD:A61876"
    }, {
      "firstName" : "G",
      "lastName" : "Sebastio",
      "authorRank" : 4,
      "name" : "Sebastio",
      "referenceId" : "RGD:A253532"
    }, {
      "firstName" : "JP",
      "lastName" : "Kraus",
      "authorRank" : 5,
      "name" : "Kraus JP",
      "referenceId" : "RGD:A15066"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070585"
    } ]
  }, {
    "primaryId" : "PMID:10408776",
    "title" : "Mutations of the VHL gene in sporadic renal cell carcinoma: definition of a risk  factor for VHL patients to develop an RCC.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Gallou C, etal., Hum Mutat. 1999;13(6):464-75.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:03:53.000-05:00",
    "volume" : "13",
    "pages" : "464-75",
    "abstract" : "To investigate the nature of somatic von Hippel-Lindau (VHL) mutations, we analyzed 173 primary sporadic human renal cell carcinomas for mutations of the VHL tumor suppressor gene, using polymerase chain reaction (PCR) and single-strand conformational polymorphism analysis (SSCP) of DNA. We detected abnormal SSCP pattern in 73 samples. After sequencing, we identified microdeletions in 58% of cases, microinsertions in 17%, nonsense mutations in 8%, and missense mutations in 17%. Among these mutations, 50% correspond to new mutations. VHL mutations were found only in the nonpapillary renal cell carcinoma (RCC) subtype, as previously reported. To compare somatic and germline mutations, we used the VHL database, which includes 507 mutations. The study of mutational events revealed a significant difference between somatic and germline mutations with mutations leading to truncated proteins observed in 78% of somatic mutations vs only 37% in germline mutations (P < 0.001). We postulated that a specific pattern of VHL mutations is associated with sporadic RCC. This pattern corresponds to mutations leading mainly to truncated proteins with few specific missense mutations. We then analyzed the occurrence of RCC in VHL families, based on the nature of mutations. We observed RCC in at least one member of the VHL families in 77% of cases with mutations leading to truncated proteins versus 55%  in cases with missense mutations (P < 0.05). Thus, mutations resulting in truncated proteins may lead to a higher risk of RCC in VHL patients.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Gallou",
      "authorRank" : 1,
      "name" : "Gallou C",
      "referenceId" : "RGD:A158856"
    }, {
      "firstName" : "D",
      "lastName" : "Joly",
      "authorRank" : 2,
      "name" : "Joly",
      "referenceId" : "RGD:A261859"
    }, {
      "firstName" : "A",
      "lastName" : "Mejean",
      "authorRank" : 3,
      "name" : "Mejean A",
      "referenceId" : "RGD:A158857"
    }, {
      "firstName" : "F",
      "lastName" : "Staroz",
      "authorRank" : 4,
      "name" : "Staroz",
      "referenceId" : "RGD:A261860"
    }, {
      "firstName" : "N",
      "lastName" : "Martin",
      "authorRank" : 5,
      "name" : "Martin N",
      "referenceId" : "RGD:A22487"
    }, {
      "firstName" : "G",
      "lastName" : "Tarlet",
      "authorRank" : 6,
      "name" : "Tarlet",
      "referenceId" : "RGD:A261861"
    }, {
      "firstName" : "MT",
      "lastName" : "Orfanelli",
      "authorRank" : 7,
      "name" : "Orfanelli",
      "referenceId" : "RGD:A261862"
    }, {
      "firstName" : "R",
      "lastName" : "Bouvier",
      "authorRank" : 8,
      "name" : "Bouvier R",
      "referenceId" : "RGD:A71575"
    }, {
      "firstName" : "D",
      "lastName" : "Droz",
      "authorRank" : 9,
      "name" : "Droz D",
      "referenceId" : "RGD:A158859"
    }, {
      "firstName" : "Y",
      "lastName" : "Chretien",
      "authorRank" : 10,
      "name" : "Chretien",
      "referenceId" : "RGD:A198167"
    }, {
      "firstName" : "JM",
      "lastName" : "Marechal",
      "authorRank" : 11,
      "name" : "Marechal JM",
      "referenceId" : "RGD:A97891"
    }, {
      "firstName" : "S",
      "lastName" : "Richard",
      "authorRank" : 12,
      "name" : "Richard S",
      "referenceId" : "RGD:A18855"
    }, {
      "firstName" : "C",
      "lastName" : "Junien",
      "authorRank" : 13,
      "name" : "Junien C",
      "referenceId" : "RGD:A60289"
    }, {
      "firstName" : "C",
      "lastName" : "Beroud",
      "authorRank" : 14,
      "name" : "Beroud C",
      "referenceId" : "RGD:A158861"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065417"
    } ]
  }, {
    "primaryId" : "PMID:10408782",
    "title" : "Molecular characterization of phenylalanine hydroxylase deficiency in Chile. Mutations in brief no. 243. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Perez B, etal., Hum Mutat. 1999;13(6):503.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:36:15.000-05:00",
    "volume" : "13",
    "pages" : "503",
    "abstract" : "Both the haplotype distribution and the mutational spectrum of the phenylalanine  hydroxylase (PAH) gene has been defined for the Chilean phenylketonuria (PKU) population. Mutation analysis was performed using a combined approach of screening for common European and Oriental mutations and application of the DGGE  scanning method in the remaining uncharacterized alleles. A total of 16 different mutations have been identified, including two novel ones, Q232X and IVS11nt5. The most frequent mutations were IVS10nt-11 and V388M present both in the 13% of the  mutant chromosomes. The rest of the mutations are rare. The haplotype association including VNTR and STR alleles, was examined to investigated the origin and distribution of PAH alleles in Chile. Our results are consistent with Southern Europeans as the major source of PAH mutations in Latin America. However, we have also detected mutations from East and Central Europe, such IVS12nt1, R408W and R252W. It is clear that the PKU mutation present in each Latin American country varies with the demographic profile and specific mutation scanning is necessary in each population both for diagnostic and prognostic purposes. The correlation between the genotypes and the phenotypes is consistent with the emerging pattern  of mutation severity deduced from previous studies in related populations.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Perez",
      "authorRank" : 1,
      "name" : "Perez B",
      "referenceId" : "RGD:A76889"
    }, {
      "firstName" : "LR",
      "lastName" : "Desviat",
      "authorRank" : 2,
      "name" : "Desviat LR",
      "referenceId" : "RGD:A76888"
    }, {
      "firstName" : "M",
      "lastName" : "De Lucca",
      "authorRank" : 3,
      "name" : "De Lucca",
      "referenceId" : "RGD:A282117"
    }, {
      "firstName" : "V",
      "lastName" : "Cornejo",
      "authorRank" : 4,
      "name" : "Cornejo",
      "referenceId" : "RGD:A281349"
    }, {
      "firstName" : "E",
      "lastName" : "Raimann",
      "authorRank" : 5,
      "name" : "Raimann",
      "referenceId" : "RGD:A282118"
    }, {
      "firstName" : "M",
      "lastName" : "Ugarte",
      "authorRank" : 6,
      "name" : "Ugarte M",
      "referenceId" : "RGD:A76891"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072482"
    } ]
  }, {
    "primaryId" : "PMID:10409197",
    "title" : "Role of PTP-1B in aortic smooth muscle cell motility and tyrosine phosphorylation of focal adhesion proteins.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Hassid A, etal., Am J Physiol. 1999 Jul;277(1):H192-8. doi: 10.1152/ajpheart.1999.277.1.H192.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-02-07T16:28:17.000-06:00",
    "volume" : "277",
    "pages" : "H192-8",
    "abstract" : "Recent studies have focused attention on the role of protein tyrosine kinases in vascular smooth muscle cell biology, but similar information regarding protein tyrosine phosphatases (PTP) is sparse. PTP-1B is a ubiquitous nonreceptor phosphatase with uncertain function and substrates that are mostly unidentified. We used antisense oligodeoxynucleotides (ODN) against PTP-1B to investigate the role of endogenous PTP-1B in motility of primary cultures of rat aortic smooth muscle cells (RASMC). Antisense ODN decreased PTP-1B protein levels and activity in a concentration-dependent fashion, whereas sense, scrambled, or three-base mismatch antisense ODN had little or no effect. Treatment of cells with antisense ODN, but not sense, scrambled, or three-base mismatch antisense ODN, enhanced cell motility and increased tyrosine phosphorylation levels of focal adhesion proteins paxillin, p130(cas), and focal adhesion kinase. Our findings indicate that PTP-1B is a negative regulator of RASMC motility via modulation of phosphotyrosine levels in several focal adhesion proteins and suggest the involvement of PTP-1B in events such as atherosclerosis and restenosis, which are associated with increased vascular smooth muscle cell motility.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Hassid",
      "authorRank" : 1,
      "name" : "Hassid A",
      "referenceId" : "RGD:A41195"
    }, {
      "firstName" : "S",
      "lastName" : "Huang",
      "authorRank" : 2,
      "name" : "Huang S",
      "referenceId" : "RGD:A19334"
    }, {
      "firstName" : "J",
      "lastName" : "Yao",
      "authorRank" : 3,
      "name" : "Yao J",
      "referenceId" : "RGD:A23266"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401965431"
    } ]
  }, {
    "primaryId" : "PMID:10409247",
    "title" : "Fatty acid translocase/CD36 mediates the uptake of palmitate by type II pneumocytes.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Guthmann F, etal., Am J Physiol 1999 Jul;277(1 Pt 1):L191-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T15:25:19.000-05:00",
    "volume" : "277",
    "pages" : "L191-6",
    "abstract" : "Type II pneumocytes, which synthesize, store, and secrete pulmonary surfactant, require exogenous fatty acids, in particular palmitic acid, for maximum surfactant synthesis. The uptake of palmitate by type II pneumocytes is thought to be protein mediated, but the protein involved has not been characterized. Here we show by RT-PCR and Northern blot analysis that rat type II pneumocytes express the mRNA for fatty acid translocase (FAT/CD36), a membrane-associated protein that is known to facilitate the uptake of fatty acids into adipocytes. The deduced amino acid sequence from rat type II pneumocytes reveals 98% identity to the FAT/CD36 sequence obtained from rat adipocytes. The uptake of palmitate by type II pneumocytes follows Michaelis-Menten kinetics (Michaelis-Menten constant = 11.9 +/- 1.8 nM; maximum velocity = 62.7 +/- 5.8 pmol. min(-1). 5 x 10(5) pneumocytes(-1)) and decreases reversibly under conditions of ATP depletion to 35% of control uptake. Incubation of cells at 0 degrees C inhibited the uptake of palmitate almost completely, whereas depletion of potassium was without effect. Preincubation of the cells with bromobimane or phloretin decreases the uptake of palmitate significantly as does preincubation with sulfo-N-succinimidyl oleate, the specific inhibitor of FAT/CD36 (C. M. Harmon, P. Luce, A. H. Beth, and N. A. Abumrad. J. Membr. Biol. 121: 261-268, 1991). From these data, we conclude that FAT/CD36 is expressed in type II pneumocytes and mediates the uptake of palmitate in a saturable and energy-dependent manner. The data suggest that the uptake process is independent of the formation of coated pits and endocytotic vesicles.",
    "issueName" : "1 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Guthmann",
      "authorRank" : 1,
      "name" : "Guthmann F",
      "referenceId" : "RGD:A23075"
    }, {
      "firstName" : "R",
      "lastName" : "Haupt",
      "authorRank" : 2,
      "name" : "Haupt R",
      "referenceId" : "RGD:A40480"
    }, {
      "firstName" : "AC",
      "lastName" : "Looman",
      "authorRank" : 3,
      "name" : "Looman AC",
      "referenceId" : "RGD:A40481"
    }, {
      "firstName" : "F",
      "lastName" : "Spener",
      "authorRank" : 4,
      "name" : "Spener F",
      "referenceId" : "RGD:A40482"
    }, {
      "firstName" : "B",
      "lastName" : "Rustow",
      "authorRank" : 5,
      "name" : "Rustow B",
      "referenceId" : "RGD:A23078"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298566"
    } ]
  }, {
    "primaryId" : "PMID:10409250",
    "title" : "Differential expression of platelet-derived growth factor-alpha receptor by Thy-1(-) and Thy-1(+) lung fibroblasts.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Hagood JS, etal., Am J Physiol. 1999 Jul;277(1 Pt 1):L218-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:37:34.000-05:00",
    "volume" : "277",
    "pages" : "L218-24",
    "abstract" : "Fibroblasts are heterogeneous with respect to surface markers, morphology, and participation in fibrotic responses. This study was undertaken to determine whether Thy-1(-) and Thy-1(+) rat lung fibroblasts, which have distinct and relevant phenotypes, differ in their proliferative responses to platelet-derived  growth factor (PDGF) isoforms. Homogeneous populations of Thy-1(-) and Thy-1(+) fibroblasts were found to proliferate equally in the presence of PDGF-BB, but PDGF-AA-mediated proliferation occurred only in Thy-1(-) cells. This differential activity correlated with significantly higher expression of PDGF-alpha receptor in Thy-1(-) fibroblasts as shown by immunoblotting, immunofluorescence, and Northern blotting. There was a rapid increase in c-myc mRNA in Thy-1(-) but not in Thy-1(+) fibroblasts on stimulation with PDGF-AA and PDGF-BB. The PDGF-alpha receptor, which mediates signaling by all PDGF isoforms, has been implicated in numerous clinical and experimental forms of fibrosis and regulates lung morphogenesis. Differential expression of the PDGF-alpha receptor supports distinct roles for Thy-1(-) and Thy-1(+) fibroblast populations in developmental  and fibrotic processes in the lung.",
    "issueName" : "1 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JS",
      "lastName" : "Hagood",
      "authorRank" : 1,
      "name" : "Hagood JS",
      "referenceId" : "RGD:A95400"
    }, {
      "firstName" : "PJ",
      "lastName" : "Miller",
      "authorRank" : 2,
      "name" : "Miller",
      "referenceId" : "RGD:A185103"
    }, {
      "firstName" : "JA",
      "lastName" : "Lasky",
      "authorRank" : 3,
      "name" : "Lasky",
      "referenceId" : "RGD:A185104"
    }, {
      "firstName" : "A",
      "lastName" : "Tousson",
      "authorRank" : 4,
      "name" : "Tousson",
      "referenceId" : "RGD:A185105"
    }, {
      "firstName" : "B",
      "lastName" : "Guo",
      "authorRank" : 5,
      "name" : "Guo B",
      "referenceId" : "RGD:A31193"
    }, {
      "firstName" : "GM",
      "lastName" : "Fuller",
      "authorRank" : 6,
      "name" : "Fuller GM",
      "referenceId" : "RGD:A30931"
    }, {
      "firstName" : "JC",
      "lastName" : "McIntosh",
      "authorRank" : 7,
      "name" : "McIntosh JC",
      "referenceId" : "RGD:A101930"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553857"
    } ]
  }, {
    "primaryId" : "PMID:10409266",
    "title" : "Transcriptional and posttranscriptional regulation of beta(2)-adrenergic receptor gene in rat liver during sepsis.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Yang J, etal., Am J Physiol. 1999 Jul;277(1 Pt 2):R132-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-03-07T11:15:13.000-06:00",
    "volume" : "277",
    "pages" : "R132-9",
    "abstract" : "Changes in beta(2)-adrenergic receptor (beta(2)-AR) gene expression in the rat liver during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit two metabolically distinct phases: an initial hyperglycemic (9 h after CLP; early sepsis) followed by a hypoglycemic phase (18 h after CLP; late sepsis). The [(3)H]dihydroalprenolol binding studies show that the density of beta(2)-AR was decreased by 12 and 35% during the early and late phases of sepsis, respectively. Western blot analyses depict that the beta(2)-AR protein level was reduced by 37 and 72% during early and late sepsis, respectively. The reverse transcription polymerase chain reaction and Southern blot analyses reveal that the steady-state level of beta(2)-AR mRNA was decreased by 37% during early phase and 77% during late phase of sepsis. Nuclear run-off assays show that the rate of transcription of beta(2)-AR mRNA was reduced by 36% during early sepsis and 64% during late sepsis. The stability assays indicate that the half-life of beta(2)-AR mRNA was shortened by 21 and 50% during the early and late phases of sepsis, respectively, indicating that the rate of degradation of beta(2)-AR mRNA was progressively enhanced during sepsis. These findings demonstrate that the beta(2)-AR gene was underexpressed in the liver during the progression of sepsis, and, furthermore, the underexpression of the beta(2)-AR gene was the result of a reduction in the rate of transcription coupled with an enhancement in the rate of degradation of beta(2)-AR gene transcripts. Thus our findings that the transcriptional and posttranscriptional regulation of beta(2)-AR gene associated with decreases in beta(2)-AR number and its protein expression may provide a molecular mechanistic  explanation for the development of hypoglycemia during the late stage of sepsis.",
    "issueName" : "1 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang",
      "referenceId" : "RGD:A416998"
    }, {
      "firstName" : "LW",
      "lastName" : "Dong",
      "authorRank" : 2,
      "name" : "Dong LW",
      "referenceId" : "RGD:A21271"
    }, {
      "firstName" : "C",
      "lastName" : "Tang",
      "authorRank" : 3,
      "name" : "Tang C",
      "referenceId" : "RGD:A21270"
    }, {
      "firstName" : "MS",
      "lastName" : "Liu",
      "authorRank" : 4,
      "name" : "Liu MS",
      "referenceId" : "RGD:A21272"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8548498"
    } ]
  }, {
    "primaryId" : "PMID:10409428",
    "title" : "Gene expression in proliferating human erythroid cells.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Gubin AN, etal., Genomics. 1999 Jul 15;59(2):168-77.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T15:03:31.000-05:00",
    "volume" : "59",
    "pages" : "168-77",
    "abstract" : "A complete understanding of human erythropoiesis will require a robust description of transcriptional activity in hematopoietic cells that proliferate and differentiate in response to erythropoietin (EPO). For this purpose, we cultured peripheral blood mononuclear cells in the presence or in the absence of  EPO and examined the transcriptional profile of those cells arising only in response to EPO. A distinct population of CD71( +) cells that demonstrated an average of six additional doublings in suspension culture and erythroid colony formation in methylcellulose was isolated. Suppression subtractive hybridization  of mRNA isolated from those cells permitted the identification of transcribed genes. A summary of 719 expressed sequence tags (ESTs) describing 505 independent transcripts is provided here with a full analysis of each EST available at http://hembase.niddk.nih.gov. Several transcripts that matched genes previously reported in the context of erythroid differentiation including 4 cell surface proteins were expressed at this developmental stage. Active chromatin remodeling  was suggested by the identification of 4 histone proteins, 4 high-mobility group  proteins, 13 transcription factors, and 6 genes involved in DNA recombination and repair. Numerous genes associated with leukemic translocations were also recognized including topoisomerases I and II, nucleophosmin, Translin, EGR1, dek, pim-1, TFG, and MLL. In addition to known transcripts, 44 novel EST were discovered. This transcriptional profile provides the first genomic-scale description of gene activity in erythroid progenitor cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AN",
      "lastName" : "Gubin",
      "authorRank" : 1,
      "name" : "Gubin",
      "referenceId" : "RGD:A240014"
    }, {
      "firstName" : "JM",
      "lastName" : "Njoroge",
      "authorRank" : 2,
      "name" : "Njoroge",
      "referenceId" : "RGD:A240015"
    }, {
      "firstName" : "GG",
      "lastName" : "Bouffard",
      "authorRank" : 3,
      "name" : "Bouffard GG",
      "referenceId" : "RGD:A47995"
    }, {
      "firstName" : "JL",
      "lastName" : "Miller",
      "authorRank" : 4,
      "name" : "Miller JL",
      "referenceId" : "RGD:A112426"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11057992"
    } ]
  }, {
    "primaryId" : "PMID:10409471",
    "title" : "Enhanced angiotensin-converting enzyme activity and impaired endothelium-dependent vasodilation in aortae from hypertensive rats: evidence for a causal link.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Goetz RM and Holtz J, Clin Sci (Lond). 1999 Aug;97(2):165-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-06-23T13:53:56.000-05:00",
    "volume" : "97",
    "pages" : "165-74",
    "abstract" : "Endothelial vasomotor function is impaired in a variety of disorders representing both early and late stages of atherosclerosis. There is experimental evidence for enhanced vascular angiotensin-converting enzyme (ACE) activity in these disorders. We explored whether enhanced vascular ACE activity accounts for endothelial dysfunction in experimental hypertension. Hypertension was induced in rats by coarctation of the aorta. At 2 weeks post-operation, the animals were randomly divided into groups receiving the ACE inhibitor quinapril (2.0 mg.kg(-1).day(-1)), the angiotensin type-1 receptor antagonist losartan (3.0 mg.kg(-1).day(-1)), the B(2) kinin receptor antagonist icatibant (0.4 mg.kg(-1).day(-1)), quinapril plus icatibant, losartan plus icatibant, or no drug. Analyses were performed 4 weeks post-operation. None of the drug treatments had any significant effect on blood pressure. ACE activity was nearly doubled in aortae from untreated hypertensive rats as compared with sham-operated rats. Quinapril reduced ACE activity in aortae from hypertensive rats by 75%, losartan caused a 40% decrease, and icatibant had no effect. Endothelium-dependent, nitric oxide-mediated vasodilator responses studied in vitro were impaired by 40% in aortae from untreated hypertensive rats as compared with sham-operated rats. Both quinapril and losartan restored endothelial vasomotor function in aortae from hypertensive rats. Co-applied icatibant negated the effects of quinapril, but not those of losartan. The level of endothelial NO synthase (eNOS) mRNA determined by competitive RNA PCR was decreased by half in aortae from untreated hypertensive rats as compared with sham-operated rats. Quinapril induced an increase in the eNOS mRNA level of 350% in aortae from hypertensive rats, which was negated by co-applied icatibant. Losartan restored eNOS mRNA expression in aortae from hypertensive rats to normal levels, and this effect was not modified by co-applied icatibant. These findings suggest that enhanced vascular ACE activity accounts for endothelial vasomotor dysfunction by impairing the bioavailability of endothelium-derived NO. Both enhanced formation of angiotensin II and enhanced metabolism of bradykinin might account for a vascular deficiency of bioactive NO.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R M",
      "lastName" : "Goetz",
      "authorRank" : 1,
      "name" : "Goetz RM",
      "referenceId" : "RGD:A445859"
    }, {
      "firstName" : "J",
      "lastName" : "Holtz",
      "authorRank" : 2,
      "name" : "Holtz J",
      "referenceId" : "RGD:A11279"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12910757"
    } ]
  }, {
    "primaryId" : "PMID:10409509",
    "title" : "F-spondin and mindin: two structurally and functionally related genes expressed in the hippocampus that promote outgrowth of embryonic hippocampal neurons.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Feinstein Y, etal., Development 1999 Aug;126(16):3637-48.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:48.000-05:00",
    "volume" : "126",
    "pages" : "3637-48",
    "abstract" : "Extracellular matrix (ECM) proteins play an important role in early cortical development, specifically in the formation of neural connections and in controlling the cyto-architecture of the central nervous system. F-spondin and Mindin are a family of matrix-attached adhesion molecules that share structural similarities and overlapping domains of expression. Genes for both proteins contain a thrombospondin type I repeat(s) at the C terminus and an FS1-FS2 (spondin) domain. Both the vertebrate F-spondin and the zebrafish mindins are expressed on the embryonic floor plate. In the current study we have cloned the rat homologue of mindin and studied its expression and activity together with F-spondin in the developing rodent brain. The two genes are abundantly expressed in the developing hippocampus. In vitro studies indicate that both F-spondin and Mindin promote adhesion and outgrowth of hippocampal embryonic neurons. We have also demonstrated that the two proteins bind to a putative receptor(s) expressed on both hippocampal and sensory neurons.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Feinstein",
      "authorRank" : 1,
      "name" : "Feinstein Y",
      "referenceId" : "RGD:A43355"
    }, {
      "firstName" : "V",
      "lastName" : "Borrell",
      "authorRank" : 2,
      "name" : "Borrell V",
      "referenceId" : "RGD:A43356"
    }, {
      "firstName" : "C",
      "lastName" : "Garcia",
      "authorRank" : 3,
      "name" : "Garcia C",
      "referenceId" : "RGD:A43357"
    }, {
      "firstName" : "T",
      "lastName" : "Burstyn-Cohen",
      "authorRank" : 4,
      "name" : "Burstyn-Cohen T",
      "referenceId" : "RGD:A43358"
    }, {
      "firstName" : "V",
      "lastName" : "Tzarfaty",
      "authorRank" : 5,
      "name" : "Tzarfaty V",
      "referenceId" : "RGD:A43359"
    }, {
      "firstName" : "A",
      "lastName" : "Frumkin",
      "authorRank" : 6,
      "name" : "Frumkin A",
      "referenceId" : "RGD:A43360"
    }, {
      "firstName" : "A",
      "lastName" : "Nose",
      "authorRank" : 7,
      "name" : "Nose A",
      "referenceId" : "RGD:A43361"
    }, {
      "firstName" : "H",
      "lastName" : "Okamoto",
      "authorRank" : 8,
      "name" : "Okamoto H",
      "referenceId" : "RGD:A156495"
    }, {
      "firstName" : "S",
      "lastName" : "Higashijima",
      "authorRank" : 9,
      "name" : "Higashijima S",
      "referenceId" : "RGD:A43363"
    }, {
      "firstName" : "E",
      "lastName" : "Soriano",
      "authorRank" : 10,
      "name" : "Soriano E",
      "referenceId" : "RGD:A24875"
    }, {
      "firstName" : "A",
      "lastName" : "Klar",
      "authorRank" : 11,
      "name" : "Klar A",
      "referenceId" : "RGD:A23186"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299546"
    } ]
  }, {
    "primaryId" : "PMID:10409658",
    "title" : "Long QT syndrome-associated mutations in the S4-S5 linker of KvLQT1 potassium channels modify gating and interaction with minK subunits.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Franqueza L, etal., J Biol Chem. 1999 Jul 23;274(30):21063-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:26:48.000-05:00",
    "volume" : "274",
    "pages" : "21063-70",
    "abstract" : "Long QT syndrome is an inherited disorder of cardiac repolarization caused by mutations in cardiac ion channel genes, including KVLQT1. In this study, the functional consequences of three long QT-associated missense mutations in KvLQT1  (R243C, W248R, E261K) were characterized using the Xenopus oocyte heterologous expression system and two-microelectrode voltage clamp techniques. These mutations are located in or near the intracellular linker between the S4 and S5 transmembrane domains, a region implicated in activation gating of potassium channels. The E261K mutation caused loss of function and did not interact with wild-type KvLQT1 subunits. R243C or W248R KvLQT1 subunits formed functional channels, but compared with wild-type KvLQT1 current, the rate of activation was  slower, and the voltage dependence of activation and inactivation was shifted to  more positive potentials. Co expression of minK and KvLQT1 channel subunits induces a slow delayed rectifier K(+) current, I(Ks), characterized by slow activation and a markedly increased magnitude compared with current induced by KvLQT1 subunits alone. Coexpression of minK with R243C or W248R KvLQT1 subunits suppressed current, suggesting that coassembly of mutant subunits with minK prevented normal channel gating. The decrease in I(Ks) caused by loss of function or altered gating properties explains the prolonged QT interval and increased risk of arrhythmia and sudden death associated with these mutations in KVLQT1.",
    "issueName" : "30",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Franqueza",
      "authorRank" : 1,
      "name" : "Franqueza",
      "referenceId" : "RGD:A263725"
    }, {
      "firstName" : "M",
      "lastName" : "Lin",
      "authorRank" : 2,
      "name" : "Lin M",
      "referenceId" : "RGD:A12788"
    }, {
      "firstName" : "J",
      "lastName" : "Shen",
      "authorRank" : 3,
      "name" : "Shen J",
      "referenceId" : "RGD:A11773"
    }, {
      "firstName" : "I",
      "lastName" : "Splawski",
      "authorRank" : 4,
      "name" : "Splawski I",
      "referenceId" : "RGD:A19586"
    }, {
      "firstName" : "MT",
      "lastName" : "Keating",
      "authorRank" : 5,
      "name" : "Keating MT",
      "referenceId" : "RGD:A18685"
    }, {
      "firstName" : "MC",
      "lastName" : "Sanguinetti",
      "authorRank" : 6,
      "name" : "Sanguinetti MC",
      "referenceId" : "RGD:A61429"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066036"
    } ]
  }, {
    "primaryId" : "PMID:10409668",
    "title" : "Interaction of the alpha(1B)-adrenergic receptor with gC1q-R, a multifunctional protein.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Xu Z, etal., J Biol Chem. 1999 Jul 23;274(30):21149-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:39:07.000-05:00",
    "volume" : "274",
    "pages" : "21149-54",
    "abstract" : "gC1q-R, a multifunctional protein, was found to bind with the carboxyl-terminal cytoplasmic domain of the alpha(1B)-adrenergic receptor (173 amino acids, amino acids 344-516) in a yeast two-hybrid screen of a cDNA library prepared from the rat liver. In a series of studies with deletion mutants in this region, the ten arginine-rich amino acids (amino acids 369-378) were identified as the site of interaction. The interaction was confirmed by specific co-immunoprecipitation of  gC1q-R with full-length alpha(1B)-adrenergic receptors expressed on transfected COS-7 cells, as well as by fluorescence confocal laser scanning microscopy, which showed co-localization of these proteins in intact cells. Interestingly, the alpha(1B)-adrenergic receptors were exclusively localized to the region of the plasma membrane in COS-7 cells that expressed the alpha(1B)-adrenergic receptor alone, whereas gC1q-R was localized in the cytoplasm in COS-7 cells that expressed gC1q-R alone; however, in cells that co-expressed alpha(1B)-adrenergic  receptors and gC1q-R, most of the alpha(1B)-adrenergic receptors were co-localized with gC1q-R in the intracellular region, and a remarkable down-regulation of receptor expression was observed. These observations suggest a new role for the previously identified complement regulatory molecule, gC1q-R, in regulating the cellular localization and expression of the alpha(1B)-adrenergic receptors.",
    "issueName" : "30",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Xu",
      "authorRank" : 1,
      "name" : "Xu Z",
      "referenceId" : "RGD:A54455"
    }, {
      "firstName" : "A",
      "lastName" : "Hirasawa",
      "authorRank" : 2,
      "name" : "Hirasawa A",
      "referenceId" : "RGD:A12310"
    }, {
      "firstName" : "H",
      "lastName" : "Shinoura",
      "authorRank" : 3,
      "name" : "Shinoura",
      "referenceId" : "RGD:A185456"
    }, {
      "firstName" : "G",
      "lastName" : "Tsujimoto",
      "authorRank" : 4,
      "name" : "Tsujimoto G",
      "referenceId" : "RGD:A12318"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554009"
    } ]
  }, {
    "primaryId" : "PMID:10409670",
    "title" : "Characterization of the murine mafF gene.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Onodera K, etal., J Biol Chem 1999 Jul 23;274(30):21162-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-02T13:39:10.000-05:00",
    "volume" : "274",
    "pages" : "21162-9",
    "abstract" : "Small Maf proteins are obligatory heterodimeric partner molecules of mammalian Cap'n'Collar proteins that together control a wide variety of eukaryotic genes. Although both MafK and MafG are expressed in overlapping but distinct tissue distribution patterns during embryonic development, the physiological consequences of loss-of-function mutations in either gene are modest. This suggested that compensation by the third small Maf protein, MafF, might be a major reason for such mild phenotypes and that further analysis of MafF might therefore provide important insights for understanding small Maf regulatory function(s). We therefore cloned, mapped, transcriptionally and developmentally characterized, and finally disrupted the mafF gene. We show that murine mafF is transcriptionally regulated by three different promoters and is most abundantly expressed in the lung. The lacZ gene inserted into the mafF locus revealed prominent expression sites in the gut, lung, liver, outflow tract of the heart, cartilage, bone membrane, and skin but not in hematopoietic cells at any developmental stage. Homozygous mafF null mutant mice were born in a normal Mendelian ratio and displayed no obvious functional deficiencies, indicating that MafF activity may be dispensable even in tissues where the expression of other small Maf proteins is quite low.",
    "issueName" : "30",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Onodera",
      "authorRank" : 1,
      "name" : "Onodera K",
      "referenceId" : "RGD:A55466"
    }, {
      "firstName" : "JA",
      "lastName" : "Shavit",
      "authorRank" : 2,
      "name" : "Shavit JA",
      "referenceId" : "RGD:A55467"
    }, {
      "firstName" : "H",
      "lastName" : "Motohashi",
      "authorRank" : 3,
      "name" : "Motohashi H",
      "referenceId" : "RGD:A55468"
    }, {
      "firstName" : "F",
      "lastName" : "Katsuoka",
      "authorRank" : 4,
      "name" : "Katsuoka F",
      "referenceId" : "RGD:A55469"
    }, {
      "firstName" : "JE",
      "lastName" : "Akasaka",
      "authorRank" : 5,
      "name" : "Akasaka JE",
      "referenceId" : "RGD:A55470"
    }, {
      "firstName" : "JD",
      "lastName" : "Engel",
      "authorRank" : 6,
      "name" : "Engel JD",
      "referenceId" : "RGD:A16149"
    }, {
      "firstName" : "M",
      "lastName" : "Yamamoto",
      "authorRank" : 7,
      "name" : "Yamamoto M",
      "referenceId" : "RGD:A5108"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549576"
    } ]
  }, {
    "primaryId" : "PMID:10410539",
    "title" : "[Adenosine deaminase activity in bronchoalveolar lavage fluid of sarcoidosis patients].",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kubota M, etal., Nihon Kokyuki Gakkai Zasshi. 1999 May;37(5):374-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-03-21T16:23:10.000-05:00",
    "volume" : "37",
    "pages" : "374-9",
    "abstract" : "We studied adenosine deaminase (ADA) activity in bronchoalveolar lavage fluid (BALF) specimens from 24 patients with sarcoidosis. Mean BALF-ADA activity was significantly (p < 0.0001) elevated in patients with sarcoidosis (1.02 +/- 1.01 IU/L, mean +/- SD) compared to the subjects in a healthy control group (0.08 +/- 0.29 IU/L). In the sarcoidosis patients with high BALF-ADA activity (> or = 1.0 IU/L), AaDO2 was significantly (p < 0.0001) elevated compared to its level in patients with normal BALF-ADA activity (< 1.0 IU/L). BALF-ADA activity was significantly (p < 0.01) higher in patients who exhibited lung-field accumulations on 67Ga scintigrams compared to those with no accumulations, and significantly (p < 0.001) higher in patients undergoing corticosteroid treatment compared to in those patients who did not receive such treatment. These findings were similar to the results of studies using data on BALF-ADA/albumin ratios. Furthermore, they suggest that the localized production of ADA may increase in sarcoidosis patients displaying 67Ga scintigram lung-field accumulations with increased AaDO2, and that BALF-ADA activity may be a useful indicator of disease activity and the need for treatment.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kubota",
      "authorRank" : 1,
      "name" : "Kubota M",
      "referenceId" : "RGD:A18643"
    }, {
      "firstName" : "M",
      "lastName" : "Katagiri",
      "authorRank" : 2,
      "name" : "Katagiri M",
      "referenceId" : "RGD:A131730"
    }, {
      "firstName" : "T",
      "lastName" : "Imasaki",
      "authorRank" : 3,
      "name" : "Imasaki T",
      "referenceId" : "RGD:A136607"
    }, {
      "firstName" : "N",
      "lastName" : "Yanase",
      "authorRank" : 4,
      "name" : "Yanase N",
      "referenceId" : "RGD:A136608"
    }, {
      "firstName" : "K",
      "lastName" : "Soma",
      "authorRank" : 5,
      "name" : "Soma K",
      "referenceId" : "RGD:A95355"
    }, {
      "firstName" : "T",
      "lastName" : "Tomita",
      "authorRank" : 6,
      "name" : "Tomita T",
      "referenceId" : "RGD:A7611"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5128856"
    } ]
  }, {
    "primaryId" : "PMID:10410961",
    "title" : "Determination of differential activities of soluble and membrane-bound catechol-O-methyltransferase in tissues and erythrocytes.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Ellingson T, etal., J Chromatogr B Biomed Sci Appl. 1999 Jun 11;729(1-2):347-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-19T16:59:34.000-05:00",
    "volume" : "729",
    "pages" : "347-53",
    "abstract" : "Catechol-O-methyltransferase (COMT) exists as two isoenzymes, a membrane-bound form (MB-COMT) and a soluble form (S-COMT), with different roles in the metabolism of catecholamines and other catechol compounds. This report documents  an HPLC assay for separate estimation of S-COMT and MB-COMT activity and examines activities of the two isoenzymes among different rat tissues and in human and rat erythrocytes. Activities of MB-COMT and S-COMT varied widely among tissues. There were higher activities of S-COMT than MB-COMT in all tissues except the adrenal medulla where MB-COMT was the predominant isoenzyme, consistent with the importance of this tissue and MB-COMT for the O-methylation of catecholamines. MB-COMT and S-COMT in rat and human erythrocytes showed divergent levels and patterns of activity. The assay represents a rapid and accurate method for quantifying MB-COMT and S-COMT in various tissues and examining the relative roles of COMT isoenzymes in the metabolism of catechol compounds in health and disease.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Ellingson",
      "authorRank" : 1,
      "name" : "Ellingson",
      "referenceId" : "RGD:A190154"
    }, {
      "firstName" : "S",
      "lastName" : "Duddempudi",
      "authorRank" : 2,
      "name" : "Duddempudi",
      "referenceId" : "RGD:A190155"
    }, {
      "firstName" : "BD",
      "lastName" : "Greenberg",
      "authorRank" : 3,
      "name" : "Greenberg BD",
      "referenceId" : "RGD:A82311"
    }, {
      "firstName" : "D",
      "lastName" : "Hooper",
      "authorRank" : 4,
      "name" : "Hooper",
      "referenceId" : "RGD:A190156"
    }, {
      "firstName" : "G",
      "lastName" : "Eisenhofer",
      "authorRank" : 5,
      "name" : "Eisenhofer G",
      "referenceId" : "RGD:A75098"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662338"
    } ]
  }, {
    "primaryId" : "PMID:10410979",
    "title" : "Specific detection by flow cytometry of histidine-tagged ligands bound to their receptors using a tag-specific monoclonal antibody.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Wilken HC, etal., J Immunol Methods. 1999 Jun 24;226(1-2):139-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-22T13:26:20.000-05:00",
    "volume" : "226",
    "pages" : "139-45",
    "abstract" : "Engineering proteins to contain a histidine (His)-tag has proved to be very useful for the purification and analyses of these molecules. In the present study, we demonstrate that the binding of His-tagged ligands to their receptors may be visualised by flow cytometry making use of a selected monoclonal antibody (mAb) against the His-tag. Employing this method, a recombinant C3a (rC3a) anaphylatoxin with a His-tag at its N-terminus could be shown to bind to C3a receptor (C3aR)-expressing RBL-2H3 transfectants with a half-maximal effective concentration (EC50) of about 3 nM which is well within the range of published affinity constants. Binding of a recombinant interleukin-8 (rIL-8) molecule with a C-terminal His-tag to RBL-2H3 cells which stably express the IL-8 receptors CXCR1 or CXCR2 could also be demonstrated using the tag-specific mAb. Furthermore, aminoterminally tagged C5a molecules of rat or human origin could be shown to bind to the human C5a receptor (C5aR). However, the fluorescence signal of the binding of rat rC5a to the human C5aR was distinctly higher over a wide range of ligand concentrations than the signal of human rC5a binding although both ligands were equally potent in the induction of chemotaxis in C5aR-expressing cells. Thus, the tag-specific mAb was able to interfere with the binding of human but not rat rC5a to the human C5aR. This observation is in agreement with the hypothesis of a two binding site model for the interaction of human C5a with its receptor whereas a different binding mode may apply for rat C5a. Our data demonstrate that the selected His-tag specific mAb may be a valuable tool for the visualisation of the binding of recombinant ligands to their receptors and may also provide useful information on the specific binding properties of the ligands.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HC",
      "lastName" : "Wilken",
      "authorRank" : 1,
      "name" : "Wilken HC",
      "referenceId" : "RGD:A78039"
    }, {
      "firstName" : "S",
      "lastName" : "Rogge",
      "authorRank" : 2,
      "name" : "Rogge S",
      "referenceId" : "RGD:A78040"
    }, {
      "firstName" : "O",
      "lastName" : "Gotze",
      "authorRank" : 3,
      "name" : "Gotze O",
      "referenceId" : "RGD:A17071"
    }, {
      "firstName" : "T",
      "lastName" : "Werfel",
      "authorRank" : 4,
      "name" : "Werfel T",
      "referenceId" : "RGD:A78041"
    }, {
      "firstName" : "J",
      "lastName" : "Zwirner",
      "authorRank" : 5,
      "name" : "Zwirner J",
      "referenceId" : "RGD:A28418"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600661"
    } ]
  }, {
    "primaryId" : "PMID:10411342",
    "title" : "Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Bilak MM, etal., J Neuropathol Exp Neurol. 1999 Jul;58(7):719-28.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-13T15:29:07.000-05:00",
    "volume" : "58",
    "pages" : "719-28",
    "abstract" : "Although pigment epithelium-derived factor (PEDF) is a neurotrophic factor that may aid the development, differentiation, and survival of adjacent neural retinae, the wider distribution of PEDF mRNA in the central nervous system suggested to us that this factor could have pleiotropic neurotrophic and neuroprotective effects on nonretinal neurons. We examined the distribution of PEDF mRNA and its transcript in the spinal cord. By immunohistochemistry and western blot analysis using an antihuman PEDF antiserum of known specificity, we  found that PEDF protein is present in spinal cord, cerebrospinal fluid, and skeletal muscle and that its mRNA appears concentrated in motor neurons of the human spinal cord. These observations indicate that PEDF could have potential autocrine and paracrine effects on motor neurons, as well as being target-derived. We analyzed the pharmacologic utility of PEDF in a postnatal organotypic culture model of motor neuron degeneration and proved it is highly neuroprotective. The effect was biologically important, significantly sparing the spinal cord's gross organotypic morphological appearance and preserving motor neuron choline acetyltransferase (ChAT). PEDF alone did not increase ChAT, indicating that the observed effect is neuroprotective, not merely an upregulation of motor neuron ChAT. Further, PEDF preserved motor neuron number, proving a survival effect. We hypothesize that PEDF may play important roles in the survival and maintenance of spinal motor neurons in their neuroprotection against acquired insults in postnatal life. It should be developed further as a therapeutic strategy for motor neuron diseases such as amyotrophic lateral sclerosis (ALS).",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Bilak",
      "authorRank" : 1,
      "name" : "Bilak",
      "referenceId" : "RGD:A187775"
    }, {
      "firstName" : "AM",
      "lastName" : "Corse",
      "authorRank" : 2,
      "name" : "Corse",
      "referenceId" : "RGD:A187776"
    }, {
      "firstName" : "SR",
      "lastName" : "Bilak",
      "authorRank" : 3,
      "name" : "Bilak SR",
      "referenceId" : "RGD:A38769"
    }, {
      "firstName" : "M",
      "lastName" : "Lehar",
      "authorRank" : 4,
      "name" : "Lehar",
      "referenceId" : "RGD:A187808"
    }, {
      "firstName" : "J",
      "lastName" : "Tombran-Tink",
      "authorRank" : 5,
      "name" : "Tombran-Tink J",
      "referenceId" : "RGD:A110458"
    }, {
      "firstName" : "RW",
      "lastName" : "Kuncl",
      "authorRank" : 6,
      "name" : "Kuncl",
      "referenceId" : "RGD:A187774"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8628906"
    } ]
  }, {
    "primaryId" : "PMID:10411542",
    "title" : "Suppression of arthritic bone destruction by adenovirus-mediated csk gene transfer to synoviocytes and osteoclasts.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Takayanagi H, etal., J Clin Invest. 1999 Jul;104(2):137-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-07-01T13:34:20.000-05:00",
    "volume" : "104",
    "pages" : "137-46",
    "abstract" : "Rheumatoid arthritis (RA) is characterized by a chronic inflammation of the synovial joints resulting from hyperplasia of synovial fibroblasts and infiltration of lymphocytes, macrophages, and plasma cells, all of which manifest signs of activation. Recent studies have revealed the essential role of osteoclasts in joint destruction in RA. Src family tyrosine kinases are implicated in various intracellular signaling pathways, including mitogenic response to growth factors in fibroblasts, activation of lymphocytes, and osteoclastic bone resorption. Therefore, inhibiting Src activity can be a good therapeutic strategy to prevent joint inflammation and destruction in RA. We constructed an adenovirus vector carrying the csk gene, which negatively regulates Src family tyrosine kinases. Csk overexpression in cultured rheumatoid synoviocytes remarkably suppressed Src kinase activity and reduced their proliferation rate and IL-6 production. Bone-resorbing activity of osteoclasts was strongly inhibited by Csk overexpression. Furthermore, local injection of the virus into rat ankle joints with adjuvant arthritis not only ameliorated inflammation but suppressed bone destruction. In conclusion, adenovirus-mediated direct transfer of the csk gene is useful in repressing bone destruction and inflammatory reactions, suggesting the involvement of Src family tyrosine kinases in arthritic joint breakdown and demonstrating the feasibility of intervention in the kinases for gene therapy in RA. off",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Takayanagi",
      "authorRank" : 1,
      "name" : "Takayanagi H",
      "referenceId" : "RGD:A141149"
    }, {
      "firstName" : "T",
      "lastName" : "Juji",
      "authorRank" : 2,
      "name" : "Juji T",
      "referenceId" : "RGD:A73240"
    }, {
      "firstName" : "T",
      "lastName" : "Miyazaki",
      "authorRank" : 3,
      "name" : "Miyazaki T",
      "referenceId" : "RGD:A5338"
    }, {
      "firstName" : "H",
      "lastName" : "Iizuka",
      "authorRank" : 4,
      "name" : "Iizuka H",
      "referenceId" : "RGD:A110438"
    }, {
      "firstName" : "T",
      "lastName" : "Takahashi",
      "authorRank" : 5,
      "name" : "Takahashi T",
      "referenceId" : "RGD:A160762"
    }, {
      "firstName" : "M",
      "lastName" : "Isshiki",
      "authorRank" : 6,
      "name" : "Isshiki M",
      "referenceId" : "RGD:A141151"
    }, {
      "firstName" : "M",
      "lastName" : "Okada",
      "authorRank" : 7,
      "name" : "Okada M",
      "referenceId" : "RGD:A12535"
    }, {
      "firstName" : "Y",
      "lastName" : "Tanaka",
      "authorRank" : 8,
      "name" : "Tanaka Y",
      "referenceId" : "RGD:A10375"
    }, {
      "firstName" : "Y",
      "lastName" : "Koshihara",
      "authorRank" : 9,
      "name" : "Koshihara Y",
      "referenceId" : "RGD:A141152"
    }, {
      "firstName" : "H",
      "lastName" : "Oda",
      "authorRank" : 10,
      "name" : "Oda H",
      "referenceId" : "RGD:A161889"
    }, {
      "firstName" : "T",
      "lastName" : "Kurokawa",
      "authorRank" : 11,
      "name" : "Kurokawa T",
      "referenceId" : "RGD:A141153"
    }, {
      "firstName" : "K",
      "lastName" : "Nakamura",
      "authorRank" : 12,
      "name" : "Nakamura K",
      "referenceId" : "RGD:A14458"
    }, {
      "firstName" : "S",
      "lastName" : "Tanaka",
      "authorRank" : 13,
      "name" : "Tanaka S",
      "referenceId" : "RGD:A161408"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5134371"
    } ]
  }, {
    "primaryId" : "PMID:10411567",
    "title" : "Use of the steroid derivative RPR 106541 in combination with site-directed mutagenesis for enhanced cytochrome P-450 3A4 structure/function analysis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Stevens JC, etal., J Pharmacol Exp Ther. 1999 Aug;290(2):594-602.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2026-01-22T09:31:38.000-06:00",
    "volume" : "290",
    "pages" : "594-602",
    "abstract" : "RPR 106541 (20R-16alpha,17alpha-[butylidenebis(oxy)]-6al pha, 9alpha-difluoro-11beta-hydroxy-17beta-(methylthio)androst a-4-en-3-one) is an airway-selective steroid developed for the treatment of asthma. Two metabolites produced by human liver microsomes were identified as R- and S-sulfoxide diastereomers based on liquid chromatography/mass spectrometry analysis, proton nuclear magnetic resonance, and cochromatography with standards. Sulfoxide formation was determined to be cytochrome P-450 (CYP) 3A4-dependent by correlation with CYP3A4-marker nifedipine oxidase activity, inhibition by cyclosporin A and troleandomycin, and inhibition of R- (70%) and S- (64%) sulfoxide formation by anti-3A antibody. Expressed CYP2C forms catalyzed RPR 106541 sulfoxidation; however, other phenotyping approaches failed to confirm the involvement of CYP2C forms in these reactions in human liver microsomes. Expressed CYP3A4 catalyzed the formation of the sulfoxide diastereomers in a 1:1 ratio, whereas CYP3A5 displayed stereoselectivity for formation of the S-diastereomer. The high rate of sulfoxidation by CYP3A4 and the blockage of oxidative metabolism at the electronically favored 6beta-position provided advantages for RPR 106541 over other substrates as an active site probe of CYP3A4. Therefore, oxidation of RPR 106541 by various CYP3A4 substrate recognition site (SRS) mutants was assessed. In SRS-4, A305V and F304A showed dramatically reduced rates of R-diastereomer formation (83 and 64% decreases, respectively), but S-diastereomer formation was affected to a lesser extent. A370V (SRS-5) showed decreased formation of the R-sulfoxide (52%) but increased formation of the S-diastereomer. In the SRS-2 region, the most dramatic change in sulfoxide ratios was observed for L210A. In conclusion, the structure of RPR 106541 imposes specific constraints on enzyme binding and activity and thus represents an improved CYP3A4 probe substrate.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J C",
      "lastName" : "Stevens",
      "authorRank" : 1,
      "name" : "Stevens JC",
      "referenceId" : "RGD:A613489"
    }, {
      "firstName" : "T L",
      "lastName" : "Domanski",
      "authorRank" : 2,
      "name" : "Domanski TL",
      "referenceId" : "RGD:A613490"
    }, {
      "firstName" : "G R",
      "lastName" : "Harlow",
      "authorRank" : 3,
      "name" : "Harlow GR",
      "referenceId" : "RGD:A613491"
    }, {
      "firstName" : "R B",
      "lastName" : "White",
      "authorRank" : 4,
      "name" : "White RB",
      "referenceId" : "RGD:A613492"
    }, {
      "firstName" : "E",
      "lastName" : "Orton",
      "authorRank" : 5,
      "name" : "Orton E",
      "referenceId" : "RGD:A613493"
    }, {
      "firstName" : "J R",
      "lastName" : "Halpert",
      "authorRank" : 6,
      "name" : "Halpert JR",
      "referenceId" : "RGD:A613494"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:631723607"
    } ]
  }, {
    "primaryId" : "PMID:10411650",
    "title" : "Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Kotera J, etal., Eur J Biochem. 1999 Jun;262(3):866-73.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-11-13T10:19:22.000-06:00",
    "volume" : "262",
    "pages" : "866-73",
    "abstract" : "We have reported alternative splice variants of cGMP-binding cGMP-specific phosphodiesterases (PDE5A), i.e. rat PDE5A2, human PDE5A1, canine PDE5A1 and PDE5A2, which possess distinct N-terminal sequences. In this study, the DNA sequences corresponding to the unique N-terminal portions of PDE5A1 and PDE5A2 were shown to be tandemly located upstream of exons encoding the common region of PDE5A in both human and rat PDE5A genes. The presence of human PDE5A2 and rat PDE5A1 transcripts in lung was confirmed by reverse transcriptase-PCR. These results indicated that two variant forms of PDE5A exist in humans, canines and rats. We examined the tissue distribution of the two variants of human PDE5A in adult and fetal humans. The patterns of expression of the two alternatively spliced transcripts of human PDE5A in human tissues differed. Many putative regulatory elements including cAMP response elements were observed in the 5'-untranslated region and intron of the PDE5A gene. The levels of the PDE5A transcripts, especially the PDE5A2 transcripts, were increased by a cAMP analogue in cultured rat vascular smooth muscle cells, indicating that the PDE5A2 is an inducible variant of PDE5A in rats.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Kotera",
      "authorRank" : 1,
      "name" : "Kotera J",
      "referenceId" : "RGD:A5018"
    }, {
      "firstName" : "K",
      "lastName" : "Fujishige",
      "authorRank" : 2,
      "name" : "Fujishige K",
      "referenceId" : "RGD:A5017"
    }, {
      "firstName" : "Y",
      "lastName" : "Imai",
      "authorRank" : 3,
      "name" : "Imai Y",
      "referenceId" : "RGD:A153662"
    }, {
      "firstName" : "E",
      "lastName" : "Kawai",
      "authorRank" : 4,
      "name" : "Kawai E",
      "referenceId" : "RGD:A69253"
    }, {
      "firstName" : "H",
      "lastName" : "Michibata",
      "authorRank" : 5,
      "name" : "Michibata H",
      "referenceId" : "RGD:A69254"
    }, {
      "firstName" : "H",
      "lastName" : "Akatsuka",
      "authorRank" : 6,
      "name" : "Akatsuka H",
      "referenceId" : "RGD:A32824"
    }, {
      "firstName" : "N",
      "lastName" : "Yanaka",
      "authorRank" : 7,
      "name" : "Yanaka N",
      "referenceId" : "RGD:A32822"
    }, {
      "firstName" : "K",
      "lastName" : "Omori",
      "authorRank" : 8,
      "name" : "Omori K",
      "referenceId" : "RGD:A5019"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1582526"
    } ]
  }, {
    "primaryId" : "PMID:10411686",
    "title" : "Monocyte chemoattractant protein-1 mediates collagen deposition in experimental glomerulonephritis by transforming growth factor-beta.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Schneider A, etal., Kidney Int. 1999 Jul;56(1):135-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-04-01T15:13:56.000-05:00",
    "volume" : "56",
    "pages" : "135-44",
    "abstract" : "BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis (GN). Because recent evidence points to possible profibrogenic effects of leukocyte-derived factors in GN, this study was designed to evaluate the role of  the chemokine MCP-1 in the fibrogenesis of experimental GN. METHODS: Rats with an anti-thy-1-induced GN were treated with a neutralizing antiserum against MCP-1. Glomerular collagen type IV, as a marker of glomerular matrix deposition, was assessed by Northern and Western blotting and immunohistology. Transforming growth factor-beta (TGF-beta), an important mediator of this matrix expansion, was studied by Northern and Western blotting. RESULTS: The induction of GN resulted in a significant increase of glomerular collagen type IV deposition and  TGF-beta synthesis. The neutralization of MCP-1 significantly reduced the enhanced collagen type IV protein synthesis and deposition without affecting collagen mRNA expression. However, both the enhanced transcription and protein synthesis of TGF-beta were inhibited by anti-MCP-1 antiserum in nephritic animals. CONCLUSIONS: In this model of GN, MCP-1 has a fibrogenic effect through  the stimulation of TGF-beta. MCP-1 is thus not only important for the recruitment of inflammatory cells, but also mediates glomerular matrix accumulation.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Schneider",
      "authorRank" : 1,
      "name" : "Schneider A",
      "referenceId" : "RGD:A48391"
    }, {
      "firstName" : "U",
      "lastName" : "Panzer",
      "authorRank" : 2,
      "name" : "Panzer U",
      "referenceId" : "RGD:A10579"
    }, {
      "firstName" : "G",
      "lastName" : "Zahner",
      "authorRank" : 3,
      "name" : "Zahner G",
      "referenceId" : "RGD:A10575"
    }, {
      "firstName" : "U",
      "lastName" : "Wenzel",
      "authorRank" : 4,
      "name" : "Wenzel U",
      "referenceId" : "RGD:A29736"
    }, {
      "firstName" : "G",
      "lastName" : "Wolf",
      "authorRank" : 5,
      "name" : "Wolf G",
      "referenceId" : "RGD:A10576"
    }, {
      "firstName" : "F",
      "lastName" : "Thaiss",
      "authorRank" : 6,
      "name" : "Thaiss F",
      "referenceId" : "RGD:A74803"
    }, {
      "firstName" : "U",
      "lastName" : "Helmchen",
      "authorRank" : 7,
      "name" : "Helmchen U",
      "referenceId" : "RGD:A158583"
    }, {
      "firstName" : "RA",
      "lastName" : "Stahl",
      "authorRank" : 8,
      "name" : "Stahl RA",
      "referenceId" : "RGD:A10581"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8549648"
    } ]
  }, {
    "primaryId" : "PMID:10411917",
    "title" : "Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Urbanek M, etal., Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8573-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-12T08:58:38.000-05:00",
    "volume" : "96",
    "pages" : "8573-8",
    "abstract" : "Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; chi(2) = 12.97; nominal P = 3.2 x 10(-4)). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P(c) = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (chi(2) >/= 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; chi(2) = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Urbanek",
      "authorRank" : 1,
      "name" : "Urbanek M",
      "referenceId" : "RGD:A80298"
    }, {
      "firstName" : "RS",
      "lastName" : "Legro",
      "authorRank" : 2,
      "name" : "Legro RS",
      "referenceId" : "RGD:A80299"
    }, {
      "firstName" : "DA",
      "lastName" : "Driscoll",
      "authorRank" : 3,
      "name" : "Driscoll DA",
      "referenceId" : "RGD:A80300"
    }, {
      "firstName" : "R",
      "lastName" : "Azziz",
      "authorRank" : 4,
      "name" : "Azziz R",
      "referenceId" : "RGD:A80301"
    }, {
      "firstName" : "DA",
      "lastName" : "Ehrmann",
      "authorRank" : 5,
      "name" : "Ehrmann DA",
      "referenceId" : "RGD:A80302"
    }, {
      "firstName" : "RJ",
      "lastName" : "Norman",
      "authorRank" : 6,
      "name" : "Norman RJ",
      "referenceId" : "RGD:A37139"
    }, {
      "firstName" : "3RD",
      "lastName" : "Strauss JF",
      "authorRank" : 7,
      "name" : "Strauss JF 3RD",
      "referenceId" : "RGD:A33931"
    }, {
      "firstName" : "RS",
      "lastName" : "Spielman",
      "authorRank" : 8,
      "name" : "Spielman RS",
      "referenceId" : "RGD:A35674"
    }, {
      "firstName" : "A",
      "lastName" : "Dunaif",
      "authorRank" : 9,
      "name" : "Dunaif A",
      "referenceId" : "RGD:A80303"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601259"
    } ]
  }, {
    "primaryId" : "PMID:10411937",
    "title" : "A heterozygous mutation of beta-actin associated with neutrophil dysfunction and  recurrent infection.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Nunoi H, etal., Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8693-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:24:39.000-05:00",
    "volume" : "96",
    "pages" : "8693-8",
    "abstract" : "A human disorder caused by mutation in nonmuscle actin has not been reported. We  report here a variant of nonmuscle actin in a female patient with recurrent infections, photosensitivity, and mental retardation. She also had abnormalities  in neutrophil chemotaxis, superoxide production, and membrane potential response. Two-dimensional PAGE analysis of proteins from neutrophils and other cell types from this patient demonstrated a unique protein spot migrating at 42 kDa with pI  shifted slightly to neutral relative to normal beta- and gamma-actin. Digestion peptide mapping and Western blotting showed this spot to be an abnormal actin. A  full-length cDNA library was constructed by using mRNA from patient's cells and cDNA encoding the mutant beta-actin molecule was identified by an in vitro translation method. Sequencing of the clones demonstrated a G-1174 to A substitution, predicting a glutamic acid-364 to lysine substitution in beta-actin and eliminating a HinfI DNase restriction site found in normal beta-actin sequence. By HinfI digestion and by sequencing, the mutation in one allele of patient's genomic DNA was confirmed. Though no defect in cell-free polymerization of actin was detected, this defect lies in a domain important for binding to profilin and other actin-regulatory molecules. In fact, the mutant actin bound to profilin less efficiently than normal actin did. Heterozygous expression of mutant beta-actin in neutrophils and other cells of this patient may act in a dominant-negative fashion to adversely affect cellular activities dependent on the function of nonmuscle actin.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Nunoi",
      "authorRank" : 1,
      "name" : "Nunoi",
      "referenceId" : "RGD:A259418"
    }, {
      "firstName" : "T",
      "lastName" : "Yamazaki",
      "authorRank" : 2,
      "name" : "Yamazaki T",
      "referenceId" : "RGD:A106005"
    }, {
      "firstName" : "H",
      "lastName" : "Tsuchiya",
      "authorRank" : 3,
      "name" : "Tsuchiya H",
      "referenceId" : "RGD:A29293"
    }, {
      "firstName" : "S",
      "lastName" : "Kato",
      "authorRank" : 4,
      "name" : "Kato S",
      "referenceId" : "RGD:A17686"
    }, {
      "firstName" : "HL",
      "lastName" : "Malech",
      "authorRank" : 5,
      "name" : "Malech HL",
      "referenceId" : "RGD:A82699"
    }, {
      "firstName" : "I",
      "lastName" : "Matsuda",
      "authorRank" : 6,
      "name" : "Matsuda I",
      "referenceId" : "RGD:A16758"
    }, {
      "firstName" : "S",
      "lastName" : "Kanegasaki",
      "authorRank" : 7,
      "name" : "Kanegasaki",
      "referenceId" : "RGD:A259419"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072274"
    } ]
  }, {
    "primaryId" : "PMID:10411999",
    "title" : "The demonstration of immunoreactive dystrophin and its developmental expression in perivascular astrocytes.",
    "datePublished" : "1999-06-12T00:00:00.000-05:00",
    "citation" : "Jancsik V and Hajós F, Brain Res. 1999 Jun 12;831(1-2):200-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-05-03T12:41:57.000-05:00",
    "volume" : "831",
    "pages" : "200-5",
    "abstract" : "Immunoreactivity of dystrophin family proteins was observed in the astrocytes of the adult and immature rat hippocampus and cerebral cortex by using Dys2, a monoclonal antibody recognizing both 427 kDa and short dystrophin isoforms. As revealed by light and electron microscopy, immunostaining of the ribosomal apparatus and of pericapillary endfeet was particularly pronounced in the adult. In the pericapillary astrocyte processes immunostaining appeared between postnatal days 10 and 20, and reached the intensity seen in the adult by postnatal day 30. In the pericapillary astrocyte process, the membrane facing the endothelial basal lamina was the earliest structure to show the immunoreaction. At later stages, the pericapillary astrocyte process was gradually filled up with immunoprecipitate. Findings suggest that dystrophins are expressed coinciding with the development of the blood-brain barrier, and it is assumed that they contribute to the formation of this system.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Jancsik",
      "authorRank" : 1,
      "name" : "Jancsik V",
      "referenceId" : "RGD:A443098"
    }, {
      "firstName" : "F",
      "lastName" : "Hajós",
      "authorRank" : 2,
      "name" : "Hajós F",
      "referenceId" : "RGD:A443110"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12880365"
    } ]
  }, {
    "primaryId" : "PMID:10412185",
    "title" : "Association analysis of exonic variants of the gene encoding the GABAB receptor and alcohol dependence.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Sander T, etal., Psychiatr Genet. 1999 Jun;9(2):69-73. doi: 10.1097/00041444-199906000-00004.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-01-26T13:37:40.000-06:00",
    "volume" : "9",
    "pages" : "69-73",
    "abstract" : "The present association study tested whether genetic variation of the GABAB receptor (GABABR1) gene confers vulnerability to alcohol dependence. The genotypes of three DNA sequence variants in exons 1a1, 7 and 11 of the GABABR1 gene were assessed in 234 German controls and 350 German alcohol-dependent subjects, including three more homogeneous subgroups of alcoholics, marked by (1) history of parental alcoholism (n = 121); (2) history of alcohol withdrawal seizure or delirium (n = 108); and (3) comorbidity of dissocial personality disorder (n = 60). The allele frequencies of none of the investigated GABABR1 variants differed significantly between the controls and the groups of alcoholics when a correction for multiple testing was taken into account (P > 0.004). However, trends (P < 0.10) towards an excess of the Ser489 allele of the exon 7 polymorphism were found in the subgroups of alcoholics, and of the common allele of the exon 11 polymorphism in the entire sample of alcoholics (P = 0.032), alcoholics with parental alcoholism (P = 0.084) and the dissocial alcoholics (P = 0.037). Our findings suggest that the investigated GABABR1 variants do not contribute a substantial effect (RR > 3) to the genetic variance of alcohol dependence. Nevertheless, the hints towards potential allelic associations of the exon 7 and 11 polymorphisms with dissocial alcoholism emphasize further studies to test more defined phenotype-genotype relationships.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Sander",
      "authorRank" : 1,
      "name" : "Sander T",
      "referenceId" : "RGD:A29424"
    }, {
      "firstName" : "J",
      "lastName" : "Samochowiec",
      "authorRank" : 2,
      "name" : "Samochowiec J",
      "referenceId" : "RGD:A85766"
    }, {
      "firstName" : "M",
      "lastName" : "Ladehoff",
      "authorRank" : 3,
      "name" : "Ladehoff M",
      "referenceId" : "RGD:A538018"
    }, {
      "firstName" : "M",
      "lastName" : "Smolka",
      "authorRank" : 4,
      "name" : "Smolka M",
      "referenceId" : "RGD:A87901"
    }, {
      "firstName" : "C",
      "lastName" : "Peters",
      "authorRank" : 5,
      "name" : "Peters C",
      "referenceId" : "RGD:A37712"
    }, {
      "firstName" : "O",
      "lastName" : "Riess",
      "authorRank" : 6,
      "name" : "Riess O",
      "referenceId" : "RGD:A156955"
    }, {
      "firstName" : "H",
      "lastName" : "Rommelspacher",
      "authorRank" : 7,
      "name" : "Rommelspacher H",
      "referenceId" : "RGD:A85770"
    }, {
      "firstName" : "L G",
      "lastName" : "Schmidt",
      "authorRank" : 8,
      "name" : "Schmidt LG",
      "referenceId" : "RGD:A538019"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401959601"
    } ]
  }, {
    "primaryId" : "PMID:10412736",
    "title" : "Mechanisms of glomerular macrophage infiltration in lipid-induced renal injury.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Hattori M, etal., Kidney Int Suppl. 1999 Jul;71:S47-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-08-26T16:29:00.000-05:00",
    "volume" : "71",
    "pages" : "S47-50",
    "abstract" : "BACKGROUND: A number of studies have demonstrated an important role for macrophages (M phi) in lipid-induced glomerular injury; however, little is known  of the mechanisms that facilitate M phi infiltration in this disease. This study  examined the expression of M phi chemotactic molecules M phi migration inhibitory factor (MIF) and leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the induction of glomerular M phi infiltration in ExHC rats, a strain that is susceptible to lipid-induced glomerular injury. METHODS: Groups of five ExHC rats were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate, and 15% olive oil and were killed after three days or one, two, or six weeks. Control animals were killed on day 0 or after six weeks on a normal diet. RESULTS: ExHC rats fed an HCD showed marked hypercholesterolemia in the absence of any increase in plasma triglyceride levels from day 3 and developed mild proteinuria and segmental glomerular lesions at week 6. Immunoperoxidase staining identified a significant increase in glomerular ED1+ M phi at week 1, which was further increased at week 6, when M phi-derived foam cells were seen in almost all glomeruli. Many of the infiltrating glomerular M phi expressed lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), which are  ligands for ICAM-1 and VCAM-1, respectively. Coincident with the induction of hypercholesterolemia on day 3 and prior to significant M phi infiltration, combined in situ hybridization and immunohistochemistry staining demonstrated a marked up-regulation of M-CSF and MIF mRNA expression by glomerular mesangial cells and podocytes. There was also a significant increase in ICAM-1 and VCAM-1 mRNA expression by intrinsic glomerular cells, including endothelial cells, on day 3 of the HCD. CONCLUSION: These results suggest that hypercholesterolemia can induce a classic proinflammatory response within the kidney glomerulus, involving production of well-described M phi chemotactic and adhesion molecules, which results in M phi recruitment and the development of glomerular injury.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Hattori",
      "authorRank" : 1,
      "name" : "Hattori M",
      "referenceId" : "RGD:A10355"
    }, {
      "firstName" : "DJ",
      "lastName" : "Nikolic-Paterson",
      "authorRank" : 2,
      "name" : "Nikolic-Paterson DJ",
      "referenceId" : "RGD:A28569"
    }, {
      "firstName" : "K",
      "lastName" : "Miyazaki",
      "authorRank" : 3,
      "name" : "Miyazaki K",
      "referenceId" : "RGD:A6663"
    }, {
      "firstName" : "NM",
      "lastName" : "Isbel",
      "authorRank" : 4,
      "name" : "Isbel NM",
      "referenceId" : "RGD:A87193"
    }, {
      "firstName" : "HY",
      "lastName" : "Lan",
      "authorRank" : 5,
      "name" : "Lan HY",
      "referenceId" : "RGD:A59515"
    }, {
      "firstName" : "RC",
      "lastName" : "Atkins",
      "authorRank" : 6,
      "name" : "Atkins RC",
      "referenceId" : "RGD:A19944"
    }, {
      "firstName" : "H",
      "lastName" : "Kawaguchi",
      "authorRank" : 7,
      "name" : "Kawaguchi H",
      "referenceId" : "RGD:A55604"
    }, {
      "firstName" : "K",
      "lastName" : "Ito",
      "authorRank" : 8,
      "name" : "Ito K",
      "referenceId" : "RGD:A4474"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7257588"
    } ]
  }, {
    "primaryId" : "PMID:10412811",
    "title" : "A case of anorexia nervosa with hyperbilirubinaemia in a patient homozygous for a mutation in the bilirubin UDP-glucuronosyltransferase gene.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Maruo Y, etal., Eur J Pediatr. 1999 Jul;158(7):547-9. doi: 10.1007/s004310051143.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:15:51.000-05:00",
    "volume" : "158",
    "pages" : "547-9",
    "abstract" : "<br><b>UNLABELLED: </b>Gilbert syndrome was diagnosed in a girl with anorexia nervosa and unconjugated hyperbilirubinaemia. Since the patient was starved and hyperbilirubinaemic, the loading test was not used for the diagnosis but analysis of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1) instead. The patient was homozygous for a missense mutation that replaced guanine with adenine at nucleotide number 211 (211G-->A: G71R). The unconjugated hyperbilirubinaemia was apparently induced by the fasting state. Homozygous missense mutations of the gene have been generally recognized as responsible for Crigler-Najjar syndrome type II; the results obtained here, however, confirm that Gilbert syndrome may also be caused by a homozygous missense mutation of UGT1A1.<br><b>CONCLUSION: </b>Since anorexia nervosa patients are in a fasting state, they may show moderate unconjugated hyperbilirubinaemia if they have Gilbert syndrome. Gene analysis of such cases will rule out hepatic damage. Homozygous missense mutations of the bilirubin-UDP-glucuronosyltransferase gene cause not only Crigler-Najjar syndrome type II but also Gilbert syndrome.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Maruo",
      "authorRank" : 1,
      "name" : "Maruo Y",
      "referenceId" : "RGD:A582386"
    }, {
      "firstName" : "S",
      "lastName" : "Wada",
      "authorRank" : 2,
      "name" : "Wada S",
      "referenceId" : "RGD:A31749"
    }, {
      "firstName" : "K",
      "lastName" : "Yamamoto",
      "authorRank" : 3,
      "name" : "Yamamoto K",
      "referenceId" : "RGD:A5107"
    }, {
      "firstName" : "H",
      "lastName" : "Sato",
      "authorRank" : 4,
      "name" : "Sato H",
      "referenceId" : "RGD:A6517"
    }, {
      "firstName" : "T",
      "lastName" : "Yamano",
      "authorRank" : 5,
      "name" : "Yamano T",
      "referenceId" : "RGD:A80712"
    }, {
      "firstName" : "M",
      "lastName" : "Shimada",
      "authorRank" : 6,
      "name" : "Shimada M",
      "referenceId" : "RGD:A161413"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598119565"
    } ]
  }, {
    "primaryId" : "PMID:10412980",
    "title" : "Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II.",
    "datePublished" : "1999-07-09T00:00:00.000-05:00",
    "citation" : "Wang J, etal., Cell. 1999 Jul 9;98(1):47-58. doi: 10.1016/S0092-8674(00)80605-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:48:29.000-05:00",
    "volume" : "98",
    "pages" : "47-58",
    "abstract" : "Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects, that harbor independent missense mutations in Caspase 10. These encode amino acid substitutions that decrease caspase activity and interfere with death receptor-induced apoptosis, particularly that stimulated by Fas ligand and TRAIL. These results provide evidence that inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang J",
      "referenceId" : "RGD:A404003"
    }, {
      "firstName" : "L",
      "lastName" : "Zheng",
      "authorRank" : 2,
      "name" : "Zheng L",
      "referenceId" : "RGD:A18139"
    }, {
      "firstName" : "A",
      "lastName" : "Lobito",
      "authorRank" : 3,
      "name" : "Lobito A",
      "referenceId" : "RGD:A571250"
    }, {
      "firstName" : "F K",
      "lastName" : "Chan",
      "authorRank" : 4,
      "name" : "Chan FK",
      "referenceId" : "RGD:A512785"
    }, {
      "firstName" : "J",
      "lastName" : "Dale",
      "authorRank" : 5,
      "name" : "Dale J",
      "referenceId" : "RGD:A443766"
    }, {
      "firstName" : "M",
      "lastName" : "Sneller",
      "authorRank" : 6,
      "name" : "Sneller M",
      "referenceId" : "RGD:A571251"
    }, {
      "firstName" : "X",
      "lastName" : "Yao",
      "authorRank" : 7,
      "name" : "Yao X",
      "referenceId" : "RGD:A48321"
    }, {
      "firstName" : "J M",
      "lastName" : "Puck",
      "authorRank" : 8,
      "name" : "Puck JM",
      "referenceId" : "RGD:A443599"
    }, {
      "firstName" : "S E",
      "lastName" : "Straus",
      "authorRank" : 9,
      "name" : "Straus SE",
      "referenceId" : "RGD:A443767"
    }, {
      "firstName" : "M J",
      "lastName" : "Lenardo",
      "authorRank" : 10,
      "name" : "Lenardo MJ",
      "referenceId" : "RGD:A443770"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598115231"
    } ]
  }, {
    "primaryId" : "PMID:10413312",
    "title" : "Coordinate up-regulation of CYP1A1 and heme oxygenase-1 (HO-1) expression and modulation of delta-aminolevulinic acid synthase and tryptophan pyrrolase activities in pyridine-treated rats.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Iba MM, etal., Biochem Pharmacol. 1999 Aug 15;58(4):723-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-04-29T12:02:44.000-05:00",
    "volume" : "58",
    "pages" : "723-34",
    "abstract" : "To determine the changes in heme metabolism associated with induction of cytochrome P450 expression by pyridine, we compared the time course of CYP1A expression with the time course of (i) expression of heme oxygenase-1 (HO-1) (EC 1.14.99.3), (ii) activity of delta-aminolevulinic acid synthetase (ALAS) (EC 2.3.1.37), and (iii) heme saturation of tryptophan pyrrolase (TPO) (EC 1.13.11.11) in tissues of rats administered a single 100 or 150 mg/kg i.p. dose of pyridine. Both mRNA and protein of HO-1 and CYP1A1 were induced in the liver, kidney, and lung, with the induction of HO-1 mRNA preceding and paralleling that of CYP1A1 mRNA in the liver and lung but not kidney. Induction of CYP1A1 mRNA expression peaked within 9-12 hr and returned to control levels by 24 hr in all tissues examined, whereas induction of HO-1 mRNA expression was sustained for 48 hr in the lung and liver. In contrast to the transient up-regulation of CYP1A1 mRNA, increased microsomal CYP1A1 protein was sustained in all three tissues. Similar to the induction of HO-1 expression, lipid peroxidation was stimulated by pyridine treatment in the kidney, lung, and liver, but with the stimulation being more persistent in the liver and lung than in the kidney. Increased hepatic CYP1A1 or CYP1A2 activity was preceded by increased activities of HO-1 and ALAS. Pyridine treatment negatively modulated heme saturation of hepatic TPO. The findings indicate that pyridine stimulates the synthesis, utilization, and degradation of heme in a coordinate manner, and suggest that these alterations in heme metabolism may contribute to CYP1A1 induction by pyridine.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Iba",
      "authorRank" : 1,
      "name" : "Iba MM",
      "referenceId" : "RGD:A105938"
    }, {
      "firstName" : "J",
      "lastName" : "Alam",
      "authorRank" : 2,
      "name" : "Alam J",
      "referenceId" : "RGD:A12997"
    }, {
      "firstName" : "C",
      "lastName" : "Touchard",
      "authorRank" : 3,
      "name" : "Touchard C",
      "referenceId" : "RGD:A105939"
    }, {
      "firstName" : "PE",
      "lastName" : "Thomas",
      "authorRank" : 4,
      "name" : "Thomas PE",
      "referenceId" : "RGD:A101006"
    }, {
      "firstName" : "A",
      "lastName" : "Ghosal",
      "authorRank" : 5,
      "name" : "Ghosal A",
      "referenceId" : "RGD:A88138"
    }, {
      "firstName" : "J",
      "lastName" : "Fung",
      "authorRank" : 6,
      "name" : "Fung J",
      "referenceId" : "RGD:A105940"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306643"
    } ]
  }, {
    "primaryId" : "PMID:10413423",
    "title" : "Frequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Chan TL, etal., J Natl Cancer Inst. 1999 Jul 21;91(14):1221-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:56:52.000-05:00",
    "volume" : "91",
    "pages" : "1221-6",
    "abstract" : "BACKGROUND: The incidence of colorectal cancer in persons under 46 years of age is substantially higher in Hong Kong than in Scotland and many other countries. Consequently, we examined whether there is a hereditary predisposition for colorectal cancer in this Southern Chinese population. METHODS: We investigated the incidence of microsatellite instability (MSI) at 10 DNA sites in 117 colorectal cancer specimens from Chinese patients of various ages. Those tumors with new alleles at 40% or more of the sites investigated were identified as highly unstable MSI (MSI-H). In young patients, we also searched for germline mutations in three mismatch repair genes (hMSH2, hMLH1, and hMSH6). RESULTS: The  incidence of MSI-H varied statistically significantly with age, being observed in more than 60% of those younger than age 31 years at diagnosis and in fewer than 15% of those age 46 years or older. In 15 patients (<46 years old) whose colorectal cancers showed MSI-H, eight possessed germline mutations in either hMSH2 or hMLH1. When mutations in hMSH6 were included, more than 80% of Chinese colorectal cancer patients younger than 31 years had germline mutations in mismatch repair genes. We found a novel germline missense mutation in hMSH6 in a  29-year-old man whose tumor showed no MSI. Two patients had a 4-base-pair insertion in exon 10 causing a truncated protein; this insertion is a common polymorphism with a population allele frequency in Chinese of 5.6%. CONCLUSIONS:  Our results indicate that germline mutations in mismatch repair genes contribute  substantially to the pathogenesis and high incidence of colorectal cancer in young Hong Kong Chinese. However, because young Chinese and Caucasians show similar proportions of colorectal cancers with MSI-H, despite the higher incidence in the former, additional factors may underlie the high susceptibility  of young Chinese to colorectal cancer.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TL",
      "lastName" : "Chan",
      "authorRank" : 1,
      "name" : "Chan",
      "referenceId" : "RGD:A191656"
    }, {
      "firstName" : "ST",
      "lastName" : "Yuen",
      "authorRank" : 2,
      "name" : "Yuen ST",
      "referenceId" : "RGD:A36474"
    }, {
      "firstName" : "LP",
      "lastName" : "Chung",
      "authorRank" : 3,
      "name" : "Chung",
      "referenceId" : "RGD:A258411"
    }, {
      "firstName" : "JW",
      "lastName" : "Ho",
      "authorRank" : 4,
      "name" : "Ho JW",
      "referenceId" : "RGD:A22402"
    }, {
      "firstName" : "KY",
      "lastName" : "Kwan",
      "authorRank" : 5,
      "name" : "Kwan",
      "referenceId" : "RGD:A283048"
    }, {
      "firstName" : "AS",
      "lastName" : "Chan",
      "authorRank" : 6,
      "name" : "Chan",
      "referenceId" : "RGD:A225195"
    }, {
      "firstName" : "JC",
      "lastName" : "Ho",
      "authorRank" : 7,
      "name" : "Ho JC",
      "referenceId" : "RGD:A78196"
    }, {
      "firstName" : "SY",
      "lastName" : "Leung",
      "authorRank" : 8,
      "name" : "Leung SY",
      "referenceId" : "RGD:A36473"
    }, {
      "firstName" : "AH",
      "lastName" : "Wyllie",
      "authorRank" : 9,
      "name" : "Wyllie",
      "referenceId" : "RGD:A276909"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072849"
    } ]
  }, {
    "primaryId" : "PMID:10413453",
    "title" : "Down-regulation of striatin, a neuronal calmodulin-binding protein, impairs rat locomotor activity.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Bartoli M, etal., J Neurobiol. 1999 Aug;40(2):234-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-07-06T15:13:48.000-05:00",
    "volume" : "40",
    "pages" : "234-43",
    "abstract" : "Striatin, an intraneuronal, calmodulin-binding protein addressed to dendrites and spines, is expressed in the motor system, particularly the striatum and motoneurons. Striatin contains a high number of domains mediating protein-protein interactions, suggesting a role within a dendritic Ca(2+)-signaling pathway. Here, we explored the hypothesis of a direct role of striatin in the motor control of behaving rats, by using an antisense strategy based on oligodeoxynucleotides (ODN). Rats were treated by intracerebroventricular infusion of a striatin antisense ODN (A-ODN) or mismatch ODN (M-ODN) delivered by osmotic pumps over 6 days. A significant decrease in the nocturnal locomotor activity of A-ODN-treated rats was observed after 5 days of treatment. Hypomotricity was correlated with a 60% decrease in striatin content of the striata of A-ODN-treated rats sacrificed on day 6. Striatin thus plays a role in the control of motor function. To approach the cellular mechanisms in which striatin is involved, striatin down-regulation was studied in a comparatively simpler model: purified rat spinal motoneurons which retain their polarity in culture. Treatment of cells by the striatin A-ODN resulted in the impairement of the growth of dendrites but not axon. The decrease in dendritic growth paralleled the loss of striatin. This model allows analysis of the molecular basis of striatin function in the dynamic changes occurring in growing dendrites, and offers clues to unravel its function within spines.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Bartoli",
      "authorRank" : 1,
      "name" : "Bartoli M",
      "referenceId" : "RGD:A8083"
    }, {
      "firstName" : "JP",
      "lastName" : "Ternaux",
      "authorRank" : 2,
      "name" : "Ternaux JP",
      "referenceId" : "RGD:A25621"
    }, {
      "firstName" : "C",
      "lastName" : "Forni",
      "authorRank" : 3,
      "name" : "Forni C",
      "referenceId" : "RGD:A13155"
    }, {
      "firstName" : "P",
      "lastName" : "Portalier",
      "authorRank" : 4,
      "name" : "Portalier P",
      "referenceId" : "RGD:A109020"
    }, {
      "firstName" : "P",
      "lastName" : "Salin",
      "authorRank" : 5,
      "name" : "Salin P",
      "referenceId" : "RGD:A8086"
    }, {
      "firstName" : "M",
      "lastName" : "Amalric",
      "authorRank" : 6,
      "name" : "Amalric M",
      "referenceId" : "RGD:A109021"
    }, {
      "firstName" : "A",
      "lastName" : "Monneron",
      "authorRank" : 7,
      "name" : "Monneron A",
      "referenceId" : "RGD:A8091"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311297"
    } ]
  }, {
    "primaryId" : "PMID:10413673",
    "title" : "The casein kinase Ialpha isoform is both physically positioned and functionally competent to regulate multiple events of mRNA metabolism.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Gross SD, etal., J Cell Sci. 1999 Aug;112 ( Pt 16):2647-56.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-25T09:51:55.000-05:00",
    "volume" : "112 ( Pt 16)",
    "pages" : "2647-56",
    "abstract" : "Casein kinase I is a highly conserved family of serine/threonine protein kinases  present in every organism tested from yeast to humans. To date, little is known about the function of the higher eukaryotic isoforms in this family. The CKI isoforms in Saccharomyces cerevisiae, however, have been genetically linked to the regulation of DNA repair, cell cycle progression and cytokinesis. It has also been established that the nuclear localization of two of these isoforms is essential for their function. The work presented here demonstrates that the higher eukaryotic CKIalpha isoform is also present within nuclei of certain established cell lines and associated with discrete nuclear structures. The nature of its nuclear localization was characterized. In this regard, CKIalpha was shown to colocalize with factors involved in pre-mRNA splicing at nuclear speckles and that its association with these structures exhibited several biochemical properties in common with known splicing factors. The kinase was also shown to be associated with a complex that contained certain splicing factors. Finally, in vitro, CKIalpha was shown to be capable of phosphorylating particular splicing factors within a region rich in serine/arginine dipeptide repeat motifs  suggesting that it has both the opportunity and the capacity to regulate one or more steps of mRNA metabolism.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SD",
      "lastName" : "Gross",
      "authorRank" : 1,
      "name" : "Gross SD",
      "referenceId" : "RGD:A9850"
    }, {
      "firstName" : "JC",
      "lastName" : "Loijens",
      "authorRank" : 2,
      "name" : "Loijens",
      "referenceId" : "RGD:A205566"
    }, {
      "firstName" : "RA",
      "lastName" : "Anderson",
      "authorRank" : 3,
      "name" : "Anderson RA",
      "referenceId" : "RGD:A9852"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10059666"
    } ]
  }, {
    "primaryId" : "PMID:10413680",
    "title" : "mAKAP: an A-kinase anchoring protein targeted to the nuclear membrane of differentiated myocytes.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Kapiloff MS, etal., J Cell Sci 1999 Aug;112 ( Pt 16):2725-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-11-26T11:40:07.000-06:00",
    "volume" : "112 ( Pt 16)",
    "pages" : "2725-36",
    "abstract" : "The compartmentalization of second messenger-activated protein kinases contributes to the fidelity of hormone-mediated signal transduction events. For example, the cAMP-dependent protein kinase is tethered at specific intracellular locations through association with A-kinase anchoring proteins (AKAPs). We now report the cloning of mAKAP, an anchoring protein found predominantly in heart, skeletal muscle and brain, and whose expression is induced in neonatal ventriculocytes by treatment with hypertrophic stimuli. mAKAP is targeted to the nuclear membrane of differentiated myocytes. Analysis of mAKAP-green fluorescent protein (GFP) fusion constructs revealed that nuclear membrane targeting is conferred by two regions of the protein, between residues 772-915 and 915-1065, which contain spectrin-like repeat sequences. Heterologous expression of the mAKAP targeting sequences displaced the endogenous anchoring protein from the nuclear membrane, demonstrating that mAKAP targeting is saturable. Collectively, these data suggest that a domain containing spectrin-like repeats mediates targeting of the anchoring protein mAKAP and the cAMP-dependent protein kinase holoenzyme to the nuclear membrane in response to differentiation signals.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MS",
      "lastName" : "Kapiloff",
      "authorRank" : 1,
      "name" : "Kapiloff MS",
      "referenceId" : "RGD:A5491"
    }, {
      "firstName" : "RV",
      "lastName" : "Schillace",
      "authorRank" : 2,
      "name" : "Schillace RV",
      "referenceId" : "RGD:A6490"
    }, {
      "firstName" : "AM",
      "lastName" : "Westphal",
      "authorRank" : 3,
      "name" : "Westphal AM",
      "referenceId" : "RGD:A6491"
    }, {
      "firstName" : "JD",
      "lastName" : "Scott",
      "authorRank" : 4,
      "name" : "Scott JD",
      "referenceId" : "RGD:A5496"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69370"
    } ]
  }, {
    "primaryId" : "PMID:10413683",
    "title" : "Human heat shock factor 1 is predominantly a nuclear protein before and after heat stress.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Mercier PA, etal., J Cell Sci. 1999 Aug;112 ( Pt 16):2765-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-11-09T20:19:41.000-06:00",
    "volume" : "112 ( Pt 16)",
    "pages" : "2765-74",
    "abstract" : "The induction of the heat shock genes in eukaryotes by heat and other forms of stress is mediated by a transcription factor known as heat shock factor 1 (HSF1). HSF1 is present in unstressed metazoan cells as a monomer with low affinity for DNA, and upon exposure to stress it is converted to an 'active' homotrimer that binds the promoters of heat shock genes with high affinity and induces their transcription. The conversion of HSF1 to its active form is hypothesized to be a  multistep process involving physical changes in the HSF1 molecule and the possible translocation of HSF1 from the cytoplasm to the nucleus. While all studies to date have found active HSF1 to be a nuclear protein, there have been conflicting reports on whether the inactive form of HSF is predominantly a cytoplasmic or nuclear protein. In this study, we have made antibodies against human HSF1 and have reexamined its localization in unstressed and heat-shocked human HeLa and A549 cells, and in green monkey Vero cells. Biochemical fractionation of heat-shocked HeLa cells followed by western blot analysis showed that HSF1 was mostly found in the nuclear fraction. In extracts made from unshocked cells, HSF1 was predominantly found in the cytoplasmic fraction using one fractionation procedure, but was distributed approximately equally between the cytoplasmic and nuclear fractions when a different procedure was used. Immunofluorescence microscopy revealed that HSF1 was predominantly a nuclear protein in both heat shocked and unstressed cells. Quantification of HSF1 staining showed that approximately 80% of HSF1 was present in the nucleus both before and after heat stress. These results suggest that HSF1 is predominantly a  nuclear protein prior to being exposed to stress, but has low affinity for the nucleus and is easily extracted using most biochemical fractionation procedures.  These results also imply that HSF1 translocation is probably not part of the multistep process in HSF1 activation for many cell types.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PA",
      "lastName" : "Mercier",
      "authorRank" : 1,
      "name" : "Mercier",
      "referenceId" : "RGD:A409266"
    }, {
      "firstName" : "NA",
      "lastName" : "Winegarden",
      "authorRank" : 2,
      "name" : "Winegarden",
      "referenceId" : "RGD:A409267"
    }, {
      "firstName" : "JT",
      "lastName" : "Westwood",
      "authorRank" : 3,
      "name" : "Westwood",
      "referenceId" : "RGD:A409268"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11561451"
    } ]
  }, {
    "primaryId" : "PMID:10413701",
    "title" : "Vitreous levels of intercellular adhesion molecule 1 (ICAM-1) as a risk indicator of proliferative vitreoretinopathy.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Limb GA and Chignell AH, Br J Ophthalmol. 1999 Aug;83(8):953-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-18T16:01:49.000-06:00",
    "volume" : "83",
    "pages" : "953-6",
    "abstract" : "AIM: To investigate whether high vitreous levels of the soluble intercellular adhesion molecule 1 (sICAM-1) may be related to clinical risk factors of proliferative vitreoretinopathy (PVR) and whether their measurement may serve as  an additional risk indicator of this complication in eyes with rhegmatogenous retinal detachment (RRD). METHODS: Levels of sICAM-1 were measured by enzyme linked immunosorbent assays (ELISA) in vitreous from 36 eyes with RRD clinically  considered to be at high risk of developing PVR (large retinal breaks, vitreous haemorrhage, long standing RRD, and previous vitreoretinal surgery). Levels of sICAM-1 in this group were compared with those in vitreous from 31 eyes with RRD  without clinical risk factors for PVR, 32 eyes with established PVR and 10 eyes with macular holes. RESULTS: Vitreous from eyes with RRD at high risk of developing PVR contained significantly higher levels of sICAM-1 (range 6.1-97.7 ng/ml; Mann-Whitney test, p=0.0002) than those from eyes with RRD at low risk of  developing this complication (range 4.8-17.7 ng/ml). Vitreous sICAM-1 levels in eyes with RRD at high risk of developing PVR were significantly lower than in eyes with established PVR (p=0.037), but higher than in eyes with macular holes (p <0.0001). Levels of sICAM-1 >/=15 ng/ml (3 x median of the levels present in control eyes) provide a useful cut off point for a highly specific test (96.7%) with high positive (91.6%) and negative (96.7%) predictive values, despite a relatively low sensitivity (30. 5%). CONCLUSIONS: The present findings suggest that laboratory measurement of sICAM-1 levels in vitreous from eyes with RRD may  constitute an additional factor for identifying patients at high risk of PVR. Hence, determination of sICAM-1 levels may aid in the monitoring of patients likely to develop this complication and in the identification of patients who may benefit from adjuvant anti-inflammatory therapy.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GA",
      "lastName" : "Limb",
      "authorRank" : 1,
      "name" : "Limb GA",
      "referenceId" : "RGD:A110849"
    }, {
      "firstName" : "AH",
      "lastName" : "Chignell",
      "authorRank" : 2,
      "name" : "Chignell AH",
      "referenceId" : "RGD:A110852"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547581"
    } ]
  }, {
    "primaryId" : "PMID:10414531",
    "title" : "Immunohistochemical evidence for the brevican-tenascin-R interaction: colocalization in perineuronal nets suggests a physiological role for the interaction in the adult rat brain.",
    "datePublished" : "1999-07-26T00:00:00.000-05:00",
    "citation" : "Hagihara K, etal., J Comp Neurol. 1999 Jul 26;410(2):256-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T02:01:00.000-05:00",
    "volume" : "410",
    "pages" : "256-64",
    "abstract" : "Brevican is one of the most abundant chondroitin sulfate proteoglycans in the adult rat brain. We have recently shown that the C-type lectin domain of brevican binds fibronectin type III domains 3-5 of tenascin-R. Here we report strong evidence for a physiological basis for this interaction. Substantial brevican immunoreactivity was detected in a number of nuclei and in the reticular formations throughout the midbrain and hindbrain, including, but not limited to, the deep cerebellar nuclei, the trapezoid body, the red nucleus, the oculomotor nucleus, the vestibular nucleus, the cochlear nucleus, the gigantocellular reticular nucleus, the motor trigeminal nucleus, and the lateral superior olive. Most of the brevican immunoreactivity exhibited pericellular and reticular staining patterns. In almost all of these sites, brevican immunoreactivity colocalized with that of tenascin-R, which was also substantially codistributed with versican, another member of the lectican family. Detailed analysis revealed that the pericellular staining of brevican resembled that in perineuronal nets in which tenascin-R has been localized. Immunoelectron microscopy identified brevican immunoreactivity in the intercellular spaces surrounding presynaptic boutons and on their surfaces, but not in the synaptic clefts or in their immediate vicinity, a distribution pattern consistent with perineuronal nets. Taken together, our results provide strong evidence that the previously reported interactions between brevican and tenascin-R may play a functional role within the perineuronal nets.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Hagihara",
      "authorRank" : 1,
      "name" : "Hagihara K",
      "referenceId" : "RGD:A49947"
    }, {
      "firstName" : "R",
      "lastName" : "Miura",
      "authorRank" : 2,
      "name" : "Miura R",
      "referenceId" : "RGD:A41254"
    }, {
      "firstName" : "R",
      "lastName" : "Kosaki",
      "authorRank" : 3,
      "name" : "Kosaki R",
      "referenceId" : "RGD:A79837"
    }, {
      "firstName" : "E",
      "lastName" : "Berglund",
      "authorRank" : 4,
      "name" : "Berglund E",
      "referenceId" : "RGD:A460457"
    }, {
      "firstName" : "B",
      "lastName" : "Ranscht",
      "authorRank" : 5,
      "name" : "Ranscht B",
      "referenceId" : "RGD:A37313"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamaguchi",
      "authorRank" : 6,
      "name" : "Yamaguchi Y",
      "referenceId" : "RGD:A5502"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702202"
    } ]
  }, {
    "primaryId" : "PMID:10414605",
    "title" : "Short-term ethanol exposure increases the expression of Kupffer cell CD14 receptor and lipopolysaccharide binding protein in rat liver.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Lukkari TA, etal., Alcohol Alcohol. 1999 May-Jun;34(3):311-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-12-14T13:33:46.000-06:00",
    "volume" : "34",
    "pages" : "311-9",
    "abstract" : "Gut-derived endotoxins (lipopolysaccharide, LPS) complexed to LPS-binding protein (LBP) activate liver Kupffer cells via their CD14 receptor. Pro-inflammatory cytokines are released and this is postulated to promote liver injury. We previously demonstrated enhanced expression of CD14 endotoxin receptor after 2 weeks of alcohol administration. A similar result, based on 6 weeks of ethanol treatment, was recently reported and suggested to correlate with alcohol-induced  liver injury. To establish whether this occurs prior to or after the initiation of damage, we investigated the temporal effect of continuous ethanol exposure on  the expression of CD14 and the associated LBP. In addition, we studied the effect of treatment with gadolinium chloride (GdCl3) that inactivates Kupffer cells and  alleviates alcohol-induced liver damage. The amount of CD14 and LBP mRNA, as determined by reverse transcriptase-polymerase chain reaction (RT-PCR), was unchanged 4-8 h after intragastric ethanol administration. However, after 24-48 h of repeated ethanol administration, CD14 and LBP mRNA both increased significantly and reached a level similar to that observed after 6 weeks of ethanol exposure by liquid diet. Immunostaining experiments with ED2 antibody demonstrated that GdCl3 efficiently inactivated Kupffer cells. However, there was no concomitant reduction in the expression of CD14 mRNA, suggesting that compensatory infiltration by ED2-negative, but CD14-positive, macrophages had occurred. Our results demonstrate that soon after the initiation of ethanol exposure, i.e. within 24-48 h, the hepatic expression of both the CD14 receptor and LBP is increased. This suggests that these increases could contribute to the  initiation of alcoholic damage rather than being a consequence of the injury.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TA",
      "lastName" : "Lukkari",
      "authorRank" : 1,
      "name" : "Lukkari TA",
      "referenceId" : "RGD:A160332"
    }, {
      "firstName" : "HA",
      "lastName" : "Jarvelainen",
      "authorRank" : 2,
      "name" : "Jarvelainen HA",
      "referenceId" : "RGD:A77373"
    }, {
      "firstName" : "T",
      "lastName" : "Oinonen",
      "authorRank" : 3,
      "name" : "Oinonen T",
      "referenceId" : "RGD:A101016"
    }, {
      "firstName" : "E",
      "lastName" : "Kettunen",
      "authorRank" : 4,
      "name" : "Kettunen E",
      "referenceId" : "RGD:A25914"
    }, {
      "firstName" : "KO",
      "lastName" : "Lindros",
      "authorRank" : 5,
      "name" : "Lindros KO",
      "referenceId" : "RGD:A77375"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7204127"
    } ]
  }, {
    "primaryId" : "PMID:10414956",
    "title" : "Myosin VIIa participates in opsin transport through the photoreceptor cilium.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Liu X, etal., J Neurosci. 1999 Aug 1;19(15):6267-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-07T20:14:21.000-06:00",
    "volume" : "19",
    "pages" : "6267-74",
    "abstract" : "Two types of Usher syndrome, a blindness-deafness disorder, result from mutations in the myosin VIIa gene. As for most other unconventional myosins, little is known about the function or functions of myosin VIIa. Here, we studied the photoreceptor cells of mice with mutant myosin VIIa by electron immunomicroscopy  and microscopic autoradiography. We found evidence that myosin VIIa functions in  the connecting cilium of each photoreceptor cell and participates in the transport of opsin through this structure. These findings provide the first direct evidence that opsin travels along the connecting cilium en route to the outer segment. They demonstrate that a myosin may function in a cilium and suggest that abnormal opsin transport might contribute to blindness in Usher syndrome.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu X",
      "referenceId" : "RGD:A17653"
    }, {
      "firstName" : "IP",
      "lastName" : "Udovichenko",
      "authorRank" : 2,
      "name" : "Udovichenko",
      "referenceId" : "RGD:A415420"
    }, {
      "firstName" : "SD",
      "lastName" : "Brown",
      "authorRank" : 3,
      "name" : "Brown SD",
      "referenceId" : "RGD:A6625"
    }, {
      "firstName" : "KP",
      "lastName" : "Steel",
      "authorRank" : 4,
      "name" : "Steel KP",
      "referenceId" : "RGD:A44636"
    }, {
      "firstName" : "DS",
      "lastName" : "Williams",
      "authorRank" : 5,
      "name" : "Williams",
      "referenceId" : "RGD:A184605"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568335"
    } ]
  }, {
    "primaryId" : "PMID:10414958",
    "title" : "L-proline and L-pipecolate induce enkephalin-sensitive currents in human embryonic kidney 293 cells transfected with the high-affinity mammalian brain L-proline transporter.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Galli A, etal., J Neurosci. 1999 Aug 1;19(15):6290-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-05-04T01:55:54.000-05:00",
    "volume" : "19",
    "pages" : "6290-7",
    "abstract" : "The high-affinity mammalian brain L-proline transporter (PROT) belongs to the GAT1 gene family, which includes Na- and Cl-dependent plasma membrane carriers for neurotransmitters, osmolites, and metabolites. These transporters couple substrate flux to transmembrane electrochemical gradients, particularly the Na gradient. In the nervous system, transporters clear synapses and help to replenish transmitters in nerve terminals. The localization of PROT to specific excitatory terminals in rat forebrain suggests a role for this carrier in excitatory transmission (). We investigated the voltage regulation and electrogenicity of this novel transporter, using human embryonic kidney (HEK) 293 cells stably transfected with rat PROT cDNA. In physiological solutions between -140 and -40 mV, L-proline (PRO) and its six-member ring congener L-pipecolate (PIP) induced inward current. The current-voltage relationship and the variance of current fluctuations were similar for PRO- and PIP-induced current, and the ratio of induced variance to the mean current ranged from 20 to 60 fA. Des-Tyr-Leu-enkephalin (GGFL), a competitive peptide inhibitor of PROT, reduced the rat PROT-associated current to control levels. GGFL alone did not elicit currents, and the GGFL-sensitive substrate-induced current was absent in nontransfected cells. Finally, GGFL inhibited PROT-mediated transport only when applied to the extracellular face of PROT. These data suggest that (1) PROT uptake is electrogenic, (2) individual transporter currents are voltage-independent, and (3) GGFL is a nonsubstrate inhibitor that interacts either with an extracellular domain of PROT or in an externally accessible pore.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Galli",
      "authorRank" : 1,
      "name" : "Galli A",
      "referenceId" : "RGD:A84659"
    }, {
      "firstName" : "L D",
      "lastName" : "Jayanthi",
      "authorRank" : 2,
      "name" : "Jayanthi LD",
      "referenceId" : "RGD:A515686"
    }, {
      "firstName" : "I S",
      "lastName" : "Ramsey",
      "authorRank" : 3,
      "name" : "Ramsey IS",
      "referenceId" : "RGD:A515687"
    }, {
      "firstName" : "J W",
      "lastName" : "Miller",
      "authorRank" : 4,
      "name" : "Miller JW",
      "referenceId" : "RGD:A515688"
    }, {
      "firstName" : "R T",
      "lastName" : "Fremeau",
      "authorRank" : 5,
      "name" : "Fremeau RT",
      "referenceId" : "RGD:A438027"
    }, {
      "firstName" : "L J",
      "lastName" : "DeFelice",
      "authorRank" : 6,
      "name" : "DeFelice LJ",
      "referenceId" : "RGD:A515689"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:152025513"
    } ]
  }, {
    "primaryId" : "PMID:10414967",
    "title" : "Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Dubal DB, etal., J Neurosci. 1999 Aug 1;19(15):6385-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-08-04T09:35:03.000-05:00",
    "volume" : "19",
    "pages" : "6385-93",
    "abstract" : "We have shown that physiological levels of estradiol exert profound protective effects on the cerebral cortex in ischemia induced by permanent middle cerebral artery occlusion. The major goal of this study was to begin to elucidate potential mechanisms of estradiol action in injury. Bcl-2 is a proto-oncogene that promotes cell survival in a variety of tissues including the brain. Because  estradiol is known to promote cell survival via Bcl-2 in non-neural tissues, we tested the hypothesis that estradiol decreases cell death by influencing bcl-2 expression in ischemic brain injury. Furthermore, because estradiol may protect the brain through estrogen receptor-mediated mechanisms, we examined expression of both receptor subtypes ERalpha and ERbeta in the normal and injured brain. We  analyzed gene expression by RT-PCR in microdissected regions of the cerebral cortex obtained from injured and sham female rats treated with estradiol or oil.  We found that estradiol prevented the injury-induced downregulation of bcl-2 expression. This effect was specific to bcl-2, as expression of other members of  the bcl-2 family (bax, bcl-x(L), bcl-x(S), and bad) was unaffected by estradiol treatment. We also found that estrogen receptors were differentially modulated in injury, with ERbeta expression paralleling bcl-2 expression. Finally, we provide  the first evidence of functional ERbeta protein that is capable of binding ligand within the region of the cortex where estradiol-mediated neuroprotection was observed in cerebral ischemia. These findings indicate that estradiol modulates the expression of bcl-2 in ischemic injury. Furthermore, our data suggest that estrogen receptors may be involved in hormone-mediated neuroprotection.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DB",
      "lastName" : "Dubal",
      "authorRank" : 1,
      "name" : "Dubal",
      "referenceId" : "RGD:A192142"
    }, {
      "firstName" : "PJ",
      "lastName" : "Shughrue",
      "authorRank" : 2,
      "name" : "Shughrue",
      "referenceId" : "RGD:A192143"
    }, {
      "firstName" : "ME",
      "lastName" : "Wilson",
      "authorRank" : 3,
      "name" : "Wilson ME",
      "referenceId" : "RGD:A104447"
    }, {
      "firstName" : "I",
      "lastName" : "Merchenthaler",
      "authorRank" : 4,
      "name" : "Merchenthaler I",
      "referenceId" : "RGD:A68273"
    }, {
      "firstName" : "PM",
      "lastName" : "Wise",
      "authorRank" : 5,
      "name" : "Wise PM",
      "referenceId" : "RGD:A144323"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8694344"
    } ]
  }, {
    "primaryId" : "PMID:10414976",
    "title" : "Ultrastructural localization of the alpha4-subunit of the neuronal acetylcholine nicotinic receptor in the rat substantia nigra.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Arroyo-Jim nez MM, etal., J Neurosci. 1999 Aug 1;19(15):6475-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T02:04:15.000-05:00",
    "volume" : "19",
    "pages" : "6475-87",
    "abstract" : "The distribution of the alpha4-subunit of the neuronal nicotinic acetylcholine receptor (nAChR) in the rat brain was examined at light and electron microscopy levels using immunohistochemical staining. In the present study we demonstrate the specificity, in both tissue homogenates and brain sections, of a polyclonal antibody raised against the rat nAChR alpha4-subunit. The characterization of this antibody involved: (1) Western blot analysis of rat brain homogenates and membrane extracts from cells previously transfected with diverse combinations of neuronal nAChR subunits, and (2) immunohistochemistry using transfected cells and rat brain tissue. At the light microscope level, the alpha4-subunit-like-immunoreactivity (LI) was widely distributed in the rat brain and matched the distribution of the alpha4-subunit transcripts observed previously by in situ hybridization. Strong immunohistochemical labeling was detected in the mesencephalic dopaminergic nuclei. The nAChRs in this region are thought to be responsible for the modulation of dopaminergic transmission. The neurotransmitter identity of alpha4-immunolabeled neurons in the substantia nigra pars compacta (SNpc) and the ventral tegmental area was thus assessed by investigating the possible colocalization of the nAChR alpha4-subunit with tyrosine hydroxylase using confocal microscopy. The double labeling experiments unambiguously indicated that the alpha4-subunit-LI is present in dopaminergic neurons. At the electron microscope level, the neurons in the SNpc exhibited alpha4-subunit-LI in association with a minority of postsynaptic densities, suggesting that the alpha4-subunit may be a component of functional nAChRs mediating synaptic transmission between midbrain cholinergic neurons and mesencephalic dopaminergic neurons.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M M",
      "lastName" : "Arroyo-Jim nez",
      "authorRank" : 1,
      "name" : "Arroyo-Jim nez MM",
      "referenceId" : "RGD:A460724"
    }, {
      "firstName" : "J P",
      "lastName" : "Bourgeois",
      "authorRank" : 2,
      "name" : "Bourgeois JP",
      "referenceId" : "RGD:A460725"
    }, {
      "firstName" : "L M",
      "lastName" : "Marubio",
      "authorRank" : 3,
      "name" : "Marubio LM",
      "referenceId" : "RGD:A460726"
    }, {
      "firstName" : "A M",
      "lastName" : "Le Sourd",
      "authorRank" : 4,
      "name" : "Le Sourd AM",
      "referenceId" : "RGD:A460727"
    }, {
      "firstName" : "O P",
      "lastName" : "Ottersen",
      "authorRank" : 5,
      "name" : "Ottersen OP",
      "referenceId" : "RGD:A460728"
    }, {
      "firstName" : "E",
      "lastName" : "Rinvik",
      "authorRank" : 6,
      "name" : "Rinvik E",
      "referenceId" : "RGD:A460729"
    }, {
      "firstName" : "A",
      "lastName" : "Fairén",
      "authorRank" : 7,
      "name" : "Fairén A",
      "referenceId" : "RGD:A460730"
    }, {
      "firstName" : "J P",
      "lastName" : "Changeux",
      "authorRank" : 8,
      "name" : "Changeux JP",
      "referenceId" : "RGD:A460731"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702273"
    } ]
  }, {
    "primaryId" : "PMID:10414979",
    "title" : "Proline-rich synapse-associated protein-1/cortactin binding protein 1 (ProSAP1/CortBP1) is a PDZ-domain protein highly enriched in the postsynaptic density.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Boeckers TM, etal., J Neurosci 1999 Aug 1;19(15):6506-18.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:01:26.000-05:00",
    "volume" : "19",
    "pages" : "6506-18",
    "abstract" : "The postsynaptic density (PSD) is crucially involved in the structural and functional organization of the postsynaptic neurotransmitter reception apparatus. Using antisera against rat brain synaptic junctional protein preparations, we isolated cDNAs coding for proline-rich synapse-associated protein-1 (ProSAP1), a PDZ-domain protein. This protein was found to be identical to the recently described cortactin-binding protein-1 (CortBP1). Homology screening identified a related protein, ProSAP2. Specific antisera raised against a C-terminal fusion construct and a central part of ProSAP1 detect a cluster of immunoreactive bands of 180 kDa in the particulate fraction of rat brain homogenates that copurify with the PSD fraction. Transcripts and immunoreactivity are widely distributed in the brain and are upregulated during the period of synapse formation in the brain. In addition, two short N-terminal insertions are detected; they are differentially regulated during brain development. Confocal microscopy of hippocampal neurons showed that ProSAP1 is predominantly localized in synapses, and immunoelectron microscopy in situ revealed a strong association with PSDs of hippocampal excitatory synapses. The accumulation of ProSAP1 at synaptic structures was analyzed in the developing cerebral cortex. During early postnatal development, strong immunoreactivity is detectable in neurites and somata, whereas from postnatal day 10 (P10) onward a punctate staining is observed. At the ultrastructural level, the immunoreactivity accumulates at developing PSDs starting from P8. Both interaction with the actin-binding protein cortactin and early appearance at postsynaptic sites suggest that ProSAP1/CortBP1 may be involved in the assembly of the PSD during neuronal differentiation.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TM",
      "lastName" : "Boeckers",
      "authorRank" : 1,
      "name" : "Boeckers TM",
      "referenceId" : "RGD:A17387"
    }, {
      "firstName" : "MR",
      "lastName" : "Kreutz",
      "authorRank" : 2,
      "name" : "Kreutz MR",
      "referenceId" : "RGD:A13765"
    }, {
      "firstName" : "C",
      "lastName" : "Winter",
      "authorRank" : 3,
      "name" : "Winter C",
      "referenceId" : "RGD:A22858"
    }, {
      "firstName" : "W",
      "lastName" : "Zuschratter",
      "authorRank" : 4,
      "name" : "Zuschratter W",
      "referenceId" : "RGD:A22859"
    }, {
      "firstName" : "KH",
      "lastName" : "Smalla",
      "authorRank" : 5,
      "name" : "Smalla KH",
      "referenceId" : "RGD:A7108"
    }, {
      "firstName" : "L",
      "lastName" : "Sanmarti-Vila",
      "authorRank" : 6,
      "name" : "Sanmarti-Vila L",
      "referenceId" : "RGD:A7103"
    }, {
      "firstName" : "H",
      "lastName" : "Wex",
      "authorRank" : 7,
      "name" : "Wex H",
      "referenceId" : "RGD:A7107"
    }, {
      "firstName" : "K",
      "lastName" : "Langnaese",
      "authorRank" : 8,
      "name" : "Langnaese K",
      "referenceId" : "RGD:A7104"
    }, {
      "firstName" : "J",
      "lastName" : "Bockmann",
      "authorRank" : 9,
      "name" : "Bockmann J",
      "referenceId" : "RGD:A13766"
    }, {
      "firstName" : "CC",
      "lastName" : "Garner",
      "authorRank" : 10,
      "name" : "Garner CC",
      "referenceId" : "RGD:A4777"
    }, {
      "firstName" : "ED",
      "lastName" : "Gundelfinger",
      "authorRank" : 11,
      "name" : "Gundelfinger ED",
      "referenceId" : "RGD:A4776"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634008"
    } ]
  }, {
    "primaryId" : "PMID:1041498",
    "title" : "Roles that nurses in the community can play in nursing research.",
    "datePublished" : "1975-05-01T00:00:00.000-05:00",
    "citation" : "Johnson MN and Okunade AO, Int Nurs Rev. 1975 Sep-Oct;22(5):147-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:33:47.000-05:00",
    "volume" : "22",
    "pages" : "147-9",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MN",
      "lastName" : "Johnson",
      "authorRank" : 1,
      "name" : "Johnson",
      "referenceId" : "RGD:A184154"
    }, {
      "firstName" : "AO",
      "lastName" : "Okunade",
      "authorRank" : 2,
      "name" : "Okunade",
      "referenceId" : "RGD:A184155"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553508"
    } ]
  }, {
    "primaryId" : "PMID:10414980",
    "title" : "Cloning and characterization of neuropilin-1-interacting protein: a PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Cai H and Reed RR, J Neurosci. 1999 Aug 1;19(15):6519-27.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:18:11.000-05:00",
    "volume" : "19",
    "pages" : "6519-27",
    "abstract" : "Neuropilin-1 (Npn-1), a receptor for semaphorin III, mediates the guidance of growth cones on extending neurites. The molecular mechanism of Npn-1 signaling remains unclear. We have used a yeast two-hybrid system to isolate a protein that interacts with the cytoplasmic domain of Npn-1. This Npn-1-interacting protein (NIP) contains a central PSD-95/Dlg/ZO-1 (PDZ) domain and a C-terminal acyl carrier protein domain. The physiological interaction of Npn-1 and NIP is supported by co-immunoprecipitation of these two proteins in extracts from a heterologous expression system and from a native tissue. The C-terminal three amino acids of Npn-1 (S-E-A-COOH), which is conserved from Xenopus to human, is responsible for interaction with the PDZ domain-containing C-terminal two-thirds  of NIP. NIP as well as Npn-1 are broadly expressed in mice as assayed by Northern and Western analysis. Immunohistochemistry and in situ hybridization experiments  revealed that NIP expression overlaps with that of Npn-1. NIP has been independently cloned as RGS-GAIP-interacting protein (GIPC), where it was identified by virtue of its interaction with the C terminus of RGS-GAIP and suggested to participate in clathrin-coated vesicular trafficking. We suggest that NIP and GIPC may participate in regulation of Npn-1-mediated signaling as a  molecular adapter that couples Npn-1 to membrane trafficking machinery in the dynamic axon growth cone.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Cai",
      "authorRank" : 1,
      "name" : "Cai H",
      "referenceId" : "RGD:A32378"
    }, {
      "firstName" : "RR",
      "lastName" : "Reed",
      "authorRank" : 2,
      "name" : "Reed RR",
      "referenceId" : "RGD:A10295"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041037"
    } ]
  }, {
    "primaryId" : "PMID:10414981",
    "title" : "Association of AMPA receptors with a subset of glutamate receptor-interacting protein in vivo.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wyszynski M, etal., J Neurosci 1999 Aug 1;19(15):6528-37.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:08:01.000-05:00",
    "volume" : "19",
    "pages" : "6528-37",
    "abstract" : "The NMDA and AMPA classes of ionotropic glutamate receptors are concentrated at postsynaptic sites in excitatory synapses. NMDA receptors interact via their NR2 subunits with PSD-95/SAP90 family proteins, whereas AMPA receptors bind via their GluR2/3 subunits to glutamate receptor-interacting protein (GRIP), AMPA receptor-binding protein (ABP), and protein interacting with C kinase 1 (PICK1). We report here a novel cDNA (termed ABP-L/GRIP2) that is virtually identical to ABP except for additional GRIP-like sequences at the N-terminal and C-terminal ends. Like GRIP (which we now term GRIP1), ABP-L/GRIP2 contains a seventh PDZ domain at its C terminus. Using antibodies that recognize both these proteins, we examined the subcellular localization of GRIP1 and ABP-L/GRIP2 (collectively termed GRIP) and their biochemical association with AMPA receptors. Immunogold electron microscopy revealed the presence of GRIP at excitatory synapses and also at nonsynaptic membranes and within intracellular compartments. The association of native GRIP and AMPA receptors was confirmed biochemically by coimmunoprecipitation from rat brain extracts. A majority of detergent-extractable GluR2/3 was complexed with GRIP in the brain. However, only approximately half of GRIP was associated with AMPA receptors. Unexpectedly, immunocytochemistry of cultured hippocampal neurons and rat brain at the light microscopic level showed enrichment of GRIP in GABAergic neurons and in GABAergic nerve terminals. Thus GRIP is associated with inhibitory as well as excitatory synapses. Collectively, these findings support a role for GRIP in the synaptic anchoring of AMPA receptors but also suggest that GRIP has additional functions unrelated to the binding of AMPA receptors.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Wyszynski",
      "authorRank" : 1,
      "name" : "Wyszynski M",
      "referenceId" : "RGD:A10693"
    }, {
      "firstName" : "JG",
      "lastName" : "Valtschanoff",
      "authorRank" : 2,
      "name" : "Valtschanoff JG",
      "referenceId" : "RGD:A10696"
    }, {
      "firstName" : "S",
      "lastName" : "Naisbitt",
      "authorRank" : 3,
      "name" : "Naisbitt S",
      "referenceId" : "RGD:A6131"
    }, {
      "firstName" : "AW",
      "lastName" : "Dunah",
      "authorRank" : 4,
      "name" : "Dunah AW",
      "referenceId" : "RGD:A10694"
    }, {
      "firstName" : "E",
      "lastName" : "Kim",
      "authorRank" : 5,
      "name" : "Kim E",
      "referenceId" : "RGD:A6132"
    }, {
      "firstName" : "DG",
      "lastName" : "Standaert",
      "authorRank" : 6,
      "name" : "Standaert DG",
      "referenceId" : "RGD:A19287"
    }, {
      "firstName" : "R",
      "lastName" : "Weinberg",
      "authorRank" : 7,
      "name" : "Weinberg R",
      "referenceId" : "RGD:A19288"
    }, {
      "firstName" : "M",
      "lastName" : "Sheng",
      "authorRank" : 8,
      "name" : "Sheng M",
      "referenceId" : "RGD:A6139"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632958"
    } ]
  }, {
    "primaryId" : "PMID:10415025",
    "title" : "Direct suppression of TCR-mediated activation of extracellular signal-regulated kinase by leukocyte protein tyrosine phosphatase, a tyrosine-specific phosphatase.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Oh-hora M, etal., J Immunol. 1999 Aug 1;163(3):1282-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-03T20:39:34.000-05:00",
    "volume" : "163",
    "pages" : "1282-8",
    "abstract" : "Leukocyte protein tyrosine phosphatase (LC-PTP)/hemopoietic PTP is a human cytoplasmic PTP that is predominantly expressed in the hemopoietic cells. Recently, it was reported that hemopoietic PTP inhibited TCR-mediated signal transduction. However, the precise mechanism of the inhibition was not identified. Here we report that extracellular signal-regulated kinase (ERK) is the direct target of LC-PTP. LC-PTP dephosphorylated ERK2 in vitro. Expression of wild-type LC-PTP in 293T cells suppressed the phosphorylation of ERK2 by a mutant MEK1, which was constitutively active regardless of upstream activation signals.  No suppression of the phosphorylation was observed by LC-PTPCS, a catalytically inactive mutant. In Jurkat cells, LC-PTP suppressed the ERK and p38 mitogen-activated protein kinase cascades. LC-PTP and LC-PTPCS made complexes with ERK1, ERK2, and p38alpha, but not with the gain-of-function sevenmaker ERK2  mutant (D321N). A small deletion (aa 1-46) in the N-terminal portion of LC-PTP or Arg to Ala substitutions at aa 41 and 42 resulted in the loss of ERK binding activity. These LC-PTP mutants revealed little inhibition of the ERK cascade activated by TCR cross-linking. On the other hand, the wild-type LC-PTP did not suppress the phosphorylation of sevenmaker ERK2 mutant. Thus, the complex formation of LC-PTP with ERK is the essential mechanism for the suppression. Taken collectively, these results indicate that LC-PTP suppresses mitogen-activated protein kinase directly in vivo.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Oh-hora",
      "authorRank" : 1,
      "name" : "Oh-hora",
      "referenceId" : "RGD:A184903"
    }, {
      "firstName" : "M",
      "lastName" : "Ogata",
      "authorRank" : 2,
      "name" : "Ogata M",
      "referenceId" : "RGD:A44889"
    }, {
      "firstName" : "Y",
      "lastName" : "Mori",
      "authorRank" : 3,
      "name" : "Mori Y",
      "referenceId" : "RGD:A8708"
    }, {
      "firstName" : "M",
      "lastName" : "Adachi",
      "authorRank" : 4,
      "name" : "Adachi",
      "referenceId" : "RGD:A391540"
    }, {
      "firstName" : "K",
      "lastName" : "Imai",
      "authorRank" : 5,
      "name" : "Imai K",
      "referenceId" : "RGD:A10772"
    }, {
      "firstName" : "A",
      "lastName" : "Kosugi",
      "authorRank" : 6,
      "name" : "Kosugi",
      "referenceId" : "RGD:A359051"
    }, {
      "firstName" : "T",
      "lastName" : "Hamaoka",
      "authorRank" : 7,
      "name" : "Hamaoka T",
      "referenceId" : "RGD:A104749"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11522543"
    } ]
  }, {
    "primaryId" : "PMID:10415058",
    "title" : "Glucocorticosteroids inhibit mRNA expression for eotaxin, eotaxin-2, and monocyte-chemotactic protein-4 in human airway inflammation with eosinophilia.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Jahnsen FL, etal., J Immunol. 1999 Aug 1;163(3):1545-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-11-04T13:34:20.000-05:00",
    "volume" : "163",
    "pages" : "1545-51",
    "abstract" : "How eosinophils are preferentially recruited to inflammatory sites remains elusive, but increasing evidence suggests that chemokines that bind to the CCR3 participate in this process. In this study, we investigated the transcript levels and chemotactic activity of CCR3-binding chemokines in nasal polyps, a disorder often showing prominent eosinophilia. We found that mRNA expression for eotaxin, eotaxin-2, and monocyte-chemotactic protein-4 was significantly increased in nasal polyps compared with turbinate mucosa from the same patients, or histologically normal nasal mucosa from control subjects. Interestingly, the novel CCR3-specific chemokine, eotaxin-2, showed the highest transcript levels. Consistent with these mRNA data, polyp tissue fluid exhibited strong chemotactic activity for eosinophils that was significantly inhibited by a blocking Ab against CCR3. When patients were treated systemically with glucocorticosteroids, the mRNA levels in the polyps were reduced to that found in turbinate mucosa for all chemokines. Together, these findings suggested an important role for CCR3-binding chemokines in eosinophil recruitment to nasal polyps. Such chemokines, therefore, most likely contribute significantly in the pathogenesis of eosinophil-related disorders; and the reduced chemokine expression observed after steroid treatment might reflect, at least in part, how steroids inhibit tissue accumulation of eosinophils.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FL",
      "lastName" : "Jahnsen",
      "authorRank" : 1,
      "name" : "Jahnsen FL",
      "referenceId" : "RGD:A130227"
    }, {
      "firstName" : "R",
      "lastName" : "Haye",
      "authorRank" : 2,
      "name" : "Haye R",
      "referenceId" : "RGD:A130228"
    }, {
      "firstName" : "E",
      "lastName" : "Gran",
      "authorRank" : 3,
      "name" : "Gran E",
      "referenceId" : "RGD:A130229"
    }, {
      "firstName" : "P",
      "lastName" : "Brandtzaeg",
      "authorRank" : 4,
      "name" : "Brandtzaeg P",
      "referenceId" : "RGD:A130230"
    }, {
      "firstName" : "FE",
      "lastName" : "Johansen",
      "authorRank" : 5,
      "name" : "Johansen FE",
      "referenceId" : "RGD:A96409"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4145448"
    } ]
  }, {
    "primaryId" : "PMID:10415068",
    "title" : "Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Maciejewski-Lenoir D, etal., J Immunol. 1999 Aug 1;163(3):1628-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-06-23T06:11:20.000-05:00",
    "volume" : "163",
    "pages" : "1628-35",
    "abstract" : "Molecular analyses of the chemokine fractalkine and its receptor CX3C-R1 in the rat brain have revealed a striking polarization: fractalkine is expressed constitutively in neurons and is up-regulated by TNF-alpha and IL-1beta in astrocytes. Expression of its specific receptor, CX3C-R1, is restricted to astrocytes and microglia. We have analyzed the functional correlates of this expression and demonstrate that fractalkine induces microglial cell migration and activation. However, the activity of this chemokine on astrocytes may also be highly relevant in inducing astrocyte-microglia cell interactions through cytokine/mediator release leading to microglial activation.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Maciejewski-Lenoir",
      "authorRank" : 1,
      "name" : "Maciejewski-Lenoir D",
      "referenceId" : "RGD:A459277"
    }, {
      "firstName" : "S",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen S",
      "referenceId" : "RGD:A157966"
    }, {
      "firstName" : "L",
      "lastName" : "Feng",
      "authorRank" : 3,
      "name" : "Feng L",
      "referenceId" : "RGD:A7447"
    }, {
      "firstName" : "R",
      "lastName" : "Maki",
      "authorRank" : 4,
      "name" : "Maki R",
      "referenceId" : "RGD:A19862"
    }, {
      "firstName" : "K B",
      "lastName" : "Bacon",
      "authorRank" : 5,
      "name" : "Bacon KB",
      "referenceId" : "RGD:A459278"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13673824"
    } ]
  }, {
    "primaryId" : "PMID:10415106",
    "title" : "Rat pregnane X receptor: molecular cloning, tissue distribution, and xenobiotic regulation.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Zhang H, etal., Arch Biochem Biophys 1999 Aug 1;368(1):14-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:56.000-05:00",
    "volume" : "368",
    "pages" : "14-22",
    "abstract" : "An orphan nuclear receptor, termed the pregnane X receptor (PXR), has recently been cloned from mouse and human and defines a novel steroid signaling pathway (Cell 92, 73-82, 1998; Proc. Natl. Acad. Sci. USA 95, 12208-122313, 1998). Transient cotransfection experiments demonstrate that the PXR responds to structurally dissimilar compounds and confers the induction of cytochrome P4503A (CYP3A), a subfamily of enzymes that involve the metabolism of two-thirds of drugs and other xenobiotics. In this report, we describe the molecular cloning, tissue distribution, and xenobiotic regulation of a rat PXR designated rPXR-1. rPXR-1 exhibits a 95% sequence identity with the mouse PXR, but only 79% identity with the human PXR, providing the molecular basis that rats and mice have a similar CYP3A induction profile but differ from humans. rPXR-1 gene was expressed abundantly in liver, intestine, and, to a lesser extent, kidney, lung, and stomach. The tissue distribution and the relative abundance of rPXR-1 mRNA among these tissues resemble those of CYP3A, suggesting that PXR is important not only for induction but also for constitutive expression of these enzymes. Xenobiotics known to induce liver microsomal enzymes showed differential effects on the rPXR-1 expression as determined by Northern blot analysis. Dexamethasone, for example, increased the accumulation of rPXR-1 mRNA, whereas troleandomycin slightly suppressed it. Compounds that increase PXR expression (inducers) and compounds that interact with PXR (ligands) likely have synergistic effects on CYP3A induction, which provides a novel molecular explanation for drug-drug interactions.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Zhang",
      "authorRank" : 1,
      "name" : "Zhang H",
      "referenceId" : "RGD:A6284"
    }, {
      "firstName" : "E",
      "lastName" : "LeCulyse",
      "authorRank" : 2,
      "name" : "LeCulyse E",
      "referenceId" : "RGD:A6285"
    }, {
      "firstName" : "L",
      "lastName" : "Liu",
      "authorRank" : 3,
      "name" : "Liu L",
      "referenceId" : "RGD:A161824"
    }, {
      "firstName" : "M",
      "lastName" : "Hu",
      "authorRank" : 4,
      "name" : "Hu M",
      "referenceId" : "RGD:A6287"
    }, {
      "firstName" : "L",
      "lastName" : "Matoney",
      "authorRank" : 5,
      "name" : "Matoney L",
      "referenceId" : "RGD:A6288"
    }, {
      "firstName" : "W",
      "lastName" : "Zhu",
      "authorRank" : 6,
      "name" : "Zhu W",
      "referenceId" : "RGD:A6289"
    }, {
      "firstName" : "B",
      "lastName" : "Yan",
      "authorRank" : 7,
      "name" : "Yan B",
      "referenceId" : "RGD:A6290"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68878"
    } ]
  }, {
    "primaryId" : "PMID:10415329",
    "title" : "Cloning, gene expression, and characterization of CP27, a novel gene in mouse embryogenesis.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Diekwisch TG, etal., Gene 1999 Jul 22;235(1-2):19-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:44:03.000-05:00",
    "volume" : "235",
    "pages" : "19-30",
    "abstract" : "We report the full-length sequencing, tissue-specific expression, and immunolocalization of cp27, a novel gene in mouse embryogenesis. The cp27 gene was isolated and cloned from a mouse E11 lambdagt11 library using a peptide antibody that recognized a distinct expression pattern in mouse craniofacial development. The cp27 gene contains an open reading frame of 295 amino acids corresponding to a predicted molecular mass of 33kDa. On Western blots, a polyclonal antibody against CP27 detected a single epitope at 27kDa. The putative CP27 protein has an isoelectric point of 4.75 and features a distinct helix-loop-helix structure according to prediction algorithms. We have cloned the human cp27 gene and mapped it to a locus on the human chromosome 16 which is in proximity to several loci associated with inherited craniofacial diseases such as fanconi anemia type A. Northern blot analysis of RNA from multiple mouse tissues demonstrated high levels of expression in developing mouse teeth, heart, lung, and liver of a single transcript of approx. 1. 8kbp. In situ hybridization using a radioactive RNA probe resulted in distinct signals in the developing neuroepithelium, cerebellum, heart, lung, liver, teeth, salivary glands, and periosteum of developing bones. Immunohistochemical staining of developing mouse tissues detected epitopes specific for CP27 in the mesenchyme surrounding the primary brain vesicles, in basement membranes, in the periosteum, in salivary glands, and in the stellate reticulum of teeth. Thus, CP27 represents a unique gene product involved in mouse embryogenesis.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TG",
      "lastName" : "Diekwisch",
      "authorRank" : 1,
      "name" : "Diekwisch TG",
      "referenceId" : "RGD:A47556"
    }, {
      "firstName" : "F",
      "lastName" : "Marches",
      "authorRank" : 2,
      "name" : "Marches F",
      "referenceId" : "RGD:A47557"
    }, {
      "firstName" : "A",
      "lastName" : "Williams",
      "authorRank" : 3,
      "name" : "Williams A",
      "referenceId" : "RGD:A47558"
    }, {
      "firstName" : "X",
      "lastName" : "Luan",
      "authorRank" : 4,
      "name" : "Luan X",
      "referenceId" : "RGD:A47559"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302860"
    } ]
  }, {
    "primaryId" : "PMID:10415332",
    "title" : "Rat endozepine-like peptide (ELP): cDNA cloning, genomic organization and tissue-specific expression.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Pusch W, etal., Gene 1999 Jul 22;235(1-2):51-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-10T16:46:04.000-05:00",
    "volume" : "235",
    "pages" : "51-7",
    "abstract" : "A cDNA encoding the rat homolog of the previously characterized murine endozepine-like peptide (ELP) was isolated by a PCR cloning strategy. Sequence comparison with the murine cDNA sequence revealed a conservation of the ELP primary structure between both rodent species with minor amino acid exchanges. We investigated the genomic organization of the rat ELP gene by genomic PCR. This indicated the presence of a single short intron of 451bp interrupting the 5' untranslated region. Tissue-dependent ELP expression was determined by Northern hybridization and semiquantitative RT-PCR. Northern hybridization showed an ELP specific transcript in both the male and the female gonad, but the level of ovarian ELP transcription was considerably lower than in the testis. RT-PCR analysis demonstrated a low and varying level of ELP background expression in all examined tissues. In contrast to the closely related ACBP gene, ELP shows a different genomic organization and a more regulated expression pattern, and may exert a specific function as a gonadal acyl-CoA pool former and transporter.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Pusch",
      "authorRank" : 1,
      "name" : "Pusch W",
      "referenceId" : "RGD:A4091"
    }, {
      "firstName" : "D",
      "lastName" : "Jahner",
      "authorRank" : 2,
      "name" : "Jahner D",
      "referenceId" : "RGD:A4092"
    }, {
      "firstName" : "AN",
      "lastName" : "Spiess",
      "authorRank" : 3,
      "name" : "Spiess AN",
      "referenceId" : "RGD:A4093"
    }, {
      "firstName" : "R",
      "lastName" : "Ivell",
      "authorRank" : 4,
      "name" : "Ivell R",
      "referenceId" : "RGD:A4094"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61789"
    } ]
  }, {
    "primaryId" : "PMID:10415339",
    "title" : "Cloning and gene structure of rat phosphatidylcholine transfer protein, Pctp.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Wu MK, etal., Gene 1999 Jul 22;235(1-2):111-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:06.000-06:00",
    "volume" : "235",
    "pages" : "111-20",
    "abstract" : "Phosphatidylcholine transfer protein (PC-TP) is a cytosolic lipid transfer protein that promotes intermembrane transfer of phosphatidylcholines but no other phospholipids. Although its physiological function remains unknown, phosphatidylcholine transfer protein is enriched in liver and evidence from model systems suggests a role in hepatocellular selection and transport of biliary phospholipids. To facilitate in vivo studies, a cDNA encoding rat PC-TP was cloned by library screening and 5'-rapid amplification of cDNA ends. Genomic cloning demonstrated the rat Pctp gene spans 10. 8kb and is comprised of six exons. The putative transcription initiation site was identified 50bp upstream of the translation initiation site. Nucleotide sequence analysis of the 5'-flanking region revealed a CAAT- but no TATA-box. Transient transfection of a series of 5'-deleted Pctp-promoter-firefly luciferase constructs into Reuber H35 rat hepatoma cells, which express Pctp mRNA, and Gunn rat fibroblasts, which do not, suggest that cis-acting elements in a 637bp promoter region contribute to enhanced expression of PC-TP in liver.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MK",
      "lastName" : "Wu",
      "authorRank" : 1,
      "name" : "Wu MK",
      "referenceId" : "RGD:A7681"
    }, {
      "firstName" : "MO",
      "lastName" : "Boylan",
      "authorRank" : 2,
      "name" : "Boylan MO",
      "referenceId" : "RGD:A7682"
    }, {
      "firstName" : "DE",
      "lastName" : "Cohen",
      "authorRank" : 3,
      "name" : "Cohen DE",
      "referenceId" : "RGD:A7683"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69923"
    } ]
  }, {
    "primaryId" : "PMID:10415398",
    "title" : "Expression of the activin axis and neuronal rescue effects of recombinant activin A following hypoxic-ischemic brain injury in the infant rat.",
    "datePublished" : "1999-07-24T00:00:00.000-05:00",
    "citation" : "Wu DD, etal., Brain Res. 1999 Jul 24;835(2):369-78. doi: 10.1016/s0006-8993(99)01638-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-04-24T16:05:11.000-05:00",
    "volume" : "835",
    "pages" : "369-78",
    "abstract" : "Neurotrophic factors are induced in the brain in response to injury and may restrict the extent of neuronal loss and facilitate recovery. We have previously reported a strong neuronal induction of activin betaA subunit mRNA expression after a hypoxic-ischemic (HI) injury in the rat brain. Here, we further extended our studies to examine a role for the activin inhibitory binding protein, follistatin after injury and also to determine the potential of activin as a neuronal rescue agent. Ribonuclease protection assay (RPA) was used to quantify the time course of the mRNA expression of activin betaA subunit and follistatin, following a 60-min HI brain injury. Activin betaA subunit mRNA level increased in the contralateral hemisphere 5 h after injury and returned to normal at 10 h post injury. In contrast, follistatin mRNA levels decreased in the same hemisphere at 5 and 10 h after injury. The effect of intracerebroventrically (i. c.v.) administered recombinant human activin A or its antagonist, inhibin A, on neuronal death after a 15-min HI brain injury was determined for a number of brain regions. One microgram activin A (n=23) reduced the neuronal loss in the hippocampal CA1/2 region, dorsolateral striatum but not in the parietal cortex. In contrast, 1 microg of inhibin A (n=18) did not have a significant effect on the extent of neuronal loss in any of the affected regions. This pattern of neuroprotection was consistent with the distribution of immunoreactivity for the activin receptor type II subunit. These results demonstrate that activin A, but not its functional antagonist inhibin A, can enhance the survival of injured hippocampal and striatal neurons. Since follistatin is thought to exert a neutralising effect on activin A activity, the down-regulation of follistatin expression post injury may be allowing activin A to become more accessible to neurons after injury. Overall, these results suggest a role of the activin axis in modulating the survival of specific populations of injured neurons.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D D",
      "lastName" : "Wu",
      "authorRank" : 1,
      "name" : "Wu DD",
      "referenceId" : "RGD:A526716"
    }, {
      "firstName" : "M",
      "lastName" : "Lai",
      "authorRank" : 2,
      "name" : "Lai M",
      "referenceId" : "RGD:A11421"
    }, {
      "firstName" : "P E",
      "lastName" : "Hughes",
      "authorRank" : 3,
      "name" : "Hughes PE",
      "referenceId" : "RGD:A526717"
    }, {
      "firstName" : "E",
      "lastName" : "Sirimanne",
      "authorRank" : 4,
      "name" : "Sirimanne E",
      "referenceId" : "RGD:A117382"
    }, {
      "firstName" : "P D",
      "lastName" : "Gluckman",
      "authorRank" : 5,
      "name" : "Gluckman PD",
      "referenceId" : "RGD:A436189"
    }, {
      "firstName" : "C E",
      "lastName" : "Williams",
      "authorRank" : 6,
      "name" : "Williams CE",
      "referenceId" : "RGD:A526718"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:329322882"
    } ]
  }, {
    "primaryId" : "PMID:10415618",
    "title" : "Preliminary data suggesting production of interleukin-12 by rat Leydig cells cultured in vitro.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Valenti S, etal., Ann N Y Acad Sci. 1999 Jun 22;876:259-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-26T17:16:20.000-06:00",
    "volume" : "876",
    "pages" : "259-61",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Valenti",
      "authorRank" : 1,
      "name" : "Valenti S",
      "referenceId" : "RGD:A76045"
    }, {
      "firstName" : "B",
      "lastName" : "Villaggio",
      "authorRank" : 2,
      "name" : "Villaggio B",
      "referenceId" : "RGD:A76046"
    }, {
      "firstName" : "M",
      "lastName" : "Cutolo",
      "authorRank" : 3,
      "name" : "Cutolo M",
      "referenceId" : "RGD:A76047"
    }, {
      "firstName" : "M",
      "lastName" : "Giusti",
      "authorRank" : 4,
      "name" : "Giusti M",
      "referenceId" : "RGD:A76048"
    }, {
      "firstName" : "G",
      "lastName" : "Giordano",
      "authorRank" : 5,
      "name" : "Giordano G",
      "referenceId" : "RGD:A76049"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600057"
    } ]
  }, {
    "primaryId" : "PMID:10415717",
    "title" : "Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Pilcher BK, etal., Ann N Y Acad Sci. 1999 Jun 30;878:12-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-26T18:08:01.000-06:00",
    "volume" : "878",
    "pages" : "12-24",
    "abstract" : "Normal wounds can heal by secondary intention (epidermal migration to cover a denuded surface) or by approximation of the wound edges (e.g., suturing). In healing by secondary intention, epidermis-derived MMPs are important. Keratinocyte migration begins within 3-6 hr post injury, as basal cells detach from underlying basal lamina and encounter a dermal substratum rich in type I collagen. Cell contact with type I collagen in vitro stimulates collagenase-1 expression, which is mediated by the alpha 2 beta 1 integrin, the major keratinocyte collagen-binding receptor. Collagenase-1 activity alone is necessary and sufficient for keratinocyte migration over a collagen subsurface. Stromelysins-1 and -2 are also found in the epidermis of normal acute wounds. Stromelysin-2 co-localizes with collagenase-1 and may facilitate cell migration over non-collagenous matrices of the dermis. In contrast, stromelysin-1 is expressed by keratinocytes behind the migrating front and which remain on basal lamina, i.e., the proliferative cell population. Studies with stromelysin-1-deficient mice that suggest this MMP plays a role in keratinocyte detachment from underlying basement membrane to initiate cell migration. In chronic ulcers, MMP levels are markedly elevated, in contrast to their precise temporal and spatial expression in acute wounds. Both collagenase-1 and stromelysin-1 are found in fibroblasts underlying the nonhealing epithelium, and  stromelysin-1 expression is especially prominent. Two key questions underlie the  use of MMP inhibitors and wound healing: (1) will these agents impair normal reepithelialization in wounds that heal by secondary intention; and (2) can MMP inhibitors be effective therapy for chronic ulcers? The answer to neither is known. Batimastat and marimastat appear not to interfere with normal wound healing, but only in sutured surgical wounds, a situation in which MMP expression has practically no role. We also show the first example of an in vivo immune response, contact hypersensitivity, which is dependent upon MMP activity. Using gene-deficient mice, we demonstrate that stromylysin-1 (MMP-3) is required for sensitization, whereas gelatinase B (MMP-9) is required for timely resolution of  the reaction to antigenic challenge.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BK",
      "lastName" : "Pilcher",
      "authorRank" : 1,
      "name" : "Pilcher",
      "referenceId" : "RGD:A180199"
    }, {
      "firstName" : "M",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang M",
      "referenceId" : "RGD:A9187"
    }, {
      "firstName" : "XJ",
      "lastName" : "Qin",
      "authorRank" : 3,
      "name" : "Qin XJ",
      "referenceId" : "RGD:A70899"
    }, {
      "firstName" : "WC",
      "lastName" : "Parks",
      "authorRank" : 4,
      "name" : "Parks WC",
      "referenceId" : "RGD:A68966"
    }, {
      "firstName" : "RM",
      "lastName" : "Senior",
      "authorRank" : 5,
      "name" : "Senior",
      "referenceId" : "RGD:A180140"
    }, {
      "firstName" : "HG",
      "lastName" : "Welgus",
      "authorRank" : 6,
      "name" : "Welgus",
      "referenceId" : "RGD:A180200"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547869"
    } ]
  }, {
    "primaryId" : "PMID:10416273",
    "title" : "Arsenite alters heme synthesis in long-term cultures of adult rat hepatocytes.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Aguilar-Gonzalez MG, etal., Toxicol Sci. 1999 Jun;49(2):281-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-02-11T14:28:08.000-06:00",
    "volume" : "49",
    "pages" : "281-9",
    "abstract" : "Arsenite (As[III]) effects on the intermediate steps of heme biosynthesis were studied in adult rat hepatocytes seeded on a feeder layer of 3T3 cells (3T3-hepatocytes) and maintained for 2 weeks with culture medium non-supplemented or supplemented with 150 microM 5-aminolevulinic acid (ALA). The activities of the intracellular enzymes porphobilinogen deaminase (PBG-D), uroporphyrinogen III synthase (UROIII-S), and uroporphyrinogen III decarboxylase (URO-D), and the intermediary uroporphyrins (URO), coproporphyrins (COPRO) and protoporphyrin IX (PROTO) were determined in these cultures. The 3T3-hepatocytes maintained the activities of PBG-D, UROIII-S and URO-D during 2 weeks and ALA addition to the culture medium increased PBG-D (2-3-fold) and UROIII-S (50%) activities and porphyrin production, which accumulated as PROTO. Exposure to 3.9 microM As(III) inhibited UROIII-S activity (down to 34%), and PBG-D and URO-D activities to a lower extent; these effects were magnified by ALA supplementation. As(III) also produced an intracellular accumulation and a decreased excretion of PROTO, and a 31% reduction of the COPRO/URO ratio in the culture medium. Additionally, As(III) caused cytoplasmic vacuolization and lipid accumulation. Our results show that As(III) exposure selectively inhibits several intermediary enzymes of heme metabolism and affects the intra- and extracellular content of porphyrins and their ratio in the culture medium. They also confirm that 3T3-hepatocytes are a suitable in vitro model to study hepatic heme metabolism and its alterations by hepatotoxic chemicals.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MG",
      "lastName" : "Aguilar-Gonzalez",
      "authorRank" : 1,
      "name" : "Aguilar-Gonzalez MG",
      "referenceId" : "RGD:A103512"
    }, {
      "firstName" : "A",
      "lastName" : "Hernandez",
      "authorRank" : 2,
      "name" : "Hernandez A",
      "referenceId" : "RGD:A13175"
    }, {
      "firstName" : "ML",
      "lastName" : "Lopez",
      "authorRank" : 3,
      "name" : "Lopez ML",
      "referenceId" : "RGD:A58463"
    }, {
      "firstName" : "T",
      "lastName" : "Mendoza-Figueroa",
      "authorRank" : 4,
      "name" : "Mendoza-Figueroa T",
      "referenceId" : "RGD:A103513"
    }, {
      "firstName" : "A",
      "lastName" : "Albores",
      "authorRank" : 5,
      "name" : "Albores A",
      "referenceId" : "RGD:A103514"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303399"
    } ]
  }, {
    "primaryId" : "PMID:10416598",
    "title" : "Transforming growth factor beta1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis.",
    "datePublished" : "1999-07-15T00:00:00.000-05:00",
    "citation" : "Engle SJ, etal., Cancer Res. 1999 Jul 15;59(14):3379-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-09-19T10:22:42.000-05:00",
    "volume" : "59",
    "pages" : "3379-86",
    "abstract" : "The transforming growth factor beta (TGF-beta) pathway is known to play an important role in both human and urine colon cancer. However, the staging, ligand specificity, and mechanism underlying the tumor suppressive activity of this pathway are unknown. We developed a mouse model for colon cancer that identifies an early role for TGF-beta1 in tumor suppression and implicates TGF-beta2 or TGF-beta3 in the prevention of metastasis. Analysis of the development of colon cancer in TGF-beta1 knockout mice pinpoints the defect to the hyperplasty/adenoma transition and reveals that the mechanism involves an inability to maintain epithelial tissue organization and not a loss of growth control, increased inflammatory activity, or increased genetic instability. These mice provide a unique opportunity to investigate the specific role of TGF-beta1 at this critical transition in the development of colon cancer.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S J",
      "lastName" : "Engle",
      "authorRank" : 1,
      "name" : "Engle SJ",
      "referenceId" : "RGD:A450779"
    }, {
      "firstName" : "J B",
      "lastName" : "Hoying",
      "authorRank" : 2,
      "name" : "Hoying JB",
      "referenceId" : "RGD:A450780"
    }, {
      "firstName" : "G P",
      "lastName" : "Boivin",
      "authorRank" : 3,
      "name" : "Boivin GP",
      "referenceId" : "RGD:A450781"
    }, {
      "firstName" : "I",
      "lastName" : "Ormsby",
      "authorRank" : 4,
      "name" : "Ormsby I",
      "referenceId" : "RGD:A450782"
    }, {
      "firstName" : "P S",
      "lastName" : "Gartside",
      "authorRank" : 5,
      "name" : "Gartside PS",
      "referenceId" : "RGD:A450783"
    }, {
      "firstName" : "T",
      "lastName" : "Doetschman",
      "authorRank" : 6,
      "name" : "Doetschman T",
      "referenceId" : "RGD:A36222"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13432084"
    } ]
  }, {
    "primaryId" : "PMID:10416615",
    "title" : "Mouse model for the DNA repair/basal transcription disorder trichothiodystrophy reveals cancer predisposition.",
    "datePublished" : "1999-07-15T00:00:00.000-05:00",
    "citation" : "de Boer J, etal., Cancer Res. 1999 Jul 15;59(14):3489-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-05-08T13:35:28.000-05:00",
    "volume" : "59",
    "pages" : "3489-94",
    "abstract" : "Patients with the nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) are highly predisposed to develop sunlight-induced skin cancer, in remarkable contrast to photosensitive NER-deficient trichothiodystrophy (TTD) patients carrying mutations in the same XPD gene. XPD encodes a helicase subunit of the dually functional DNA repair/basal transcription complex TFIIH. The pleiotropic disease phenotype is hypothesized to be, in part, derived from a repair defect causing UV sensitivity and, in part, from a subtle, viable basal transcription deficiency accounting for the cutaneous, developmental, and the typical brittle hair features of TTD. To understand the relationship between deficient NER and tumor susceptibility, we used a mouse model for TTD that mimics an XPD point mutation of a TTD patient in the mouse germline. Like the fibroblasts from the patient, mouse cells exhibit a partial NER defect, evident from the reduced UV-induced DNA repair synthesis (residual repair capacity approximately 25%), limited recovery of RNA synthesis after UV exposure, and a relatively mild hypersensitivity to cell killing by UV or 7,12-dimethylbenz[a]anthracene. In accordance with the cellular studies, TTD mice exhibit a modestly increased sensitivity to UV-induced inflammation and hyperplasia of the skin. In striking contrast to the human syndrome, TTD mice manifest a dear susceptibility to UV- and 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis, albeit not as pronounced as the totally NER-deficient XPA mice. These findings open up the possibility that TTD is associated with a so far unnoticed cancer predisposition and support the notion that a NER deficiency enhances cancer susceptibility. These findings have important implications for the etiology of the human disorder and for the impact of NER on carcinogenesis.",
    "issueName" : "14",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "de Boer",
      "authorRank" : 1,
      "name" : "de Boer J",
      "referenceId" : "RGD:A443289"
    }, {
      "firstName" : "H",
      "lastName" : "van Steeg",
      "authorRank" : 2,
      "name" : "van Steeg H",
      "referenceId" : "RGD:A443290"
    }, {
      "firstName" : "R J",
      "lastName" : "Berg",
      "authorRank" : 3,
      "name" : "Berg RJ",
      "referenceId" : "RGD:A443291"
    }, {
      "firstName" : "J",
      "lastName" : "Garssen",
      "authorRank" : 4,
      "name" : "Garssen J",
      "referenceId" : "RGD:A443292"
    }, {
      "firstName" : "J",
      "lastName" : "de Wit",
      "authorRank" : 5,
      "name" : "de Wit J",
      "referenceId" : "RGD:A443293"
    }, {
      "firstName" : "C T",
      "lastName" : "van Oostrum",
      "authorRank" : 6,
      "name" : "van Oostrum CT",
      "referenceId" : "RGD:A443294"
    }, {
      "firstName" : "R B",
      "lastName" : "Beems",
      "authorRank" : 7,
      "name" : "Beems RB",
      "referenceId" : "RGD:A443295"
    }, {
      "firstName" : "G T",
      "lastName" : "van der Horst",
      "authorRank" : 8,
      "name" : "van der Horst GT",
      "referenceId" : "RGD:A443296"
    }, {
      "firstName" : "C F",
      "lastName" : "van Kreijl",
      "authorRank" : 9,
      "name" : "van Kreijl CF",
      "referenceId" : "RGD:A443297"
    }, {
      "firstName" : "F R",
      "lastName" : "de Gruijl",
      "authorRank" : 10,
      "name" : "de Gruijl FR",
      "referenceId" : "RGD:A443298"
    }, {
      "firstName" : "D",
      "lastName" : "Bootsma",
      "authorRank" : 11,
      "name" : "Bootsma D",
      "referenceId" : "RGD:A38522"
    }, {
      "firstName" : "J H",
      "lastName" : "Hoeijmakers",
      "authorRank" : 12,
      "name" : "Hoeijmakers JH",
      "referenceId" : "RGD:A443299"
    }, {
      "firstName" : "G",
      "lastName" : "Weeda",
      "authorRank" : 13,
      "name" : "Weeda G",
      "referenceId" : "RGD:A50573"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12880441"
    } ]
  }, {
    "primaryId" : "PMID:10416826",
    "title" : "The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria.",
    "datePublished" : "1000-10-01T00:00:00.000-06:00",
    "citation" : "Tishler PV Life Sci. 1999;65(2):207-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-10-14T09:33:05.000-05:00",
    "volume" : "65",
    "pages" : "207-14",
    "abstract" : "Drugs and toxins precipitate life-threatening acute attacks in patients with intermittent acute porphyria. These materials may act by directly inhibiting enzyme activity, thus further reducing porphobilinogen (PBG) deaminase activity below the ca. 50% level that results from the gene defect. To test this, we studied the effects of drugs that precipitate acute attacks (lead, phenobarbital, griseofulvin, phenytoin, sulfanilamide, sulfisoxazole, 17alpha-ethinyl estradiol, 5beta-pregnan-3alpha-ol-20-one), drugs that are safe (lithium, magnesium, chlorpromazine, promethazine), and those with uncertain effects (ethyl alcohol, imipramine, diazepam, haloperidol) on activity of PBG deaminase in vitro and in vivo. In the in vitro studies, of PBG deaminase from human erythrocytes from normals and individuals with IAP, only lead (> or = .01 mM) inhibited enzyme activity. Chlorpromazine (> or = .01 mM), promethazine (> or = .01 mM) and imipramine (1 mM) seemed to increase enzyme activity. In most in vivo experiments, male rats were injected intraperitoneally with test material twice daily for 3 days and once on day four; and erythrocyte and hepatic PBG deaminase activity was assayed thereafter. Effects on enzyme activity were observed only with 17alpha-ethinyl estradiol (0.05 microg/kg/day; reduction of 11% in erythrocyte enzyme [NS], and of 20% in liver enzyme [P=.02]), and imipramine (12.5 mg/kg/day; reduction in erythrocyte enzyme activity of 13% [P<.001]). Rats given lead acetate in their drinking water (10 mg/ml) for the first 60 days of life, resulting in high blood and liver lead levels, had increased erythrocyte PBG deaminase (167% of control; P=.004). Thus, enzyme inhibition by lead in vitro was not reflected in a similar in vivo inhibition. The only inhibitory effects in vivo, with ethinyl estradiol and imipramine, appear to be mild and biologically inconsequential. We conclude that inhibition of PBG deaminase activity by materials that precipitate acute attacks is an unlikely mechanism by which these materials exert their harmful effects in patients with IAP.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PV",
      "lastName" : "Tishler",
      "authorRank" : 1,
      "name" : "Tishler PV",
      "referenceId" : "RGD:A51275"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4144786"
    } ]
  }, {
    "primaryId" : "PMID:10416873",
    "title" : "Peripherin immunoreactivity labels small diameter vestibular 'bouton' afferents in rodents.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Lysakowski A, etal., Hear Res. 1999 Jul;133(1-2):149-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-19T10:52:21.000-05:00",
    "volume" : "133",
    "pages" : "149-54",
    "abstract" : "Recent morphophysiological studies have described three different subpopulations  of vestibular afferents. The purpose of this study was to determine whether peripherin, a 56-kDa type III intermediate filament protein present in small sensory neurons in dorsal root ganglion and spiral ganglion cells, would also label thin vestibular afferents. Peripherin immunohistochemistry was done on vestibular sensory organs (cristae ampullares, utriculi and sacculi) of chinchillas, rats, and mice. In these sensory organs, immunoreactivity was confined to the extrastriolar region of the utriculus and the peripheral region of the crista. The labelled terminals were all boutons, except for an occasional  calyx. In vestibular ganglia, immunoreactivity was restricted to small vestibular ganglion cells with thin axons. The immunoreactive central axons of vestibular ganglion cells form narrow bundles as they pass through the caudal spinal trigeminal tract. As they exit this tract, several bundles coalesce to form a single, narrow bundle passing caudally through the ventral part of the lateral vestibular nucleus. Finally, we conclude that all labelled axons and terminals were vestibular afferents rather than efferents, as no immunoreactivity in the vestibular efferent nucleus of the brainstem was observed.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Lysakowski",
      "authorRank" : 1,
      "name" : "Lysakowski A",
      "referenceId" : "RGD:A76896"
    }, {
      "firstName" : "A",
      "lastName" : "Alonto",
      "authorRank" : 2,
      "name" : "Alonto",
      "referenceId" : "RGD:A397864"
    }, {
      "firstName" : "L",
      "lastName" : "Jacobson",
      "authorRank" : 3,
      "name" : "Jacobson",
      "referenceId" : "RGD:A213698"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11554026"
    } ]
  }, {
    "primaryId" : "PMID:10417273",
    "title" : "Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Colige A, etal., Am J Hum Genet. 1999 Aug;65(2):308-17.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-16T19:12:45.000-06:00",
    "volume" : "65",
    "pages" : "308-17",
    "abstract" : "Ehlers-Danlos syndrome (EDS) type VIIC is a recessively inherited connective-tissue disorder, characterized by extreme skin fragility, characteristic facies, joint laxity, droopy skin, umbilical hernia, and blue sclera. Like the animal model dermatosparaxis, EDS type VIIC results from the absence of activity of procollagen I N-proteinase (pNPI), the enzyme that excises the N-propeptide of type I and type II procollagens. The pNPI enzyme is a metalloproteinase containing properdin repeats and a cysteine-rich domain with similarities to the disintegrin domain of reprolysins. We used bovine cDNA to isolate human pNPI. The human enzyme exists in two forms: a long version similar to the bovine enzyme and a short version that contains the Zn++-binding catalytic site but lacks the entire C-terminal domain in which the properdin repeats are located. We have identified the mutations that cause EDS type VIIC in the six known affected human individuals and also in one strain of dermatosparactic calf. Five of the individuals with EDS type VIIC were homozygous for a C-->T transition that results in a premature termination codon, Q225X. Four of these five patients were homozygous at three downstream polymorphic sites. The sixth patient was homozygous for a different transition that results in a premature termination codon, W795X. In the dermatosparactic calf, the mutation is a 17-bp deletion that changes the reading frame of the message. These data provide direct evidence that EDS type VIIC and dermatosparaxis result from mutations in the pNPI gene.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Colige",
      "authorRank" : 1,
      "name" : "Colige A",
      "referenceId" : "RGD:A71347"
    }, {
      "firstName" : "AL",
      "lastName" : "Sieron",
      "authorRank" : 2,
      "name" : "Sieron AL",
      "referenceId" : "RGD:A71358"
    }, {
      "firstName" : "SW",
      "lastName" : "Li",
      "authorRank" : 3,
      "name" : "Li SW",
      "referenceId" : "RGD:A26437"
    }, {
      "firstName" : "U",
      "lastName" : "Schwarze",
      "authorRank" : 4,
      "name" : "Schwarze U",
      "referenceId" : "RGD:A37350"
    }, {
      "firstName" : "E",
      "lastName" : "Petty",
      "authorRank" : 5,
      "name" : "Petty E",
      "referenceId" : "RGD:A71359"
    }, {
      "firstName" : "W",
      "lastName" : "Wertelecki",
      "authorRank" : 6,
      "name" : "Wertelecki W",
      "referenceId" : "RGD:A71360"
    }, {
      "firstName" : "W",
      "lastName" : "Wilcox",
      "authorRank" : 7,
      "name" : "Wilcox W",
      "referenceId" : "RGD:A71361"
    }, {
      "firstName" : "D",
      "lastName" : "Krakow",
      "authorRank" : 8,
      "name" : "Krakow D",
      "referenceId" : "RGD:A71362"
    }, {
      "firstName" : "DH",
      "lastName" : "Cohn",
      "authorRank" : 9,
      "name" : "Cohn DH",
      "referenceId" : "RGD:A37395"
    }, {
      "firstName" : "W",
      "lastName" : "Reardon",
      "authorRank" : 10,
      "name" : "Reardon W",
      "referenceId" : "RGD:A40773"
    }, {
      "firstName" : "PH",
      "lastName" : "Byers",
      "authorRank" : 11,
      "name" : "Byers PH",
      "referenceId" : "RGD:A37340"
    }, {
      "firstName" : "CM",
      "lastName" : "Lapiere",
      "authorRank" : 12,
      "name" : "Lapiere CM",
      "referenceId" : "RGD:A71356"
    }, {
      "firstName" : "DJ",
      "lastName" : "Prockop",
      "authorRank" : 13,
      "name" : "Prockop DJ",
      "referenceId" : "RGD:A37331"
    }, {
      "firstName" : "BV",
      "lastName" : "Nusgens",
      "authorRank" : 14,
      "name" : "Nusgens BV",
      "referenceId" : "RGD:A71357"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598739"
    } ]
  }, {
    "primaryId" : "PMID:10417275",
    "title" : "Identification of a mutation cluster in mevalonate kinase deficiency, including a new mutation in a patient of Mennonite ancestry.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hinson DD, etal., Am J Hum Genet. 1999 Aug;65(2):327-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:08:21.000-05:00",
    "volume" : "65",
    "pages" : "327-35",
    "abstract" : "Mevalonate kinase (MKase) deficiency (MKD) is a rare autosomal recessive disorder in the pathway of cholesterol and nonsterol isoprenoid biosynthesis. Thus far, two disease-causing missense alleles have been identified, N301T and A334T. We report four additional mutations associated with MKD: L264F, T243I, L265P, and I268T, the last found in a patient of Mennonite ancestry. Electrophoretic analysis of bacterially expressed wild-type and mutant MKase indicated that I268T and T243I mutants produced normal or somewhat reduced amounts of MKase protein; conversely, L264F and L265P mutations resulted in considerably decreased, or absent, MKase protein. Immunoblot analysis of MKase from all patients suggested that the MKase polypeptide was grossly intact and produced in amounts comparable  to control levels. Three mutations resulted in significantly diminished MKase enzyme activity (<2%), whereas the I268T allele yielded approximately 20% residual enzyme activity. Our results should allow more-accurate identification of carriers and indicate a mutation \"cluster\" within amino acids 240-270 of the mature MKase polypeptide.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DD",
      "lastName" : "Hinson",
      "authorRank" : 1,
      "name" : "Hinson DD",
      "referenceId" : "RGD:A16898"
    }, {
      "firstName" : "RM",
      "lastName" : "Ross",
      "authorRank" : 2,
      "name" : "Ross",
      "referenceId" : "RGD:A262293"
    }, {
      "firstName" : "S",
      "lastName" : "Krisans",
      "authorRank" : 3,
      "name" : "Krisans",
      "referenceId" : "RGD:A262294"
    }, {
      "firstName" : "JL",
      "lastName" : "Shaw",
      "authorRank" : 4,
      "name" : "Shaw",
      "referenceId" : "RGD:A262295"
    }, {
      "firstName" : "V",
      "lastName" : "Kozich",
      "authorRank" : 5,
      "name" : "Kozich V",
      "referenceId" : "RGD:A61876"
    }, {
      "firstName" : "MO",
      "lastName" : "Rolland",
      "authorRank" : 6,
      "name" : "Rolland",
      "referenceId" : "RGD:A251407"
    }, {
      "firstName" : "P",
      "lastName" : "Divry",
      "authorRank" : 7,
      "name" : "Divry",
      "referenceId" : "RGD:A252328"
    }, {
      "firstName" : "J",
      "lastName" : "Mancini",
      "authorRank" : 8,
      "name" : "Mancini J",
      "referenceId" : "RGD:A99660"
    }, {
      "firstName" : "GF",
      "lastName" : "Hoffmann",
      "authorRank" : 9,
      "name" : "Hoffmann GF",
      "referenceId" : "RGD:A60766"
    }, {
      "firstName" : "KM",
      "lastName" : "Gibson",
      "authorRank" : 10,
      "name" : "Gibson KM",
      "referenceId" : "RGD:A16902"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065556"
    } ]
  }, {
    "primaryId" : "PMID:10417282",
    "title" : "A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Aouizerat BE, etal., Am J Hum Genet 1999 Aug;65(2):397-412.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-03T08:12:24.000-06:00",
    "volume" : "65",
    "pages" : "397-412",
    "abstract" : "Familial combined hyperlipidemia (FCHL) is a common familial lipid disorder characterized by a variable pattern of elevated levels of plasma cholesterol and/or triglycerides. It is present in 10%-20% of patients with premature coronary heart disease. The genetic etiology of the disease, including the number of genes involved and the magnitude of their effects, is unknown. Using a subset of 35 Dutch families ascertained for FCHL, we screened the genome, with a panel of 399 genetic markers, for chromosomal regions linked to genes contributing to FCHL. The results were analyzed by use of parametric-linkage methods in a two-stage study design. Four loci, on chromosomes 2p, 11p, 16q, and 19q, exhibited suggestive evidence for linkage with FCHL (LOD scores of 1.3-2.6). Markers within each of these regions were then examined in the original sample and in additional Dutch families with FCHL. The locus on chromosome 2 failed to show evidence for linkage, and the loci on chromosome 16q and 19q yielded only equivocal or suggestive evidence for linkage. However, one locus, near marker D11S1324 on the short arm of human chromosome 11, continued to show evidence for linkage with FCHL, in the second stage of this design. This region does not contain any strong candidate genes. These results provide evidence for a candidate chromosomal region for FCHL and support the concept that FCHL is complex and heterogeneous.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BE",
      "lastName" : "Aouizerat",
      "authorRank" : 1,
      "name" : "Aouizerat BE",
      "referenceId" : "RGD:A39800"
    }, {
      "firstName" : "H",
      "lastName" : "Allayee",
      "authorRank" : 2,
      "name" : "Allayee H",
      "referenceId" : "RGD:A35860"
    }, {
      "firstName" : "RM",
      "lastName" : "Cantor",
      "authorRank" : 3,
      "name" : "Cantor RM",
      "referenceId" : "RGD:A39797"
    }, {
      "firstName" : "RC",
      "lastName" : "Davis",
      "authorRank" : 4,
      "name" : "Davis RC",
      "referenceId" : "RGD:A56621"
    }, {
      "firstName" : "CD",
      "lastName" : "Lanning",
      "authorRank" : 5,
      "name" : "Lanning CD",
      "referenceId" : "RGD:A56622"
    }, {
      "firstName" : "PZ",
      "lastName" : "Wen",
      "authorRank" : 6,
      "name" : "Wen PZ",
      "referenceId" : "RGD:A51382"
    }, {
      "firstName" : "GM",
      "lastName" : "Dallinga-Thie",
      "authorRank" : 7,
      "name" : "Dallinga-Thie GM",
      "referenceId" : "RGD:A56623"
    }, {
      "firstName" : "TW",
      "lastName" : "De Bruin",
      "authorRank" : 8,
      "name" : "De Bruin TW",
      "referenceId" : "RGD:A39793"
    }, {
      "firstName" : "JI",
      "lastName" : "Rotter",
      "authorRank" : 9,
      "name" : "Rotter JI",
      "referenceId" : "RGD:A35709"
    }, {
      "firstName" : "AJ",
      "lastName" : "Lusis",
      "authorRank" : 10,
      "name" : "Lusis AJ",
      "referenceId" : "RGD:A7267"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556549"
    } ]
  }, {
    "primaryId" : "PMID:10417314",
    "title" : "Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Bröer S, etal., Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. doi: 10.1042/0264-6021:3410529.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-06-29T01:56:03.000-05:00",
    "volume" : "341 ( Pt 3)",
    "pages" : "529-35",
    "abstract" : "Observations on lactate transport in brain cells and cardiac myocytes indicate the presence of a high-affinity monocarboxylate transporter. The rat monocarboxylate transporter isoform MCT2 was analysed by expression in Xenopus laevis oocytes and the results were compared with the known characteristics of lactate transport in heart and brain. Monocarboxylate transport via MCT2 was driven by the H(+) gradient over the plasma membrane. Uptake of lactate strongly increased with decreasing pH, showing half-maximal stimulation at pH 7.2. A wide variety of monocarboxylates and ketone bodies, including lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, 2-oxoisovalerate and 2-oxoisohexanoate, were substrates of MCT2. All substrates had a high affinity for MCT2. For lactate a K(m) value of 0.74+/-0.07 mM was determined at pH 7.0. For the other substrates, K(i) values between 100 microM and 1 mM were measured for inhibition of lactate transport, which is about one-tenth of the corresponding values for the ubiquitously expressed monocarboxylate transporter isoform MCT1. Monocarboxylate transport via MCT2 could be inhibited by alpha-cyano-4-hydroxycinnamate, anion-channel inhibitors and flavonoids. It is suggested that cells which express MCT2 preferentially use lactate and ketone bodies as energy sources.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Bröer",
      "authorRank" : 1,
      "name" : "Bröer S",
      "referenceId" : "RGD:A517693"
    }, {
      "firstName" : "A",
      "lastName" : "Bröer",
      "authorRank" : 2,
      "name" : "Bröer A",
      "referenceId" : "RGD:A517694"
    }, {
      "firstName" : "H P",
      "lastName" : "Schneider",
      "authorRank" : 3,
      "name" : "Schneider HP",
      "referenceId" : "RGD:A517695"
    }, {
      "firstName" : "C",
      "lastName" : "Stegen",
      "authorRank" : 4,
      "name" : "Stegen C",
      "referenceId" : "RGD:A517696"
    }, {
      "firstName" : "A P",
      "lastName" : "Halestrap",
      "authorRank" : 5,
      "name" : "Halestrap AP",
      "referenceId" : "RGD:A461042"
    }, {
      "firstName" : "J W",
      "lastName" : "Deitmer",
      "authorRank" : 6,
      "name" : "Deitmer JW",
      "referenceId" : "RGD:A517697"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:152995554"
    } ]
  }, {
    "primaryId" : "PMID:10417332",
    "title" : "Characterization of a human MHC class III region gene product with S-thioesterase activity.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Aguado B and Campbell RD, Biochem J 1999 Aug 1;341 ( Pt 3):679-89.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-04-15T10:38:38.000-05:00",
    "volume" : "341 ( Pt 3)",
    "pages" : "679-89",
    "abstract" : "Palmitoylated proteins contain a 16-carbon saturated fatty acyl group that is post-translationally attached by a labile thioester bond. These modified proteins are mainly membrane-bound; the lability of the thioester bond allows the process to be reversible, a unique property of this modification. We report here that the gene for G14, located in the class III region of the human MHC, encodes a polypeptide with significant sequence similarity to mammalian palmitoyl protein thioesterase (PPT1), an enzyme that removes palmitate from palmitoylated proteins. The gene for G14, also known as PPT2, is transcribed as at least five different transcripts, which are expressed in different cell lines of the immune system. Immunoprecipitation of these mammalian cells, with an anti-G14 antiserum, showed a specific band of approx. 42 kDa in cell extracts and supernatants. Expression of the G14 cDNA in the baculovirus system revealed that it encoded a secreted glycosylated polypeptide with S-thioesterase activity. The enzymic activity of the recombinant G14 protein was further characterized in quantitative spectrophotometric assays, which revealed that it had the highest S-thioesterase activity for the acyl groups palmitic and myristic acid followed by other long-chain acyl substrates. The S-thioesterase activity of the G14 protein was found to be considerably higher in supernatants than in cell extracts, which was consistent with the protein's being secreted. The G14 polypeptide contains, in addition to an N-terminal lipase domain, a C-terminal domain common to the cytokine receptor superfamily, which might determine the substrate specificity and/or the protein target of the G14 protein.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Aguado",
      "authorRank" : 1,
      "name" : "Aguado B",
      "referenceId" : "RGD:A51619"
    }, {
      "firstName" : "RD",
      "lastName" : "Campbell",
      "authorRank" : 2,
      "name" : "Campbell RD",
      "referenceId" : "RGD:A40325"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1357944"
    } ]
  }, {
    "primaryId" : "PMID:10417397",
    "title" : "Spatiotemporal development and distribution of intercellular junctions in adult rat cardiomyocytes in culture.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Kostin S, etal., Circ Res. 1999 Jul 23;85(2):154-67.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-10-18T11:26:05.000-05:00",
    "volume" : "85",
    "pages" : "154-67",
    "abstract" : "The mode of development of the intercalated disk (ID) is largely unknown, and the hypothesis was tested that the assembly of cell adhesion junctions may precede the formation of gap junctions (GJ) in developing ID in adult rat cardiomyocyte (ARC) in long-term culture. Immunostaining for connexin 43 (Cx43) and for cell adhesion junction proteins (N-cadherin, catenins, and desmoplakin) in single- and double-label techniques was analyzed and quantified by confocal and electron microscopy. All proteins investigated disappeared 48 hours after ARC isolation and reappeared parallel to redifferentiation of ARC. The newly formed ID, observed after 5 days, showed the presence of N-cadherin, catenins, and desmoplakin, low levels of Cx43, and absence of ultrastructurally discernible gap junctions. A progressive incorporation of Cx43 within ID was observed after 6 days, when cell adhesion junction proteins were already organized as zipper-like structures. Quantitative confocal analysis revealed a progressive augmentation of the fluorescence intensity of Cx43, associated with an increase in both the number and size of GJ, resulting in a substantial increase in the percentage of total GJ length per reassembled ID from 1.67% (day 6) to 15.58% (day 12). In the present study, we show that (1) the formation of the ID can be followed in ARC in culture and (2) the assembly of the adhering type of junction is the prerequisite for subsequent GJ formation within the ID. These findings may have clinical relevance in elaborating strategies for using myocardial grafts and for the potential restoration of GJ communication in cardiac diseases.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kostin",
      "authorRank" : 1,
      "name" : "Kostin S",
      "referenceId" : "RGD:A24001"
    }, {
      "firstName" : "S",
      "lastName" : "Hein",
      "authorRank" : 2,
      "name" : "Hein S",
      "referenceId" : "RGD:A67084"
    }, {
      "firstName" : "EP",
      "lastName" : "Bauer",
      "authorRank" : 3,
      "name" : "Bauer EP",
      "referenceId" : "RGD:A67085"
    }, {
      "firstName" : "J",
      "lastName" : "Schaper",
      "authorRank" : 4,
      "name" : "Schaper J",
      "referenceId" : "RGD:A24004"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581668"
    } ]
  }, {
    "primaryId" : "PMID:10417400",
    "title" : "BTEB2, a Kruppel-like transcription factor, regulates expression of the SMemb/Nonmuscle myosin heavy chain B (SMemb/NMHC-B) gene.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Watanabe N, etal., Circ Res. 1999 Jul 23;85(2):182-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-10-24T10:36:02.000-05:00",
    "volume" : "85",
    "pages" : "182-91",
    "abstract" : "We have recently characterized the promoter region of the rabbit embryonic smooth muscle myosin heavy chain (SMemb/NMHC-B) gene and identified the 15-bp sequence, designated SE1, located at -105 from the transcriptional start site as an important regulatory element for its transcriptional activity in a smooth muscle cell (SMC) line. In this study, we attempted to isolate cDNA clones encoding for the transcription factors that control the expression of the SMemb gene through binding to this cis-regulatory element. We screened a lambdagt11 cDNA library prepared from C2/2 cells, a rabbit-derived SMC line, by using a radiolabeled concatenated oligonucleotide containing SE1 as a probe. Sequence analysis revealed that one of the cDNA clones corresponds to the rabbit homologue of basic transcriptional element binding protein-2 (BTEB2), which has previously been identified as one of the Kruppel-like transcription factor. Gel mobility shift assays and antibody supershift analyses with nuclear extracts from C2/2 cells indicate that BTEB2 is a major component of nuclear factor:SE1 complexes. Furthermore, a glutathione S-transferase-BTEB2 fusion protein binds to the SE1 in a sequence-specific manner. In support of the functionality of BTEB2 binding, basal promoter activity and BTEB2-induced transcriptional activation were markedly attenuated by the disruption of the SE1. In adult rabbit tissues, BTEB2 mRNA was most highly expressed in intestine, urinary bladder, and uterus. BTEB2 mRNA levels were downregulated in rabbit aorta during normal development. Moreover, immunohistochemical analysis indicated a marked induction of BTEB2 protein in the neointimal SMC after balloon injury in rat aorta. These results suggest that BTEB2 mediates the transcriptional regulation of the SMemb/NMHC-B gene and possibly plays a role in regulating gene expression during phenotypic modulation of vascular SMC.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Watanabe",
      "authorRank" : 1,
      "name" : "Watanabe N",
      "referenceId" : "RGD:A6006"
    }, {
      "firstName" : "M",
      "lastName" : "Kurabayashi",
      "authorRank" : 2,
      "name" : "Kurabayashi M",
      "referenceId" : "RGD:A19975"
    }, {
      "firstName" : "Y",
      "lastName" : "Shimomura",
      "authorRank" : 3,
      "name" : "Shimomura Y",
      "referenceId" : "RGD:A116010"
    }, {
      "firstName" : "K",
      "lastName" : "Kawai-Kowase",
      "authorRank" : 4,
      "name" : "Kawai-Kowase K",
      "referenceId" : "RGD:A67320"
    }, {
      "firstName" : "Y",
      "lastName" : "Hoshino",
      "authorRank" : 5,
      "name" : "Hoshino Y",
      "referenceId" : "RGD:A67321"
    }, {
      "firstName" : "I",
      "lastName" : "Manabe",
      "authorRank" : 6,
      "name" : "Manabe I",
      "referenceId" : "RGD:A49345"
    }, {
      "firstName" : "M",
      "lastName" : "Watanabe",
      "authorRank" : 7,
      "name" : "Watanabe M",
      "referenceId" : "RGD:A161340"
    }, {
      "firstName" : "M",
      "lastName" : "Aikawa",
      "authorRank" : 8,
      "name" : "Aikawa M",
      "referenceId" : "RGD:A53731"
    }, {
      "firstName" : "M",
      "lastName" : "Kuro-o",
      "authorRank" : 9,
      "name" : "Kuro-o M",
      "referenceId" : "RGD:A19981"
    }, {
      "firstName" : "T",
      "lastName" : "Suzuki",
      "authorRank" : 10,
      "name" : "Suzuki T",
      "referenceId" : "RGD:A4733"
    }, {
      "firstName" : "Y",
      "lastName" : "Yazaki",
      "authorRank" : 11,
      "name" : "Yazaki Y",
      "referenceId" : "RGD:A161904"
    }, {
      "firstName" : "R",
      "lastName" : "Nagai",
      "authorRank" : 12,
      "name" : "Nagai R",
      "referenceId" : "RGD:A9180"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581746"
    } ]
  }, {
    "primaryId" : "PMID:10417663",
    "title" : "Insulin-like growth factors and binding proteins in multiple sclerosis plaques.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Gveric D, etal., Neuropathol Appl Neurobiol. 1999 Jun;25(3):215-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-11-18T10:52:02.000-06:00",
    "volume" : "25",
    "pages" : "215-25",
    "abstract" : "Insulin-like growth factors (IGFs) play an important role in development and myelination in the central nervous system (CNS) as well as in the proliferation and differentiation of cells of the immune system. To assess the influence of this growth factor family on demyelination and repair in multiple sclerosis (MS), the expression of IGF-I, IGF-II, insulin, IGF binding proteins (IGFBP) 1-3 and IGF-I receptor (IGF-IR) in CNS tissue from MS and normal control cases was studied by immunocytochemistry. In active MS lesions, the expression of IGF-I, insulin and IGFBP1 was detected in hypertrophic astrocytes while that of IGF-II and IGFBP2 and 3 was confined to foamy macrophages within lesions and activated microglia in adjacent white matter. IGF-IR, the major IGF receptor, was immunolocalized in macrophages and an astrocyte subpopulation in plaques. Oligodendrocytes in normal-appearing white matter expressed only IGFBP1, not IGFs or IGF-IR. As the remyelinating capacity of oligodendrocytes could be impaired owing to the absence of IGF-IR, the prevailing role of IGFs in inflammatory demyelination may be to promote phagocytosis of myelin and astrogliosis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Gveric",
      "authorRank" : 1,
      "name" : "Gveric D",
      "referenceId" : "RGD:A146537"
    }, {
      "firstName" : "ML",
      "lastName" : "Cuzner",
      "authorRank" : 2,
      "name" : "Cuzner ML",
      "referenceId" : "RGD:A59779"
    }, {
      "firstName" : "J",
      "lastName" : "Newcombe",
      "authorRank" : 3,
      "name" : "Newcombe J",
      "referenceId" : "RGD:A147880"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5510017"
    } ]
  }, {
    "primaryId" : "PMID:10417753",
    "title" : "In vivo characterization of keratinocyte growth factor-2 as a potential wound healing agent.",
    "datePublished" : "0001-12-01T00:00:00.000-06:00",
    "citation" : "Soler PM, etal., Wound Repair Regen. 1999 May-Jun;7(3):172-8. doi: 10.1046/j.1524-475x.1999.00172.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-05-27T14:44:08.000-05:00",
    "volume" : "7",
    "pages" : "172-8",
    "abstract" : "Human keratinocyte growth factor-2 exerts a proliferative effect on epithelial cells and mediates keratinocyte migration. It has also been shown to increase both deposition of granulation tissue and collagen and maturation of collagen. Because these properties should affect the healing trajectory of wounds, this study set out to investigate the effects of keratinocyte growth factor-2 on the healing of three different types of wounds. Human meshed skin grafts explanted to athymic \"nude\" rats, surgical incisions in Sprague-Dawley rats, and acute excisional rat wounds inoculated with Escherichia coli were used. Two concentrations of recombinant human keratinocyte growth factor-2 were compared to a vehicle control and keratinocyte growth factor-1. Keratinocyte growth factor-2 significantly accelerated the rate of epithelialization in the meshed skin graft model and effected a modestly more rapid gain in breaking strength of surgical incisions than keratinocyte growth factor-1 or the vehicle control treatment. Neither keratinocyte growth factors accelerated wound closure by contraction of the excisional wounds. Based on these data, keratinocyte growth factor-2 may be useful in accelerating healing in wounds healing mainly by the process of epithelialization such as venous stasis ulcers, partial thickness burn wounds, and skin graft donor sites. It might also accelerate the gain in incisional wound strength in acute surgical or traumatic wounds.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P M",
      "lastName" : "Soler",
      "authorRank" : 1,
      "name" : "Soler PM",
      "referenceId" : "RGD:A499969"
    }, {
      "firstName" : "T E",
      "lastName" : "Wright",
      "authorRank" : 2,
      "name" : "Wright TE",
      "referenceId" : "RGD:A499970"
    }, {
      "firstName" : "P D",
      "lastName" : "Smith",
      "authorRank" : 3,
      "name" : "Smith PD",
      "referenceId" : "RGD:A499971"
    }, {
      "firstName" : "S P",
      "lastName" : "Maggi",
      "authorRank" : 4,
      "name" : "Maggi SP",
      "referenceId" : "RGD:A499972"
    }, {
      "firstName" : "D P",
      "lastName" : "Hill",
      "authorRank" : 5,
      "name" : "Hill DP",
      "referenceId" : "RGD:A439980"
    }, {
      "firstName" : "F",
      "lastName" : "Ko",
      "authorRank" : 6,
      "name" : "Ko F",
      "referenceId" : "RGD:A66645"
    }, {
      "firstName" : "P A",
      "lastName" : "Jimenez",
      "authorRank" : 7,
      "name" : "Jimenez PA",
      "referenceId" : "RGD:A499973"
    }, {
      "firstName" : "M C",
      "lastName" : "Robson",
      "authorRank" : 8,
      "name" : "Robson MC",
      "referenceId" : "RGD:A499974"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:126928129"
    } ]
  }, {
    "primaryId" : "PMID:10419135",
    "title" : "Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase and carnitine palmitoyltransferase II are potential control sites of hepatic ketogenesis under conditions of peroxisome proliferation.",
    "datePublished" : "1000-06-01T00:00:00.000-06:00",
    "citation" : "Berge RK, etal., Lipids. 1999;34 Suppl:S163.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-24T16:52:04.000-05:00",
    "volume" : "34 Suppl",
    "pages" : "S163",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RK",
      "lastName" : "Berge",
      "authorRank" : 1,
      "name" : "Berge RK",
      "referenceId" : "RGD:A98350"
    }, {
      "firstName" : "A",
      "lastName" : "Garras",
      "authorRank" : 2,
      "name" : "Garras A",
      "referenceId" : "RGD:A125329"
    }, {
      "firstName" : "G",
      "lastName" : "Asins",
      "authorRank" : 3,
      "name" : "Asins G",
      "referenceId" : "RGD:A28438"
    }, {
      "firstName" : "D",
      "lastName" : "Serra",
      "authorRank" : 4,
      "name" : "Serra D",
      "referenceId" : "RGD:A28437"
    }, {
      "firstName" : "FG",
      "lastName" : "Hegardt",
      "authorRank" : 5,
      "name" : "Hegardt FG",
      "referenceId" : "RGD:A28436"
    }, {
      "firstName" : "L",
      "lastName" : "Madsen",
      "authorRank" : 6,
      "name" : "Madsen L",
      "referenceId" : "RGD:A125328"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2326127"
    } ]
  }, {
    "primaryId" : "PMID:10419291",
    "title" : "Inhibition of the acid lipase activity by apolipoprotein A-I in the presence of lysosomal proteases.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Inoue Y, etal., Biosci Biotechnol Biochem. 1999 May;63(5):937-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-08-03T17:43:05.000-05:00",
    "volume" : "63",
    "pages" : "937-9",
    "abstract" : "It was found that the inhibition of the lysosomal acid lipase activity by rat apolipoprotein A-I (apo A-I) was increased with the degradation of apo A-I by the lysosomal proteases. We demonstrated that apo A-I could effectively inhibit the acid lipase activity even in the presence of the lysosomal proteases using the hepatic lysosomal fraction.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Inoue",
      "authorRank" : 1,
      "name" : "Inoue Y",
      "referenceId" : "RGD:A161343"
    }, {
      "firstName" : "T",
      "lastName" : "Ose",
      "authorRank" : 2,
      "name" : "Ose T",
      "referenceId" : "RGD:A85990"
    }, {
      "firstName" : "S",
      "lastName" : "Mukai",
      "authorRank" : 3,
      "name" : "Mukai S",
      "referenceId" : "RGD:A5033"
    }, {
      "firstName" : "S",
      "lastName" : "Ehira",
      "authorRank" : 4,
      "name" : "Ehira S",
      "referenceId" : "RGD:A85991"
    }, {
      "firstName" : "M",
      "lastName" : "Yonekura",
      "authorRank" : 5,
      "name" : "Yonekura M",
      "referenceId" : "RGD:A51595"
    }, {
      "firstName" : "DX",
      "lastName" : "Hou",
      "authorRank" : 6,
      "name" : "Hou DX",
      "referenceId" : "RGD:A85992"
    }, {
      "firstName" : "M",
      "lastName" : "Fujii",
      "authorRank" : 7,
      "name" : "Fujii M",
      "referenceId" : "RGD:A33844"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1626385"
    } ]
  }, {
    "primaryId" : "PMID:10419476",
    "title" : "Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Poon WW, etal., J Biol Chem. 1999 Jul 30;274(31):21665-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-10-15T12:10:01.000-05:00",
    "volume" : "274",
    "pages" : "21665-72",
    "abstract" : "Ubiquinone (coenzyme Q or Q) is a lipid that functions in the electron transport  chain in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes. Q-deficient mutants of Saccharomyces cerevisiae harbor defects in one of eight COQ genes (coq1-coq8) and are unable to grow on nonfermentable carbon sources. The biosynthesis of Q involves two separate O-methylation steps.  In yeast, the first O-methylation utilizes 3, 4-dihydroxy-5-hexaprenylbenzoic acid as a substrate and is thought to be catalyzed by Coq3p, a 32.7-kDa protein that is 40% identical to the Escherichia coli O-methyltransferase, UbiG. In this  study, farnesylated analogs corresponding to the second O-methylation step, demethyl-Q(3) and Q(3), have been chemically synthesized and used to study Q biosynthesis in yeast mitochondria in vitro. Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. In addition, E. coli UbiGp was purified and found to catalyze both O-methylation steps. Futhermore, antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria. The  results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes and that Q biosynthesis is carried out within the matrix compartment of yeast mitochondria.",
    "issueName" : "31",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WW",
      "lastName" : "Poon",
      "authorRank" : 1,
      "name" : "Poon WW",
      "referenceId" : "RGD:A158718"
    }, {
      "firstName" : "RJ",
      "lastName" : "Barkovich",
      "authorRank" : 2,
      "name" : "Barkovich",
      "referenceId" : "RGD:A207239"
    }, {
      "firstName" : "AY",
      "lastName" : "Hsu",
      "authorRank" : 3,
      "name" : "Hsu",
      "referenceId" : "RGD:A207240"
    }, {
      "firstName" : "A",
      "lastName" : "Frankel",
      "authorRank" : 4,
      "name" : "Frankel",
      "referenceId" : "RGD:A207241"
    }, {
      "firstName" : "PT",
      "lastName" : "Lee",
      "authorRank" : 5,
      "name" : "Lee PT",
      "referenceId" : "RGD:A17535"
    }, {
      "firstName" : "JN",
      "lastName" : "Shepherd",
      "authorRank" : 6,
      "name" : "Shepherd",
      "referenceId" : "RGD:A207242"
    }, {
      "firstName" : "DC",
      "lastName" : "Myles",
      "authorRank" : 7,
      "name" : "Myles",
      "referenceId" : "RGD:A207243"
    }, {
      "firstName" : "CF",
      "lastName" : "Clarke",
      "authorRank" : 8,
      "name" : "Clarke CF",
      "referenceId" : "RGD:A7262"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10402079"
    } ]
  }, {
    "primaryId" : "PMID:10419495",
    "title" : "Characterization of PECI, a novel monofunctional Delta(3), Delta(2)-enoyl-CoA isomerase of mammalian peroxisomes.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Geisbrecht BV, etal., J Biol Chem 1999 Jul 30;274(31):21797-803.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-10-31T09:11:45.000-06:00",
    "volume" : "274",
    "pages" : "21797-803",
    "abstract" : "We report here the identification and characterization of human and mouse PECI, a novel gene that encodes a monofunctional peroxisomal Delta(3),Delta(2)-enoyl-CoA isomerase. Human and mouse PECI were identified on the basis of their sequence similarity to Eci1p, a recently characterized peroxisomal Delta(3),Delta(2)-enoyl-CoA isomerase from the yeast Saccharomyces cerevisiae. Cloning and sequencing of the human PECI cDNA revealed the presence of a 1077-base pair open reading frame predicted to encode a 359-amino acid protein with a mass of 39.6 kDa. The corresponding mouse cDNA contains a 1074-base pair open reading frame that encodes a 358-amino acid-long protein with a deduced mass of 39.4 kDa. Northern blot analysis demonstrated human PECI mRNA is expressed in all tissues. A bacterially expressed form of human PECI catalyzed the isomerization of 3-cis-octenoyl-CoA to 2-trans-octenoyl-CoA with a specific activity of 27 units/mg of protein. The human and mouse PECI proteins contain type-1 peroxisomal targeting signals, and human PECI was localized to peroxisomes by both subcellular fractionation and immunofluorescence microscopy techniques. The potential roles for this monofunctional Delta(3),Delta(2)-enoyl-CoA isomerase in peroxisomal metabolism are discussed.",
    "issueName" : "31",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BV",
      "lastName" : "Geisbrecht",
      "authorRank" : 1,
      "name" : "Geisbrecht BV",
      "referenceId" : "RGD:A56347"
    }, {
      "firstName" : "D",
      "lastName" : "Zhang",
      "authorRank" : 2,
      "name" : "Zhang D",
      "referenceId" : "RGD:A18841"
    }, {
      "firstName" : "H",
      "lastName" : "Schulz",
      "authorRank" : 3,
      "name" : "Schulz H",
      "referenceId" : "RGD:A5908"
    }, {
      "firstName" : "SJ",
      "lastName" : "Gould",
      "authorRank" : 4,
      "name" : "Gould SJ",
      "referenceId" : "RGD:A27102"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556496"
    } ]
  }, {
    "primaryId" : "PMID:10419532",
    "title" : "Structural variation of type XII collagen at its carboxyl-terminal NC1 domain generated by tissue-specific alternative splicing.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Kania AM, etal., J Biol Chem 1999 Jul 30;274(31):22053-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:54:53.000-06:00",
    "volume" : "274",
    "pages" : "22053-9",
    "abstract" : "This paper reports the identification of two structural variations in the NC1 domain of rat and mouse type XII collagen. The long NC1 domain encoding 74 amino acids showed homology to chicken type XII and XIV collagens. The short NC1 domain was composed of 19 amino acids. Through genomic DNA analyses, two alternative exons were identified, each of which contained the variable NC1 sequence. With the amino-terminal NC3 splicing alternatives, we propose here a new descriptive nomenclature: types XIIA-1 and XIIB-1 which include a long NC1 sequence encoded by exon 1 (from the 3'-end), and types XIIA-2 and XIIB-2 which include a short NC1 sequence encoded by exon 2. Types XIIA-1 and XIIB-1, the predominant transcripts in 15-day old mouse embryos, showed decreased expression in 17-day old embryos when type XIIB-2 expression was sustained at constant levels. In adult mice, type XIIB-1 associates with ligament and tendon, whereas type XIIB-2 is expressed in various other tissues. The long NC1 domain contains an extended acidic region (pI = 3.4) followed by a terminal basic region (pI = 13.8). Because the short NC1 domain lacks these features, structural variations in the type XII collagen NC1 domain suggests different functional roles in a tissue-specific fashion.",
    "issueName" : "31",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AM",
      "lastName" : "Kania",
      "authorRank" : 1,
      "name" : "Kania AM",
      "referenceId" : "RGD:A27200"
    }, {
      "firstName" : "E",
      "lastName" : "Reichenberger",
      "authorRank" : 2,
      "name" : "Reichenberger E",
      "referenceId" : "RGD:A27201"
    }, {
      "firstName" : "ST",
      "lastName" : "Baur",
      "authorRank" : 3,
      "name" : "Baur ST",
      "referenceId" : "RGD:A27202"
    }, {
      "firstName" : "NY",
      "lastName" : "Karimbux",
      "authorRank" : 4,
      "name" : "Karimbux NY",
      "referenceId" : "RGD:A27203"
    }, {
      "firstName" : "RW",
      "lastName" : "Taylor",
      "authorRank" : 5,
      "name" : "Taylor RW",
      "referenceId" : "RGD:A27204"
    }, {
      "firstName" : "BR",
      "lastName" : "Olsen",
      "authorRank" : 6,
      "name" : "Olsen BR",
      "referenceId" : "RGD:A27205"
    }, {
      "firstName" : "I",
      "lastName" : "Nishimura",
      "authorRank" : 7,
      "name" : "Nishimura I",
      "referenceId" : "RGD:A20833"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727275"
    } ]
  }, {
    "primaryId" : "PMID:10419598",
    "title" : "Cyclin D1 expression in astrocytomas is associated with cell proliferation activity and patient prognosis.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Sallinen SL, etal., J Pathol. 1999 Jul;188(3):289-93. doi: 10.1002/(SICI)1096-9896(199907)188:3<289::AID-PATH351>3.0.CO;2-X.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-12T17:58:03.000-05:00",
    "volume" : "188",
    "pages" : "289-93",
    "abstract" : "An important positive regulator of the cell cycle, cyclin D1, is often amplified and overexpressed in malignancies. Cyclin D1 aberrations were analysed in grade II-IV astrocytomas by fluorescence in situ hybridization (FISH), mRNA in situ hybridization and immunohistochemistry. Proliferation activity was determined by Ki-67(MIB-1) immunolabelling and mitotic counting. High cyclin D1 expression was observed in grade IV astrocytomas (grades II-III versus grade IV; mRNA expression: p<0.001; immunoexpression: p=0.013), and correlated with poor patient survival (p<0.001, n=46). Upregulated cyclin D1 expression was also closely associated with poor patient prognosis in grade II-III astrocytomas (p<0.001, n=30). Cyclin D1 gene was not found to be amplified (n=7). Cell proliferation activity was significantly increased in tumours exhibiting high cyclin D1 mRNA levels (Ki-67(MIB-1): p<0.001; mitotic count: p<0.001) and high cyclin D1 protein expression (Ki-67(MIB-1): p=0.002; mitotic count: p=0.012). These results indicate that increased production of cyclin D1 is closely associated with high cell proliferation activity and aggressive behaviour in diffusely infiltrating astrocytomas.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S L",
      "lastName" : "Sallinen",
      "authorRank" : 1,
      "name" : "Sallinen SL",
      "referenceId" : "RGD:A459960"
    }, {
      "firstName" : "P K",
      "lastName" : "Sallinen",
      "authorRank" : 2,
      "name" : "Sallinen PK",
      "referenceId" : "RGD:A459961"
    }, {
      "firstName" : "J T",
      "lastName" : "Kononen",
      "authorRank" : 3,
      "name" : "Kononen JT",
      "referenceId" : "RGD:A459962"
    }, {
      "firstName" : "K M",
      "lastName" : "Syrjäkoski",
      "authorRank" : 4,
      "name" : "Syrjäkoski KM",
      "referenceId" : "RGD:A459963"
    }, {
      "firstName" : "N N",
      "lastName" : "Nupponen",
      "authorRank" : 5,
      "name" : "Nupponen NN",
      "referenceId" : "RGD:A459964"
    }, {
      "firstName" : "I S",
      "lastName" : "Rantala",
      "authorRank" : 6,
      "name" : "Rantala IS",
      "referenceId" : "RGD:A459965"
    }, {
      "firstName" : "P T",
      "lastName" : "Helén",
      "authorRank" : 7,
      "name" : "Helén PT",
      "referenceId" : "RGD:A459966"
    }, {
      "firstName" : "H J",
      "lastName" : "Helin",
      "authorRank" : 8,
      "name" : "Helin HJ",
      "referenceId" : "RGD:A459967"
    }, {
      "firstName" : "H K",
      "lastName" : "Haapasalo",
      "authorRank" : 9,
      "name" : "Haapasalo HK",
      "referenceId" : "RGD:A459968"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13681931"
    } ]
  }, {
    "primaryId" : "PMID:10419693",
    "title" : "Neurestin: putative transmembrane molecule implicated in neuronal development.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Otaki JM and Firestein S, Dev Biol 1999 Aug 1;212(1):165-81.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:49:39.000-05:00",
    "volume" : "212",
    "pages" : "165-81",
    "abstract" : "We have cloned a novel cDNA encoding a putative transmembrane protein, neurestin, from the rat olfactory bulb. Neurestin was identified based on a sequence similar to that of the second extracellular loops of odorant receptors in the cysteine-rich CC box located immediately after EGF-like motifs. Neurestin shows homology to a neuregulin gene product, human gamma-heregulin, a Drosophila receptor-type pair-rule gene product, Odd Oz (Odz) / Ten(m), and Ten(a), suggesting a possible function in synapse formation and morphogenesis. Recently, a mouse neurestin homolog has independently been cloned as DOC4 from the NIH-3T3 cell line. Northern blot analysis showed that neurestin is highly expressed in the brain and also in other tissues at much lower levels. In situ hybridization studies showed that neurestin is expressed in many types of neurons, including pyramidal cells in the cerebral cortex and tufted cells in the olfactory bulb during development. In adults, neurestin is mainly expressed in olfactory and hippocampal granule cells, which are known to be generated throughout adulthood. Nonetheless, in adults the expression of neurestin was experimentally induced in external tufted cells during regeneration of olfactory sensory neurons. These results suggest a role for neurestin in neuronal development and regeneration in the central nervous system.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Otaki",
      "authorRank" : 1,
      "name" : "Otaki JM",
      "referenceId" : "RGD:A43527"
    }, {
      "firstName" : "S",
      "lastName" : "Firestein",
      "authorRank" : 2,
      "name" : "Firestein S",
      "referenceId" : "RGD:A43528"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299591"
    } ]
  }, {
    "primaryId" : "PMID:10419698",
    "title" : "Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Yang Q, etal., Dev Biol 1999 Aug 1;212(1):229-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:17.000-05:00",
    "volume" : "212",
    "pages" : "229-42",
    "abstract" : "Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for alphavbeta3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had approximately 88% homology with human fibrillin-2 and had Ca(2+) binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an approximately 10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an approximately 350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2-specific radioincorporation were reduced. Anti-alphav and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial:mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang Q",
      "referenceId" : "RGD:A15596"
    }, {
      "firstName" : "K",
      "lastName" : "Ota",
      "authorRank" : 2,
      "name" : "Ota K",
      "referenceId" : "RGD:A18177"
    }, {
      "firstName" : "Y",
      "lastName" : "Tian",
      "authorRank" : 3,
      "name" : "Tian Y",
      "referenceId" : "RGD:A15599"
    }, {
      "firstName" : "A",
      "lastName" : "Kumar",
      "authorRank" : 4,
      "name" : "Kumar A",
      "referenceId" : "RGD:A18178"
    }, {
      "firstName" : "J",
      "lastName" : "Wada",
      "authorRank" : 5,
      "name" : "Wada J",
      "referenceId" : "RGD:A15598"
    }, {
      "firstName" : "N",
      "lastName" : "Kashihara",
      "authorRank" : 6,
      "name" : "Kashihara N",
      "referenceId" : "RGD:A18179"
    }, {
      "firstName" : "E",
      "lastName" : "Wallner",
      "authorRank" : 7,
      "name" : "Wallner E",
      "referenceId" : "RGD:A18207"
    }, {
      "firstName" : "YS",
      "lastName" : "Kanwar",
      "authorRank" : 8,
      "name" : "Kanwar YS",
      "referenceId" : "RGD:A15602"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632680"
    } ]
  }, {
    "primaryId" : "PMID:10419986",
    "title" : "Expression of the growth arrest genes (GAS and GADD) changes during organogenesis in the rat fetus.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Rees WD, etal., J Nutr 1999 Aug;129(8):1532-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-25T16:57:45.000-05:00",
    "volume" : "129",
    "pages" : "1532-6",
    "abstract" : "Mammalian cells mount an active response to nutrient limitation by overexpressing the growth arrest specific (GAS) and the growth arrest and DNA damage (GADD) genes. During embryogenesis in rats, there are quantitative and temporal differences in GAS and GADD gene expression during the development of the placenta, heart and kidney. Genes associated with the inhibition of DNA synthesis (p53 and GAS1) were predominantly expressed during the early stages of development, whereas those genes associated with inhibition of protein synthesis [GADD153 (also known as CHOP-10 or Ddit3) and C/EBP-beta] were more highly expressed during the later stages. The GADD45 gene was expressed throughout development. There were distinct periods of GAS3 and GAS6 gene expression during the development of the placenta, heart and kidneys, which is consistent with the proposed roles of these genes in cell interactions. These results show that there is a change in the expression of genes associated with the negative regulation of growth as the fetus develops.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WD",
      "lastName" : "Rees",
      "authorRank" : 1,
      "name" : "Rees WD",
      "referenceId" : "RGD:A4161"
    }, {
      "firstName" : "SM",
      "lastName" : "Hay",
      "authorRank" : 2,
      "name" : "Hay SM",
      "referenceId" : "RGD:A4162"
    }, {
      "firstName" : "NC",
      "lastName" : "Fontanier-Razzaq",
      "authorRank" : 3,
      "name" : "Fontanier-Razzaq NC",
      "referenceId" : "RGD:A4163"
    }, {
      "firstName" : "C",
      "lastName" : "Antipatis",
      "authorRank" : 4,
      "name" : "Antipatis C",
      "referenceId" : "RGD:A4164"
    }, {
      "firstName" : "DN",
      "lastName" : "Harries",
      "authorRank" : 5,
      "name" : "Harries DN",
      "referenceId" : "RGD:A4165"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:62382"
    } ]
  }, {
    "primaryId" : "PMID:10420199",
    "title" : "Retinitis pigmentosa, mental retardation, marked short stature, and brachydactyly in two sibs.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Lorda-Sanchez I, etal., Ophthalmic Genet. 1999 Jun;20(2):127-31. doi: 10.1076/opge.20.2.127.2289.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:25:04.000-05:00",
    "volume" : "20",
    "pages" : "127-31",
    "abstract" : "We present two siblings with retinitis pigmentosa, mental retardation, markedly short stature, and brachydactyly. This association of clinical findings appears to be distinct from previously described syndromes and seems to represent the pleiotropic effects of a single autosomal recessive gene.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Lorda-Sanchez",
      "authorRank" : 1,
      "name" : "Lorda-Sanchez I",
      "referenceId" : "RGD:A591934"
    }, {
      "firstName" : "M J",
      "lastName" : "Trujillo",
      "authorRank" : 2,
      "name" : "Trujillo MJ",
      "referenceId" : "RGD:A591935"
    }, {
      "firstName" : "A",
      "lastName" : "Gimenez",
      "authorRank" : 3,
      "name" : "Gimenez A",
      "referenceId" : "RGD:A591936"
    }, {
      "firstName" : "B",
      "lastName" : "Garcia-Sandoval",
      "authorRank" : 4,
      "name" : "Garcia-Sandoval B",
      "referenceId" : "RGD:A591937"
    }, {
      "firstName" : "A",
      "lastName" : "Franco",
      "authorRank" : 5,
      "name" : "Franco A",
      "referenceId" : "RGD:A591938"
    }, {
      "firstName" : "R",
      "lastName" : "Sanz",
      "authorRank" : 6,
      "name" : "Sanz R",
      "referenceId" : "RGD:A119912"
    }, {
      "firstName" : "M",
      "lastName" : "Rodriguez de Alba",
      "authorRank" : 7,
      "name" : "Rodriguez de Alba M",
      "referenceId" : "RGD:A591939"
    }, {
      "firstName" : "C",
      "lastName" : "Ramos",
      "authorRank" : 8,
      "name" : "Ramos C",
      "referenceId" : "RGD:A140678"
    }, {
      "firstName" : "C",
      "lastName" : "Ayuso",
      "authorRank" : 9,
      "name" : "Ayuso C",
      "referenceId" : "RGD:A142267"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118058"
    } ]
  }, {
    "primaryId" : "PMID:10420202",
    "title" : "Interleukin 6 and its soluble receptor are elevated in aqueous humor of patients  with uveitis.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Petrinovic-Doresic J, etal., Ocul Immunol Inflamm. 1999 Jun;7(2):75-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-22T15:49:20.000-06:00",
    "volume" : "7",
    "pages" : "75-84",
    "abstract" : "PURPOSE: To determine the levels of interleukin 6 (IL-6) and its soluble receptor (sIL-6R) in the aqueous humor (AH) of patients with different uveitis entities. PATIENTS AND METHODS: AH and serum samples were collected from 35 patients (39 eyes) who underwent surgery for uveitis complications and from 10 controls (senile cataract). In the studied group, seven patients had HLA-B27(+) anterior uveitis, two had Fuchs' heterochromic iridocyclitis, 12 had chronic anterior uveitis of unknown etiology, and in the remaining 14 the causative agent was exogenous. The cytokine and receptor levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: In controls, the median IL-6 level in AH was higher than that in corresponding sera (40.4 pg/ml and 5.2 pg/ml, respectively). In contrast, sIL-6R showed an inverse relation: there were less sIL-6R in control AH than in control sera (378.9 pg/ml and 52749.0 pg/ml, respectively). The same qualitative relationship was observed in patients with uveitis. Quantitatively, in comparison to controls, elevated levels of IL-6 and sIL-6R were found in AH of patients with uveitis. As expected, the maximal IL-6 and sIL-6R values were observed in the patients with uveitis of exogenous etiology (1558.3 and 1326.2 pg/ml, respectively). sIL-6R was also significantly elevated in AH of patients with HLA-B27( +) anterior uveitis (p<0. 01). In all individuals under study, sIL-6R levels in AH samples were 2-10 times higher than  IL-6 levels. In serum samples, sIL-6R level were 10000 times higher than corresponding IL-6 values. CONCLUSION: The results confirmed the role of IL-6 in  intraocular inflammation and gave new information regarding the presence of its sR in normal and inflamed eyes. Low levels of sIL-6R in AH compared to those found in serum suggest the presence of active local regulatory mechanisms that require further investigation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Petrinovic-Doresic",
      "authorRank" : 1,
      "name" : "Petrinovic-Doresic",
      "referenceId" : "RGD:A178358"
    }, {
      "firstName" : "R",
      "lastName" : "Mazuran",
      "authorRank" : 2,
      "name" : "Mazuran",
      "referenceId" : "RGD:A178359"
    }, {
      "firstName" : "L",
      "lastName" : "Henc-Petrinovic",
      "authorRank" : 3,
      "name" : "Henc-Petrinovic",
      "referenceId" : "RGD:A178360"
    }, {
      "firstName" : "B",
      "lastName" : "Kuzmanovic",
      "authorRank" : 4,
      "name" : "Kuzmanovic",
      "referenceId" : "RGD:A178361"
    }, {
      "firstName" : "A",
      "lastName" : "Jovicic",
      "authorRank" : 5,
      "name" : "Jovicic",
      "referenceId" : "RGD:A178362"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7829723"
    } ]
  }, {
    "primaryId" : "PMID:10421225",
    "title" : "The codon 64 polymorphism of the beta3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Pulkkinen A, etal., Metabolism. 1999 Jul;48(7):853-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-01-26T13:12:17.000-06:00",
    "volume" : "48",
    "pages" : "853-6",
    "abstract" : "Hyperinsulinemia has been shown to predict coronary heart disease (CHD) events in both nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, defects in genes that regulate insulin action could be responsible for an increased risk of CHD. The Trp64Arg polymorphism of the beta3-adrenergic receptor gene has been linked with abdominal obesity, insulin resistance, and early-onset NIDDM. Therefore, we screened for this polymorphism among 185 unrelated nondiabetic subjects (101 men and 84 women; age, 56+/-1 years [mean +/- SEM]; body mass index [BMI], 27.8+/-0.3 kg/m2) with angiographically confirmed CHD (stenosis > 50% in > or = two coronary arteries), among 119 unrelated patients with NIDDM (90 men and 29 women; age, 62+/-1 years; BMI, 28.7+/-0.4 kg/m2; 95 had CHD by the same criteria and 24 had definite myocardial infarction [MI]), and among 82 healthy men (age, 54+/-1 years; BMI, 26.3+/-0.4 kg/m2) from our previous study. The frequency of the Trp64Arg allele of the beta3-adrenergic receptor gene was similar in nondiabetic patients with CHD (8%), NIDDM patients with CHD (7%), and nondiabetic subjects without CHD (7%). No association was found between cardiovascular risk factors and the codon 64 polymorphism of the beta3-adrenergic receptor gene in patients with CHD. Similarly, this polymorphism was not significantly related to insulin resistance in nondiabetic and NIDDM subjects with CHD evaluated by the euglycemic clamp technique. These results indicate that the Trp64Arg allele of the beta3-adrenergic receptor gene does not contribute to the risk of CHD in nondiabetic subjects and NIDDM patients.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Pulkkinen",
      "authorRank" : 1,
      "name" : "Pulkkinen A",
      "referenceId" : "RGD:A58092"
    }, {
      "firstName" : "A",
      "lastName" : "Kareinen",
      "authorRank" : 2,
      "name" : "Kareinen A",
      "referenceId" : "RGD:A58093"
    }, {
      "firstName" : "L",
      "lastName" : "Saarinen",
      "authorRank" : 3,
      "name" : "Saarinen L",
      "referenceId" : "RGD:A58094"
    }, {
      "firstName" : "S",
      "lastName" : "Heikkinen",
      "authorRank" : 4,
      "name" : "Heikkinen S",
      "referenceId" : "RGD:A58095"
    }, {
      "firstName" : "S",
      "lastName" : "Lehto",
      "authorRank" : 5,
      "name" : "Lehto S",
      "referenceId" : "RGD:A58096"
    }, {
      "firstName" : "M",
      "lastName" : "Laakso",
      "authorRank" : 6,
      "name" : "Laakso M",
      "referenceId" : "RGD:A164269"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1559326"
    } ]
  }, {
    "primaryId" : "PMID:10421268",
    "title" : "Increased angiogenin expression in the tumor tissue and serum of urothelial carcinoma patients is related to disease progression and recurrence.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Miyake H, etal., Cancer. 1999 Jul 15;86(2):316-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-06-07T13:38:39.000-05:00",
    "volume" : "86",
    "pages" : "316-24",
    "abstract" : "BACKGROUND: The progression of solid tumors is at least partly dependent on angiogenesis, the induction of which is mediated by several angiogenic factors, including angiogenin (ANG). The authors evaluated the expression of ANG in the tumor tissue and serum of patients with urothelial carcinoma. METHODS: The expression of ANG in 5 human bladder carcinoma cell lines and 24 urothelial carcinomas (10 superficial carcinomas and 14 invasive carcinomas) and in corresponding normal urothelial tissues was investigated by reverse transcriptase-polymerase chain reaction and Northern blot analysis. Serum levels of ANG in 52 healthy volunteers and in 135 patients with urothelial carcinomas (81 superficial carcinomas and 54 invasive carcinomas) were measured by using a sandwich enzyme immunoassay. RESULTS: ANG mRNA transcripts were detected in all of the bladder carcinoma cell lines, urothelial carcinomas, and normal tissues. The mean level of ANG expression in invasive urothelial carcinomas was 4-fold higher than in superficial carcinomas and 5-fold higher than in normal tissues. The mean serum ANG concentration for invasive urothelial carcinoma patients (514.6+/-211.1 ng/mL) was significantly higher than for superficial urothelial carcinoma patients (381.7+/-169.3 ng/mL) and healthy volunteers (337.5+/-71.4 ng/mL). The overall survival rate of patients with elevated serum levels of ANG was significantly lower than that of patients with normal levels. Moreover, among the 47 patients with advanced urothelial carcinoma who underwent complete resection, the disease free survival rate of patients with elevated serum levels of ANG was significantly lower than that of patients with normal levels. CONCLUSIONS: These results indicate that ANG is strongly expressed in the tumor tissue and is present in high levels in the serum of patients with invasive urothelial carcinoma compared with superficial carcinoma patients and that elevation of serum ANG level could be used as a novel predictor of the prognoses of patients with urothelial carcinoma.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Miyake",
      "authorRank" : 1,
      "name" : "Miyake H",
      "referenceId" : "RGD:A81036"
    }, {
      "firstName" : "I",
      "lastName" : "Hara",
      "authorRank" : 2,
      "name" : "Hara I",
      "referenceId" : "RGD:A48626"
    }, {
      "firstName" : "K",
      "lastName" : "Yamanaka",
      "authorRank" : 3,
      "name" : "Yamanaka K",
      "referenceId" : "RGD:A95926"
    }, {
      "firstName" : "K",
      "lastName" : "Gohji",
      "authorRank" : 4,
      "name" : "Gohji K",
      "referenceId" : "RGD:A117271"
    }, {
      "firstName" : "S",
      "lastName" : "Arakawa",
      "authorRank" : 5,
      "name" : "Arakawa S",
      "referenceId" : "RGD:A120257"
    }, {
      "firstName" : "S",
      "lastName" : "Kamidono",
      "authorRank" : 6,
      "name" : "Kamidono S",
      "referenceId" : "RGD:A120258"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2325710"
    } ]
  }, {
    "primaryId" : "PMID:10421367",
    "title" : "Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Chambers J, etal., Nature. 1999 Jul 15;400(6741):261-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-09-20T09:58:59.000-05:00",
    "volume" : "400",
    "pages" : "261-5",
    "abstract" : "The underlying causes of obesity are poorly understood but probably involve complex interactions between many neurotransmitter and neuropeptide systems involved in the regulation of food intake and energy balance. Three pieces of evidence indicate that the neuropeptide melanin-concentrating hormone (MCH) is an important component of this system. First, MCH stimulates feeding when injected directly into rat brains; second, the messenger RNA for the MCH precursor is upregulated in the hypothalamus of genetically obese mice and in fasted animals; and third, mice lacking MCH eat less and are lean. MCH antagonists might, therefore, provide a treatment for obesity. However, the development of such molecules has been hampered because the identity of the MCH receptor has been unknown until now. Here we show that the 353-amino-acid human orphan G-protein-coupled receptor SLC-1 expressed in HEK293 cells binds MCH with sub-nanomolar affinity, and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin-elevated cyclic AMP levels. We also show that SLC-1 messenger RNA and protein is expressed in the ventromedial and dorsomedial nuclei of the hypothalamus, consistent with a role for SLC-1 in mediating the effects of MCH on feeding.",
    "issueName" : "6741",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Chambers",
      "authorRank" : 1,
      "name" : "Chambers J",
      "referenceId" : "RGD:A88199"
    }, {
      "firstName" : "RS",
      "lastName" : "Ames",
      "authorRank" : 2,
      "name" : "Ames RS",
      "referenceId" : "RGD:A19413"
    }, {
      "firstName" : "D",
      "lastName" : "Bergsma",
      "authorRank" : 3,
      "name" : "Bergsma D",
      "referenceId" : "RGD:A88200"
    }, {
      "firstName" : "A",
      "lastName" : "Muir",
      "authorRank" : 4,
      "name" : "Muir A",
      "referenceId" : "RGD:A88201"
    }, {
      "firstName" : "LR",
      "lastName" : "Fitzgerald",
      "authorRank" : 5,
      "name" : "Fitzgerald LR",
      "referenceId" : "RGD:A33554"
    }, {
      "firstName" : "G",
      "lastName" : "Hervieu",
      "authorRank" : 6,
      "name" : "Hervieu G",
      "referenceId" : "RGD:A15808"
    }, {
      "firstName" : "GM",
      "lastName" : "Dytko",
      "authorRank" : 7,
      "name" : "Dytko GM",
      "referenceId" : "RGD:A88202"
    }, {
      "firstName" : "JJ",
      "lastName" : "Foley",
      "authorRank" : 8,
      "name" : "Foley JJ",
      "referenceId" : "RGD:A19412"
    }, {
      "firstName" : "J",
      "lastName" : "Martin",
      "authorRank" : 9,
      "name" : "Martin J",
      "referenceId" : "RGD:A20184"
    }, {
      "firstName" : "WS",
      "lastName" : "Liu",
      "authorRank" : 10,
      "name" : "Liu WS",
      "referenceId" : "RGD:A30208"
    }, {
      "firstName" : "J",
      "lastName" : "Park",
      "authorRank" : 11,
      "name" : "Park J",
      "referenceId" : "RGD:A10241"
    }, {
      "firstName" : "C",
      "lastName" : "Ellis",
      "authorRank" : 12,
      "name" : "Ellis C",
      "referenceId" : "RGD:A15805"
    }, {
      "firstName" : "S",
      "lastName" : "Ganguly",
      "authorRank" : 13,
      "name" : "Ganguly S",
      "referenceId" : "RGD:A49604"
    }, {
      "firstName" : "S",
      "lastName" : "Konchar",
      "authorRank" : 14,
      "name" : "Konchar S",
      "referenceId" : "RGD:A88203"
    }, {
      "firstName" : "J",
      "lastName" : "Cluderay",
      "authorRank" : 15,
      "name" : "Cluderay J",
      "referenceId" : "RGD:A88204"
    }, {
      "firstName" : "R",
      "lastName" : "Leslie",
      "authorRank" : 16,
      "name" : "Leslie R",
      "referenceId" : "RGD:A88205"
    }, {
      "firstName" : "S",
      "lastName" : "Wilson",
      "authorRank" : 17,
      "name" : "Wilson S",
      "referenceId" : "RGD:A19271"
    }, {
      "firstName" : "HM",
      "lastName" : "Sarau",
      "authorRank" : 18,
      "name" : "Sarau HM",
      "referenceId" : "RGD:A14350"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642494"
    } ]
  }, {
    "primaryId" : "PMID:10421602",
    "title" : "Neuregulin in cardiac hypertrophy in rats with aortic stenosis. Differential expression of erbB2 and erbB4 receptors.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Rohrbach S, etal., Circulation. 1999 Jul 27;100(4):407-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-09-07T18:17:38.000-05:00",
    "volume" : "100",
    "pages" : "407-12",
    "abstract" : "BACKGROUND: Neuregulins are a family of peptide growth factors that promote cell growth and viability. The potential role of neuregulin-erbB signaling in hypertrophic growth and later failure in the adult heart in vivo is not known. METHODS AND RESULTS: We used ribonuclease protection assays to quantify mRNA levels of neuregulin, erbB2, and erbB4 in left ventricular (LV) tissue and myocytes of normal rats and rats with aortic stenosis with pressure-overload hypertrophy 6 and 22 weeks after banding. At both stages of hypertrophy, Northern blot analyses of mRNA from LV myocytes showed upregulation of atrial natriuretic peptide, a molecular marker of hypertrophy (P<0.05). LV tissue neuregulin message levels were similar in animals with aortic stenosis compared with controls (P=NS) and were not detectable in myocytes. LV erbB2 and erbB4 message levels in LV tissue and myocytes were maintained during early compensatory hypertrophy in 6-week aortic stenosis animals compared with age-matched controls; in contrast, erbB2 and erbB4 message levels were depressed in 22-week aortic stenosis animals at the stage of early failure (both P<0.01 vs age-matched controls). Immunoblotting of erbB2 and erbB4 also showed normal protein levels in 6-week aortic stenosis animals compared with controls; however, erbB2 and erbB4 protein levels were depressed in 22-week aortic stenosis animals (48% decrease in erbB2, P<0.05, and 43% decrease in erbB4, P<0.01) relative to age-matched controls. CONCLUSIONS: The neuregulin receptors erbB2 and erbB4 are downregulated at both the message and protein levels at the stage of early failure in animals with chronic hypertrophy secondary to aortic stenosis. These data suggest a role for disabled erbB receptor signaling in the transition from compensatory hypertrophy to failure.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Rohrbach",
      "authorRank" : 1,
      "name" : "Rohrbach S",
      "referenceId" : "RGD:A65010"
    }, {
      "firstName" : "X",
      "lastName" : "Yan",
      "authorRank" : 2,
      "name" : "Yan X",
      "referenceId" : "RGD:A17893"
    }, {
      "firstName" : "EO",
      "lastName" : "Weinberg",
      "authorRank" : 3,
      "name" : "Weinberg EO",
      "referenceId" : "RGD:A12406"
    }, {
      "firstName" : "F",
      "lastName" : "Hasan",
      "authorRank" : 4,
      "name" : "Hasan F",
      "referenceId" : "RGD:A65013"
    }, {
      "firstName" : "J",
      "lastName" : "Bartunek",
      "authorRank" : 5,
      "name" : "Bartunek J",
      "referenceId" : "RGD:A65014"
    }, {
      "firstName" : "MA",
      "lastName" : "Marchionni",
      "authorRank" : 6,
      "name" : "Marchionni MA",
      "referenceId" : "RGD:A65015"
    }, {
      "firstName" : "BH",
      "lastName" : "Lorell",
      "authorRank" : 7,
      "name" : "Lorell BH",
      "referenceId" : "RGD:A65016"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580989"
    } ]
  }, {
    "primaryId" : "PMID:10421642",
    "title" : "Anomalous development of the hepatobiliary system in the Inv mouse.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Mazziotti MV, etal., Hepatology. 1999 Aug;30(2):372-8. doi: 10.1002/hep.510300223.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-01-06T11:19:05.000-06:00",
    "volume" : "30",
    "pages" : "372-8",
    "abstract" : "Extrahepatic biliary atresia (BA) is a devastating disease of the neonate in which the hepatic and/or common bile duct is obliterated or interrupted. Infants and children with this diagnosis constitute 50% to 60% of the pediatric population that undergoes orthotopic liver transplantation. However, there is still very little known about the etiology and pathogenesis of BA. Several recent studies have demonstrated that anomalies of situs determination are more commonly associated with BA than previously recognized. In this study, we examined the pathogenesis of jaundice in the inv mouse, a transgenic mouse in which a recessive deletion of the inversin gene results in situs inversus and jaundice. The results show that these mice have cholestasis with conjugated hyperbilirubinemia, failure to excrete technetium-labeled mebrofenin from the liver into the small intestine, lack of continuity between the extrahepatic biliary tree and the small intestine as demonstrated by Trypan blue cholangiography, and a liver histological picture indicative of extrahepatic biliary obstruction with negligible inflammation/necrosis within the hepatic parenchyma. Lectin histochemical staining of biliary epithelial cells in serial sections suggests the presence of several different anomalies in the architecture of the extrahepatic biliary system. These results suggest that the inversin gene plays an essential role in the morphogenesis of the hepatobiliary system and raise the possibility that alterations in the human orthologue of inversin account for some of the cases of BA in which there are also anomalies of situs determination.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M V",
      "lastName" : "Mazziotti",
      "authorRank" : 1,
      "name" : "Mazziotti MV",
      "referenceId" : "RGD:A523842"
    }, {
      "firstName" : "L K",
      "lastName" : "Willis",
      "authorRank" : 2,
      "name" : "Willis LK",
      "referenceId" : "RGD:A523843"
    }, {
      "firstName" : "R O",
      "lastName" : "Heuckeroth",
      "authorRank" : 3,
      "name" : "Heuckeroth RO",
      "referenceId" : "RGD:A523844"
    }, {
      "firstName" : "M C",
      "lastName" : "LaRegina",
      "authorRank" : 4,
      "name" : "LaRegina MC",
      "referenceId" : "RGD:A523845"
    }, {
      "firstName" : "P E",
      "lastName" : "Swanson",
      "authorRank" : 5,
      "name" : "Swanson PE",
      "referenceId" : "RGD:A523846"
    }, {
      "firstName" : "P A",
      "lastName" : "Overbeek",
      "authorRank" : 6,
      "name" : "Overbeek PA",
      "referenceId" : "RGD:A523847"
    }, {
      "firstName" : "D H",
      "lastName" : "Perlmutter",
      "authorRank" : 7,
      "name" : "Perlmutter DH",
      "referenceId" : "RGD:A523848"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:155791685"
    } ]
  }, {
    "primaryId" : "PMID:10421654",
    "title" : "Increase by anaphylatoxin C5a of glucose output in perfused rat liver via prostanoids derived from nonparenchymal cells: direct action of prostaglandins and indirect action of thromboxane A(2) on hepatocytes.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Schieferdecker HL, etal., Hepatology. 1999 Aug;30(2):454-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-22T13:22:53.000-05:00",
    "volume" : "30",
    "pages" : "454-61",
    "abstract" : "In the perfused rat liver the anaphylatoxin C5a enhanced glucose output, reduced flow, and elevated prostanoid overflow. Because hepatocytes (HCs) do not express C5a receptors, the metabolic C5a actions must be indirect, mediated by e.g. prostanoids from Kupffer cells (KCs) and hepatic stellate cells (HSCs), which possess C5a receptors. Surprisingly, the metabolic C5a effects were not only impaired by the prostanoid synthesis inhibitor, indomethacin, but also by the thromboxane A(2) (TXA(2)) receptor antagonist, daltroban, even though HCs do not express TXA(2) receptors. TXA(2) did not induce prostaglandin (PG) or an unknown factor release from KCs or sinusoidal endothelial cells (SECs), which express TXA(2) receptors, because (1) daltroban did neither influence the C5a-induced release of prostanoids from cultured KCs nor the C5a-dependent activation of glycogen phosphorylase in KC/HC cocultures and because (2) the TXA(2) analog, U46619, failed to stimulate prostanoid release from cultured KCs or SECs or to activate glycogen phosphorylase in KC/HC or SEC/HC cocultures. In the perfused liver, Ca(2+)-deprivation inhibited not only flow reduction but also glucose output elicited by C5a to similar extents as daltroban. Similarly, in the absence of extracellular Ca(2+), flow reduction and glucose output induced by U46619 were almost completely prevented, whereas glucose output induced by the directly acting PGF(2alpha) was only slightly lowered. Thus, in the perfused rat liver PGs released after C5a-stimulation from KCs and HSCs directly activated glycogen phosphorylase in HCs, and TXA(2) enhanced glucose output indirectly mainly by causing hypoxia as a result of flow reduction.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HL",
      "lastName" : "Schieferdecker",
      "authorRank" : 1,
      "name" : "Schieferdecker HL",
      "referenceId" : "RGD:A24841"
    }, {
      "firstName" : "S",
      "lastName" : "Pestel",
      "authorRank" : 2,
      "name" : "Pestel S",
      "referenceId" : "RGD:A78038"
    }, {
      "firstName" : "GP",
      "lastName" : "Puschel",
      "authorRank" : 3,
      "name" : "Puschel GP",
      "referenceId" : "RGD:A33942"
    }, {
      "firstName" : "O",
      "lastName" : "Gotze",
      "authorRank" : 4,
      "name" : "Gotze O",
      "referenceId" : "RGD:A17071"
    }, {
      "firstName" : "K",
      "lastName" : "Jungermann",
      "authorRank" : 5,
      "name" : "Jungermann K",
      "referenceId" : "RGD:A4580"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600660"
    } ]
  }, {
    "primaryId" : "PMID:10421658",
    "title" : "Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kamisako T, etal., Hepatology. 1999 Aug;30(2):485-90. doi: 10.1002/hep.510300220.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-02-27T06:06:07.000-06:00",
    "volume" : "30",
    "pages" : "485-90",
    "abstract" : "The secretion of bilirubin conjugates from hepatocytes into bile represents a decisive step in the prevention of hyperbilirubinemia. The bilirubin conjugates, monoglucuronosyl bilirubin (MGB) and bisglucuronosyl bilirubin (BGB), were previously suggested to be endogenous substrates for the apical multidrug resistance protein (MRP2), a member of the adenosine triphosphate (ATP)-binding cassette family of transporters (symbol ABCC2), also termed canalicular multispecific organic anion transporter. We have characterized this ATP-dependent transport using membrane vesicles from human embryonic kidney (HEK) cells expressing recombinant rat as well as human MRP2. MGB and BGB, (3)H-labeled in the glucuronosyl moiety, were synthesized enzymatically with recombinant UDP-glucuronosyltransferase 1A1, and stabilized with ascorbate. Rates for ATP-dependent transport of MGB and BGB (0.5 micromol/L each) by human MRP2 were 183 and 104 pmol x mg protein(-1) x min(-1), respectively. K(m) values were 0.7 and 0.9 micromol/L for human MRP2, and 0.8 and 0.5 micromol/L for rat MRP2, with MGB and BGB as substrates, respectively. Leukotriene C(4) and 17beta-glucuronosyl estradiol, which are both known high-affinity substrates for human MRP2, inhibited [(3)H]MGB transport with IC(50) values of 2.3 and 30 micromol/L, respectively. Cyclosporin A competitively inhibited human and rat MRP2-mediated transport of [(3)H]MGB, with K(i) values of 21 and 10 micromol/L, respectively. Our results provide direct evidence that recombinant MRP2, cloned from rat as well as human liver, mediates the primary-active ATP-dependent transport of the bilirubin conjugates MGB and BGB.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kamisako",
      "authorRank" : 1,
      "name" : "Kamisako T",
      "referenceId" : "RGD:A26830"
    }, {
      "firstName" : "I",
      "lastName" : "Leier",
      "authorRank" : 2,
      "name" : "Leier I",
      "referenceId" : "RGD:A495273"
    }, {
      "firstName" : "Y",
      "lastName" : "Cui",
      "authorRank" : 3,
      "name" : "Cui Y",
      "referenceId" : "RGD:A44680"
    }, {
      "firstName" : "J",
      "lastName" : "König",
      "authorRank" : 4,
      "name" : "König J",
      "referenceId" : "RGD:A495274"
    }, {
      "firstName" : "U",
      "lastName" : "Buchholz",
      "authorRank" : 5,
      "name" : "Buchholz U",
      "referenceId" : "RGD:A495275"
    }, {
      "firstName" : "J",
      "lastName" : "Hummel-Eisenbeiss",
      "authorRank" : 6,
      "name" : "Hummel-Eisenbeiss J",
      "referenceId" : "RGD:A495276"
    }, {
      "firstName" : "D",
      "lastName" : "Keppler",
      "authorRank" : 7,
      "name" : "Keppler D",
      "referenceId" : "RGD:A15689"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:42721987"
    } ]
  }, {
    "primaryId" : "PMID:10421803",
    "title" : "Two-dimensional gel analysis of human endometrial proteins: characterization of proteins with increased expression in hyperplasia and adenocarcinoma.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Byrjalsen I, etal., Mol Hum Reprod. 1999 Aug;5(8):748-56.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-17T12:09:14.000-05:00",
    "volume" : "5",
    "pages" : "748-56",
    "abstract" : "In the search for new markers of human endometrial hyperplasia and adenocarcinoma the method of quantitative two-dimensional gel electrophoresis was applied to study the protein expression profiles of metabolically [(35)S]-methionine-labelled proteins of endometrial explants. Approximately 1700 protein spots were resolved by the two-dimensional gel electrophoresis, and the expression pattern of each of these proteins was assessed for increased expression during hyperplasia or adenocarcinoma. In total, six protein spots showed increased expression in hyperplasia, 19 in carcinoma, and eight in both hyperplasia and carcinoma. Twelve of these 33 differentially expressed proteins were identified by peptide mass mapping combined with sequence database searching. Among the identified proteins were proteins involved in cellular transport and chaperoning, i.e. heat shock protein 27 kDa protein, heat shock 70 kDa protein, heat shock cognate 71 kDa protein, and serotransferrin. Other identified proteins were: regulatory chain protein of cAMP-dependent protein kinase, prohibitin, and heterogeneous nuclear ribonucleoprotein A2/B1. Finally we identified proteins associated with the cytoskeleton, vimentin and tropomyosin isoform 3, and the glycolytic pathway, alpha enolase, and phosphoglycerate kinase. The remaining unidentified proteins were either not contained in the database and must be assumed to be novel proteins, or were present in too low amounts to allow characterization.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Byrjalsen",
      "authorRank" : 1,
      "name" : "Byrjalsen I",
      "referenceId" : "RGD:A94912"
    }, {
      "firstName" : "P",
      "lastName" : "Mose Larsen",
      "authorRank" : 2,
      "name" : "Mose Larsen P",
      "referenceId" : "RGD:A94913"
    }, {
      "firstName" : "SJ",
      "lastName" : "Fey",
      "authorRank" : 3,
      "name" : "Fey SJ",
      "referenceId" : "RGD:A31756"
    }, {
      "firstName" : "L",
      "lastName" : "Nilas",
      "authorRank" : 4,
      "name" : "Nilas L",
      "referenceId" : "RGD:A94914"
    }, {
      "firstName" : "MR",
      "lastName" : "Larsen",
      "authorRank" : 5,
      "name" : "Larsen MR",
      "referenceId" : "RGD:A52757"
    }, {
      "firstName" : "C",
      "lastName" : "Christiansen",
      "authorRank" : 6,
      "name" : "Christiansen C",
      "referenceId" : "RGD:A94915"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292406"
    } ]
  }, {
    "primaryId" : "PMID:10421839",
    "title" : "Involvement of CRM1, a nuclear export receptor, in mRNA export in mammalian cells and fission yeast.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Watanabe M, etal., Genes Cells. 1999 May;4(5):291-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-03-11T15:15:19.000-05:00",
    "volume" : "4",
    "pages" : "291-7",
    "abstract" : "BACKGROUND: CRM1, an evolutionarily conserved protein, was shown to be a receptor for leucine-rich nuclear export signal (NES)-dependent protein transport. In lower eukaryotes CRM1 is reported to be required for the export of mRNA, however, involvement of the NES-dependent transport pathway in mRNA export in higher eukaryotes has not been established. RESULTS: We have found that treatment of mammalian cells with leptomycin B (LMB), a specific inhibitor of CRM1, induces the nuclear accumulation of endogenous mRNA, probably due to the inhibition of its export. In fission yeasts, the nuclear accumulation of mRNA also occurred in  cells treated with LMB or in a temperature-sensitive crm1 mutant at a restrictive temperature. A synthetic mRNA that was injected into the nucleus of mammalian cultured cells was exported from the nucleus within 5 h. This export was inhibited by both wheat germ agglutinin and a temperature of 4 degrees C. Importantly, this mRNA export was inhibited by LMB or by an excess amount of the  NES peptide-conjugates. LMB treatment, on the other hand, rapidly induced the nuclear entry of RanBP1, a factor involved in the active nucleocytoplasmic transport, although the treatment did not interfere with a nuclear localization signal-dependent transport system within 7 h. CONCLUSION: These results suggest that CRM1 is involved in mRNA export in eukaryotic cells.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Watanabe",
      "authorRank" : 1,
      "name" : "Watanabe",
      "referenceId" : "RGD:A417010"
    }, {
      "firstName" : "M",
      "lastName" : "Fukuda",
      "authorRank" : 2,
      "name" : "Fukuda M",
      "referenceId" : "RGD:A11173"
    }, {
      "firstName" : "M",
      "lastName" : "Yoshida",
      "authorRank" : 3,
      "name" : "Yoshida M",
      "referenceId" : "RGD:A15115"
    }, {
      "firstName" : "M",
      "lastName" : "Yanagida",
      "authorRank" : 4,
      "name" : "Yanagida M",
      "referenceId" : "RGD:A86443"
    }, {
      "firstName" : "E",
      "lastName" : "Nishida",
      "authorRank" : 5,
      "name" : "Nishida E",
      "referenceId" : "RGD:A26931"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9834999"
    } ]
  }, {
    "primaryId" : "PMID:10422644",
    "title" : "Neuropeptide Y-induced contraction is mediated by neuropeptide Y Y2 and Y4 receptors in the rat colon.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Pheng LH, etal., Eur J Pharmacol. 1999 Jun 11;374(1):85-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-10-03T10:38:17.000-05:00",
    "volume" : "374",
    "pages" : "85-91",
    "abstract" : "Ascending and descending segments of the rat colon were studied to analyze their contractile responses to neuropeptide Y and related peptides. These responses are (a) completely eliminated by tetrodotoxin (1 microM), (b) reduced to a variable extent (20 to 60%) by atropine (1 microM) and (c) not modified by indomethacin, diphenhydramine or methysergide. The order of potency of agonists for peptides related to neuropeptide Y was as follows: human pancreatic polypeptide = rat pancreatic polypeptide > peptide YY = peptide YY-(3-36) = [Leu31,Pro34]neuropeptide Y > neuropeptide Y-(2-36) > C2-neuropeptide Y = neuropeptide Y > neuropeptide Y-(13-36), with minor differences observed between the two parts of the colon. This selectivity pattern does not correspond to the profile of any known cloned neuropeptide Y receptors. BIBP3226, a selective antagonist for the neuropeptide Y Y1 receptor sub-type, was found to be inactive, while a neuropeptide Y Y2 receptor antagonist, T4-[NPY-(33-36)]4, reduced the effects of neuropeptide Y, peptide YY, peptide YY-(3-36) and C2-neuropeptide Y without affecting those of human pancreatic polypeptide, rat pancreatic polypeptide and [Leu31,Pro34]neuropeptide Y. JCF 104 (compound 28), a putative neuropeptide Y Y5 receptor antagonist, showed no effect or a weak inhibition of human pancreatic polypeptide or [Leu31,Pro34]neuropeptide Y-induced contraction. Taken together, these data suggest that: (1) at least two neuropeptide Y receptor types are present in the rat colon autonomic nerve terminals and modulate the release of acetylcholine and possibly other transmitters; (2) a proportion of the receptors mediating the contractile response of the rat colon (especially descending part) to neuropeptide Y and related peptides appears to be of the Y2 type and (3) the significant portion of the response is mediated by a receptor which is insensitive to neuropeptide Y Y1, Y2 and to neuropeptide Y Y5 receptor antagonists. This receptor behaves as a neuropeptide Y Y4 receptor sub-type and appears to be located on enteric nerves.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LH",
      "lastName" : "Pheng",
      "authorRank" : 1,
      "name" : "Pheng LH",
      "referenceId" : "RGD:A88560"
    }, {
      "firstName" : "A",
      "lastName" : "Perron",
      "authorRank" : 2,
      "name" : "Perron A",
      "referenceId" : "RGD:A88561"
    }, {
      "firstName" : "R",
      "lastName" : "Quirion",
      "authorRank" : 3,
      "name" : "Quirion R",
      "referenceId" : "RGD:A16887"
    }, {
      "firstName" : "A",
      "lastName" : "Cadieux",
      "authorRank" : 4,
      "name" : "Cadieux A",
      "referenceId" : "RGD:A88562"
    }, {
      "firstName" : "JL",
      "lastName" : "Fauchere",
      "authorRank" : 5,
      "name" : "Fauchere JL",
      "referenceId" : "RGD:A88563"
    }, {
      "firstName" : "Y",
      "lastName" : "Dumont",
      "authorRank" : 6,
      "name" : "Dumont Y",
      "referenceId" : "RGD:A51457"
    }, {
      "firstName" : "D",
      "lastName" : "Regoli",
      "authorRank" : 7,
      "name" : "Regoli D",
      "referenceId" : "RGD:A25483"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642606"
    } ]
  }, {
    "primaryId" : "PMID:10422773",
    "title" : "Functional expression of the fractalkine (CX3C) receptor and its regulation by lipopolysaccharide in rat microglia.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Boddeke EW, etal., Eur J Pharmacol. 1999 Jun 18;374(2):309-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-27T17:49:40.000-06:00",
    "volume" : "374",
    "pages" : "309-13",
    "abstract" : "Functional expression of CX3CR1, a recently discovered receptor for the chemokine fractalkine, was investigated in cultured rat microglia. Reverse transcriptase polymerase chain reaction (PCR) experiments show abundant expression of fractalkine receptor mRNA in microglia. mRNA expression of fractalkine was undetectable in astrocytes and microglia but was very strong in cortical neurons. Incubation of microglia with lipopolysaccharide (100 ng/ml) transiently suppressed expression of fractalkine receptor mRNA. Fractalkine induced a concentration-dependent (10(-10)-10(-8) M) and, at high concentrations, oscillatory mobilization of intracellular Ca2+ in microglia The concentration-response curve of fractalkine was shifted to the right after 12 h incubation with lipopolysaccharide. It is concluded that treatment with endotoxin downregulates expression of fractalkine receptor mRNA in rat microglia and suppresses the functional response to fractalkine.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EW",
      "lastName" : "Boddeke",
      "authorRank" : 1,
      "name" : "Boddeke EW",
      "referenceId" : "RGD:A134232"
    }, {
      "firstName" : "I",
      "lastName" : "Meigel",
      "authorRank" : 2,
      "name" : "Meigel I",
      "referenceId" : "RGD:A134233"
    }, {
      "firstName" : "S",
      "lastName" : "Frentzel",
      "authorRank" : 3,
      "name" : "Frentzel S",
      "referenceId" : "RGD:A43390"
    }, {
      "firstName" : "K",
      "lastName" : "Biber",
      "authorRank" : 4,
      "name" : "Biber K",
      "referenceId" : "RGD:A134234"
    }, {
      "firstName" : "LQ",
      "lastName" : "Renn",
      "authorRank" : 5,
      "name" : "Renn LQ",
      "referenceId" : "RGD:A134235"
    }, {
      "firstName" : "P",
      "lastName" : "Gebicke-Harter",
      "authorRank" : 6,
      "name" : "Gebicke-Harter P",
      "referenceId" : "RGD:A134236"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892028"
    } ]
  }, {
    "primaryId" : "PMID:10422787",
    "title" : "Molecular characterisation of cloned bradykinin B1 receptors from rat and human.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Jones C, etal., Eur J Pharmacol. 1999 Jun 25;374(3):423-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-06-28T14:18:05.000-05:00",
    "volume" : "374",
    "pages" : "423-33",
    "abstract" : "This report describes the characterisation of cloned rat and human bradykinin B1 receptors in African green monkey kidney fibroblast (Cos-7) cells. A ligand binding assay with [3H]des-Arg10-kallidin was used to compare their pharmacology with respect to known bradykinin B1 and B2 receptor ligands. In addition, the pharmacology of T-kinin and its' derivative des-Arg11-T-kinin was investigated. The cloned rat receptor had a similar pharmacology to that of the recently described mouse receptor and differs from that described for the human receptor. The rat receptor had a higher affinity for des-Arg11-T-kinin than the human receptor. These differences in pharmacological properties may relate to the presence of T-kinin, bradykinin and their des-Arg derivatives as the major physiological peptides in rat and the predominance of kallidin and its derivatives in human. We confirm that the rat bradykinin B1 receptor gene is organised in a two exon structure and differs from the human gene which has a three exon structure and we further examine the inducible expression of this gene in a wide range of tissues using Northern blotting.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Jones",
      "authorRank" : 1,
      "name" : "Jones C",
      "referenceId" : "RGD:A40863"
    }, {
      "firstName" : "E",
      "lastName" : "Phillips",
      "authorRank" : 2,
      "name" : "Phillips E",
      "referenceId" : "RGD:A33838"
    }, {
      "firstName" : "C",
      "lastName" : "Davis",
      "authorRank" : 3,
      "name" : "Davis C",
      "referenceId" : "RGD:A84935"
    }, {
      "firstName" : "J",
      "lastName" : "Arbuckle",
      "authorRank" : 4,
      "name" : "Arbuckle J",
      "referenceId" : "RGD:A84936"
    }, {
      "firstName" : "M",
      "lastName" : "Yaqoob",
      "authorRank" : 5,
      "name" : "Yaqoob M",
      "referenceId" : "RGD:A84937"
    }, {
      "firstName" : "GM",
      "lastName" : "Burgess",
      "authorRank" : 6,
      "name" : "Burgess GM",
      "referenceId" : "RGD:A84938"
    }, {
      "firstName" : "RJ",
      "lastName" : "Docherty",
      "authorRank" : 7,
      "name" : "Docherty RJ",
      "referenceId" : "RGD:A84939"
    }, {
      "firstName" : "M",
      "lastName" : "Webb",
      "authorRank" : 8,
      "name" : "Webb M",
      "referenceId" : "RGD:A84940"
    }, {
      "firstName" : "SJ",
      "lastName" : "Bevan",
      "authorRank" : 9,
      "name" : "Bevan SJ",
      "referenceId" : "RGD:A84941"
    }, {
      "firstName" : "P",
      "lastName" : "McIntyre",
      "authorRank" : 10,
      "name" : "McIntyre P",
      "referenceId" : "RGD:A21076"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1625744"
    } ]
  }, {
    "primaryId" : "PMID:10422802",
    "title" : "Three novel small deletion mutations of the LDL receptor gene in Korean patients  with familial hypercholesterolemia.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Chae JJ, etal., Clin Genet. 1999 May;55(5):325-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:16:48.000-05:00",
    "volume" : "55",
    "pages" : "325-31",
    "abstract" : "The low-density lipoprotein (LDL) receptor gene from 80 unrelated Korean patients with familial hypercholesterolemia (FH) was analyzed to screen for small structural rearrangements that could not be detected by Southern blot hybridization. Three different small deletions were detected in exon 11 of 3 FH patients and were characterized by DNA sequence analysis. Of them two mutations are in-frame 36-bp (FH 2) and 9-bp (FH 34) deletions that result in the loss of twelve amino acids (from Met510 to Ile521) and three amino acids (Thr513, Asp514  and Trp515), respectively. Both mutations are located in the third of the five YWTD motifs of the LDL receptor gene. The third mutation (FH 400) is a 2-bp deletion that shifts the translational reading frame and results in a prematurely terminated receptor protein. The generation of a 36-bp deletion can be explained  by the formation of a hairpin-loop structure mediated by inverted repeat sequences. On the other hand, the mechanism responsible for the 9- and the 2-bp deletions is probably strand-slippage mispairing mediated by short direct repeats. All of these three deletions are novel mutations. Each of the three deletions was detected only in a single pedigree out of 80 FH families analyzed.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JJ",
      "lastName" : "Chae",
      "authorRank" : 1,
      "name" : "Chae",
      "referenceId" : "RGD:A386748"
    }, {
      "firstName" : "SH",
      "lastName" : "Kim",
      "authorRank" : 2,
      "name" : "Kim SH",
      "referenceId" : "RGD:A19748"
    }, {
      "firstName" : "UK",
      "lastName" : "Kim",
      "authorRank" : 3,
      "name" : "Kim",
      "referenceId" : "RGD:A175206"
    }, {
      "firstName" : "KH",
      "lastName" : "Han",
      "authorRank" : 4,
      "name" : "Han KH",
      "referenceId" : "RGD:A27451"
    }, {
      "firstName" : "HS",
      "lastName" : "Kim",
      "authorRank" : 5,
      "name" : "Kim HS",
      "referenceId" : "RGD:A17205"
    }, {
      "firstName" : "DL",
      "lastName" : "Kastner",
      "authorRank" : 6,
      "name" : "Kastner",
      "referenceId" : "RGD:A386751"
    }, {
      "firstName" : "Y",
      "lastName" : "Namkoong",
      "authorRank" : 7,
      "name" : "Namkoong",
      "referenceId" : "RGD:A360067"
    }, {
      "firstName" : "YB",
      "lastName" : "Park",
      "authorRank" : 8,
      "name" : "Park YB",
      "referenceId" : "RGD:A78055"
    }, {
      "firstName" : "CC",
      "lastName" : "Lee",
      "authorRank" : 9,
      "name" : "Lee CC",
      "referenceId" : "RGD:A6178"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11526454"
    } ]
  }, {
    "primaryId" : "PMID:10422803",
    "title" : "An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F).",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Ekstrom U, etal., Clin Genet. 1999 May;55(5):332-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:53:51.000-05:00",
    "volume" : "55",
    "pages" : "332-9",
    "abstract" : "Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant  way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very  low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects  cross-linking through the unpaired cysteine residue in the binding domain. Cells  expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "U",
      "lastName" : "Ekstrom",
      "authorRank" : 1,
      "name" : "Ekstrom",
      "referenceId" : "RGD:A183488"
    }, {
      "firstName" : "M",
      "lastName" : "Abrahamson",
      "authorRank" : 2,
      "name" : "Abrahamson M",
      "referenceId" : "RGD:A37616"
    }, {
      "firstName" : "CH",
      "lastName" : "Floren",
      "authorRank" : 3,
      "name" : "Floren",
      "referenceId" : "RGD:A360363"
    }, {
      "firstName" : "H",
      "lastName" : "Tollig",
      "authorRank" : 4,
      "name" : "Tollig",
      "referenceId" : "RGD:A365546"
    }, {
      "firstName" : "G",
      "lastName" : "Wettrell",
      "authorRank" : 5,
      "name" : "Wettrell",
      "referenceId" : "RGD:A252635"
    }, {
      "firstName" : "G",
      "lastName" : "Nilsson",
      "authorRank" : 6,
      "name" : "Nilsson G",
      "referenceId" : "RGD:A36352"
    }, {
      "firstName" : "XM",
      "lastName" : "Sun",
      "authorRank" : 7,
      "name" : "Sun XM",
      "referenceId" : "RGD:A65064"
    }, {
      "firstName" : "AK",
      "lastName" : "Soutar",
      "authorRank" : 8,
      "name" : "Soutar AK",
      "referenceId" : "RGD:A57218"
    }, {
      "firstName" : "P",
      "lastName" : "Nilsson-Ehle",
      "authorRank" : 9,
      "name" : "Nilsson-Ehle P",
      "referenceId" : "RGD:A51902"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11528131"
    } ]
  }, {
    "primaryId" : "PMID:10422804",
    "title" : "Founder mutations in the LDL receptor gene contribute significantly to the familial hypercholesterolemia phenotype in the indigenous South African population of mixed ancestry.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Loubser O, etal., Clin Genet. 1999 May;55(5):340-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:25:55.000-05:00",
    "volume" : "55",
    "pages" : "340-5",
    "abstract" : "The South African population harbors genes that are derived from varying degrees  of admixture between indigenous groups and immigrants from Europe and the East. This study represents the first direct mutation-based attempt to determine the impact of admixture from other gene pools on the familial hypercholesterolemia (FH) phenotype in the recently founded Coloured population of South Africa, a people of mixed ancestry. A cohort of 236 apparently unrelated patients with clinical features of FH was screened for a common mutation causing familial defective apolipoprotein B-100 (FDB) and seven low-density lipoprotein receptor (LDLR) gene defects known to be relatively common in South Africans with FH. Six  founder-type 'South African mutations' were responsible for FH in approximately 20% of the study population, while only 1 patient tested positive for the familial defective apolipoprotein B-100 mutation R3500Q. The detection of multiple founder-type LDLR gene mutations originating from European, Indian and Jewish populations provides direct genetic evidence that Caucasoid admixture contributes significantly to the apparently high prevalence of FH in South African patients of mixed ancestry. This study contributes to our knowledge of the biological history of this unique population and illustrates the potential consequences of recent admixture in populations with different disease risks.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Loubser",
      "authorRank" : 1,
      "name" : "Loubser",
      "referenceId" : "RGD:A366024"
    }, {
      "firstName" : "AD",
      "lastName" : "Marais",
      "authorRank" : 2,
      "name" : "Marais",
      "referenceId" : "RGD:A360280"
    }, {
      "firstName" : "MJ",
      "lastName" : "Kotze",
      "authorRank" : 3,
      "name" : "Kotze MJ",
      "referenceId" : "RGD:A148949"
    }, {
      "firstName" : "N",
      "lastName" : "Godenir",
      "authorRank" : 4,
      "name" : "Godenir",
      "referenceId" : "RGD:A362227"
    }, {
      "firstName" : "R",
      "lastName" : "Thiart",
      "authorRank" : 5,
      "name" : "Thiart",
      "referenceId" : "RGD:A282254"
    }, {
      "firstName" : "CL",
      "lastName" : "Scholtz",
      "authorRank" : 6,
      "name" : "Scholtz",
      "referenceId" : "RGD:A282255"
    }, {
      "firstName" : "JN",
      "lastName" : "De Villiers",
      "authorRank" : 7,
      "name" : "De Villiers",
      "referenceId" : "RGD:A282258"
    }, {
      "firstName" : "R",
      "lastName" : "Hillermann",
      "authorRank" : 8,
      "name" : "Hillermann",
      "referenceId" : "RGD:A360540"
    }, {
      "firstName" : "JC",
      "lastName" : "Firth",
      "authorRank" : 9,
      "name" : "Firth",
      "referenceId" : "RGD:A362228"
    }, {
      "firstName" : "HF",
      "lastName" : "Weich",
      "authorRank" : 10,
      "name" : "Weich",
      "referenceId" : "RGD:A362229"
    }, {
      "firstName" : "F",
      "lastName" : "Maritz",
      "authorRank" : 11,
      "name" : "Maritz",
      "referenceId" : "RGD:A362230"
    }, {
      "firstName" : "S",
      "lastName" : "Jones",
      "authorRank" : 12,
      "name" : "Jones S",
      "referenceId" : "RGD:A48002"
    }, {
      "firstName" : "DR",
      "lastName" : "Van der Westhuyzen",
      "authorRank" : 13,
      "name" : "Van der Westhuyzen DR",
      "referenceId" : "RGD:A144571"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11526941"
    } ]
  }, {
    "primaryId" : "PMID:10423016",
    "title" : "Localization of ADAM10 and Notch receptors in bone.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Dallas DJ, etal., Bone 1999 Jul;25(1):9-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-19T15:25:05.000-05:00",
    "volume" : "25",
    "pages" : "9-15",
    "abstract" : "In Drosophila melanogaster, the role of the metallodisintegrin, Kuzbanian (kuz), is thought to involve activation of the Drosophila Notch receptor that plays a role in cell-fate determination during neurogenesis and myoblast differentiation. To understand the possible function(s) of a-disintegrin and metalloproteinase (ADAM10), the mammalian ortholog of kuz, in the skeleton, we studied its expression as well as the messenger RNA (mRNA) encoding one candidate substrate, the mammalian Notch2 receptor in bone, bone cells, and cartilage. In sections of neonatal rat tibiae, ADAM10 is expressed in specific regions of articular cartilage and metaphyseal bone. Expression of ADAM10 in articular cartilage occurs predominantly in superficial chondrocytes and becomes more sporadic with increasing distance from the articular surface. In bone, ADAM10 is expressed by periosteal cells, osteoblasts, and osteocytes at locations of active bone formation. Osteoclasts did not express ADAM10. Notch2 mRNA expression was not detectable in superficial chondrocytes. However it colocalized at all sites of ADAM10 expression in bone cells. In vitro, both primary human osteoblasts and osteoblast cell lines expressed a single 4.5 kb and 7.5 kb transcript of ADAM10 and the Notch2 receptor homolog, respectively. Subcellular localization of the ADAM10 protein in MG-63 cells was determined using immunofluorescent techniques. These observations showed clearly that the ADAM10 protein was expressed in the trans-Golgi network and on the plasma membrane. Western blot analysis of fractionated cells showed that, in the plasma membrane fraction, the previously characterized 58 kDa and 56 kDa isoforms were present, whereas, in the trans-Golgi network, the ADAM10 protein was present in several additional bands, possibly indicative of further interdomain processing of the ADAM10 protein. The metallodisintegrins (ADAMs) have several putative functions, including modulation of cell adhesion, membrane-associated proteolysis, and cell-cell signaling. These observations suggest that, in bone but not cartilage, ADAM10 has catalytic activity within the transGolgi network and may play a role in the activation of Notch receptor homologs. This implicates ADAM10 in cell-fate determination of osteoblast progenitor cells, possibly during skeletal development and normal bone remodeling. Plasma-membrane-associated ADAM10 may confer alternative functions.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Dallas",
      "authorRank" : 1,
      "name" : "Dallas DJ",
      "referenceId" : "RGD:A15377"
    }, {
      "firstName" : "PG",
      "lastName" : "Genever",
      "authorRank" : 2,
      "name" : "Genever PG",
      "referenceId" : "RGD:A15378"
    }, {
      "firstName" : "AJ",
      "lastName" : "Patton",
      "authorRank" : 3,
      "name" : "Patton AJ",
      "referenceId" : "RGD:A15379"
    }, {
      "firstName" : "MI",
      "lastName" : "Millichip",
      "authorRank" : 4,
      "name" : "Millichip MI",
      "referenceId" : "RGD:A15380"
    }, {
      "firstName" : "N",
      "lastName" : "McKie",
      "authorRank" : 5,
      "name" : "McKie N",
      "referenceId" : "RGD:A15381"
    }, {
      "firstName" : "TM",
      "lastName" : "Skerry",
      "authorRank" : 6,
      "name" : "Skerry TM",
      "referenceId" : "RGD:A15382"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:631800"
    } ]
  }, {
    "primaryId" : "PMID:10423332",
    "title" : "Proteases and protease inhibitors in cerulein-induced acute pancreatitis in rats.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kruse P, etal., J Surg Res. 1999 Aug;85(2):294-300.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-06-13T14:04:33.000-05:00",
    "volume" : "85",
    "pages" : "294-300",
    "abstract" : "BACKGROUND: Proteases and protease inhibitors are important in acute pancreatitis (AP), although little is known about the time course in cerulein-induced AP in the rat. MATERIALS AND METHODS: AP was induced by supramaximal stimulation of cerulein, 10 microgram/kg/h, and during 72 h we measured lipase, amylase, albumin, prekallikrein, factor X, alpha(1)-protease inhibitor, alpha(1)-macroglobulin, alpha(2)-antiplasmin, antithrombin III (all in plasma) and macroscopic and histologic variables. RESULTS: Within 12 h an edematous pancreatitis was evident with peak values of peritoneal exudate, pancreatic wet weight ratio, and plasma amylase and lipase activities. Histologically, edema and vacuolization were prominent already after 3 and 6 h, respectively, while inflammation, necrosis, and total histological score gradually increase to reach peak levels at 48 h. Proenzymes and most plasma protease inhibitors decreased to low levels after 6-12 h followed by a gradual increase. The sequential changes over time indicate that kallikrein - kinin activation, and plasminogen activation are probably early events in cerulein-induced AP in rats. alpha(1)-Macroglobulin and alpha(1)-protease inhibitor gradually decreased during the whole study period, probably being \"second line\" defense inhibitors. Levels above normal were seen for alpha(2)-antiplasmin and factor X at 48 h, normalizing at 72 h. CONCLUSIONS: These results suggest that protease activation and protease inhibitor consumption occur in cerulein-induced AP in the rat.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Kruse",
      "authorRank" : 1,
      "name" : "Kruse P",
      "referenceId" : "RGD:A84308"
    }, {
      "firstName" : "A",
      "lastName" : "Lasson",
      "authorRank" : 2,
      "name" : "Lasson A",
      "referenceId" : "RGD:A84309"
    }, {
      "firstName" : "E",
      "lastName" : "Hage",
      "authorRank" : 3,
      "name" : "Hage E",
      "referenceId" : "RGD:A17933"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1625538"
    } ]
  }, {
    "primaryId" : "PMID:10423530",
    "title" : "Up-regulation of telomerase in primary cultured rat hepatocytes.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Nozawa K, etal., J Biochem (Tokyo) 1999 Aug;126(2):361-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:44:00.000-05:00",
    "volume" : "126",
    "pages" : "361-7",
    "abstract" : "Telomerase is a unique reverse transcriptase involved in the maintenance of telomeric DNA, which is generally undetectable in normal human somatic cells. However, it has been found in organs of normal adult rodents including the liver. In order to elucidate relevant control mechanisms operating in normal somatic cells, we examined telomerase activity in primary cultured rat hepatocytes. During culture under serum-free conditions, rat hepatocytes rapidly lose the ability of organ-specific expression of serum albumin, apolipoprotein A-I, and hepatocyte nuclear factor 4, and the capacity for cytochrome P-450 induction by xenobiotics. The telomerase activity was found to be concomitantly increased about 2. 5-fold at 48 h and 3-fold at 72 h. Northern blot and RT-PCR analyses with primary cultured hepatocytes revealed the associated accumulation of rat telomerase RNA subunits (TR), and the mRNAs for a telomerase reverse transcriptase (TERT) and a telomerase-associated protein (TEP1). The activity of hepatocyte telomerase, which was elevated during the primary culture, increased further when the cells were stimulated with hepatocyte growth factor. In this case, however, the levels of TR, TERT, and TEP1 mRNA did not show any detectable changes.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Nozawa",
      "authorRank" : 1,
      "name" : "Nozawa K",
      "referenceId" : "RGD:A27461"
    }, {
      "firstName" : "Y",
      "lastName" : "Kurumiya",
      "authorRank" : 2,
      "name" : "Kurumiya Y",
      "referenceId" : "RGD:A43394"
    }, {
      "firstName" : "A",
      "lastName" : "Yamamoto",
      "authorRank" : 3,
      "name" : "Yamamoto A",
      "referenceId" : "RGD:A158768"
    }, {
      "firstName" : "Y",
      "lastName" : "Isobe",
      "authorRank" : 4,
      "name" : "Isobe Y",
      "referenceId" : "RGD:A6059"
    }, {
      "firstName" : "M",
      "lastName" : "Suzuki",
      "authorRank" : 5,
      "name" : "Suzuki M",
      "referenceId" : "RGD:A299767"
    }, {
      "firstName" : "S",
      "lastName" : "Yoshida",
      "authorRank" : 6,
      "name" : "Yoshida S",
      "referenceId" : "RGD:A4855"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299555"
    } ]
  }, {
    "primaryId" : "PMID:10424289",
    "title" : "Expression of platelet-derived growth factor in newly formed cholangiocytes during experimental biliary fibrosis in rats.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Grappone C, etal., J Hepatol. 1999 Jul;31(1):100-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-07T14:52:04.000-06:00",
    "volume" : "31",
    "pages" : "100-9",
    "abstract" : "BACKGROUND/AIMS: Chronic cholestasis stimulates a fibroductular reaction which may progress to secondary biliary fibrosis and cirrhosis. Since platelet-derived  growth factor has been indicated as a major fibrogenic factor in chronic liver disease, we analyzed its expression and that of its receptor beta subunit in a rat model of chronic cholestasis. METHODS: Liver tissue samples collected at 7, 10, 21, and 28 days after induction of cholestasis obtained by bile duct ligation, were analyzed by immunohistochemistry, in situ hybridization and RNase  protection assay for the expression of platelet-derived growth factor (PDGF)-B chain and receptor beta subunit. Furthermore, the expression of PDGF-B chain mRNA was analyzed in highly purified cholangiocytes from normal and cholestatic rat liver. RESULTS: In cholestatic liver, platelet-derived growth factor-BB and B chain mRNA expression increased up to 4 weeks in epithelial cells of proliferating bile ducts, and periductular mesenchymal cells. The increased expression of PDGF-B chain mRNA was confirmed in highly purified cholangiocytes obtained from normal and cholestatic rat liver. The expression of the receptor beta subunit progressively increased after induction of cholestasis and was mainly localized to desmin-positive periductular hepatic stellate cells. CONCLUSIONS: These data suggest that platelet-derived growth factor-B chain can be synthesized by cholangiocytes during chronic cholestasis. The presence of its  receptor on periductular hepatic stellate cells raises the possibility that, in this experimental setting, this cytokine might contribute to fibrogenesis in vivo.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Grappone",
      "authorRank" : 1,
      "name" : "Grappone",
      "referenceId" : "RGD:A202074"
    }, {
      "firstName" : "M",
      "lastName" : "Pinzani",
      "authorRank" : 2,
      "name" : "Pinzani",
      "referenceId" : "RGD:A209867"
    }, {
      "firstName" : "M",
      "lastName" : "Parola",
      "authorRank" : 3,
      "name" : "Parola M",
      "referenceId" : "RGD:A12703"
    }, {
      "firstName" : "G",
      "lastName" : "Pellegrini",
      "authorRank" : 4,
      "name" : "Pellegrini",
      "referenceId" : "RGD:A202075"
    }, {
      "firstName" : "A",
      "lastName" : "Caligiuri",
      "authorRank" : 5,
      "name" : "Caligiuri",
      "referenceId" : "RGD:A209868"
    }, {
      "firstName" : "R",
      "lastName" : "DeFranco",
      "authorRank" : 6,
      "name" : "DeFranco",
      "referenceId" : "RGD:A209869"
    }, {
      "firstName" : "F",
      "lastName" : "Marra",
      "authorRank" : 7,
      "name" : "Marra",
      "referenceId" : "RGD:A209870"
    }, {
      "firstName" : "H",
      "lastName" : "Herbst",
      "authorRank" : 8,
      "name" : "Herbst H",
      "referenceId" : "RGD:A17039"
    }, {
      "firstName" : "G",
      "lastName" : "Alpini",
      "authorRank" : 9,
      "name" : "Alpini G",
      "referenceId" : "RGD:A21544"
    }, {
      "firstName" : "S",
      "lastName" : "Milani",
      "authorRank" : 10,
      "name" : "Milani",
      "referenceId" : "RGD:A192153"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10449495"
    } ]
  }, {
    "primaryId" : "PMID:10424451",
    "title" : "Identification of the rat homologue of the human NKp46 triggering receptor.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Falco M, etal., Immunol Lett 1999 Jun 1;68(2-3):411-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:43.000-05:00",
    "volume" : "68",
    "pages" : "411-4",
    "issueName" : "2-3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Falco",
      "authorRank" : 1,
      "name" : "Falco M",
      "referenceId" : "RGD:A20537"
    }, {
      "firstName" : "C",
      "lastName" : "Cantoni",
      "authorRank" : 2,
      "name" : "Cantoni C",
      "referenceId" : "RGD:A20538"
    }, {
      "firstName" : "C",
      "lastName" : "Bottino",
      "authorRank" : 3,
      "name" : "Bottino C",
      "referenceId" : "RGD:A20539"
    }, {
      "firstName" : "A",
      "lastName" : "Moretta",
      "authorRank" : 4,
      "name" : "Moretta A",
      "referenceId" : "RGD:A20540"
    }, {
      "firstName" : "R",
      "lastName" : "Biassoni",
      "authorRank" : 5,
      "name" : "Biassoni R",
      "referenceId" : "RGD:A20541"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633317"
    } ]
  }, {
    "primaryId" : "PMID:10424669",
    "title" : "Over-expression of GAPDH induces apoptosis in COS-7 cells transfected with cloned GAPDH cDNAs.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Tajima H, etal., Neuroreport 1999 Jul 13;10(10):2029-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:54.000-05:00",
    "volume" : "10",
    "pages" : "2029-33",
    "abstract" : "The cDNAs for glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) were cloned from cerebellar neurons undergoing age-induced apoptosis and/or healthy cells. COS-7 cells were transfected with the isolated GAPDH cDNAs using to the Lipofectamine method. Assessment of cell death in this paradigm was performed by monitoring the co-transfected luciferase activities and the characterization of cell death was examined by the DNA fragmentation assay and Hoechst dye nuclear staining. These observations show that over-expression of GAPDH occurring from both cDNAs robustly induces apoptotic death in the transfected COS-7 cell cultures. Confocal-immunocytochemical studies using this GAPDH-specific monoclonal antibody revealed that nuclear translocation of overexpressed GAPDH is a primary apoptotic event. Our results directly demonstrate that over-expressed GAPDH functions as a 'killing protein' in apoptosis.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Tajima",
      "authorRank" : 1,
      "name" : "Tajima H",
      "referenceId" : "RGD:A18561"
    }, {
      "firstName" : "K",
      "lastName" : "Tsuchiya",
      "authorRank" : 2,
      "name" : "Tsuchiya K",
      "referenceId" : "RGD:A18562"
    }, {
      "firstName" : "M",
      "lastName" : "Yamada",
      "authorRank" : 3,
      "name" : "Yamada M",
      "referenceId" : "RGD:A161371"
    }, {
      "firstName" : "K",
      "lastName" : "Kondo",
      "authorRank" : 4,
      "name" : "Kondo K",
      "referenceId" : "RGD:A15491"
    }, {
      "firstName" : "N",
      "lastName" : "Katsube",
      "authorRank" : 5,
      "name" : "Katsube N",
      "referenceId" : "RGD:A18563"
    }, {
      "firstName" : "R",
      "lastName" : "Ishitani",
      "authorRank" : 6,
      "name" : "Ishitani R",
      "referenceId" : "RGD:A18564"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632777"
    } ]
  }, {
    "primaryId" : "PMID:10424772",
    "title" : "Aldose reductase, a key enzyme in the oxidative deamination of norepinephrine in  rats.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kawamura M, etal., Biochem Pharmacol. 1999 Aug 1;58(3):517-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-03-19T13:04:19.000-05:00",
    "volume" : "58",
    "pages" : "517-24",
    "abstract" : "The sympathoneural neurotransmitter norepinephrine (NE) is deaminated to 3,4-dihydroxymandelaldehyde (DHMAL) and subsequently converted to either 3,4-dihydroxymandelic acid (DHMA) or 3,4-dihydroxyphenylglycol (DHPG). In this study, we investigated the relative importance of aldose reductase versus aldehyde reductase in the formation of DHPG from DHMAL. The in vitro incubation of NE with aldose reductase in the presence of monoamine oxidase (MAO) resulted in the formation of DHPG, which was confirmed by mass spectrometry. Although aldehyde reductase also generated DHPG, its activity was much lower than that of  aldose reductase. With northern blotting, the expression of both aldose reductase and aldehyde reductase was detected in rat superior cervical ganglia. However, with western blotting, only aldose reductase was immunologically detectable. Treatment of rats with aldose reductase inhibitors for 3 days increased the plasma level of DHMA. There was no correlation between the selectivity of inhibitors and effects on NE metabolite levels. A significant decrease in DHPG, however, was obtained only with an extremely high dose (9 mg/kg/day) of the nonselective inhibitor AL 1576. The present study confirmed that aldose reductase generates DHPG from NE in the presence of MAO. In rat sympathetic neurons, aldose reductase appears to be more important than aldehyde reductase for the formation  of DHPG. However, when aldose reductase is inhibited, it appears that aldehyde reductase can compensate for the conversion of DHMAL to DHPG, indicating redundancy in the reduction pathway.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kawamura",
      "authorRank" : 1,
      "name" : "Kawamura M",
      "referenceId" : "RGD:A25749"
    }, {
      "firstName" : "G",
      "lastName" : "Eisenhofer",
      "authorRank" : 2,
      "name" : "Eisenhofer G",
      "referenceId" : "RGD:A75098"
    }, {
      "firstName" : "IJ",
      "lastName" : "Kopin",
      "authorRank" : 3,
      "name" : "Kopin IJ",
      "referenceId" : "RGD:A16370"
    }, {
      "firstName" : "PF",
      "lastName" : "Kador",
      "authorRank" : 4,
      "name" : "Kador PF",
      "referenceId" : "RGD:A74929"
    }, {
      "firstName" : "YS",
      "lastName" : "Lee",
      "authorRank" : 5,
      "name" : "Lee YS",
      "referenceId" : "RGD:A32513"
    }, {
      "firstName" : "JY",
      "lastName" : "Tsai",
      "authorRank" : 6,
      "name" : "Tsai JY",
      "referenceId" : "RGD:A47877"
    }, {
      "firstName" : "S",
      "lastName" : "Fujisawa",
      "authorRank" : 7,
      "name" : "Fujisawa S",
      "referenceId" : "RGD:A95645"
    }, {
      "firstName" : "MJ",
      "lastName" : "Lizak",
      "authorRank" : 8,
      "name" : "Lizak",
      "referenceId" : "RGD:A181046"
    }, {
      "firstName" : "A",
      "lastName" : "Sinz",
      "authorRank" : 9,
      "name" : "Sinz",
      "referenceId" : "RGD:A168035"
    }, {
      "firstName" : "S",
      "lastName" : "Sato",
      "authorRank" : 10,
      "name" : "Sato S",
      "referenceId" : "RGD:A23501"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8548769"
    } ]
  }, {
    "primaryId" : "PMID:10424818",
    "title" : "Angelman syndrome resulting from UBE3A mutations in 14 patients from eight families: clinical manifestations and genetic counselling.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Moncla A, etal., J Med Genet. 1999 Jul;36(7):554-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-07-29T19:25:03.000-05:00",
    "volume" : "36",
    "pages" : "554-60",
    "abstract" : "Angelman syndrome (AS) is a neurological disorder with a heterogeneous genetic aetiology. It most frequently results from a de novo interstitial deletion in the 15q11-q13 region, but in a few cases it is caused by paternal uniparental disomy (UPD) or an imprinting mutation. The remaining 20 to 30% of AS patients exhibit biparental inheritance and a normal pattern of allelic methylation in the 15q11-q13 region. In this latter group, mutations in the UBE3A gene have recently been shown to be a cause of AS. Here we describe the phenotypic expression in 14 AS cases involving eight UBE3A mutations. These comprise 11 familial cases from five families and three sporadic cases. Subtle differences from the typical phenotype of AS were found. Consistent manifestations were psychomotor delay, a happy disposition, a hyperexcitable personality, EEG abnormalities, and mental retardation with severe speech impairment. The other main manifestations of AS, ataxia, epilepsy, and microcephaly, were either milder or absent in various combinations among the patients. In addition, myoclonus of cortical origin was frequently observed with severe fits inducing myoclonic seizures. The majority of the patients were overweight. This study showed that ataxia, myoclonus, EEG abnormalities, speech impairment, characteristic behavioural phenotype, and abnormal head circumference are attributable to a deficiency in the maternally inherited UBE3A allele. Furthermore, analysis of mutation transmission showed an unexpectedly high rate of somatic mosaicism in normal carriers. These data have important consequences for genetic counselling.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Moncla",
      "authorRank" : 1,
      "name" : "Moncla A",
      "referenceId" : "RGD:A485500"
    }, {
      "firstName" : "P",
      "lastName" : "Malzac",
      "authorRank" : 2,
      "name" : "Malzac P",
      "referenceId" : "RGD:A485501"
    }, {
      "firstName" : "M O",
      "lastName" : "Livet",
      "authorRank" : 3,
      "name" : "Livet MO",
      "referenceId" : "RGD:A485502"
    }, {
      "firstName" : "M A",
      "lastName" : "Voelckel",
      "authorRank" : 4,
      "name" : "Voelckel MA",
      "referenceId" : "RGD:A485503"
    }, {
      "firstName" : "J",
      "lastName" : "Mancini",
      "authorRank" : 5,
      "name" : "Mancini J",
      "referenceId" : "RGD:A99660"
    }, {
      "firstName" : "J C",
      "lastName" : "Delaroziere",
      "authorRank" : 6,
      "name" : "Delaroziere JC",
      "referenceId" : "RGD:A485504"
    }, {
      "firstName" : "N",
      "lastName" : "Philip",
      "authorRank" : 7,
      "name" : "Philip N",
      "referenceId" : "RGD:A71980"
    }, {
      "firstName" : "J F",
      "lastName" : "Mattei",
      "authorRank" : 8,
      "name" : "Mattei JF",
      "referenceId" : "RGD:A485505"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:36174229"
    } ]
  }, {
    "primaryId" : "PMID:10424825",
    "title" : "Presence of a deletion in the 5' upstream region of the GALT gene in Duarte (D2)  alleles.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kozak L, etal., J Med Genet. 1999 Jul;36(7):576-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:04:23.000-05:00",
    "volume" : "36",
    "pages" : "576-8",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Kozak",
      "authorRank" : 1,
      "name" : "Kozak",
      "referenceId" : "RGD:A252489"
    }, {
      "firstName" : "H",
      "lastName" : "Francova",
      "authorRank" : 2,
      "name" : "Francova",
      "referenceId" : "RGD:A254844"
    }, {
      "firstName" : "A",
      "lastName" : "Pijackova",
      "authorRank" : 3,
      "name" : "Pijackova",
      "referenceId" : "RGD:A254845"
    }, {
      "firstName" : "J",
      "lastName" : "Macku",
      "authorRank" : 4,
      "name" : "Macku",
      "referenceId" : "RGD:A254846"
    }, {
      "firstName" : "S",
      "lastName" : "Stastna",
      "authorRank" : 5,
      "name" : "Stastna",
      "referenceId" : "RGD:A254847"
    }, {
      "firstName" : "K",
      "lastName" : "Peskovova",
      "authorRank" : 6,
      "name" : "Peskovova",
      "referenceId" : "RGD:A254848"
    }, {
      "firstName" : "O",
      "lastName" : "Martincova",
      "authorRank" : 7,
      "name" : "Martincova",
      "referenceId" : "RGD:A254849"
    }, {
      "firstName" : "J",
      "lastName" : "Krijt",
      "authorRank" : 8,
      "name" : "Krijt J",
      "referenceId" : "RGD:A77946"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063365"
    } ]
  }, {
    "primaryId" : "PMID:10424878",
    "title" : "Immunohistochemistry of myoepithelial cells during development of the rat salivary glands.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ogawa Y, etal., Anat Embryol (Berl). 1999 Aug;200(2):215-28.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-01T16:22:47.000-06:00",
    "volume" : "200",
    "pages" : "215-28",
    "abstract" : "Using a battery of monoclonal antibodies specific for rat proteins, immunohistochemistry was carried out on the developing myoepithelial cells (MECs) of the rat major salivary glands. The proteins examined were alpha-smooth muscle actin (alphaSMA), h1-calponin (calponin), keratin 14 (K14), beta subunit of S-100 protein (S-100beta), vimentin and glial fibrillary acidic protein (GFAP). The MECs exhibited immunoreactivity for alphaSMA, calponin and K14, but not that for S-100beta, vimentin and GFAP. Immunoreactivity for alphaSMA appeared in the MECs from the time when the microfilaments were initially deposited in these cells, i.e., at 20 days in utero in the sublingual and submandibular glands and at birth in the parotid gland. Calponin immunoreactivity was seen 1 day earlier than alphaSMA. The appearance was almost at the same time as the onset of the MEC differentiation in each gland. A small number of the MECs expressed weak K14 immunoreactivity from the time when the acinus-intercalated duct structure was established, i.e., at 21 days in utero in the sublingual gland, at 5 days after birth in the perotid gland and after 5 weeks post-natally in the submandibular gland. In addition, K14 immunoreactivity was observed in the basal cells of the striated and excretory ducts. The first appearance of K14 in these cells again coincided with the emergence of the duct system in each gland, i.e., at 20 days in utero in the sublingual gland, at 21 days in utero in the submandibular gland and at 3 days after birth in the parotid gland. Finally, the MECs in all the glands were found to redistribute as the acini matured. As the acini grew rapidly during the weaning period in the parotid and the sublingual glands, the MECs ceased to surround the acini. Thereafter, they disappeared from the acini in the parotid gland, whereas they reappeared in the sublingual gland. In the submandibular gland, the MECs were confined to the terminal tubules until 4 weeks after birth. Thereafter, the acini were established and invested by the MECs. In conclusion, immunohistochemistry of calponin and alphaSMA is a useful tool for identification of the MEC during its earliest differentiation, which has hitherto been possible only electron microscopically. In addition, it is suggested that the MEC is heterogeneous and the functionally differentiated MEC appears after weaning around acini of the mucous and seromucous glands.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Ogawa",
      "authorRank" : 1,
      "name" : "Ogawa Y",
      "referenceId" : "RGD:A159942"
    }, {
      "firstName" : "S",
      "lastName" : "Yamauchi",
      "authorRank" : 2,
      "name" : "Yamauchi S",
      "referenceId" : "RGD:A28478"
    }, {
      "firstName" : "A",
      "lastName" : "Ohnishi",
      "authorRank" : 3,
      "name" : "Ohnishi A",
      "referenceId" : "RGD:A76419"
    }, {
      "firstName" : "R",
      "lastName" : "Ito",
      "authorRank" : 4,
      "name" : "Ito R",
      "referenceId" : "RGD:A69687"
    }, {
      "firstName" : "N",
      "lastName" : "Ijuhin",
      "authorRank" : 5,
      "name" : "Ijuhin N",
      "referenceId" : "RGD:A76420"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600179"
    } ]
  }, {
    "primaryId" : "PMID:10425038",
    "title" : "New mutations, polymorphisms, and rare variants in the ATM gene detected by a novel SSCP strategy.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Castellvi-Bel S, etal., Hum Mutat. 1999;14(2):156-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:15:19.000-05:00",
    "volume" : "14",
    "pages" : "156-62",
    "abstract" : "The gene for ataxia-telangiectasia, ATM, spans about 150 kb of genomic DNA. ATM mutations are found along the entire gene, with no evidence of a mutational hot spot. Using DNA as the starting material, we screened the ATM gene in 92 A-T patients, using an optimized single-strand conformation polymorphism (SSCP) technique that detected all previously known mutations in the polymerase chain reaction (PCR) segments being analyzed. To expedite screening, we sequentially loaded the SSCP gels with three different sets of PCR products that were pretested to avoid overlapping patterns. Many of the DNA changes we detected were intragenic polymorphisms. Of an expected 177 unknown mutations, we detected approximately 70%, mostly protein truncating mutations (that would have been detectable by protein truncation testing if RNA starting material had been available). Mutations have now been defined for every exon of the ATM gene. Herein, we present 35 new mutations and 34 new intragenic polymorphisms or rare variants within the ATM gene. This is the most comprehensive compilation of ATM polymorphisms assembled to date. Defining polymorphic sites as well as mutations  in the ATM gene will be of great importance in designing automated methods for detecting mutations.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Castellvi-Bel",
      "authorRank" : 1,
      "name" : "Castellvi-Bel",
      "referenceId" : "RGD:A215227"
    }, {
      "firstName" : "S",
      "lastName" : "Sheikhavandi",
      "authorRank" : 2,
      "name" : "Sheikhavandi",
      "referenceId" : "RGD:A256341"
    }, {
      "firstName" : "M",
      "lastName" : "Telatar",
      "authorRank" : 3,
      "name" : "Telatar M",
      "referenceId" : "RGD:A110605"
    }, {
      "firstName" : "LQ",
      "lastName" : "Tai",
      "authorRank" : 4,
      "name" : "Tai",
      "referenceId" : "RGD:A256342"
    }, {
      "firstName" : "M",
      "lastName" : "Hwang",
      "authorRank" : 5,
      "name" : "Hwang",
      "referenceId" : "RGD:A248970"
    }, {
      "firstName" : "Z",
      "lastName" : "Wang",
      "authorRank" : 6,
      "name" : "Wang",
      "referenceId" : "RGD:A416946"
    }, {
      "firstName" : "Z",
      "lastName" : "Yang",
      "authorRank" : 7,
      "name" : "Yang Z",
      "referenceId" : "RGD:A8813"
    }, {
      "firstName" : "R",
      "lastName" : "Cheng",
      "authorRank" : 8,
      "name" : "Cheng R",
      "referenceId" : "RGD:A9599"
    }, {
      "firstName" : "RA",
      "lastName" : "Gatti",
      "authorRank" : 9,
      "name" : "Gatti RA",
      "referenceId" : "RGD:A76615"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063774"
    } ]
  }, {
    "primaryId" : "PMID:10425042",
    "title" : "A novel mutation (A246T) in exon 6 of the proteolipid protein gene associated with connatal Pelizaeus-Merzbacher disease.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Yamamoto T and Nanba E, Hum Mutat 1999 Aug 19;14(2):182.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-06-16T09:41:22.000-05:00",
    "volume" : "14",
    "pages" : "182",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Yamamoto",
      "authorRank" : 1,
      "name" : "Yamamoto T",
      "referenceId" : "RGD:A161440"
    }, {
      "firstName" : "E",
      "lastName" : "Nanba",
      "authorRank" : 2,
      "name" : "Nanba E",
      "referenceId" : "RGD:A53044"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1358559"
    } ]
  }, {
    "primaryId" : "PMID:10425080",
    "title" : "Identification of three novel mutations in the MYO7A gene",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Cuevas JM, etal., Hum Mutat. 1999;14(2):181.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:53:27.000-05:00",
    "volume" : "14",
    "pages" : "181",
    "abstract" : "Three new mutations in the myosin VIIA gene involved in the pathogenesis of Usher syndrome type Ib are reported. These mutations are K1080X in exon 25, E1170K in exon 28, and Y1719C in exon 37. It is presumed that these mutations are involved  in the Usher syndrome Ib phenotype. Hum Mutat 14:181, 1999. Copyright 1999 Wiley-Liss, Inc.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Cuevas",
      "authorRank" : 1,
      "name" : "Cuevas",
      "referenceId" : "RGD:A253087"
    }, {
      "firstName" : "C",
      "lastName" : "Espin s",
      "authorRank" : 2,
      "name" : "Espin s",
      "referenceId" : "RGD:A253088"
    }, {
      "firstName" : "JM",
      "lastName" : "Millan",
      "authorRank" : 3,
      "name" : "Millan",
      "referenceId" : "RGD:A180401"
    }, {
      "firstName" : "F",
      "lastName" : "Sanchez",
      "authorRank" : 4,
      "name" : "Sanchez F",
      "referenceId" : "RGD:A30692"
    }, {
      "firstName" : "MJ",
      "lastName" : "Trujillo",
      "authorRank" : 5,
      "name" : "Trujillo",
      "referenceId" : "RGD:A253089"
    }, {
      "firstName" : "C",
      "lastName" : "Ayuso",
      "authorRank" : 6,
      "name" : "Ayuso C",
      "referenceId" : "RGD:A142267"
    }, {
      "firstName" : "M",
      "lastName" : "Beneyto",
      "authorRank" : 7,
      "name" : "Beneyto",
      "referenceId" : "RGD:A180404"
    }, {
      "firstName" : "C",
      "lastName" : "Najera",
      "authorRank" : 8,
      "name" : "Najera",
      "referenceId" : "RGD:A180400"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062927"
    } ]
  }, {
    "primaryId" : "PMID:10425186",
    "title" : "Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Hiroi S, etal., Biochem Biophys Res Commun. 1999 Aug 2;261(2):332-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-28T16:23:36.000-05:00",
    "volume" : "261",
    "pages" : "332-9",
    "abstract" : "To reveal genetic risk factors of nonfamilial idiopathic cardiomyopathy (IDC) in Japanese, polymorphisms in the SOD2 and HLA-DRB1 genes were investigated in 86 patients and 380 healthy controls. There was a significant excess of homozygotes for the V allele [Val versus Ala (A allele), a polymorphism in the leader peptide of manganese superoxide dismutase at position 16] of the SOD2 gene in the patients compared with the controls (87.2% versus 74.7%, odds ratio = 2.30, p = 0.013, pc < 0.03), and a significant increase in the frequency of HLA-DRB1*1401 in the patients was confirmed (14.0% vs 4.5%, odds ratio = 3.46, p = 0.001, pc < 0.03). A two-locus analysis suggested that these two genetic markers (SOD2-VV genotype and DRB1*1401) may play a synergistic role in controlling the susceptibility to nonfamilial IDC. In addition, processing efficiency of Val-type SOD2 leader peptide in the presence of mitochondria was siginificantly lower than that of the Ala-type by 11 +/- 4%, suggesting that this lower processing efficiency was in part an underlying mechanism of the association between the SOD2-VV genotype and nonfamilial IDC.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Hiroi",
      "authorRank" : 1,
      "name" : "Hiroi S",
      "referenceId" : "RGD:A26144"
    }, {
      "firstName" : "H",
      "lastName" : "Harada",
      "authorRank" : 2,
      "name" : "Harada H",
      "referenceId" : "RGD:A55770"
    }, {
      "firstName" : "H",
      "lastName" : "Nishi",
      "authorRank" : 3,
      "name" : "Nishi H",
      "referenceId" : "RGD:A64297"
    }, {
      "firstName" : "M",
      "lastName" : "Satoh",
      "authorRank" : 4,
      "name" : "Satoh M",
      "referenceId" : "RGD:A31606"
    }, {
      "firstName" : "R",
      "lastName" : "Nagai",
      "authorRank" : 5,
      "name" : "Nagai R",
      "referenceId" : "RGD:A9180"
    }, {
      "firstName" : "A",
      "lastName" : "Kimura",
      "authorRank" : 6,
      "name" : "Kimura A",
      "referenceId" : "RGD:A18580"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580837"
    } ]
  }, {
    "primaryId" : "PMID:10425188",
    "title" : "Increased vasoconstrictor response of the mouse lacking angiotensin II type 2 receptor.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Akishita M, etal., Biochem Biophys Res Commun 1999 Aug 2;261(2):345-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-31T15:18:33.000-05:00",
    "volume" : "261",
    "pages" : "345-9",
    "abstract" : "The angiotensin II (Ang II) type 1 receptor mediates various actions of Ang II, whereas the function of the type 2 (AT2) receptor is not well understood. In the mice lacking the gene encoding the AT2 receptor, the pressor response to Ang II was increased although the underlying mechanism is unknown. We tested the hypothesis that vasoconstrictor response is exaggerated in the AT2 receptor null mice. We measured hemodynamic parameters and evaluated systemic vascular resistance (SVR) in the anesthetized open-chest wild-type and AT2 receptor null mice. Ang II infusion caused dose-dependent increases in SVR in both strains, while the response was significantly higher at 0.5 microgram/kg Ang II in the AT2 receptor null mice (305 +/- 53% of baseline) than in the wild-type mice (179 +/- 27% of baseline). To investigate further the vascular contractility, we examined contraction of aortic rings in vitro. The contraction induced by 1 microM Ang II was increased in the AT2 receptor null mice compared with that in the wild-type mice (0.82 +/- 0.11 vs. 0.54 +/- 0.12 g). Ang II-induced contraction was still greater in the AT2 receptor null mice when calibrated by the maximum tension induced by 90 mM KCl. These data suggest that the AT2 receptor modulates vascular contractility, which may influence blood pressure.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Akishita",
      "authorRank" : 1,
      "name" : "Akishita M",
      "referenceId" : "RGD:A55117"
    }, {
      "firstName" : "H",
      "lastName" : "Yamada",
      "authorRank" : 2,
      "name" : "Yamada H",
      "referenceId" : "RGD:A13790"
    }, {
      "firstName" : "VJ",
      "lastName" : "Dzau",
      "authorRank" : 3,
      "name" : "Dzau VJ",
      "referenceId" : "RGD:A118092"
    }, {
      "firstName" : "M",
      "lastName" : "Horiuchi",
      "authorRank" : 4,
      "name" : "Horiuchi M",
      "referenceId" : "RGD:A17967"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549470"
    } ]
  }, {
    "primaryId" : "PMID:10425199",
    "title" : "Molecular cloning of rat efp: expression and regulation in primary osteoblasts.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Inoue S, etal., Biochem Biophys Res Commun 1999 Aug 2;261(2):412-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:45.000-05:00",
    "volume" : "261",
    "pages" : "412-8",
    "abstract" : "We have previously identified an estrogen-responsive gene, efp (estrogen-responsive finger protein), by genomic binding-site cloning method. Here, we isolated a rat homologue of efp cDNA that encodes an open reading frame of 644 amino acids sharing high homology with human efp (69% identity at the protein level) and mouse efp (80% identity at the protein level). The efp protein has a RING finger, a variant type of zinc finger motif, B1 box and B2 box, each having a pair of zinc fingers, and coiled-coil domain, belonging to the RING finger-B box-Coiled Coil (RBCC) family. Several members of RBCC family including efp have characteristic C-terminal domain, forming a subfamily. Next, we detected efp mRNA in primary osteoblasts, one of estrogen target cells, derived from the calvariae of rat fetus. An anti-efp antibody revealed the efp protein is expressed and regulated by estrogen in the primary osteoblasts. Interestingly, the efp protein in primary osteoblasts is down-regulated by 1alpha,25-dihydroxyvitamin D(3) treatment that promotes the differentiation of the cells, whereas it is up-regulated by TGF-beta1 treatment that inhibits the differentiation of the cells. These findings suggest the possible involvement of the efp in the differentiation of osteoblastic cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Inoue",
      "authorRank" : 1,
      "name" : "Inoue S",
      "referenceId" : "RGD:A1261"
    }, {
      "firstName" : "T",
      "lastName" : "Urano",
      "authorRank" : 2,
      "name" : "Urano T",
      "referenceId" : "RGD:A162553"
    }, {
      "firstName" : "S",
      "lastName" : "Ogawa",
      "authorRank" : 3,
      "name" : "Ogawa S",
      "referenceId" : "RGD:A6091"
    }, {
      "firstName" : "T",
      "lastName" : "Saito",
      "authorRank" : 4,
      "name" : "Saito T",
      "referenceId" : "RGD:A161595"
    }, {
      "firstName" : "A",
      "lastName" : "Orimo",
      "authorRank" : 5,
      "name" : "Orimo A",
      "referenceId" : "RGD:A1264"
    }, {
      "firstName" : "T",
      "lastName" : "Hosoi",
      "authorRank" : 6,
      "name" : "Hosoi T",
      "referenceId" : "RGD:A1263"
    }, {
      "firstName" : "Y",
      "lastName" : "Ouchi",
      "authorRank" : 7,
      "name" : "Ouchi Y",
      "referenceId" : "RGD:A6093"
    }, {
      "firstName" : "M",
      "lastName" : "Muramatsu",
      "authorRank" : 8,
      "name" : "Muramatsu M",
      "referenceId" : "RGD:A156703"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300518"
    } ]
  }, {
    "primaryId" : "PMID:10425221",
    "title" : "Identification of a novel splice variant of heat shock cognate protein 70 after chronic antidepressant treatment in rat frontal cortex.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Yamada M, etal., Biochem Biophys Res Commun. 1999 Aug 2;261(2):541-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-13T17:38:05.000-05:00",
    "volume" : "261",
    "pages" : "541-5",
    "abstract" : "In this study, we identified a novel splice variant of 70-kDa heat shock cognate  protein (HSC70), while screening differentially expressed molecules in rat brain  after chronic antidepressant treatment. This clone, named HSC49, lacked 470 bp of nucleotides of rat HSC70. HSC49 encoded 442 amino acid residues with a calculated molecular mass of 48.6 kDa. DNA sequence analysis revealed that HSC49 lacked the  entire Exon 7 and Exon 8 of the HSC70 gene. Chronic treatment with antidepressant, imipramine or sertraline, induced a 38.5 or 22.5% increase in mRNA levels in rat frontal cortex, respectively, when compared to controls. Western blot analysis also revealed that the protein expression of HSC49 was increased after antidepressant treatment. Our data suggest that HSC49 may be one  of the common molecules induced after chronic antidepressant treatment.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Yamada",
      "authorRank" : 1,
      "name" : "Yamada",
      "referenceId" : "RGD:A398379"
    }, {
      "firstName" : "M",
      "lastName" : "Yamada",
      "authorRank" : 2,
      "name" : "Yamada",
      "referenceId" : "RGD:A398379"
    }, {
      "firstName" : "Y",
      "lastName" : "Kiuchi",
      "authorRank" : 3,
      "name" : "Kiuchi",
      "referenceId" : "RGD:A301631"
    }, {
      "firstName" : "K",
      "lastName" : "Nara",
      "authorRank" : 4,
      "name" : "Nara",
      "referenceId" : "RGD:A205329"
    }, {
      "firstName" : "Y",
      "lastName" : "Kanda",
      "authorRank" : 5,
      "name" : "Kanda Y",
      "referenceId" : "RGD:A125075"
    }, {
      "firstName" : "S",
      "lastName" : "Morinobu",
      "authorRank" : 6,
      "name" : "Morinobu S",
      "referenceId" : "RGD:A86333"
    }, {
      "firstName" : "K",
      "lastName" : "Momose",
      "authorRank" : 7,
      "name" : "Momose",
      "referenceId" : "RGD:A288425"
    }, {
      "firstName" : "K",
      "lastName" : "Oguchi",
      "authorRank" : 8,
      "name" : "Oguchi",
      "referenceId" : "RGD:A414925"
    }, {
      "firstName" : "K",
      "lastName" : "Kamijima",
      "authorRank" : 9,
      "name" : "Kamijima",
      "referenceId" : "RGD:A328666"
    }, {
      "firstName" : "T",
      "lastName" : "Higuchi",
      "authorRank" : 10,
      "name" : "Higuchi",
      "referenceId" : "RGD:A370005"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10059382"
    } ]
  }, {
    "primaryId" : "PMID:10425447",
    "title" : "Glycodelin mRNA is expressed in the genital tract of male and female rats (Rattus norvegicus).",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Keil C, etal., J Mol Endocrinol 1999 Aug;23(1):57-66.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-02T15:33:01.000-06:00",
    "volume" : "23",
    "pages" : "57-66",
    "abstract" : "In the present study we demonstrate for the first time the expression of glycodelin mRNA in the female and male genital tracts of rats using non-radioactive in situ hybridisation. Glycodelin fragment 1 (+41 to +141) shares 100% homology with the human gene sequence. In the ovary, glycodelin mRNA was restricted to granulosa cells. In the uterus, glycodelin mRNA was expressed in all epithelial cells of the endometrium. In the male reproductive tract, glycodelin mRNA was distributed in all epithelial cells of the epididymis, the prostate and the seminal vesicle. However, in the testis, glycodelin mRNA was predominantly found in spermatogonia and in spermatocytes of the seminiferous epithelium. The expression in several reproductive organs of rats offers an excellent tool to study further the physiological role of glycodelin, which is so far thought to act as an immunosuppressive factor.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Keil",
      "authorRank" : 1,
      "name" : "Keil C",
      "referenceId" : "RGD:A56611"
    }, {
      "firstName" : "B",
      "lastName" : "Husen",
      "authorRank" : 2,
      "name" : "Husen B",
      "referenceId" : "RGD:A56612"
    }, {
      "firstName" : "J",
      "lastName" : "Giebel",
      "authorRank" : 3,
      "name" : "Giebel J",
      "referenceId" : "RGD:A56613"
    }, {
      "firstName" : "G",
      "lastName" : "Rune",
      "authorRank" : 4,
      "name" : "Rune G",
      "referenceId" : "RGD:A56614"
    }, {
      "firstName" : "R",
      "lastName" : "Walther",
      "authorRank" : 5,
      "name" : "Walther R",
      "referenceId" : "RGD:A18335"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556545"
    } ]
  }, {
    "primaryId" : "PMID:10426189",
    "title" : "Type 1 inositol 1,4,5-trisphosphate receptor knock-out mice: their phenotypes and their meaning in neuroscience and clinical practice.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Matsumoto M and Nagata E, J Mol Med (Berl). 1999 May;77(5):406-11.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-05-04T14:16:55.000-05:00",
    "volume" : "77",
    "pages" : "406-11",
    "abstract" : "Cytoplasmic calcium, which acts as a second messenger, is derived not only from outside the cell but also from intracellular stores. A receptor for inositol 1,4,5-trisphosphate (IP3), an intracellular second messenger, is located on these internal calcium stores and functions as a calcium releasing channel. The \"type 1\" IP3 receptor (IP3R1) is concentrated predominantly in cerebellar Purkinje cells and is also widely present in other neural and peripheral tissues, but many of its physiological roles in these cells are still unclear. We have previously succeeded in obtaining mice with disruption of this IP3R1 gene, in which brain IP3-induced calcium release was almost completely abolished. They were rarely born alive, indicating that IP3R1 has some functions during embryonic development. Animals exhibited severe neurological symptoms, ataxia and epilepsy, and were shown to be deficient in the cerebellar long-term depression. They give  us promising clues regarding the physiological roles of calcium release from internal stores and serve as a model for the relevant human disease states.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Matsumoto",
      "authorRank" : 1,
      "name" : "Matsumoto M",
      "referenceId" : "RGD:A9603"
    }, {
      "firstName" : "E",
      "lastName" : "Nagata",
      "authorRank" : 2,
      "name" : "Nagata E",
      "referenceId" : "RGD:A19066"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6482816"
    } ]
  }, {
    "primaryId" : "PMID:10426194",
    "title" : "Loss of heterozygosity and protein expression of APC gene in renal cell carcinomas.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Pecina-Slaus N, etal., J Mol Med (Berl). 1999 May;77(5):446-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-03-26T13:44:29.000-05:00",
    "volume" : "77",
    "pages" : "446-53",
    "abstract" : "This study evaluated the potential contribution of the APC gene to malignant transformation in patients with renal cell carcinoma. We tested 36 human renal cell carcinoma samples and 18 adjacent normal kidney tissues for the expression of APC protein, both wild and truncated types, by western blot using antibodies that recognize either the carboxy or the amino epitope of the APC protein. The same tumor samples together with autologous peripheral blood were also analyzed at the DNA level. Using specific oligonucleotide primers for exons 11 and 15, gene instability was followed by polymerase chain reaction/loss of heterozygosity (LOH) (on the basis of restriction fragment length polymorphism). Molecular data  were also compared to pathohistological diagnosis, TNM stage, and patient's age using multivariate statistical methods. All normal renal tissues revealed expression of the wild-type APC protein. Neither wild nor mutant type proteins were found in 36% (13/36) of tumor samples; the rest of tumor tissues expressed the wild-type protein (312 kDa). Mutated APC protein, with a molecular weight of  117 kDa, was found in only one tumor sample. From 36 tumor samples 16 (44.4%) were informative for RsaI exon 11 polymorphic site, while only half of these (8/16) demonstrated LOH. From 13 tumor samples that had no detectable protein product by western blot analysis eight were homozygous for the exon 11 polymorphism and were tested for another polymorphic site, MspI/exon 15. The overall proportion of LOH cases for both polymorphisms tested was 52.9% (9/17). Pathohistological diagnosis and molecular data showed no correlation. However, multivariate analysis determined a stage strong positive correlation of age and TNM with the presence of LOH and the absence of the wild-type APC protein. Out results suggest that the APC tumor suppressor gene plays a role in renal carcinogenesis. Alterations in this gene are responsible for tumor evolution and  progression, but cannot be considered as a first event in tumor initiation.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Pecina-SLaus",
      "authorRank" : 1,
      "name" : "Pecina-SLaus",
      "referenceId" : "RGD:A168580"
    }, {
      "firstName" : "K",
      "lastName" : "Pavelic",
      "authorRank" : 2,
      "name" : "Pavelic K",
      "referenceId" : "RGD:A121529"
    }, {
      "firstName" : "J",
      "lastName" : "Pavelic",
      "authorRank" : 3,
      "name" : "Pavelic",
      "referenceId" : "RGD:A168585"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7242060"
    } ]
  }, {
    "primaryId" : "PMID:10426374",
    "title" : "Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Patti ME, etal., Diabetes. 1999 Aug;48(8):1562-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-05-31T12:20:07.000-05:00",
    "volume" : "48",
    "pages" : "1562-71",
    "abstract" : "To explore potential cellular mechanisms by which activation of the hexosamine pathway induces insulin resistance, we have evaluated insulin signaling in conscious fasted rats infused for 2-6 h with saline, insulin (18 mU x kg(-1) x min(-1)), or insulin and glucosamine (30 micromol x kg(-1) x min(-1)) under euglycemic conditions. Glucosamine infusion increased muscle UDP-N-acetylglucosamine concentrations 3.9- and 4.3-fold over saline- or insulin-infused animals, respectively (P < 0.001). Glucosamine induced significant insulin resistance to glucose uptake both at the level of the whole body and in rectus abdominis muscle, and it blunted the insulin-induced increase in muscle glycogen content. At a cellular level, these metabolic effects were paralleled by inhibition of postreceptor insulin signaling critical for glucose transport and glycogen storage, including a 45% reduction in insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation (P = 0.02), a 44% decrease in IRS-1 association with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase (P = 0.03), a 34% reduction in IRS-1-associated PI 3-kinase activity (P = 0.03), and a 51% reduction in insulin-stimulated glycogen synthase activity (P = 0.03). These alterations in postreceptor insulin signaling were time-dependent and paralleled closely the progressive inhibition of systemic glucose disposal from 2 to 6 h of glucosamine infusion. We also demonstrated that glucosamine infusion results in O-linked N-acetylglucosamine modification of IRS-1 and IRS-2. These data indicate that activation of the hexosamine pathway may directly modulate early postreceptor insulin signal transduction, perhaps via posttranslation modification of IRS proteins, and thus contribute to the insulin resistance induced by chronic hyperglycemia.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ME",
      "lastName" : "Patti",
      "authorRank" : 1,
      "name" : "Patti ME",
      "referenceId" : "RGD:A83530"
    }, {
      "firstName" : "A",
      "lastName" : "Virkamaki",
      "authorRank" : 2,
      "name" : "Virkamaki A",
      "referenceId" : "RGD:A83531"
    }, {
      "firstName" : "EJ",
      "lastName" : "Landaker",
      "authorRank" : 3,
      "name" : "Landaker EJ",
      "referenceId" : "RGD:A83532"
    }, {
      "firstName" : "CR",
      "lastName" : "Kahn",
      "authorRank" : 4,
      "name" : "Kahn CR",
      "referenceId" : "RGD:A30954"
    }, {
      "firstName" : "H",
      "lastName" : "Yki-Jarvinen",
      "authorRank" : 5,
      "name" : "Yki-Jarvinen H",
      "referenceId" : "RGD:A83533"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1625262"
    } ]
  }, {
    "primaryId" : "PMID:10426381",
    "title" : "Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Masuzaki H, etal., Diabetes. 1999 Aug;48(8):1615-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-10-30T12:09:17.000-05:00",
    "volume" : "48",
    "pages" : "1615-22",
    "abstract" : "Leptin acts as an adipocyte-derived blood-borne satiety factor that can increase glucose metabolism. To elucidate the therapeutic implications of leptin for obesity-associated diabetes, we crossed transgenic skinny mice overexpressing leptin (Tg/+), which we have developed recently, and lethal yellow KKAy mice (Ay/+), a genetic model for obesity-diabetes syndrome, and examined the metabolic phenotypes of F1 animals. At 6 weeks of age, plasma leptin concentrations in Tg/+ mice with the Ay allele (Tg/+:Ay/+) were significantly higher than those in Ay/+ mice. Although no significant differences in body weight were noted among Tg/+:Ay/+ mice, Ay/+ mice, and their wild-type lean littermates (+/+), glucose and insulin tolerance tests revealed increased glucose tolerance and insulin sensitivity in Tg/+:Ay/+ compared with Ay/+ mice. However, at 12 weeks of age, when plasma leptin concentrations in Ay/+ mice were comparable to those in Tg/+:Ay/+ mice, Tg/+:Ay/+ mice developed obesity-diabetes syndrome similar to that of Ay/+ mice. Body weights of 12-week-old Tg/+:Ay/+ and Ay/+ mice were reduced to those of +/+ mice by a 3-week food restriction; when plasma leptin concentrations remained high in Tg/+:Ay/+ mice but were markedly reduced in Ay/+ and +/+ mice, glucose tolerance and insulin sensitivity in Tg/+:Ay/+ mice were markedly improved as compared with Ay/+ and +/+ mice. The present study demonstrates that hyperleptinemia can delay the onset of impaired glucose metabolism and accelerate the recovery from diabetes during caloric restriction in Tg/+:Ay/+ mice, thereby suggesting the potential usefulness of leptin in combination with a long-term caloric restriction for the treatment of obesity-associated diabetes.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Masuzaki",
      "authorRank" : 1,
      "name" : "Masuzaki H",
      "referenceId" : "RGD:A30314"
    }, {
      "firstName" : "Y",
      "lastName" : "Ogawa",
      "authorRank" : 2,
      "name" : "Ogawa Y",
      "referenceId" : "RGD:A159942"
    }, {
      "firstName" : "M",
      "lastName" : "Aizawa-Abe",
      "authorRank" : 3,
      "name" : "Aizawa-Abe M",
      "referenceId" : "RGD:A114324"
    }, {
      "firstName" : "K",
      "lastName" : "Hosoda",
      "authorRank" : 4,
      "name" : "Hosoda K",
      "referenceId" : "RGD:A12678"
    }, {
      "firstName" : "J",
      "lastName" : "Suga",
      "authorRank" : 5,
      "name" : "Suga J",
      "referenceId" : "RGD:A114325"
    }, {
      "firstName" : "K",
      "lastName" : "Ebihara",
      "authorRank" : 6,
      "name" : "Ebihara K",
      "referenceId" : "RGD:A12675"
    }, {
      "firstName" : "N",
      "lastName" : "Satoh",
      "authorRank" : 7,
      "name" : "Satoh N",
      "referenceId" : "RGD:A56495"
    }, {
      "firstName" : "H",
      "lastName" : "Iwai",
      "authorRank" : 8,
      "name" : "Iwai H",
      "referenceId" : "RGD:A114326"
    }, {
      "firstName" : "G",
      "lastName" : "Inoue",
      "authorRank" : 9,
      "name" : "Inoue G",
      "referenceId" : "RGD:A42065"
    }, {
      "firstName" : "H",
      "lastName" : "Nishimura",
      "authorRank" : 10,
      "name" : "Nishimura H",
      "referenceId" : "RGD:A23369"
    }, {
      "firstName" : "Y",
      "lastName" : "Yoshimasa",
      "authorRank" : 11,
      "name" : "Yoshimasa Y",
      "referenceId" : "RGD:A42066"
    }, {
      "firstName" : "K",
      "lastName" : "Nakao",
      "authorRank" : 12,
      "name" : "Nakao K",
      "referenceId" : "RGD:A158633"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2314006"
    } ]
  }, {
    "primaryId" : "PMID:10426412",
    "title" : "Neocortical projections regulate the neostriatal proenkephalin gene expression.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Just L, etal., Cereb Cortex. 1999 Jun;9(4):332-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-04-28T14:53:51.000-05:00",
    "volume" : "9",
    "pages" : "332-9",
    "abstract" : "There is controversial evidence that neocortical projections to the neostriatum may regulate the neostriatal expression of the proenkephalin (PEnk) gene. Therefore, we have studied PEnk gene expression in organotypic neocortico-neostriatal co-cultures as well as cultures of isolated neostriata. PEnk mRNA was determined with in situ hybridization. Removal of the neocortex caused a time-dependent reduction in the number of neostriatal cells which showed expression of the PEnk gene. A maximal decrease was seen after 3 days. Within 2 days after blockade of glutamate receptors of the NMDA type significantly fewer neostriatal cells expressed the PEnk gene, indicating that NMDA receptors mediated the expression of the gene. In isolated neostriatal slices in which the  expression of the PEnk gene had been down-regulated, NMDA increased the number of cells which expressed the gene in a time-dependent manner. Maximal expression was observed after 3 days. This induction was reduced by nimodipine, which blocks L-type Ca2(+)-channels. The slow increase in PEnk gene expression caused by NMDA  resembled a recruiting process. It seems to be specific for the neostriatum and may be due to the latter's neuronal organization.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Just",
      "authorRank" : 1,
      "name" : "Just",
      "referenceId" : "RGD:A201161"
    }, {
      "firstName" : "C",
      "lastName" : "Olenik",
      "authorRank" : 2,
      "name" : "Olenik",
      "referenceId" : "RGD:A200839"
    }, {
      "firstName" : "DK",
      "lastName" : "Meyer",
      "authorRank" : 3,
      "name" : "Meyer DK",
      "referenceId" : "RGD:A124055"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10002788"
    } ]
  }, {
    "primaryId" : "PMID:10426994",
    "title" : "An activating immunoreceptor complex formed by NKG2D and DAP10.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Wu J, etal., Science 1999 Jul 30;285(5428):730-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-18T10:21:33.000-06:00",
    "volume" : "285",
    "pages" : "730-2",
    "abstract" : "Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain-binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.",
    "issueName" : "5428",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Wu",
      "authorRank" : 1,
      "name" : "Wu J",
      "referenceId" : "RGD:A160329"
    }, {
      "firstName" : "Y",
      "lastName" : "Song",
      "authorRank" : 2,
      "name" : "Song Y",
      "referenceId" : "RGD:A7952"
    }, {
      "firstName" : "AB",
      "lastName" : "Bakker",
      "authorRank" : 3,
      "name" : "Bakker AB",
      "referenceId" : "RGD:A57291"
    }, {
      "firstName" : "S",
      "lastName" : "Bauer",
      "authorRank" : 4,
      "name" : "Bauer S",
      "referenceId" : "RGD:A57292"
    }, {
      "firstName" : "T",
      "lastName" : "Spies",
      "authorRank" : 5,
      "name" : "Spies T",
      "referenceId" : "RGD:A57293"
    }, {
      "firstName" : "LL",
      "lastName" : "Lanier",
      "authorRank" : 6,
      "name" : "Lanier LL",
      "referenceId" : "RGD:A20385"
    }, {
      "firstName" : "JH",
      "lastName" : "Phillips",
      "authorRank" : 7,
      "name" : "Phillips JH",
      "referenceId" : "RGD:A43525"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556778"
    } ]
  }, {
    "primaryId" : "PMID:10427002",
    "title" : "Two-metal-Ion catalysis in adenylyl cyclase.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Tesmer JJ, etal., Science. 1999 Jul 30;285(5428):756-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-09-19T08:24:18.000-05:00",
    "volume" : "285",
    "pages" : "756-60",
    "abstract" : "Adenylyl cyclase (AC) converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate, a ubiquitous second messenger that regulates many cellular functions. Recent structural studies have revealed much about the structure and function of mammalian AC but have not fully defined its active site or catalytic  mechanism. Four crystal structures were determined of the catalytic domains of AC in complex with two different ATP analogs and various divalent metal ions. These  structures provide a model for the enzyme-substrate complex and conclusively demonstrate that two metal ions bind in the active site. The similarity of the active site of AC to those of DNA polymerases suggests that the enzymes catalyze  phosphoryl transfer by the same two-metal-ion mechanism and likely have evolved from a common ancestor.",
    "issueName" : "5428",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JJ",
      "lastName" : "Tesmer",
      "authorRank" : 1,
      "name" : "Tesmer JJ",
      "referenceId" : "RGD:A157885"
    }, {
      "firstName" : "RK",
      "lastName" : "Sunahara",
      "authorRank" : 2,
      "name" : "Sunahara RK",
      "referenceId" : "RGD:A6382"
    }, {
      "firstName" : "RA",
      "lastName" : "Johnson",
      "authorRank" : 3,
      "name" : "Johnson RA",
      "referenceId" : "RGD:A14053"
    }, {
      "firstName" : "G",
      "lastName" : "Gosselin",
      "authorRank" : 4,
      "name" : "Gosselin",
      "referenceId" : "RGD:A206088"
    }, {
      "firstName" : "AG",
      "lastName" : "Gilman",
      "authorRank" : 5,
      "name" : "Gilman AG",
      "referenceId" : "RGD:A6954"
    }, {
      "firstName" : "SR",
      "lastName" : "Sprang",
      "authorRank" : 6,
      "name" : "Sprang SR",
      "referenceId" : "RGD:A49715"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10400857"
    } ]
  }, {
    "primaryId" : "PMID:10427124",
    "title" : "Stromal expression of thrombospondin-1 is correlated with growth and metastasis of human gallbladder carcinoma.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Ohtani Y, etal., Int J Oncol. 1999 Sep;15(3):453-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-05-19T17:46:02.000-05:00",
    "volume" : "15",
    "pages" : "453-7",
    "abstract" : "Thrombospondin-1 (TSP1) is one of the extracellular matrix glycoproteins that affect cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we examined TSP1 expression in human gallbladder adenocarcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 74.5% (29/39) of the T2 and T3 gallbladder cancers were TSP1-positive, while none (0/14) of the T1 cancers showed TSP1 expression (p<0.001). Lymph node metastasis and venous involvement were frequently found in the TSP1-positive cases (90.0% and 87.1%, respectively) of gallbladder adenocarcinoma (p<0.001). These observations suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human gallbladder adenocarcinomas, and that stromal TSP1 immunoreactivity is a good predictor of vascular involvement and lymph node metastasis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Ohtani",
      "authorRank" : 1,
      "name" : "Ohtani Y",
      "referenceId" : "RGD:A32177"
    }, {
      "firstName" : "H",
      "lastName" : "Kijima",
      "authorRank" : 2,
      "name" : "Kijima H",
      "referenceId" : "RGD:A123095"
    }, {
      "firstName" : "S",
      "lastName" : "Dowaki",
      "authorRank" : 3,
      "name" : "Dowaki S",
      "referenceId" : "RGD:A123096"
    }, {
      "firstName" : "H",
      "lastName" : "Kashiwagi",
      "authorRank" : 4,
      "name" : "Kashiwagi H",
      "referenceId" : "RGD:A61493"
    }, {
      "firstName" : "K",
      "lastName" : "Tobita",
      "authorRank" : 5,
      "name" : "Tobita K",
      "referenceId" : "RGD:A123097"
    }, {
      "firstName" : "M",
      "lastName" : "Tsukui",
      "authorRank" : 6,
      "name" : "Tsukui M",
      "referenceId" : "RGD:A123540"
    }, {
      "firstName" : "Y",
      "lastName" : "Tanaka",
      "authorRank" : 7,
      "name" : "Tanaka Y",
      "referenceId" : "RGD:A10375"
    }, {
      "firstName" : "T",
      "lastName" : "Tsuchida",
      "authorRank" : 8,
      "name" : "Tsuchida T",
      "referenceId" : "RGD:A8228"
    }, {
      "firstName" : "T",
      "lastName" : "Tokunaga",
      "authorRank" : 9,
      "name" : "Tokunaga T",
      "referenceId" : "RGD:A44597"
    }, {
      "firstName" : "H",
      "lastName" : "Yamazaki",
      "authorRank" : 10,
      "name" : "Yamazaki H",
      "referenceId" : "RGD:A9875"
    }, {
      "firstName" : "M",
      "lastName" : "Nakamura",
      "authorRank" : 11,
      "name" : "Nakamura M",
      "referenceId" : "RGD:A295475"
    }, {
      "firstName" : "Y",
      "lastName" : "Ueyama",
      "authorRank" : 12,
      "name" : "Ueyama Y",
      "referenceId" : "RGD:A123099"
    }, {
      "firstName" : "M",
      "lastName" : "Tanaka",
      "authorRank" : 13,
      "name" : "Tanaka M",
      "referenceId" : "RGD:A159970"
    }, {
      "firstName" : "T",
      "lastName" : "Tajima",
      "authorRank" : 14,
      "name" : "Tajima T",
      "referenceId" : "RGD:A123543"
    }, {
      "firstName" : "H",
      "lastName" : "Makuuchi",
      "authorRank" : 15,
      "name" : "Makuuchi H",
      "referenceId" : "RGD:A123101"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2325029"
    } ]
  }, {
    "primaryId" : "PMID:10427606",
    "title" : "Effects of clozapine and haloperidol on 5-HT6 receptor mRNA levels in rat brain.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Frederick JA and Meador-Woodruff JH, Schizophr Res. 1999 Jul 27;38(1):7-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-10T12:53:25.000-06:00",
    "volume" : "38",
    "pages" : "7-12",
    "abstract" : "The high affinity of 5-HT6 receptors for atypical antipsychotic drugs, and their localization in limbic and cortical regions of the brain, suggest that they might play a role in the pathophysiology of schizophrenia. To determine if this receptor is regulated by antipsychotics, rats were injected with clozapine (20 mg/kg/day), haloperidol (2 mg/kg/day), or vehicle daily for 2 weeks, and 5-HT6 receptor mRNA levels were measured by in situ hybridization. Clozapine but not haloperidol significantly decreased 5-HT6 expression in all subfields of the hippocampus. No drug effects were observed in cortical or forebrain structures. These results suggest that downregulation of this receptor in the hippocampus might be a characteristic of atypical antipsychotic drugs, although this hypothesis will require testing with other atypical antipsychotics.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Frederick",
      "authorRank" : 1,
      "name" : "Frederick JA",
      "referenceId" : "RGD:A120204"
    }, {
      "firstName" : "JH",
      "lastName" : "Meador-Woodruff",
      "authorRank" : 2,
      "name" : "Meador-Woodruff JH",
      "referenceId" : "RGD:A101076"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317012"
    } ]
  }, {
    "primaryId" : "PMID:10427970",
    "title" : "Characteristics of the immunoglobulin Vkappa genes, pseudogenes, relics and orphons in the mouse genome.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Schable KF, etal., Eur J Immunol. 1999 Jul;29(7):2082-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-20T17:47:08.000-05:00",
    "volume" : "29",
    "pages" : "2082-6",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KF",
      "lastName" : "Schable",
      "authorRank" : 1,
      "name" : "Schable",
      "referenceId" : "RGD:A218626"
    }, {
      "firstName" : "R",
      "lastName" : "Thiebe",
      "authorRank" : 2,
      "name" : "Thiebe",
      "referenceId" : "RGD:A216791"
    }, {
      "firstName" : "A",
      "lastName" : "Bensch",
      "authorRank" : 3,
      "name" : "Bensch",
      "referenceId" : "RGD:A247157"
    }, {
      "firstName" : "J",
      "lastName" : "Brensing-Kuppers",
      "authorRank" : 4,
      "name" : "Brensing-Kuppers",
      "referenceId" : "RGD:A238217"
    }, {
      "firstName" : "V",
      "lastName" : "Heim",
      "authorRank" : 5,
      "name" : "Heim",
      "referenceId" : "RGD:A217288"
    }, {
      "firstName" : "T",
      "lastName" : "Kirschbaum",
      "authorRank" : 6,
      "name" : "Kirschbaum",
      "referenceId" : "RGD:A217284"
    }, {
      "firstName" : "R",
      "lastName" : "Lamm",
      "authorRank" : 7,
      "name" : "Lamm",
      "referenceId" : "RGD:A218627"
    }, {
      "firstName" : "M",
      "lastName" : "Ohnrich",
      "authorRank" : 8,
      "name" : "Ohnrich",
      "referenceId" : "RGD:A247158"
    }, {
      "firstName" : "S",
      "lastName" : "Pourrajabi",
      "authorRank" : 9,
      "name" : "Pourrajabi",
      "referenceId" : "RGD:A217285"
    }, {
      "firstName" : "F",
      "lastName" : "Roschenthaler",
      "authorRank" : 10,
      "name" : "Roschenthaler",
      "referenceId" : "RGD:A217289"
    }, {
      "firstName" : "J",
      "lastName" : "Schwendinger",
      "authorRank" : 11,
      "name" : "Schwendinger",
      "referenceId" : "RGD:A217287"
    }, {
      "firstName" : "D",
      "lastName" : "Wichelhaus",
      "authorRank" : 12,
      "name" : "Wichelhaus",
      "referenceId" : "RGD:A247159"
    }, {
      "firstName" : "I",
      "lastName" : "Zocher",
      "authorRank" : 13,
      "name" : "Zocher",
      "referenceId" : "RGD:A217286"
    }, {
      "firstName" : "HG",
      "lastName" : "Zachau",
      "authorRank" : 14,
      "name" : "Zachau",
      "referenceId" : "RGD:A216793"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11061253"
    } ]
  }, {
    "primaryId" : "PMID:10427979",
    "title" : "B cells are programmed to activate kappa and lambda for rearrangement at consecutive developmental stages.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Engel H, etal., Eur J Immunol. 1999 Jul;29(7):2167-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-29T19:31:50.000-05:00",
    "volume" : "29",
    "pages" : "2167-76",
    "abstract" : "Kappa and lambda, the two types of immunoglobulin light (L) chains present in mammals, contribute differently to the L chain pool of each species. Here we show that the extreme preponderance of kappa in the mouse results from programmed sequential activation of the kappa and lambda loci. Activation--a prerequisite of rearrangement--was monitored by analyzing transcription of unrearranged J-C clusters. Upon in vitro differentiation of a rearrangement-deficient pro/pre-B line, germ-line transcripts of the lambda J-C clusters, that are newly described  here, became detectable 2 days later than their counterparts of J-C kappa. Clear  differences could also be observed in vivo: germ-line transcripts of kappa were already present in large B220+ CD25+ pre B-II cells whereas germ-line lambda transcripts first became detectable at the consecutive developmental stage of small B220+ CD25+ pre-B-II cells. This activation pattern was found to be identical in mice which can not rearrange kappa due to a targeted deletion or inactivation of kappa. This suggests that pre-B-II cells follow a hit-and-run mechanism of development which includes programmed transitions and differential activation of the L chain loci, i.e. kappa first, then lambda. Thus, privileged activation of kappa might be the decisive factor in setting the 10:1 ratio of kappa to lambda present in the mouse.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Engel",
      "authorRank" : 1,
      "name" : "Engel H",
      "referenceId" : "RGD:A27109"
    }, {
      "firstName" : "A",
      "lastName" : "Rolink",
      "authorRank" : 2,
      "name" : "Rolink",
      "referenceId" : "RGD:A239065"
    }, {
      "firstName" : "S",
      "lastName" : "Weiss",
      "authorRank" : 3,
      "name" : "Weiss",
      "referenceId" : "RGD:A412748"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11340408"
    } ]
  }, {
    "primaryId" : "PMID:10428026",
    "title" : "The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Sternlicht MD, etal., Cell. 1999 Jul 23;98(2):137-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-26T15:58:43.000-05:00",
    "volume" : "98",
    "pages" : "137-46",
    "abstract" : "Matrix metalloproteinases (MMPs) are invariably upregulated in the stromal compartment of epithelial cancers and appear to promote invasion and metastasis.  Here we report that phenotypically normal mammary epithelial cells with tetracycline-regulated expression of MMP3/stromelysin-1 (Str1) form epithelial glandular structures in vivo without Str1 but form invasive mesenchymal-like tumors with Str1. Once initiated, the tumors become independent of continued Str1 expression. Str1 also promotes spontaneous premalignant changes and malignant conversion in mammary glands of transgenic mice. These changes are blocked by coexpression of a TIMP1 transgene. The premalignant and malignant lesions have stereotyped genomic changes unlike those seen in other murine mammary cancer models. These data indicate that Str1 influences tumor initiation and alters neoplastic risk.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MD",
      "lastName" : "Sternlicht",
      "authorRank" : 1,
      "name" : "Sternlicht",
      "referenceId" : "RGD:A190667"
    }, {
      "firstName" : "A",
      "lastName" : "Lochter",
      "authorRank" : 2,
      "name" : "Lochter",
      "referenceId" : "RGD:A190668"
    }, {
      "firstName" : "CJ",
      "lastName" : "Sympson",
      "authorRank" : 3,
      "name" : "Sympson",
      "referenceId" : "RGD:A190669"
    }, {
      "firstName" : "B",
      "lastName" : "Huey",
      "authorRank" : 4,
      "name" : "Huey B",
      "referenceId" : "RGD:A102948"
    }, {
      "firstName" : "JP",
      "lastName" : "Rougier",
      "authorRank" : 5,
      "name" : "Rougier",
      "referenceId" : "RGD:A167990"
    }, {
      "firstName" : "JW",
      "lastName" : "Gray",
      "authorRank" : 6,
      "name" : "Gray JW",
      "referenceId" : "RGD:A90949"
    }, {
      "firstName" : "D",
      "lastName" : "Pinkel",
      "authorRank" : 7,
      "name" : "Pinkel D",
      "referenceId" : "RGD:A24956"
    }, {
      "firstName" : "MJ",
      "lastName" : "Bissell",
      "authorRank" : 8,
      "name" : "Bissell",
      "referenceId" : "RGD:A180123"
    }, {
      "firstName" : "Z",
      "lastName" : "Werb",
      "authorRank" : 9,
      "name" : "Werb Z",
      "referenceId" : "RGD:A104849"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662909"
    } ]
  }, {
    "primaryId" : "PMID:10428031",
    "title" : "mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Kume K, etal., Cell 1999 Jul 23;98(2):193-205.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:44:02.000-05:00",
    "volume" : "98",
    "pages" : "193-205",
    "abstract" : "We determined that two mouse cryptochrome genes, mCry1 and mCry2, act in the negative limb of the clock feedback loop. In cell lines, mPER proteins (alone or in combination) have modest effects on their cellular location and ability to inhibit CLOCK:BMAL1 -mediated transcription. This suggested cryptochrome involvement in the negative limb of the feedback loop. Indeed, mCry1 and mCry2 RNA levels are reduced in the central and peripheral clocks of Clock/Clock mutant mice. mCRY1 and mCRY2 are nuclear proteins that interact with each of the mPER proteins, translocate each mPER protein from cytoplasm to nucleus, and are rhythmically expressed in the suprachiasmatic circadian clock. Luciferase reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E box-mediated transcription. The mPER and mCRY proteins appear to inhibit the transcriptional complex differentially.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Kume",
      "authorRank" : 1,
      "name" : "Kume K",
      "referenceId" : "RGD:A9627"
    }, {
      "firstName" : "MJ",
      "lastName" : "Zylka",
      "authorRank" : 2,
      "name" : "Zylka MJ",
      "referenceId" : "RGD:A39768"
    }, {
      "firstName" : "S",
      "lastName" : "Sriram",
      "authorRank" : 3,
      "name" : "Sriram S",
      "referenceId" : "RGD:A47573"
    }, {
      "firstName" : "LP",
      "lastName" : "Shearman",
      "authorRank" : 4,
      "name" : "Shearman LP",
      "referenceId" : "RGD:A47574"
    }, {
      "firstName" : "DR",
      "lastName" : "Weaver",
      "authorRank" : 5,
      "name" : "Weaver DR",
      "referenceId" : "RGD:A6978"
    }, {
      "firstName" : "X",
      "lastName" : "Jin",
      "authorRank" : 6,
      "name" : "Jin X",
      "referenceId" : "RGD:A47575"
    }, {
      "firstName" : "ES",
      "lastName" : "Maywood",
      "authorRank" : 7,
      "name" : "Maywood ES",
      "referenceId" : "RGD:A43477"
    }, {
      "firstName" : "MH",
      "lastName" : "Hastings",
      "authorRank" : 8,
      "name" : "Hastings MH",
      "referenceId" : "RGD:A43478"
    }, {
      "firstName" : "SM",
      "lastName" : "Reppert",
      "authorRank" : 9,
      "name" : "Reppert SM",
      "referenceId" : "RGD:A6980"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302864"
    } ]
  }, {
    "primaryId" : "PMID:10428045",
    "title" : "Prostate apoptosis response-4 mediates trophic factor withdrawal-induced apoptosis of hippocampal neurons: actions prior to mitochondrial dysfunction and  caspase activation.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Chan SL, etal., J Neurochem. 1999 Aug;73(2):502-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-03-18T10:43:52.000-05:00",
    "volume" : "73",
    "pages" : "502-12",
    "abstract" : "Prostate apoptosis response-4 (Par-4) is the product of a gene up-regulated in prostate cancer cells undergoing apoptosis. We now report that Par-4 mRNA and protein levels rapidly and progressively increase 4-24 h following trophic factor withdrawal (TFW) in cultured embryonic rat hippocampal neurons. The increased Par-4 levels follow an increase of reactive oxygen species, and precede mitochondrial membrane depolarization, caspase activation, and nuclear chromatin  condensation/fragmentation. Pretreatment of cultures with 17beta-estradiol, vitamin E, and uric acid largely prevented Par-4 induction and cell death following TFW, demonstrating necessary roles for oxidative stress and membrane lipid peroxidation in TFW-induced neuronal apoptosis. Par-4 antisense oligonucleotide treatment blocked Par-4 protein increases and attenuated mitochondrial dysfunction, caspase activation, and cell death following TFW. Collectively, our data identify Par-4 as an early and pivotal player in neuronal  apoptosis resulting from TFW and suggest that estrogen and antioxidants may prevent apoptosis, in part, by suppressing Par-4 production.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SL",
      "lastName" : "Chan",
      "authorRank" : 1,
      "name" : "Chan SL",
      "referenceId" : "RGD:A4926"
    }, {
      "firstName" : "SP",
      "lastName" : "Tammariello",
      "authorRank" : 2,
      "name" : "Tammariello SP",
      "referenceId" : "RGD:A115153"
    }, {
      "firstName" : "S",
      "lastName" : "Estus",
      "authorRank" : 3,
      "name" : "Estus S",
      "referenceId" : "RGD:A78008"
    }, {
      "firstName" : "MP",
      "lastName" : "Mattson",
      "authorRank" : 4,
      "name" : "Mattson MP",
      "referenceId" : "RGD:A8873"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9835341"
    } ]
  }, {
    "primaryId" : "PMID:10428057",
    "title" : "A proline- and glutamine-rich protein promotes apoptosis in neuronal cells.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Gomes I, etal., J Neurochem 1999 Aug;73(2):612-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-11T15:05:31.000-06:00",
    "volume" : "73",
    "pages" : "612-22",
    "abstract" : "During development, excess neurons are eliminated by programmed cell death. Similarly, conditionally immortalized (SV40-Tts) rat hippocampal and septal cells undergo cell death following differentiation with several factors such as fibroblast growth factor, constitutively activated Raf-1, or phorbol esters. The mechanism by which cell death occurs has not been identified. Using RNA differential display, we have identified and characterized a novel immediate early gene (denoted PQR for proline- and glutamine-rich) induced during differentiation of both rat hippocampal and septal cell lines. The 44-kDa PQR protein, rich in PQ, PH, and QQ repeats, is homologous to a murine protein (TDAG51) required for Fas-mediated apoptosis in T cells. To determine whether PQR acts as a mediator of apoptosis in neuronal cells, the hippocampal H19-7 cells were microinjected with either a plasmid expressing PQR cDNA or an antibody against PQR. Microinjection of differentiating H19-7 cells with a neutralizing antibody against PQR increased the number of surviving cells by 50%. Transient expression of PQR in both differentiating and nondifferentiating H19-7 cells decreased the number of surviving cells by 35-50%; this reduction was reversed by microinjection of PQR antibody. Finally, levels of Fas transcripts are not increased in the neuronal cells, indicating that the mechanism of action differs from that in T cells. These results demonstrate that PQR can be induced by growth factors and differentiating agents and can itself induce apoptosis in hippocampal H19-7 cells. Furthermore, these data suggest that PQR can function more generally as a mediator of apoptosis and provide a possible mechanism for induction of programmed cell death during neuronal development.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Gomes",
      "authorRank" : 1,
      "name" : "Gomes I",
      "referenceId" : "RGD:A8109"
    }, {
      "firstName" : "W",
      "lastName" : "Xiong",
      "authorRank" : 2,
      "name" : "Xiong W",
      "referenceId" : "RGD:A8110"
    }, {
      "firstName" : "T",
      "lastName" : "Miki",
      "authorRank" : 3,
      "name" : "Miki T",
      "referenceId" : "RGD:A4673"
    }, {
      "firstName" : "MR",
      "lastName" : "Rosner",
      "authorRank" : 4,
      "name" : "Rosner MR",
      "referenceId" : "RGD:A8111"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70034"
    } ]
  }, {
    "primaryId" : "PMID:10428310",
    "title" : "Lack of association between genetic variations of apo A-I-C-III-A-IV gene cluster and myocardial infarction in a sample of European male: ECTIM study.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kee F, etal., Atherosclerosis. 1999 Jul;145(1):187-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-23T15:54:00.000-06:00",
    "volume" : "145",
    "pages" : "187-95",
    "abstract" : "The goal of the present study was to compare the allele frequency of four polymorphisms at the apo A-I C-III A-IV cluster gene locus-ApoA-I: XmnI and PstI; ApoC-III: SstI; ApoA-IV: XbaI-between male patients who had had a myocardial infarction (n= 614) and matched controls (n = 764). The association with a number of lipid lipoprotein, apolipoprotein and lipoprotein particle variables was also assessed. Patients and subjects were recruited in Belfast, Lille, Strasbourg and Toulouse in the framework of the ECTIM study. In the control group, the frequencies of the different polymorphic alleles were homogeneous among recruitment centres suggesting the absence of any European North to South gradient for these cluster polymorphisms. There was no evidence for a significant difference in allelic distribution between cases and controls suggesting that apo A-I, C-III, A-IV gene cluster polymorphisms do not explain MI survival in this sample of European men. There was no statistically significant association between apo A-I C-III A-IV cluster gene polymorphisms and lipid, lipoprotein, apolipoprotein, and lipoprotein particle levels. In conclusion, in the ECTIM study, the apo A-I, C-III, A-IV gene cluster polymorphism is associated with neither circulating plasma variables nor MI survival.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Kee",
      "authorRank" : 1,
      "name" : "Kee F",
      "referenceId" : "RGD:A59000"
    }, {
      "firstName" : "P",
      "lastName" : "Amouyel",
      "authorRank" : 2,
      "name" : "Amouyel P",
      "referenceId" : "RGD:A39171"
    }, {
      "firstName" : "F",
      "lastName" : "Fumeron",
      "authorRank" : 3,
      "name" : "Fumeron F",
      "referenceId" : "RGD:A59001"
    }, {
      "firstName" : "D",
      "lastName" : "Arveiler",
      "authorRank" : 4,
      "name" : "Arveiler D",
      "referenceId" : "RGD:A59002"
    }, {
      "firstName" : "JP",
      "lastName" : "Cambou",
      "authorRank" : 5,
      "name" : "Cambou JP",
      "referenceId" : "RGD:A59003"
    }, {
      "firstName" : "A",
      "lastName" : "Evans",
      "authorRank" : 6,
      "name" : "Evans A",
      "referenceId" : "RGD:A59004"
    }, {
      "firstName" : "F",
      "lastName" : "Cambien",
      "authorRank" : 7,
      "name" : "Cambien F",
      "referenceId" : "RGD:A59005"
    }, {
      "firstName" : "JC",
      "lastName" : "Fruchart",
      "authorRank" : 8,
      "name" : "Fruchart JC",
      "referenceId" : "RGD:A16018"
    }, {
      "firstName" : "P",
      "lastName" : "Ducimetiere",
      "authorRank" : 9,
      "name" : "Ducimetiere P",
      "referenceId" : "RGD:A39169"
    }, {
      "firstName" : "J",
      "lastName" : "Dallongeville",
      "authorRank" : 10,
      "name" : "Dallongeville J",
      "referenceId" : "RGD:A36012"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578442"
    } ]
  }, {
    "primaryId" : "PMID:10428430",
    "title" : "Mutation analysis in Emery-Dreifuss muscular dystrophy.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Nevo Y, etal., Pediatr Neurol. 1999 Jul;21(1):456-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:56:39.000-05:00",
    "volume" : "21",
    "pages" : "456-9",
    "abstract" : "The purpose of this study was to search for STA gene defects in three families with clinically typical Emery-Dreifuss muscular dystrophy. Emery-Dreifuss is an X-linked muscular dystrophy with humeroperoneal weakness and life-threatening, but treatable, cardiac abnormalities in male patients and in female carriers. The defect is in the gene coding for emerin, a 254 amino acid protein of unknown function. Complementary and genomic DNA from T lymphocytes from the reported patients and their family members were amplified, cloned, and sequenced. A novel  mutation, a 26 base-pair deletion in three brothers and a carrier mother, was detected in one family. A splicing mutation with one base pair insertion and a five base-pair deletion, which have been described previously, were found in the  second and third families, respectively. The additional novel mutation detected and the findings of three different mutations in these three families support the idea of genetic heterogeneity of Emery-Dreifuss muscular dystrophy with different mutations in different families.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Nevo",
      "authorRank" : 1,
      "name" : "Nevo",
      "referenceId" : "RGD:A238483"
    }, {
      "firstName" : "M",
      "lastName" : "Al-Lozi",
      "authorRank" : 2,
      "name" : "Al-Lozi",
      "referenceId" : "RGD:A280299"
    }, {
      "firstName" : "AS",
      "lastName" : "Parsadanian",
      "authorRank" : 3,
      "name" : "Parsadanian",
      "referenceId" : "RGD:A280300"
    }, {
      "firstName" : "JL",
      "lastName" : "Elliott",
      "authorRank" : 4,
      "name" : "Elliott JL",
      "referenceId" : "RGD:A152886"
    }, {
      "firstName" : "AM",
      "lastName" : "Connolly",
      "authorRank" : 5,
      "name" : "Connolly",
      "referenceId" : "RGD:A252341"
    }, {
      "firstName" : "A",
      "lastName" : "Pestronk",
      "authorRank" : 6,
      "name" : "Pestronk A",
      "referenceId" : "RGD:A74958"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071737"
    } ]
  }, {
    "primaryId" : "PMID:10428808",
    "title" : "Isolation and characterization of ARA160 as the first androgen receptor N-terminal-associated coactivator in human prostate cells.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Hsiao PW and Chang C, J Biol Chem 1999 Aug 6;274(32):22373-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-22T15:29:53.000-05:00",
    "volume" : "274",
    "pages" : "22373-9",
    "abstract" : "The androgen receptor (AR) is a member of the steroid receptor superfamily that may require coactivators for proper or maximal transactivation. Using a purified AR N-terminal peptide as a probe to screen the human testis expression library, we identified an androgen-enhanced AR N-terminal-associated protein ARA160, which consists of 1,093 amino acids with an apparent molecular mass of 160 kDa. Sequence comparison in GenBank(TM) reveals that ARA160 shares an identical sequence with a HIV-1 TATA element modulatory factor, TMF. The far-Western blotting and co-immunoprecipitation assays demonstrate that the AR can interact directly with ARA160/TMF. Affinity gel pull-down and mammalian two-hybrid assays further suggest androgen can enhance significantly the interaction between AR and ARA160. Transient transfection assays demonstrated that ARA160 might function as a coactivator for AR-mediated transactivation in human prostate cancer PC-3 cells. Our data further suggest that this AR N-terminal coactivator can function cooperatively with AR C-terminal coactivator, ARA70, in PC-3 cells. Together, our data demonstrate that ARA160 might represent the first identified androgen-enhanced N-terminal coactivator for the AR.",
    "issueName" : "32",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PW",
      "lastName" : "Hsiao",
      "authorRank" : 1,
      "name" : "Hsiao PW",
      "referenceId" : "RGD:A26933"
    }, {
      "firstName" : "C",
      "lastName" : "Chang",
      "authorRank" : 2,
      "name" : "Chang C",
      "referenceId" : "RGD:A23824"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:724782"
    } ]
  }, {
    "primaryId" : "PMID:10428811",
    "title" : "A tyrosine-phosphorylated protein that binds to an important regulatory region on the cool family of p21-activated kinase-binding proteins.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Bagrodia S, etal., J Biol Chem 1999 Aug 6;274(32):22393-400.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-02T14:14:09.000-05:00",
    "volume" : "274",
    "pages" : "22393-400",
    "abstract" : "The p21-activated kinases (Pak) are major targets of the small GTPases Cdc42 and Rac. We, and others, recently identified a family of proteins termed Cool/Pix, which interact with Pak3. In cells, p50(Cool-1) suppresses Pak activation by upstream activators; p85(Cool-1) has a permissive effect on Pak activation, and we now show that the closely related Cool-2 stimulates Pak kinase activity. To understand the differential regulation of Pak by Cool proteins, we screened for Cool-interacting proteins by affinity purification and microsequencing. This has led to the identification of two closely related proteins called Cat (Cool-associated, tyrosine phosphorylated), which contain a zinc finger followed by three ankyrin repeats. Cat-1 is identical to the recently identified binding partner for the beta-adrenergic receptor kinase (betaARK or GRK-2), which was shown to have Arf-GAP activity. Cat-1 and Cat-2 both bind to the COOH-terminal region of p85(Cool-1) and p85(Cool-2) but do not bind to p50(Cool-1). Cat-1 is tyrosine-phosphorylated in growing NIH 3T3 fibroblasts, and its tyrosine phosphorylation is increased following cell spreading on fibronectin, decreased in cells arrested in mitosis, and increased in the ensuing G(1) phase. Cat proteins are tyrosine-phosphorylated when co-expressed in cells with the focal adhesion kinase Fak and Src. These findings suggest that in addition to playing a role in Cool/Pak interactions, Cat proteins may serve as points of convergence between G protein-coupled receptors, integrins, Arf GTPases, cell cycle regulators, and Cdc42/Rac/Pak signaling pathways.",
    "issueName" : "32",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Bagrodia",
      "authorRank" : 1,
      "name" : "Bagrodia S",
      "referenceId" : "RGD:A55513"
    }, {
      "firstName" : "D",
      "lastName" : "Bailey",
      "authorRank" : 2,
      "name" : "Bailey D",
      "referenceId" : "RGD:A55514"
    }, {
      "firstName" : "Z",
      "lastName" : "Lenard",
      "authorRank" : 3,
      "name" : "Lenard Z",
      "referenceId" : "RGD:A55515"
    }, {
      "firstName" : "M",
      "lastName" : "Hart",
      "authorRank" : 4,
      "name" : "Hart M",
      "referenceId" : "RGD:A55516"
    }, {
      "firstName" : "JL",
      "lastName" : "Guan",
      "authorRank" : 5,
      "name" : "Guan JL",
      "referenceId" : "RGD:A30350"
    }, {
      "firstName" : "RT",
      "lastName" : "Premont",
      "authorRank" : 6,
      "name" : "Premont RT",
      "referenceId" : "RGD:A151579"
    }, {
      "firstName" : "SJ",
      "lastName" : "Taylor",
      "authorRank" : 7,
      "name" : "Taylor SJ",
      "referenceId" : "RGD:A55518"
    }, {
      "firstName" : "RA",
      "lastName" : "Cerione",
      "authorRank" : 8,
      "name" : "Cerione RA",
      "referenceId" : "RGD:A55519"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549595"
    } ]
  }, {
    "primaryId" : "PMID:10428823",
    "title" : "DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Nakamura T, etal., J Biol Chem 1999 Aug 6;274(32):22476-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:04.000-06:00",
    "volume" : "274",
    "pages" : "22476-83",
    "abstract" : "We have identified and characterized mouse, rat, and human cDNAs that encode a novel secreted protein of 448 amino acids named DANCE (developmental arteries and neural crest epidermal growth factor (EGF)-like). DANCE contains six calcium-binding EGF-like domains, one of which includes an RGD motif. Overexpression studies of recombinant DANCE protein document that DANCE is a secreted 66-kDa protein. DANCE and recently described protein S1-5 comprise a new EGF-like protein family. The human DANCE gene was mapped at chromosome 14q32.1. DANCE mRNA is mainly expressed in heart, ovary, and colon in adult human tissues. Expression profile analysis by in situ hybridization revealed prominent DANCE expression in developing arteries. DANCE is also expressed in neural crest cell derivatives, endocardial cushion tissue, and several other mesenchymal tissues. In adult vessels, DANCE expression is largely diminished but is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells that lose their ability to proliferate in late stage of injury. DANCE protein was shown to promote adhesion of endothelial cells through interaction of integrins and the RGD motif of DANCE. DANCE is thus a novel vascular ligand for integrin receptors and may play a role in vascular development and remodeling.",
    "issueName" : "32",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Nakamura",
      "authorRank" : 1,
      "name" : "Nakamura T",
      "referenceId" : "RGD:A158959"
    }, {
      "firstName" : "P",
      "lastName" : "Ruiz-Lozano",
      "authorRank" : 2,
      "name" : "Ruiz-Lozano P",
      "referenceId" : "RGD:A7316"
    }, {
      "firstName" : "V",
      "lastName" : "Lindner",
      "authorRank" : 3,
      "name" : "Lindner V",
      "referenceId" : "RGD:A7317"
    }, {
      "firstName" : "D",
      "lastName" : "Yabe",
      "authorRank" : 4,
      "name" : "Yabe D",
      "referenceId" : "RGD:A7318"
    }, {
      "firstName" : "M",
      "lastName" : "Taniwaki",
      "authorRank" : 5,
      "name" : "Taniwaki M",
      "referenceId" : "RGD:A7319"
    }, {
      "firstName" : "Y",
      "lastName" : "Furukawa",
      "authorRank" : 6,
      "name" : "Furukawa Y",
      "referenceId" : "RGD:A7320"
    }, {
      "firstName" : "K",
      "lastName" : "Kobuke",
      "authorRank" : 7,
      "name" : "Kobuke K",
      "referenceId" : "RGD:A7321"
    }, {
      "firstName" : "K",
      "lastName" : "Tashiro",
      "authorRank" : 8,
      "name" : "Tashiro K",
      "referenceId" : "RGD:A4602"
    }, {
      "firstName" : "Z",
      "lastName" : "Lu",
      "authorRank" : 9,
      "name" : "Lu Z",
      "referenceId" : "RGD:A161102"
    }, {
      "firstName" : "NL",
      "lastName" : "Andon",
      "authorRank" : 10,
      "name" : "Andon NL",
      "referenceId" : "RGD:A7322"
    }, {
      "firstName" : "R",
      "lastName" : "Schaub",
      "authorRank" : 11,
      "name" : "Schaub R",
      "referenceId" : "RGD:A7323"
    }, {
      "firstName" : "A",
      "lastName" : "Matsumori",
      "authorRank" : 12,
      "name" : "Matsumori A",
      "referenceId" : "RGD:A7324"
    }, {
      "firstName" : "S",
      "lastName" : "Sasayama",
      "authorRank" : 13,
      "name" : "Sasayama S",
      "referenceId" : "RGD:A7325"
    }, {
      "firstName" : "KR",
      "lastName" : "Chien",
      "authorRank" : 14,
      "name" : "Chien KR",
      "referenceId" : "RGD:A7326"
    }, {
      "firstName" : "T",
      "lastName" : "Honjo",
      "authorRank" : 15,
      "name" : "Honjo T",
      "referenceId" : "RGD:A7327"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69830"
    } ]
  }, {
    "primaryId" : "PMID:10428857",
    "title" : "Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Peng JB, etal., J Biol Chem 1999 Aug 6;274(32):22739-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:56.000-05:00",
    "volume" : "274",
    "pages" : "22739-46",
    "abstract" : "Calcium is a major component of the mineral phase of bone and serves as a key intracellular second messenger. Postnatally, all bodily calcium must be absorbed from the diet through the intestine. Here we report the properties of a calcium transport protein (CaT1) cloned from rat duodenum using an expression cloning strategy in Xenopus laevis oocytes, which likely plays a key role in the intestinal uptake of calcium. CaT1 shows homology (75% amino acid sequence identity) to the apical calcium channel ECaC recently cloned from vitamin D-responsive cells of rabbit kidney and is structurally related to the capsaicin receptor and the TRP family of ion channels. Based on Northern analysis of rat tissues, a 3-kilobase CaT1 transcript is present in rat duodenum, proximal jejunum, cecum, and colon, and a 6.5-kilobase transcript is present in brain, thymus, and adrenal gland. In situ hybridization revealed strong CaT1 mRNA expression in enterocytes of duodenum, proximal jejunum, and cecum. No signals were detected in kidney, heart, liver, lung, spleen, and skeletal muscle. When expressed in Xenopus oocytes, CaT1 mediates saturable Ca(2+) uptake with a Michaelis constant of 0.44 mM. Transport of Ca(2+) by CaT1 is electrogenic, voltage-dependent, and exhibits a charge/Ca(2+) uptake ratio close to 2:1, indicating that CaT1-mediated Ca(2+) influx is not coupled to other ions. CaT1 activity is pH-sensitive, exhibiting significant inhibition by low pH. CaT1 is also permeant to Sr(2+) and Ba(2+) (but not Mg(2+)), although the currents evoked by Sr(2+) and Ba(2+) are much smaller than those evoked by Ca(2+). The trivalent cations Gd(3+) and La(3+) and the divalent cations Cu(2+), Pb(2+), Cd(2+), Co(2+), and Ni(2+) (each at 100 microM) do not evoke currents themselves, but inhibit CaT1-mediated Ca(2+) transport. Fe(3+), Fe(2+), Mn(2+), and Zn(2+) have no significant effects at 100 microM on CaT1-mediated Ca(2+) transport. CaT1 mRNA levels are not responsive to 1,25-dihydroxyvitamin D(3) administration or to calcium deficiency. Our studies strongly suggest that CaT1 provides the principal mechanism for Ca(2+) entry into enterocytes as part of the transcellular pathway of calcium absorption in the intestine.",
    "issueName" : "32",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JB",
      "lastName" : "Peng",
      "authorRank" : 1,
      "name" : "Peng JB",
      "referenceId" : "RGD:A6023"
    }, {
      "firstName" : "XZ",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen XZ",
      "referenceId" : "RGD:A159956"
    }, {
      "firstName" : "UV",
      "lastName" : "Berger",
      "authorRank" : 3,
      "name" : "Berger UV",
      "referenceId" : "RGD:A63295"
    }, {
      "firstName" : "PM",
      "lastName" : "Vassilev",
      "authorRank" : 4,
      "name" : "Vassilev PM",
      "referenceId" : "RGD:A6025"
    }, {
      "firstName" : "H",
      "lastName" : "Tsukaguchi",
      "authorRank" : 5,
      "name" : "Tsukaguchi H",
      "referenceId" : "RGD:A23434"
    }, {
      "firstName" : "EM",
      "lastName" : "Brown",
      "authorRank" : 6,
      "name" : "Brown EM",
      "referenceId" : "RGD:A6027"
    }, {
      "firstName" : "MA",
      "lastName" : "Hediger",
      "authorRank" : 7,
      "name" : "Hediger MA",
      "referenceId" : "RGD:A63297"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68825"
    } ]
  }, {
    "primaryId" : "PMID:10428862",
    "title" : "Independent SH2-binding sites mediate interaction of Dok-related protein with RasGTPase-activating protein and Nck.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Lock P, etal., J Biol Chem. 1999 Aug 6;274(32):22775-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T13:47:11.000-05:00",
    "volume" : "274",
    "pages" : "22775-84",
    "abstract" : "A murine embryonic cDNA library was screened for potential substrates of the Src  family kinase, Lyn, using a phosphorylation-screening strategy. One cDNA that we  identified encodes Dok-related protein (DokR), a protein with homology to p62(dok) (Dok), and members of the insulin receptor substrate-1 family of proteins. Analysis of murine tissue extracts with DokR-specific antisera revealed that DokR protein is expressed at highest levels in lymphoid tissues. Co-expression of a FLAG epitope-tagged form of DokR (FLAG-DokR) with Lyn in embryonic kidney 293T cells resulted in constitutive phosphorylation of FLAG-DokR on tyrosine residues and consequential physical association with RasGTPase-activating protein (GAP) and the Nck adaptor protein. Stimulation of BaF/3 hematopoietic cells co-expressing the epidermal growth factor (EGF) receptor tyrosine kinase and FLAG-DokR with EGF also induced phosphorylation of FLAG-DokR and promoted its association with GAP. Immunoprecipitation experiments  using DokR-specific antibodies revealed an interaction between endogenous DokR and a 150-kDa protein that is tyrosine-phosphorylated in EGF-stimulated BaF/3 cells. The molecular basis of the interactions involving DokR with GAP and Nck was investigated using a novel glutathione S-transferase fusion protein binding assay and/or site-directed mutagenesis. Tandem SH2-binding sites containing Tyr-276 and Tyr-304 were shown to mediate binding of DokR to GAP, whereas Tyr-351 mediated the binding of DokR to Nck. These results suggest that DokR participates in numerous signaling pathways.",
    "issueName" : "32",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Lock",
      "authorRank" : 1,
      "name" : "Lock P",
      "referenceId" : "RGD:A41568"
    }, {
      "firstName" : "F",
      "lastName" : "Casagranda",
      "authorRank" : 2,
      "name" : "Casagranda",
      "referenceId" : "RGD:A224372"
    }, {
      "firstName" : "AR",
      "lastName" : "Dunn",
      "authorRank" : 3,
      "name" : "Dunn AR",
      "referenceId" : "RGD:A41573"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11053953"
    } ]
  }, {
    "primaryId" : "PMID:10428863",
    "title" : "AP180 and AP-2 interact directly in a complex that cooperatively assembles clathrin.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Hao W, etal., J Biol Chem. 1999 Aug 6;274(32):22785-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:33:21.000-05:00",
    "volume" : "274",
    "pages" : "22785-94",
    "abstract" : "Clathrin-coated vesicles are involved in protein and lipid trafficking between intracellular compartments in eukaryotic cells. AP-2 and AP180 are the resident coat proteins of clathrin-coated vesicles in nerve terminals, and interactions between these proteins could be important in vesicle dynamics. AP180 and AP-2 each assemble clathrin efficiently under acidic conditions, but neither protein will assemble clathrin efficiently at physiological pH. We find that there is a direct, clathrin-independent interaction between AP180 and AP-2 and that the AP180-AP-2 complex is more efficient at assembling clathrin under physiological conditions than is either protein alone. AP180 is phosphorylated in vivo, and in  crude vesicle extracts its phosphorylation is enhanced by stimulation of casein kinase II, which is known to be present in coated vesicles. We find that recombinant AP180 is a substrate for casein kinase II in vitro and that its phosphorylation weakens both the binding of AP-2 by AP180 and the cooperative clathrin assembly activity of these proteins. We have localized the binding site  for AP-2 to amino acids 623-680 of AP180. The AP180/AP-2 interaction can be disrupted by a recombinant AP180 fragment containing the AP-2 binding site, and this fragment also disrupts the cooperative clathrin assembly activity of the AP180-AP-2 complex. These results indicate that AP180 and AP-2 interact directly  to form a complex that assembles clathrin more efficiently than either protein alone. Phosphorylation of AP180, by modulating the affinity of AP180 for AP-2, may contribute to the regulation of clathrin assembly in vivo.",
    "issueName" : "32",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "W",
      "lastName" : "Hao",
      "authorRank" : 1,
      "name" : "Hao W",
      "referenceId" : "RGD:A15126"
    }, {
      "firstName" : "Z",
      "lastName" : "Luo",
      "authorRank" : 2,
      "name" : "Luo Z",
      "referenceId" : "RGD:A26226"
    }, {
      "firstName" : "L",
      "lastName" : "Zheng",
      "authorRank" : 3,
      "name" : "Zheng L",
      "referenceId" : "RGD:A18139"
    }, {
      "firstName" : "K",
      "lastName" : "Prasad",
      "authorRank" : 4,
      "name" : "Prasad K",
      "referenceId" : "RGD:A117826"
    }, {
      "firstName" : "EM",
      "lastName" : "Lafer",
      "authorRank" : 5,
      "name" : "Lafer",
      "referenceId" : "RGD:A184046"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553466"
    } ]
  }, {
    "primaryId" : "PMID:10428953",
    "title" : "Stilbenes and fenamates rescue the loss of I(KS) channel function induced by an LQT5 mutation and other IsK mutants.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Abitbol I, etal., EMBO J. 1999 Aug 2;18(15):4137-48.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:14:44.000-05:00",
    "volume" : "18",
    "pages" : "4137-48",
    "abstract" : "Genetic and physiological studies have established a link between potassium channel dysfunction and a number of neurological and muscular disorders. Many 'channelopathies' are accounted for by a dominant-lethal suppression of potassium channel function. In the cardiac I(KS) channel complex comprising the alpha and beta subunits, KvLQT1 and IsK, respectively, several mutations lead to a dominant-negative loss of channel function. These defects are responsible for a human cardiovascular disease called long QT (LQT) syndrome. Here we show that binding of I(KS) channel activators, such as stilbenes and fenamates, to an extracellular domain flanking the human IsK transmembrane segment, restores normal I(KS) channel gating in otherwise inactive IsK C-terminal mutants, including the naturally occurring LQT5 mutant, D76N. Our data support a model in  which allosteric interactions exist between the extracellular and intracellular boundaries of the IsK transmembrane segment as well as between domains of the alpha and beta subunits. Disruption of this allosteric interplay impedes slow activation gating, decreases current amplitude and restores channel inactivation. Owing to allosteric interactions, stilbene and fenamate compounds can rescue the  dominant-negative suppression of I(KS) produced by IsK mutations and thus, may have important therapeutic relevance for LQT syndrome.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Abitbol",
      "authorRank" : 1,
      "name" : "Abitbol",
      "referenceId" : "RGD:A256243"
    }, {
      "firstName" : "A",
      "lastName" : "Peretz",
      "authorRank" : 2,
      "name" : "Peretz",
      "referenceId" : "RGD:A256244"
    }, {
      "firstName" : "C",
      "lastName" : "Lerche",
      "authorRank" : 3,
      "name" : "Lerche",
      "referenceId" : "RGD:A256245"
    }, {
      "firstName" : "AE",
      "lastName" : "Busch",
      "authorRank" : 4,
      "name" : "Busch AE",
      "referenceId" : "RGD:A18087"
    }, {
      "firstName" : "B",
      "lastName" : "Attali",
      "authorRank" : 5,
      "name" : "Attali B",
      "referenceId" : "RGD:A10023"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063758"
    } ]
  }, {
    "primaryId" : "PMID:10429205",
    "title" : "Activation of the ubiquitin proteolytic system in murine acquired immunodeficiency syndrome affects IkappaBalpha turnover.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Crinelli R, etal., Eur J Biochem. 1999 Jul;263(1):202-11. doi: 10.1046/j.1432-1327.1999.00485.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-06-16T10:05:08.000-05:00",
    "volume" : "263",
    "pages" : "202-11",
    "abstract" : "Murine acquired immunodeficiency syndrome (MAIDS) is a complex immunopathology caused by a defective murine leukemia virus (LP-BM5) that mainly targets B-lymphocytes. Lymphadenophathy, splenomegaly, hypergammaglobulinemia and progressive immunodeficiency are prominent features of MAIDS. Previously, we showed that the ubiquitin proteolytic system was upregulated in infected lymph nodes [Crinelli, R., Fraternale, A., Casabianca, A. & Magnani, M. (1997) Eur. J. Biochem. 247, 91-97]. In this report, we demonstrate that increased 26S proteasome activity is responsible for accelerated turnover of the IkappaBalpha inhibitor in lymph node extracts derived from animals with MAIDS. The molecular mechanisms mediating IkappaBalpha proteolysis involved constitutive phosphorylation of IkappaBalpha at Ser32 and Ser36 and subsequent ubiquitination, suggesting persistent activation of an NF-kappaB inducing pathway. Interestingly, enhanced IkappaBalpha degradation did not result in enhanced NF-kappaB DNA binding activity, but rather in a different subunit composition. The modulation of NF-kappaB/IkappaB system may affect multiple immunoregulatory pathways and may in part explain the mechanisms leading to the profound immune dysregulation involved in MAIDS pathogenesis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Crinelli",
      "authorRank" : 1,
      "name" : "Crinelli R",
      "referenceId" : "RGD:A500827"
    }, {
      "firstName" : "M",
      "lastName" : "Bianchi",
      "authorRank" : 2,
      "name" : "Bianchi M",
      "referenceId" : "RGD:A40827"
    }, {
      "firstName" : "L",
      "lastName" : "Gentilini",
      "authorRank" : 3,
      "name" : "Gentilini L",
      "referenceId" : "RGD:A500828"
    }, {
      "firstName" : "M",
      "lastName" : "Magnani",
      "authorRank" : 4,
      "name" : "Magnani M",
      "referenceId" : "RGD:A81282"
    }, {
      "firstName" : "J",
      "lastName" : "Hiscott",
      "authorRank" : 5,
      "name" : "Hiscott J",
      "referenceId" : "RGD:A500829"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:127285021"
    } ]
  }, {
    "primaryId" : "PMID:10429654",
    "title" : "Mutational analysis of STK11 gene in ovarian carcinomas.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Nishioka Y, etal., Jpn J Cancer Res. 1999 Jun;90(6):629-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-07-10T17:11:22.000-05:00",
    "volume" : "90",
    "pages" : "629-32",
    "abstract" : "Recently STK11, the causative gene of Peutz-Jeghers syndrome (PJS) was identified on chromosome 19p13.3. PJS is often accompanied by several malignancies, including breast tumor, adenoma malignum of the uterine cervix, and ovarian tumor. To investigate the involvement of STK11 gene in the development of ovarian carcinomas, we analyzed 30 ovarian carcinomas for loss of heterozygosity (LOH) and STK11 gene mutations. We found one missense mutation (codon 281, Pro to Leu) with heterozygous and somatic status. This mutation occurred at codon 281, which lies within the mutational hot spot (codon 279-281) of STK11 gene previously reported in PJS. We also detected LOH in 2 (11%) of 19 informative ovarian carcinomas. Our results suggest that mutations of the STK11 gene may play a limited role in the development of ovarian carcinomas.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Nishioka",
      "authorRank" : 1,
      "name" : "Nishioka Y",
      "referenceId" : "RGD:A97845"
    }, {
      "firstName" : "K",
      "lastName" : "Kobayashi",
      "authorRank" : 2,
      "name" : "Kobayashi K",
      "referenceId" : "RGD:A314641"
    }, {
      "firstName" : "S",
      "lastName" : "Sagae",
      "authorRank" : 3,
      "name" : "Sagae S",
      "referenceId" : "RGD:A97847"
    }, {
      "firstName" : "M",
      "lastName" : "Sugimura",
      "authorRank" : 4,
      "name" : "Sugimura M",
      "referenceId" : "RGD:A97848"
    }, {
      "firstName" : "S",
      "lastName" : "Ishioka",
      "authorRank" : 5,
      "name" : "Ishioka S",
      "referenceId" : "RGD:A97849"
    }, {
      "firstName" : "M",
      "lastName" : "Nagata",
      "authorRank" : 6,
      "name" : "Nagata M",
      "referenceId" : "RGD:A5370"
    }, {
      "firstName" : "K",
      "lastName" : "Terasawa",
      "authorRank" : 7,
      "name" : "Terasawa K",
      "referenceId" : "RGD:A82135"
    }, {
      "firstName" : "T",
      "lastName" : "Tokino",
      "authorRank" : 8,
      "name" : "Tokino T",
      "referenceId" : "RGD:A6252"
    }, {
      "firstName" : "R",
      "lastName" : "Kudo",
      "authorRank" : 9,
      "name" : "Kudo R",
      "referenceId" : "RGD:A97850"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2298556"
    } ]
  }, {
    "primaryId" : "PMID:10430032",
    "title" : "Localization of rat cathepsin K in osteoclasts and resorption pits: inhibition of bone resorption and cathepsin K-activity by peptidyl vinyl sulfones.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Xia L, etal., Biol Chem. 1999 Jun;380(6):679-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-04T09:55:10.000-05:00",
    "volume" : "380",
    "pages" : "679-87",
    "abstract" : "We have localized cathepsin K in rat osteoclasts and within exposed resorption pits by immuno-fluorescence microscopy. Intracellular staining using an antibody raised against recombinant mouse cathepsin K was vesicular and uniformly distributed throughout the cell. Confocal microscopy analysis did not reveal an accumulation of cathepsin K containing vesicles opposing the ruffled border and the resorption lacuna. Exposed resorption pits exhibited a uniform distribution of cathepsin K, and no differences were observed between the edges and the centers of the pits. The immunostaining of resorption pits with anti-cathepsin K antibodies demonstrates that the protease is secreted into the sub-osteoclastic compartment. Cathepsin K-specific inhibition using peptidyl vinyl sulfones as selective cysteine protease inactivators reduced bone resorption by 80% in a dose-dependent manner at sub-micromolar concentrations. No reduction of bone resorption was observed at those low concentrations using a potent cathepsin L, S, B-specific inhibitor. That the inhibition of bone resorption can be attributed to cathepsin K-like protease inhibition was corroborated by the selective inhibition of the osteoclastic Z-Gly-Pro-Arg-MbetaNA hydrolyzing activity by the cathepsin K, L, S, B-inhibitor, but not by the cathepsin L, B, and S inhibitor. Z-Gly-Pro-Arg-MbetaNA is efficiently hydrolyzed by cathepsin K but only poorly by cathepsins L, S, and B. On the contrary, the intracellular hydrolysis of the cathepsin B-specific substrate, Z-Arg-Arg-MbetaNA, was prevented by both types of inhibitors. The identification of cathepsin K in resorption pits and the inhibition of bone resorption and intracellular cathepsin K activity by selective vinyl sulfone inhibitors indicate the critical role of the protease in osteoclastic bone resorption.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Xia",
      "authorRank" : 1,
      "name" : "Xia L",
      "referenceId" : "RGD:A23760"
    }, {
      "firstName" : "J",
      "lastName" : "Kilb",
      "authorRank" : 2,
      "name" : "Kilb J",
      "referenceId" : "RGD:A79330"
    }, {
      "firstName" : "H",
      "lastName" : "Wex",
      "authorRank" : 3,
      "name" : "Wex H",
      "referenceId" : "RGD:A7107"
    }, {
      "firstName" : "Z",
      "lastName" : "Li",
      "authorRank" : 4,
      "name" : "Li Z",
      "referenceId" : "RGD:A17098"
    }, {
      "firstName" : "A",
      "lastName" : "Lipyansky",
      "authorRank" : 5,
      "name" : "Lipyansky A",
      "referenceId" : "RGD:A51705"
    }, {
      "firstName" : "V",
      "lastName" : "Breuil",
      "authorRank" : 6,
      "name" : "Breuil V",
      "referenceId" : "RGD:A79331"
    }, {
      "firstName" : "L",
      "lastName" : "Stein",
      "authorRank" : 7,
      "name" : "Stein L",
      "referenceId" : "RGD:A79332"
    }, {
      "firstName" : "JT",
      "lastName" : "Palmer",
      "authorRank" : 8,
      "name" : "Palmer JT",
      "referenceId" : "RGD:A79333"
    }, {
      "firstName" : "DW",
      "lastName" : "Dempster",
      "authorRank" : 9,
      "name" : "Dempster DW",
      "referenceId" : "RGD:A79334"
    }, {
      "firstName" : "D",
      "lastName" : "Bromme",
      "authorRank" : 10,
      "name" : "Bromme D",
      "referenceId" : "RGD:A51706"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601030"
    } ]
  }, {
    "primaryId" : "PMID:10430362",
    "title" : "The role of polyamines in growth factor induced DNA synthesis in cultured rat hepatocytes.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Higaki I, etal., Hepatogastroenterology. 1999 May-Jun;46(27):1874-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-03T14:36:46.000-06:00",
    "volume" : "46",
    "pages" : "1874-9",
    "abstract" : "BACKGROUND/AIMS: Hepatocyte growth factor and transforming growth factor-alpha are growth factors with important roles in hepatocyte proliferation. The polyamines, putrescine, spermidine, and spermine are widely distributed in many different cells and play an essential role in cell growth and differentiation. The present study examined the role of polyamine in this growth promoting factor-induced hepatocyte proliferation, in primary cultured rat hepatocytes. METHODOLOGY: Hepatocytes were isolated from rats by the collagenase perfusion method. Ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were measured as the release of 14CO2 from L-[-14C]ornithine and S-adenosyl-L-[carboxyl14C]methionine, respectively. The concentration of polyamine was analyzed by high performance liquid chromatography. RESULTS: When transforming growth factor-alpha and hepatocyte growth factor were added to the hepatocyte culture simultaneously, ornithine decarboxylase activity, S-adenosylmethionine decarboxylase activity, polyamine concentration and DNA synthesis increased additively. The increase in DNA synthesis caused by transforming growth factor-alpha, hepatocyte growth factor, or both was completely inhibited by alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone). The inhibition was reversed by exogenous spermidine or spermine, but not by putrescine. CONCLUSIONS: Increased spermidine or spermine levels are essential for hepatocyte proliferation in cultured rat hepatocytes.",
    "issueName" : "27",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Higaki",
      "authorRank" : 1,
      "name" : "Higaki I",
      "referenceId" : "RGD:A58536"
    }, {
      "firstName" : "I",
      "lastName" : "Matsui-Yuasa",
      "authorRank" : 2,
      "name" : "Matsui-Yuasa I",
      "referenceId" : "RGD:A58537"
    }, {
      "firstName" : "K",
      "lastName" : "Hirohashi",
      "authorRank" : 3,
      "name" : "Hirohashi K",
      "referenceId" : "RGD:A58538"
    }, {
      "firstName" : "H",
      "lastName" : "Kinoshita",
      "authorRank" : 4,
      "name" : "Kinoshita H",
      "referenceId" : "RGD:A58539"
    }, {
      "firstName" : "S",
      "lastName" : "Otani",
      "authorRank" : 5,
      "name" : "Otani S",
      "referenceId" : "RGD:A16567"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578320"
    } ]
  }, {
    "primaryId" : "PMID:10430466",
    "title" : "Immunohistochemical distribution of the two isoforms of synaphin/complexin involved in neurotransmitter release: localization at the distinct central nervous system regions and synaptic types.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Yamada M, etal., Neuroscience. 1999;93(1):7-18.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T01:59:29.000-05:00",
    "volume" : "93",
    "pages" : "7-18",
    "abstract" : "The cellular and subcellular localization of the two synaphin isoforms, proteins associated with the docking/fusion complex crucial to neurotransmitter release, was studied in the rat central nervous system by using light microscopic and electron microscopic immunohistochemistry with monoclonal antibodies specific to each isoform. Synaphin 1 (complexin II) was predominantly expressed in neurons of the central nervous system regions such as cerebral cortex (the II, III and VI cortical layers), claustrum, hippocampus, entorhinal cortex, amygdaloid nuclei, substantia nigra pars compacta, superior colliculus, pontine reticulotegmental nucleus and inferior olive, whereas synaphin 2 (complexin I) was in the cerebral cortex (the IV cortical layer), thalamus, locus coeruleus, gigantocellular reticular field, cuneate nucleus and cerebellar basket and stellate cells. In some regions, including the caudate-putamen, globus pallidus, pontine reticular nucleus, cerebellar nuclei and spinal gray matter, synaphin 1 was mainly present in small or medium-sized neurons, while synaphin 2 was in large cells. Medial habenular nucleus and cerebellar granule cells showed both immunoreactivities. In the neuropil of the cerebral cortex and hippocampus, synaphin 1 expression was accentuated in the axon terminals of axospinal and axodendritic synapses, while synaphin 2 was predominant in the axon terminals of axosomatic synapses. In the axon terminals, both immunolabelings were associated with synaptic vesicles and the plasma membrane, being accentuated in the vicinity of synaptic contacts. In the cerebral cortex, both immunoreactivities were also present occasionally in dendrites and dendritic spines, associated with microtubules and the plasma membrane including the postsynaptic densities. These results suggest that the two isoforms of synaphin are involved in synaptic function at the distinct presynaptic regions in the central nervous system, and that some dendrites are another functional site for the proteins.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Yamada",
      "authorRank" : 1,
      "name" : "Yamada M",
      "referenceId" : "RGD:A161371"
    }, {
      "firstName" : "H",
      "lastName" : "Saisu",
      "authorRank" : 2,
      "name" : "Saisu H",
      "referenceId" : "RGD:A9837"
    }, {
      "firstName" : "T",
      "lastName" : "Ishizuka",
      "authorRank" : 3,
      "name" : "Ishizuka T",
      "referenceId" : "RGD:A9836"
    }, {
      "firstName" : "H",
      "lastName" : "Takahashi",
      "authorRank" : 4,
      "name" : "Takahashi H",
      "referenceId" : "RGD:A161445"
    }, {
      "firstName" : "T",
      "lastName" : "Abe",
      "authorRank" : 5,
      "name" : "Abe T",
      "referenceId" : "RGD:A8476"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702170"
    } ]
  }, {
    "primaryId" : "PMID:10430499",
    "title" : "Central and peripheral expression of neurokinin-1 and neurokinin-3 receptor and substance P-encoding messenger RNAs: peripheral regulation during formalin-induced inflammation and lack of neurokinin receptor expression in primary afferent sensory neurons.",
    "datePublished" : "1000-03-01T00:00:00.000-06:00",
    "citation" : "McCarson KE Neuroscience. 1999;93(1):361-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-03-16T15:04:28.000-05:00",
    "volume" : "93",
    "pages" : "361-70",
    "abstract" : "The neurokinin-1 receptor and its tachykinin neuropeptide ligand substance P are associated with the mediation of nociception. Substance P released from primary afferent sensory neurons activates neurokinin receptors on both central and peripheral targets that mediate specific aspects of central sensitization and inflammatory function; however, an autoreceptor function for the neurokinin-1 receptor remains highly controversial. Activation of the neurokinin-1 receptor by substance P during chronic nociception increases neurokinin-1 receptor gene expression in the spinal cord. Similarly, neurokinin-3 receptors on peripheral or target tissues or neurons could play an important role in the sensitization of sensory neurons. Therefore, this study (i) mapped the steady-state levels of substance P-encoding preprotachykinin, neurokinin-1 and neurokinin-3 receptor messenger RNAs in central and peripheral tissues including sensory ganglia, and (ii) investigated whether formalin-evoked nociception altered the quantity or location of neurokinin-1 or neurokinin-3 receptor messenger RNAs in the sensory ganglia or inflamed peripheral targets for substance P. Solution hybridization-nuclease protection assays quantified neurokinin receptor messenger RNA levels in central and peripheral tissues from normal and formalin-inflamed rats. High concentrations of the neurokinin-1 receptor were found in whole brain, spinal cord, and peripheral target organs innervated by substance P-containing neurons. Measurable levels of neurokinin-3 receptor messenger RNA were found only in brain, spinal cord and urinary bladder. Results also show that neither neurokinin-1 nor neurokinin-3 receptor messenger RNAs were detectable in primary afferent sensory neurons in the dorsal root ganglia of normal or formalin-inflamed rats. Neurokinin-1 receptor messenger RNA levels were, however, significantly increased in hindpaw tissues inflamed by formalin for 6 h. These results indicate that the plasticity of neurokinin-1 receptor gene expression in non-neuronal peripheral cells could regulate sensitivity to substance P in a manner similar to that in the spinal cord dorsal horn. Altered neurokinin-1 receptor gene expression provides a useful marker of long-term nociceptive activation and may mediate peripheral mechanisms of hyperalgesia and cellular sensitization during inflammation. Importantly, inflammation does not induce a phenotypic change in afferent sensory neurons providing neurokinin receptor targets for the direct sensitization of these neurons by substance P.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KE",
      "lastName" : "McCarson",
      "authorRank" : 1,
      "name" : "McCarson KE",
      "referenceId" : "RGD:A18746"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2305958"
    } ]
  }, {
    "primaryId" : "PMID:10430608",
    "title" : "Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Frantz S, etal., J Clin Invest 1999 Aug;104(3):271-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-11T15:05:31.000-06:00",
    "volume" : "104",
    "pages" : "271-80",
    "abstract" : "Expression of innate immune response proteins, including IL-1beta, TNF, and the cytokine-inducible isoform of nitric oxide synthase (iNOS), have been documented in the hearts of humans and experimental animals with heart failure regardless of etiology, although the proximal events leading to their expression are unknown. Noting that expression of a human homologue of Drosophila Toll, a proximal innate immunity transmembrane signaling protein in the fly, now termed human Toll-like receptor 4 (hTLR4), appeared to be relatively high in the heart, we examined TLR4 mRNA and protein abundance in isolated cellular constituents of cardiac muscle and in normal and abnormal murine, rat, and human myocardium. TLR4 expression levels in cardiac myocytes and in coronary microvascular endothelial cells could be enhanced by either LPS or IL-1beta, an effect inhibited by the oxygen radical scavenger PDTC. Transfection of a constitutively active TLR4 construct, CD4/hTLR4, resulted in activation of a nuclear factor-kappaB reporter construct, but not of an AP-1 or an iNOS reporter construct, in cardiac myocytes. In normal murine, rat, and human myocardium, TLR4 expression was diffuse, and presumably cytoplasmic, in cardiac myocytes. However, in remodeling murine myocardium remote from sites of ischemic injury and in heart tissue from patients with idiopathic dilated cardiomyopathy, focal areas of intense TLR4 staining were observed in juxtaposed regions of 2 or more adjacent myocytes; this staining was not observed in control myocardium. Increased expression and signaling by TLR4, and perhaps other Toll homologues, may contribute to the activation of innate immunity in injured myocardium.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Frantz",
      "authorRank" : 1,
      "name" : "Frantz S",
      "referenceId" : "RGD:A8130"
    }, {
      "firstName" : "L",
      "lastName" : "Kobzik",
      "authorRank" : 2,
      "name" : "Kobzik L",
      "referenceId" : "RGD:A8131"
    }, {
      "firstName" : "YD",
      "lastName" : "Kim",
      "authorRank" : 3,
      "name" : "Kim YD",
      "referenceId" : "RGD:A8132"
    }, {
      "firstName" : "R",
      "lastName" : "Fukazawa",
      "authorRank" : 4,
      "name" : "Fukazawa R",
      "referenceId" : "RGD:A8133"
    }, {
      "firstName" : "R",
      "lastName" : "Medzhitov",
      "authorRank" : 5,
      "name" : "Medzhitov R",
      "referenceId" : "RGD:A8134"
    }, {
      "firstName" : "RT",
      "lastName" : "Lee",
      "authorRank" : 6,
      "name" : "Lee RT",
      "referenceId" : "RGD:A8135"
    }, {
      "firstName" : "RA",
      "lastName" : "Kelly",
      "authorRank" : 7,
      "name" : "Kelly RA",
      "referenceId" : "RGD:A8136"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70040"
    } ]
  }, {
    "primaryId" : "PMID:10430755",
    "title" : "Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "NO_AUTHOR, Am J Respir Crit Care Med. 1999 Aug;160(2):736-55. doi: 10.1164/ajrccm.160.2.ats4-99.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:21:02.000-05:00",
    "volume" : "160",
    "pages" : "736-55",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598117937"
    } ]
  }, {
    "primaryId" : "PMID:10430757",
    "title" : "Desmin mutation responsible for idiopathic dilated cardiomyopathy.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Li D, etal., Circulation 1999 Aug 3;100(5):461-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T16:09:31.000-06:00",
    "volume" : "100",
    "pages" : "461-4",
    "abstract" : "BACKGROUND: Idiopathic dilated cardiomyopathy, of which approximately 20% of cases are familial (FDCM), is a primary myocardial disorder characterized by ventricular dilatation and impaired systolic function. It is a common cause of heart failure and the need for cardiac transplantation. Although 6 chromosomal loci responsible for autosomal dominant FDCM have been mapped by linkage analysis, none of these genes have been identified. By use of the candidate-gene approach, actin was identified recently as being responsible for dilated cardiomyopathy. Considerable evidence suggests desmin, a muscle-specific intermediate filament, plays a significant role in cardiac growth and development. METHODS AND RESULTS: To determine whether a defect of desmin induces dilated cardiomyopathy, 44 probands with FDCM underwent clinical evaluation and DNA analysis. Diagnostic criteria, detected by echocardiography, consisted of ventricular dimension of >/=2.7 cm/m(2) with an ejection fraction </=50% in the absence of other potential causes. After amplification by polymerase chain reaction, the exons of the desmin gene were sequenced. A missense desmin mutation, Ile451Met, which cosegregates with FDCM without clinically evident skeletal muscle abnormalities, was identified in a 4-generation family but was not detected in 460 unrelated healthy individuals. CONCLUSIONS: A novel missense mutation of desmin, Ile451Met, was identified as the genetic cause of idiopathic dilated cardiomyopathy. This finding is of particular significance because this is the first mutation detected in the desmin tail domain, and the function of the desmin tail remains unknown. Because this mutation leads to a restricted cardiac phenotype in the family studied in the present report, it suggests that the tail of desmin plays an important functional role in cardiac tissue.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li D",
      "referenceId" : "RGD:A11822"
    }, {
      "firstName" : "T",
      "lastName" : "Tapscoft",
      "authorRank" : 2,
      "name" : "Tapscoft T",
      "referenceId" : "RGD:A37868"
    }, {
      "firstName" : "O",
      "lastName" : "Gonzalez",
      "authorRank" : 3,
      "name" : "Gonzalez O",
      "referenceId" : "RGD:A37869"
    }, {
      "firstName" : "PE",
      "lastName" : "Burch",
      "authorRank" : 4,
      "name" : "Burch PE",
      "referenceId" : "RGD:A37870"
    }, {
      "firstName" : "MA",
      "lastName" : "Quinones",
      "authorRank" : 5,
      "name" : "Quinones MA",
      "referenceId" : "RGD:A37871"
    }, {
      "firstName" : "WA",
      "lastName" : "Zoghbi",
      "authorRank" : 6,
      "name" : "Zoghbi WA",
      "referenceId" : "RGD:A37872"
    }, {
      "firstName" : "R",
      "lastName" : "Hill",
      "authorRank" : 7,
      "name" : "Hill R",
      "referenceId" : "RGD:A37873"
    }, {
      "firstName" : "LL",
      "lastName" : "Bachinski",
      "authorRank" : 8,
      "name" : "Bachinski LL",
      "referenceId" : "RGD:A37874"
    }, {
      "firstName" : "DL",
      "lastName" : "Mann",
      "authorRank" : 9,
      "name" : "Mann DL",
      "referenceId" : "RGD:A37875"
    }, {
      "firstName" : "R",
      "lastName" : "Roberts",
      "authorRank" : 10,
      "name" : "Roberts R",
      "referenceId" : "RGD:A37876"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734883"
    } ]
  }, {
    "primaryId" : "PMID:10430840",
    "title" : "Differential expression of matrix metalloproteinases in bacterial meningitis.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kieseier BC, etal., Brain. 1999 Aug;122 ( Pt 8):1579-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-03-04T13:12:52.000-06:00",
    "volume" : "122 ( Pt 8)",
    "pages" : "1579-87",
    "abstract" : "Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of various inflammatory diseases of the central nervous system. Evidence is accumulating that gelatinase B (MMP-9) might be involved in the pathogenesis of meningitis, but the spectrum of different MMPs involved in the inflammatory reaction of this  disease has not been determined. We investigated the temporal and spatial mRNA expression pattern of gelatinase B in experimental meningococcal meningitis in rats. In contrast to controls, increased mRNA levels with peak values 6 h after injection with menigococci were found in brain specimens of the animals. Elevated MMP-9 mRNA expression was accompanied by enhanced proteolytic activity, as demonstrated by gelatin zymography, and positive immunoreactivity. The mRNA expression pattern of six other MMPs was investigated. Collagenase-3 and stromelysin-1 mRNAs were also found to be upregulated. In contrast, mRNA levels for gelatinase A, matrilysin, stromelysin-2 and stromelysin-3 remained unchanged. As evidenced by significantly increased intracranial pressure and by leakage of intravenously injected Evans blue through the blood vessel walls into the brain parenchyma, the animals injected with meningococci revealed signs of blood-brain  barrier disruption. Augmented proteolytic activity of MMP-9 could also be demonstrated in CSF samples obtained from patients with bacterial meningitis, underlining the clinical relevance of our experimental findings. Our data indicate that gelatinase B, collagenase-3 and stromelysin-1 are selectively upregulated in bacterial meningitis and thus may contribute to the pathogenesis of this infectious disease of the central nervous system.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BC",
      "lastName" : "Kieseier",
      "authorRank" : 1,
      "name" : "Kieseier BC",
      "referenceId" : "RGD:A151131"
    }, {
      "firstName" : "R",
      "lastName" : "Paul",
      "authorRank" : 2,
      "name" : "Paul R",
      "referenceId" : "RGD:A57792"
    }, {
      "firstName" : "U",
      "lastName" : "Koedel",
      "authorRank" : 3,
      "name" : "Koedel",
      "referenceId" : "RGD:A180455"
    }, {
      "firstName" : "T",
      "lastName" : "Seifert",
      "authorRank" : 4,
      "name" : "Seifert",
      "referenceId" : "RGD:A180456"
    }, {
      "firstName" : "JM",
      "lastName" : "Clements",
      "authorRank" : 5,
      "name" : "Clements",
      "referenceId" : "RGD:A180225"
    }, {
      "firstName" : "AJ",
      "lastName" : "Gearing",
      "authorRank" : 6,
      "name" : "Gearing AJ",
      "referenceId" : "RGD:A69587"
    }, {
      "firstName" : "HW",
      "lastName" : "Pfister",
      "authorRank" : 7,
      "name" : "Pfister",
      "referenceId" : "RGD:A180457"
    }, {
      "firstName" : "HP",
      "lastName" : "Hartung",
      "authorRank" : 8,
      "name" : "Hartung HP",
      "referenceId" : "RGD:A65535"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547971"
    } ]
  }, {
    "primaryId" : "PMID:10430869",
    "title" : "Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Traub LM, etal., Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8907-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:17:56.000-05:00",
    "volume" : "96",
    "pages" : "8907-12",
    "abstract" : "AP-2 adaptors regulate clathrin-bud formation at the cell surface by recruiting clathrin trimers to the plasma membrane and by selecting certain membrane proteins for inclusion within the developing clathrin-coat structure. These functions are performed by discrete subunits of the adaptor heterotetramer. The carboxyl-terminal appendage of the AP-2 alpha subunit appears to regulate the translocation of several endocytic accessory proteins to the bud site. We have determined the crystal structure of the alpha appendage at 1.4-A resolution by multiwavelength anomalous diffraction phasing. It is composed of two distinct structural modules, a beta-sandwich domain and a mixed alpha-beta platform domain. Structure-based mutagenesis shows that alterations to the molecular surface of a highly conserved region on the platform domain differentially affect associations of the appendage with amphiphysin, eps15, epsin, and AP180, revealing a common protein-binding interface.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LM",
      "lastName" : "Traub",
      "authorRank" : 1,
      "name" : "Traub LM",
      "referenceId" : "RGD:A51529"
    }, {
      "firstName" : "MA",
      "lastName" : "Downs",
      "authorRank" : 2,
      "name" : "Downs MA",
      "referenceId" : "RGD:A158289"
    }, {
      "firstName" : "JL",
      "lastName" : "Westrich",
      "authorRank" : 3,
      "name" : "Westrich",
      "referenceId" : "RGD:A214019"
    }, {
      "firstName" : "DH",
      "lastName" : "Fremont",
      "authorRank" : 4,
      "name" : "Fremont DH",
      "referenceId" : "RGD:A109231"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041016"
    } ]
  }, {
    "primaryId" : "PMID:10430900",
    "title" : "p21(WAF1/Cip1) functions as a suppressor of malignant skin tumor formation and a  determinant of keratinocyte stem-cell potential.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Topley GI, etal., Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9089-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-24T12:09:07.000-05:00",
    "volume" : "96",
    "pages" : "9089-94",
    "abstract" : "p21(WAF1/Cip1) is one of the best characterized downstream targets of p53, and the growth suppressing function of this cyclin-dependent kinase inhibitor is well established. However, whether p21 exerts a tumor-suppressing function of its own  remains to be established. We report here that, similarly to loss of p53, disruption of the p21(WAF1/Cip1) gene results in a markedly increased susceptibility to chemically induced skin carcinoma formation, whereas the number of papillomas is reduced. Previous evidence indicates that malignant versus benign keratinocyte tumor formation is likely to involve distinct target-cell populations with a different commitment to differentiation. In parallel with the  increased susceptibility to carcinoma formation, loss of p21(WAF1/Cip1) was found to promote keratinocyte subpopulations with increased growth/differentiation potential, including clonal growth capability, reversible commitment to differentiation, and capability to generate all types of terminally differentiated keratinocytes present in vivo, not only in the interfollicular epidermis but also in hair follicles. Thus, these findings have revealed a function of p21 as a suppressor of malignant but not benign skin-tumor formation  and a determinant of the growth/differentiation potential of keratinocyte subpopulations.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GI",
      "lastName" : "Topley",
      "authorRank" : 1,
      "name" : "Topley",
      "referenceId" : "RGD:A190401"
    }, {
      "firstName" : "R",
      "lastName" : "Okuyama",
      "authorRank" : 2,
      "name" : "Okuyama R",
      "referenceId" : "RGD:A77184"
    }, {
      "firstName" : "JG",
      "lastName" : "Gonzales",
      "authorRank" : 3,
      "name" : "Gonzales",
      "referenceId" : "RGD:A190402"
    }, {
      "firstName" : "C",
      "lastName" : "Conti",
      "authorRank" : 4,
      "name" : "Conti C",
      "referenceId" : "RGD:A118282"
    }, {
      "firstName" : "GP",
      "lastName" : "Dotto",
      "authorRank" : 5,
      "name" : "Dotto GP",
      "referenceId" : "RGD:A37177"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662432"
    } ]
  }, {
    "primaryId" : "PMID:10430935",
    "title" : "High expression of a specific T-cell receptor gamma transcript in epithelial cells of the prostate.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Essand M, etal., Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9287-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:18:15.000-05:00",
    "volume" : "96",
    "pages" : "9287-92",
    "abstract" : "We have identified expression of T-cell receptor gamma chain (TCRgamma) mRNA in human prostate and have shown that it originates from epithelial cells of the prostate and not from infiltrating T-lymphocytes. In contrast, the T-cell receptor delta chain (TCRdelta) gene is silent in human prostate. The major TCRgamma transcript in prostate has a different size than the transcript expressed in thymus, spleen, and blood leukocytes. It is expressed in normal prostate epithelium, adenocarcinoma of the prostate, and the prostatic adenocarcinoma cell line LNCaP. The RNA originates from an unrearranged TCRgamma  locus, and it is initiated within the intronic sequence directly upstream of the  Jgamma1.2 gene segment. The prostate-specific TCRgamma transcript consists of the Jgamma1.2 and Cgamma1 gene segments, and it has an untranslated sequence including a polyadenylation signal and poly(A) sequence at the 3'end. The finding that prostate epithelial cells express a high level of a transcript from a gene that was thought to by exclusively expressed by T-lymphocytes is highly unexpected.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Essand",
      "authorRank" : 1,
      "name" : "Essand",
      "referenceId" : "RGD:A232353"
    }, {
      "firstName" : "G",
      "lastName" : "Vasmatzis",
      "authorRank" : 2,
      "name" : "Vasmatzis G",
      "referenceId" : "RGD:A116566"
    }, {
      "firstName" : "U",
      "lastName" : "Brinkmann",
      "authorRank" : 3,
      "name" : "Brinkmann U",
      "referenceId" : "RGD:A52193"
    }, {
      "firstName" : "P",
      "lastName" : "Duray",
      "authorRank" : 4,
      "name" : "Duray P",
      "referenceId" : "RGD:A71887"
    }, {
      "firstName" : "B",
      "lastName" : "Lee",
      "authorRank" : 5,
      "name" : "Lee B",
      "referenceId" : "RGD:A5385"
    }, {
      "firstName" : "I",
      "lastName" : "Pastan",
      "authorRank" : 6,
      "name" : "Pastan I",
      "referenceId" : "RGD:A48332"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11055965"
    } ]
  }, {
    "primaryId" : "PMID:10430976",
    "title" : "Role of platelet-activating factor acetylhydrolase gene mutation in Japanese childhood IgA nephropathy.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Tanaka R, etal., Am J Kidney Dis. 1999 Aug;34(2):289-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-08-20T15:19:42.000-05:00",
    "volume" : "34",
    "pages" : "289-95",
    "abstract" : "Platelet-activating factor (PAF) is a potent mediator of inflammatory injury in renal diseases. PAF is degraded to inactive products by PAF acetylhydrolase. Recently, a point mutation (G to T transversion) of the PAF acetylhydrolase gene  was observed at position 994, and this mutation was found to contribute to the variability in plasma PAF levels, with undetectable plasma PAF acetylhydrolase activity occurring in homozygous patients (TT genotype) and reduced levels of activity in heterozygous patients (GT genotype). Therefore, we investigated the effect of the PAF acetylhydrolase gene mutation on the pathogenesis and progression of immunoglobulin A (IgA) nephropathy. Genomic DNA was obtained from  89 children with IgA nephropathy and 100 controls. We identified the PAF acetylhydrolase gene mutation (G994T) by polymerase chain reaction. There was no  significant difference in genotypic frequency between patients and controls. However, urinary protein excretion at the time of biopsy was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype.  The percentage of glomeruli with mesangial cell proliferation was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype.  These results indicate the PAF acetylhydrolase gene mutation may influence the degree of proteinuria and the extent of mesangial proliferation in the early stage of childhood IgA nephropathy.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Tanaka",
      "authorRank" : 1,
      "name" : "Tanaka R",
      "referenceId" : "RGD:A68588"
    }, {
      "firstName" : "K",
      "lastName" : "Iijima",
      "authorRank" : 2,
      "name" : "Iijima K",
      "referenceId" : "RGD:A118221"
    }, {
      "firstName" : "H",
      "lastName" : "Xu",
      "authorRank" : 3,
      "name" : "Xu H",
      "referenceId" : "RGD:A14579"
    }, {
      "firstName" : "Y",
      "lastName" : "Inoue",
      "authorRank" : 4,
      "name" : "Inoue",
      "referenceId" : "RGD:A408571"
    }, {
      "firstName" : "R",
      "lastName" : "Murakami",
      "authorRank" : 5,
      "name" : "Murakami R",
      "referenceId" : "RGD:A67244"
    }, {
      "firstName" : "T",
      "lastName" : "Shirakawa",
      "authorRank" : 6,
      "name" : "Shirakawa T",
      "referenceId" : "RGD:A38490"
    }, {
      "firstName" : "K",
      "lastName" : "Nishiyama",
      "authorRank" : 7,
      "name" : "Nishiyama K",
      "referenceId" : "RGD:A25173"
    }, {
      "firstName" : "M",
      "lastName" : "Miwa",
      "authorRank" : 8,
      "name" : "Miwa M",
      "referenceId" : "RGD:A23179"
    }, {
      "firstName" : "S",
      "lastName" : "Shiozawa",
      "authorRank" : 9,
      "name" : "Shiozawa S",
      "referenceId" : "RGD:A40070"
    }, {
      "firstName" : "H",
      "lastName" : "Nakamura",
      "authorRank" : 10,
      "name" : "Nakamura",
      "referenceId" : "RGD:A401423"
    }, {
      "firstName" : "N",
      "lastName" : "Yoshikawa",
      "authorRank" : 11,
      "name" : "Yoshikawa",
      "referenceId" : "RGD:A172022"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7248792"
    } ]
  }, {
    "primaryId" : "PMID:10431236",
    "title" : "Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Brooks-Wilson A, etal., Nat Genet 1999 Aug;22(4):336-45.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T15:32:27.000-05:00",
    "volume" : "22",
    "pages" : "336-45",
    "abstract" : "Genes have a major role in the control of high-density lipoprotein (HDL) cholesterol (HDL-C) levels. Here we have identified two Tangier disease (TD) families, confirmed 9q31 linkage and refined the disease locus to a limited genomic region containing the gene encoding the ATP-binding cassette transporter (ABC1). Familial HDL deficiency (FHA) is a more frequent cause of low HDL levels. On the basis of independent linkage and meiotic recombinants, we localized the FHA locus to the same genomic region as the TD locus. Mutations in ABC1 were detected in both TD and FHA, indicating that TD and FHA are allelic. This indicates that the protein encoded by ABC1 is a key gatekeeper influencing intracellular cholesterol transport, hence we have named it cholesterol efflux regulatory protein (CERP).",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Brooks-Wilson",
      "authorRank" : 1,
      "name" : "Brooks-Wilson A",
      "referenceId" : "RGD:A161972"
    }, {
      "firstName" : "M",
      "lastName" : "Marcil",
      "authorRank" : 2,
      "name" : "Marcil M",
      "referenceId" : "RGD:A161973"
    }, {
      "firstName" : "SM",
      "lastName" : "Clee",
      "authorRank" : 3,
      "name" : "Clee SM",
      "referenceId" : "RGD:A40495"
    }, {
      "firstName" : "LH",
      "lastName" : "Zhang",
      "authorRank" : 4,
      "name" : "Zhang LH",
      "referenceId" : "RGD:A40496"
    }, {
      "firstName" : "K",
      "lastName" : "Roomp",
      "authorRank" : 5,
      "name" : "Roomp K",
      "referenceId" : "RGD:A161976"
    }, {
      "firstName" : "M",
      "lastName" : "Van Dam",
      "authorRank" : 6,
      "name" : "Van Dam M",
      "referenceId" : "RGD:A40498"
    }, {
      "firstName" : "L",
      "lastName" : "Yu",
      "authorRank" : 7,
      "name" : "Yu L",
      "referenceId" : "RGD:A404015"
    }, {
      "firstName" : "C",
      "lastName" : "Brewer",
      "authorRank" : 8,
      "name" : "Brewer C",
      "referenceId" : "RGD:A161979"
    }, {
      "firstName" : "JA",
      "lastName" : "Collins",
      "authorRank" : 9,
      "name" : "Collins JA",
      "referenceId" : "RGD:A40501"
    }, {
      "firstName" : "HO",
      "lastName" : "Molhuizen",
      "authorRank" : 10,
      "name" : "Molhuizen HO",
      "referenceId" : "RGD:A40502"
    }, {
      "firstName" : "O",
      "lastName" : "Loubser",
      "authorRank" : 11,
      "name" : "Loubser O",
      "referenceId" : "RGD:A161982"
    }, {
      "firstName" : "BF",
      "lastName" : "Ouelette",
      "authorRank" : 12,
      "name" : "Ouelette BF",
      "referenceId" : "RGD:A40504"
    }, {
      "firstName" : "K",
      "lastName" : "Fichter",
      "authorRank" : 13,
      "name" : "Fichter K",
      "referenceId" : "RGD:A161984"
    }, {
      "firstName" : "KJ",
      "lastName" : "Ashbourne-Excoffon",
      "authorRank" : 14,
      "name" : "Ashbourne-Excoffon KJ",
      "referenceId" : "RGD:A40506"
    }, {
      "firstName" : "CW",
      "lastName" : "Sensen",
      "authorRank" : 15,
      "name" : "Sensen CW",
      "referenceId" : "RGD:A40507"
    }, {
      "firstName" : "S",
      "lastName" : "Scherer",
      "authorRank" : 16,
      "name" : "Scherer S",
      "referenceId" : "RGD:A161987"
    }, {
      "firstName" : "S",
      "lastName" : "Mott",
      "authorRank" : 17,
      "name" : "Mott S",
      "referenceId" : "RGD:A161988"
    }, {
      "firstName" : "M",
      "lastName" : "Denis",
      "authorRank" : 18,
      "name" : "Denis M",
      "referenceId" : "RGD:A161989"
    }, {
      "firstName" : "D",
      "lastName" : "Martindale",
      "authorRank" : 19,
      "name" : "Martindale D",
      "referenceId" : "RGD:A161990"
    }, {
      "firstName" : "J",
      "lastName" : "Frohlich",
      "authorRank" : 20,
      "name" : "Frohlich J",
      "referenceId" : "RGD:A161991"
    }, {
      "firstName" : "K",
      "lastName" : "Morgan",
      "authorRank" : 21,
      "name" : "Morgan K",
      "referenceId" : "RGD:A161992"
    }, {
      "firstName" : "B",
      "lastName" : "Koop",
      "authorRank" : 22,
      "name" : "Koop B",
      "referenceId" : "RGD:A161993"
    }, {
      "firstName" : "S",
      "lastName" : "Pimstone",
      "authorRank" : 23,
      "name" : "Pimstone S",
      "referenceId" : "RGD:A161994"
    }, {
      "firstName" : "JJ",
      "lastName" : "Kastelein",
      "authorRank" : 24,
      "name" : "Kastelein JJ",
      "referenceId" : "RGD:A40514"
    }, {
      "firstName" : "MR",
      "lastName" : "Hayden",
      "authorRank" : 25,
      "name" : "Hayden MR",
      "referenceId" : "RGD:A25874"
    }, {
      "firstName" : "M R",
      "lastName" : "Hayden",
      "authorRank" : 26,
      "name" : "Hayden M R",
      "referenceId" : "RGD:A161997"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298571"
    } ]
  }, {
    "primaryId" : "PMID:10431237",
    "title" : "The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Bodzioch M, etal., Nat Genet 1999 Aug;22(4):347-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T15:23:52.000-05:00",
    "volume" : "22",
    "pages" : "347-51",
    "abstract" : "Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors. In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism. HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts, which have a reduced in vitro growth rate. The TD locus has been mapped to chromosome 9q31. Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22-31. We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Bodzioch",
      "authorRank" : 1,
      "name" : "Bodzioch M",
      "referenceId" : "RGD:A40398"
    }, {
      "firstName" : "E",
      "lastName" : "Orso",
      "authorRank" : 2,
      "name" : "Orso E",
      "referenceId" : "RGD:A40399"
    }, {
      "firstName" : "J",
      "lastName" : "Klucken",
      "authorRank" : 3,
      "name" : "Klucken J",
      "referenceId" : "RGD:A40400"
    }, {
      "firstName" : "T",
      "lastName" : "Langmann",
      "authorRank" : 4,
      "name" : "Langmann T",
      "referenceId" : "RGD:A24438"
    }, {
      "firstName" : "A",
      "lastName" : "Bottcher",
      "authorRank" : 5,
      "name" : "Bottcher A",
      "referenceId" : "RGD:A40401"
    }, {
      "firstName" : "W",
      "lastName" : "Diederich",
      "authorRank" : 6,
      "name" : "Diederich W",
      "referenceId" : "RGD:A40402"
    }, {
      "firstName" : "W",
      "lastName" : "Drobnik",
      "authorRank" : 7,
      "name" : "Drobnik W",
      "referenceId" : "RGD:A40403"
    }, {
      "firstName" : "S",
      "lastName" : "Barlage",
      "authorRank" : 8,
      "name" : "Barlage S",
      "referenceId" : "RGD:A40404"
    }, {
      "firstName" : "C",
      "lastName" : "Buchler",
      "authorRank" : 9,
      "name" : "Buchler C",
      "referenceId" : "RGD:A40405"
    }, {
      "firstName" : "M",
      "lastName" : "Porsch-Ozcurumez",
      "authorRank" : 10,
      "name" : "Porsch-Ozcurumez M",
      "referenceId" : "RGD:A40406"
    }, {
      "firstName" : "WE",
      "lastName" : "Kaminski",
      "authorRank" : 11,
      "name" : "Kaminski WE",
      "referenceId" : "RGD:A40407"
    }, {
      "firstName" : "HW",
      "lastName" : "Hahmann",
      "authorRank" : 12,
      "name" : "Hahmann HW",
      "referenceId" : "RGD:A40408"
    }, {
      "firstName" : "K",
      "lastName" : "Oette",
      "authorRank" : 13,
      "name" : "Oette K",
      "referenceId" : "RGD:A40409"
    }, {
      "firstName" : "G",
      "lastName" : "Rothe",
      "authorRank" : 14,
      "name" : "Rothe G",
      "referenceId" : "RGD:A40410"
    }, {
      "firstName" : "C",
      "lastName" : "Aslanidis",
      "authorRank" : 15,
      "name" : "Aslanidis C",
      "referenceId" : "RGD:A40411"
    }, {
      "firstName" : "KJ",
      "lastName" : "Lackner",
      "authorRank" : 16,
      "name" : "Lackner KJ",
      "referenceId" : "RGD:A40412"
    }, {
      "firstName" : "G",
      "lastName" : "Schmitz",
      "authorRank" : 17,
      "name" : "Schmitz G",
      "referenceId" : "RGD:A24437"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298541"
    } ]
  }, {
    "primaryId" : "PMID:10431241",
    "title" : "Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Monreal AW, etal., Nat Genet. 1999 Aug;22(4):366-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-20T08:44:53.000-06:00",
    "volume" : "22",
    "pages" : "366-9",
    "abstract" : "X-linked hypohidrotic ectodermal dysplasia results in abnormal morphogenesis of teeth, hair and eccrine sweat glands. The gene (ED1) responsible for the disorder has been identified, as well as the analogous X-linked gene (Ta) in the mouse. Autosomal recessive disorders, phenotypically indistinguishable from the X-linked forms, exist in humans and at two separate loci (crinkled, cr, and downless, dl) in mice. Dominant disorders, possibly allelic to the recessive loci, are seen in both species (ED3, Dlslk). A candidate gene has recently been identified at the dl locus that is mutated in both dl and Dlslk mutant alleles. We isolated and characterized its human DL homologue, and identified mutations in three families displaying recessive inheritance and two with dominant inheritance. The disorder does not map to the candidate gene locus in all autosomal recessive families, implying the existence of at least one additional human locus. The putative protein is predicted to have a single transmembrane domain, and shows similarity to two separate domains of the tumour necrosis factor receptor (TNFR) family.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AW",
      "lastName" : "Monreal",
      "authorRank" : 1,
      "name" : "Monreal AW",
      "referenceId" : "RGD:A71604"
    }, {
      "firstName" : "BM",
      "lastName" : "Ferguson",
      "authorRank" : 2,
      "name" : "Ferguson BM",
      "referenceId" : "RGD:A71605"
    }, {
      "firstName" : "DJ",
      "lastName" : "Headon",
      "authorRank" : 3,
      "name" : "Headon DJ",
      "referenceId" : "RGD:A71606"
    }, {
      "firstName" : "SL",
      "lastName" : "Street",
      "authorRank" : 4,
      "name" : "Street SL",
      "referenceId" : "RGD:A71607"
    }, {
      "firstName" : "PA",
      "lastName" : "Overbeek",
      "authorRank" : 5,
      "name" : "Overbeek PA",
      "referenceId" : "RGD:A8558"
    }, {
      "firstName" : "J",
      "lastName" : "Zonana",
      "authorRank" : 6,
      "name" : "Zonana J",
      "referenceId" : "RGD:A71591"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598883"
    } ]
  }, {
    "primaryId" : "PMID:10431243",
    "title" : "Engineering a mouse balancer chromosome.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Zheng B, etal., Nat Genet. 1999 Aug;22(4):375-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-05-18T19:53:12.000-05:00",
    "volume" : "22",
    "pages" : "375-8",
    "abstract" : "Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. Despite their utility, balancer chromosomes are rarely used in mice because they are difficult  to generate using conventional methods. Here we describe the engineering of a mouse balancer chromosome with the Cre-loxP recombination system. The chromosome  features a 24-centiMorgan (cM) inversion between Trp53 (also known as p53) and Wnt3 on mouse chromosome 11 that is recessive lethal and dominantly marked with a K14-Agouti transgene. When allelic to a wild-type chromosome, the inversion suppresses crossing over in the inversion interval, accompanied by elevated recombination in the flanking regions. The inversion functions as a balancer chromosome because it can be used to maintain a lethal mutation in the inversion  interval as a self-sustaining trans-heterozygous stock. This strategy can be used to generate similar genetic reagents throughout the mouse genome. Engineering of  visibly marked inversions and deficiencies is an important step toward functional analyses of the mouse genome and will facilitate large-scale mutagenesis programs.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Zheng",
      "authorRank" : 1,
      "name" : "Zheng B",
      "referenceId" : "RGD:A4850"
    }, {
      "firstName" : "M",
      "lastName" : "Sage",
      "authorRank" : 2,
      "name" : "Sage",
      "referenceId" : "RGD:A304542"
    }, {
      "firstName" : "WW",
      "lastName" : "Cai",
      "authorRank" : 3,
      "name" : "Cai",
      "referenceId" : "RGD:A203521"
    }, {
      "firstName" : "DM",
      "lastName" : "Thompson",
      "authorRank" : 4,
      "name" : "Thompson",
      "referenceId" : "RGD:A304543"
    }, {
      "firstName" : "BC",
      "lastName" : "Tavsanli",
      "authorRank" : 5,
      "name" : "Tavsanli",
      "referenceId" : "RGD:A304544"
    }, {
      "firstName" : "YC",
      "lastName" : "Cheah",
      "authorRank" : 6,
      "name" : "Cheah",
      "referenceId" : "RGD:A304545"
    }, {
      "firstName" : "A",
      "lastName" : "Bradley",
      "authorRank" : 7,
      "name" : "Bradley A",
      "referenceId" : "RGD:A39009"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11080464"
    } ]
  }, {
    "primaryId" : "PMID:10431246",
    "title" : "A YAC-based physical map of the mouse genome.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Nusbaum C, etal., Nat Genet 1999 Aug;22(4):388-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-11-18T10:21:34.000-06:00",
    "volume" : "22",
    "pages" : "388-93",
    "abstract" : "A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Nusbaum",
      "authorRank" : 1,
      "name" : "Nusbaum C",
      "referenceId" : "RGD:A57294"
    }, {
      "firstName" : "DK",
      "lastName" : "Slonim",
      "authorRank" : 2,
      "name" : "Slonim DK",
      "referenceId" : "RGD:A57295"
    }, {
      "firstName" : "KL",
      "lastName" : "Harris",
      "authorRank" : 3,
      "name" : "Harris KL",
      "referenceId" : "RGD:A57296"
    }, {
      "firstName" : "BW",
      "lastName" : "Birren",
      "authorRank" : 4,
      "name" : "Birren BW",
      "referenceId" : "RGD:A20254"
    }, {
      "firstName" : "RG",
      "lastName" : "Steen",
      "authorRank" : 5,
      "name" : "Steen RG",
      "referenceId" : "RGD:A95444"
    }, {
      "firstName" : "LD",
      "lastName" : "Stein",
      "authorRank" : 6,
      "name" : "Stein LD",
      "referenceId" : "RGD:A57298"
    }, {
      "firstName" : "J",
      "lastName" : "Miller",
      "authorRank" : 7,
      "name" : "Miller J",
      "referenceId" : "RGD:A162361"
    }, {
      "firstName" : "WF",
      "lastName" : "Dietrich",
      "authorRank" : 8,
      "name" : "Dietrich WF",
      "referenceId" : "RGD:A57299"
    }, {
      "firstName" : "R",
      "lastName" : "Nahf",
      "authorRank" : 9,
      "name" : "Nahf R",
      "referenceId" : "RGD:A57300"
    }, {
      "firstName" : "V",
      "lastName" : "Wang",
      "authorRank" : 10,
      "name" : "Wang V",
      "referenceId" : "RGD:A57301"
    }, {
      "firstName" : "O",
      "lastName" : "Merport",
      "authorRank" : 11,
      "name" : "Merport O",
      "referenceId" : "RGD:A57302"
    }, {
      "firstName" : "AB",
      "lastName" : "Castle",
      "authorRank" : 12,
      "name" : "Castle AB",
      "referenceId" : "RGD:A6609"
    }, {
      "firstName" : "Z",
      "lastName" : "Husain",
      "authorRank" : 13,
      "name" : "Husain Z",
      "referenceId" : "RGD:A57303"
    }, {
      "firstName" : "G",
      "lastName" : "Farino",
      "authorRank" : 14,
      "name" : "Farino G",
      "referenceId" : "RGD:A57304"
    }, {
      "firstName" : "D",
      "lastName" : "Gray",
      "authorRank" : 15,
      "name" : "Gray D",
      "referenceId" : "RGD:A57305"
    }, {
      "firstName" : "MO",
      "lastName" : "Anderson",
      "authorRank" : 16,
      "name" : "Anderson MO",
      "referenceId" : "RGD:A57306"
    }, {
      "firstName" : "R",
      "lastName" : "Devine",
      "authorRank" : 17,
      "name" : "Devine R",
      "referenceId" : "RGD:A57307"
    }, {
      "firstName" : "JR",
      "lastName" : "Horton LT",
      "authorRank" : 18,
      "name" : "Horton LT JR",
      "referenceId" : "RGD:A57308"
    }, {
      "firstName" : "W",
      "lastName" : "Ye",
      "authorRank" : 19,
      "name" : "Ye W",
      "referenceId" : "RGD:A52392"
    }, {
      "firstName" : "X",
      "lastName" : "Wu",
      "authorRank" : 20,
      "name" : "Wu X",
      "referenceId" : "RGD:A8038"
    }, {
      "firstName" : "V",
      "lastName" : "Kouyoumjian",
      "authorRank" : 21,
      "name" : "Kouyoumjian V",
      "referenceId" : "RGD:A57309"
    }, {
      "firstName" : "IS",
      "lastName" : "Zemsteva",
      "authorRank" : 22,
      "name" : "Zemsteva IS",
      "referenceId" : "RGD:A57310"
    }, {
      "firstName" : "Y",
      "lastName" : "Wu",
      "authorRank" : 23,
      "name" : "Wu Y",
      "referenceId" : "RGD:A17025"
    }, {
      "firstName" : "AJ",
      "lastName" : "Collymore",
      "authorRank" : 24,
      "name" : "Collymore AJ",
      "referenceId" : "RGD:A57311"
    }, {
      "firstName" : "DF",
      "lastName" : "Courtney",
      "authorRank" : 25,
      "name" : "Courtney DF",
      "referenceId" : "RGD:A57312"
    }, {
      "firstName" : "J",
      "lastName" : "Tam",
      "authorRank" : 26,
      "name" : "Tam J",
      "referenceId" : "RGD:A12228"
    }, {
      "firstName" : "M",
      "lastName" : "Cadman",
      "authorRank" : 27,
      "name" : "Cadman M",
      "referenceId" : "RGD:A57313"
    }, {
      "firstName" : "AR",
      "lastName" : "Haynes",
      "authorRank" : 28,
      "name" : "Haynes AR",
      "referenceId" : "RGD:A6617"
    }, {
      "firstName" : "C",
      "lastName" : "Heuston",
      "authorRank" : 29,
      "name" : "Heuston C",
      "referenceId" : "RGD:A6612"
    }, {
      "firstName" : "T",
      "lastName" : "Marsland",
      "authorRank" : 30,
      "name" : "Marsland T",
      "referenceId" : "RGD:A57314"
    }, {
      "firstName" : "A",
      "lastName" : "Southwell",
      "authorRank" : 31,
      "name" : "Southwell A",
      "referenceId" : "RGD:A6614"
    }, {
      "firstName" : "P",
      "lastName" : "Trickett",
      "authorRank" : 32,
      "name" : "Trickett P",
      "referenceId" : "RGD:A6611"
    }, {
      "firstName" : "MA",
      "lastName" : "Strivens",
      "authorRank" : 33,
      "name" : "Strivens MA",
      "referenceId" : "RGD:A6610"
    }, {
      "firstName" : "MT",
      "lastName" : "Ross",
      "authorRank" : 34,
      "name" : "Ross MT",
      "referenceId" : "RGD:A46296"
    }, {
      "firstName" : "W",
      "lastName" : "Makalowski",
      "authorRank" : 35,
      "name" : "Makalowski W",
      "referenceId" : "RGD:A20874"
    }, {
      "firstName" : "Y",
      "lastName" : "Xu",
      "authorRank" : 36,
      "name" : "Xu Y",
      "referenceId" : "RGD:A160328"
    }, {
      "firstName" : "MS",
      "lastName" : "Boguski",
      "authorRank" : 37,
      "name" : "Boguski MS",
      "referenceId" : "RGD:A24622"
    }, {
      "firstName" : "NP",
      "lastName" : "Carter",
      "authorRank" : 38,
      "name" : "Carter NP",
      "referenceId" : "RGD:A57316"
    }, {
      "firstName" : "P",
      "lastName" : "Denny",
      "authorRank" : 39,
      "name" : "Denny P",
      "referenceId" : "RGD:A6627"
    }, {
      "firstName" : "SD",
      "lastName" : "Brown",
      "authorRank" : 40,
      "name" : "Brown SD",
      "referenceId" : "RGD:A6625"
    }, {
      "firstName" : "TJ",
      "lastName" : "Hudson",
      "authorRank" : 41,
      "name" : "Hudson TJ",
      "referenceId" : "RGD:A6603"
    }, {
      "firstName" : "ES",
      "lastName" : "Lander",
      "authorRank" : 42,
      "name" : "Lander ES",
      "referenceId" : "RGD:A144400"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1556779"
    } ]
  }, {
    "primaryId" : "PMID:10431248",
    "title" : "Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Gedeon AK, etal., Nat Genet. 1999 Aug;22(4):400-4. doi: 10.1038/11976.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:18:53.000-05:00",
    "volume" : "22",
    "pages" : "400-4",
    "abstract" : "Spondyloepiphyseal dysplasia tarda (SEDL; MIM 313400) is an X-linked recessive osteochondrodysplasia that occurs in approximately two of every one million people. This progressive skeletal disorder which manifests in childhood is characterized by disproportionate short stature with short neck and trunk, barrel chest and absence of systemic complications. Distinctive radiological signs are platyspondyly with hump-shaped central and posterior portions, narrow disc spaces, and mild to moderate epiphyseal dysplasia. The latter usually leads to premature secondary osteoarthritis often requiring hip arthroplasty. Obligate female carriers are generally clinically and radiographically indistinguishable from the general population, although some cases have phenotypic changes consistent with expression of the gene defect. The SEDL gene has been localized to Xp22 (refs 8,9) in the approximately 2-Mb interval between DXS16 and DXS987 (ref. 10). Here we confirm and refine this localization to an interval of less than 170 kb by critical recombination events at DXS16 and AFMa124wc1 in two families. In one candidate gene we detected three dinucleotide deletions in three Australian families which effect frameshifts causing premature stop codons. The gene designated SEDL is transcribed as a 2.8-kb transcript in many tissues including fetal cartilage. SEDL encodes a 140 amino acid protein with a putative role in endoplasmic reticulum (ER)-to-Golgi vesicular transport.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A K",
      "lastName" : "Gedeon",
      "authorRank" : 1,
      "name" : "Gedeon AK",
      "referenceId" : "RGD:A449132"
    }, {
      "firstName" : "A",
      "lastName" : "Colley",
      "authorRank" : 2,
      "name" : "Colley A",
      "referenceId" : "RGD:A577876"
    }, {
      "firstName" : "R",
      "lastName" : "Jamieson",
      "authorRank" : 3,
      "name" : "Jamieson R",
      "referenceId" : "RGD:A577877"
    }, {
      "firstName" : "E M",
      "lastName" : "Thompson",
      "authorRank" : 4,
      "name" : "Thompson EM",
      "referenceId" : "RGD:A577878"
    }, {
      "firstName" : "J",
      "lastName" : "Rogers",
      "authorRank" : 5,
      "name" : "Rogers J",
      "referenceId" : "RGD:A298689"
    }, {
      "firstName" : "D",
      "lastName" : "Sillence",
      "authorRank" : 6,
      "name" : "Sillence D",
      "referenceId" : "RGD:A49916"
    }, {
      "firstName" : "G E",
      "lastName" : "Tiller",
      "authorRank" : 7,
      "name" : "Tiller GE",
      "referenceId" : "RGD:A444212"
    }, {
      "firstName" : "J C",
      "lastName" : "Mulley",
      "authorRank" : 8,
      "name" : "Mulley JC",
      "referenceId" : "RGD:A575678"
    }, {
      "firstName" : "J",
      "lastName" : "Gécz",
      "authorRank" : 9,
      "name" : "Gécz J",
      "referenceId" : "RGD:A570611"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598116109"
    } ]
  }, {
    "primaryId" : "PMID:10431686",
    "title" : "Efficacy of repeated cycles of chemo-immunotherapy with thymosin alpha1 and interleukin-2 after intraperitoneal 5-fluorouracil delivery.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Silecchia G, etal., Cancer Immunol Immunother. 1999 Jul;48(4):172-8. doi: 10.1007/s002620050562.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-12-01T11:37:39.000-06:00",
    "volume" : "48",
    "pages" : "172-8",
    "abstract" : "We have used chemo-immunotherapy with 5-fluorouracil (5-FU), thymosin alpha1 (T alpha1) and interleukin-2 (IL-2) to treat multiple liver metastases from colorectal cancer induced by DHD/K12 cells in syngeneic BDIX rats, comparing one and two cycles of treatment, and different treatment combinations. 5-FU was delivered loco-regionally as a continuous infusion via an intraperitoneal (i.p.) catheter from a subcutaneously implanted mini-pump, a method we developed for this study. We show here that two cycles of a triple chemo-immunotherapy regimen significantly increased the average survival time compared to one cycle, and compared to untreated controls or those treated with two cycles of 5-FU alone. At 150 days, two rats treated with two cycles of triple therapy were cured, showing no signs of cancer at autopsy; all the other rats died before this time. Triple chemo-immunotherapy resulted in significantly fewer extra-hepatic metastases than in the controls and in those treated with 5-FU only. Further, we found that two cycles of triple treatment significantly increased the absolute number of peripheral T cells expressing IL-2 receptor, CD4 and CD8 compared to controls. We conclude that two cycles of chemo-immunotherapy with 5-FU, T alpha1 and IL-2 were superior to one cycle of treatment and to other treatments tested. Our results suggest that the triple therapy acts by increasing numbers of effector T cells. This method shows promise for the use of multi-cycle chemo-immunotherapy in the treatment of unresectable metastases of colorectal cancer in humans.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Silecchia",
      "authorRank" : 1,
      "name" : "Silecchia G",
      "referenceId" : "RGD:A507333"
    }, {
      "firstName" : "E",
      "lastName" : "Guarino",
      "authorRank" : 2,
      "name" : "Guarino E",
      "referenceId" : "RGD:A507334"
    }, {
      "firstName" : "P",
      "lastName" : "Sinibaldi-Vallebona",
      "authorRank" : 3,
      "name" : "Sinibaldi-Vallebona P",
      "referenceId" : "RGD:A507335"
    }, {
      "firstName" : "P",
      "lastName" : "Pierimarchi",
      "authorRank" : 4,
      "name" : "Pierimarchi P",
      "referenceId" : "RGD:A156766"
    }, {
      "firstName" : "A",
      "lastName" : "Restuccia",
      "authorRank" : 5,
      "name" : "Restuccia A",
      "referenceId" : "RGD:A507336"
    }, {
      "firstName" : "E",
      "lastName" : "Spaziani",
      "authorRank" : 6,
      "name" : "Spaziani E",
      "referenceId" : "RGD:A507337"
    }, {
      "firstName" : "P",
      "lastName" : "Bernard",
      "authorRank" : 7,
      "name" : "Bernard P",
      "referenceId" : "RGD:A112500"
    }, {
      "firstName" : "C",
      "lastName" : "Tuthill",
      "authorRank" : 8,
      "name" : "Tuthill C",
      "referenceId" : "RGD:A507338"
    }, {
      "firstName" : "E",
      "lastName" : "Garaci",
      "authorRank" : 9,
      "name" : "Garaci E",
      "referenceId" : "RGD:A507339"
    }, {
      "firstName" : "G",
      "lastName" : "Rasi",
      "authorRank" : 10,
      "name" : "Rasi G",
      "referenceId" : "RGD:A156765"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:150526807"
    } ]
  }, {
    "primaryId" : "PMID:10431747",
    "title" : "Subclass profile of specific IgG antibodies in rats challenged during acute and chronic primary infection with Fasciola hepatica.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Paz A, etal., Parasitol Res. 1999 Aug;85(8-9):770-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-06-26T13:46:12.000-05:00",
    "volume" : "85",
    "pages" : "770-5",
    "abstract" : "The influence of a previous infection (acute and chronic) on the kinetics of the  immune humoral response in rats challenged with Fasciola hepatica was studied. Two infected groups were reinfected at different times--one, at 4 weeks after primary infection (w.a.p.i.); and the other, at 11 w.a.p.i. Signs of reinfection  were observed in the two challenged groups as evidenced by an increment in glutamate dehydrogenase and gamma-glutamyl transpeptidase activity after secondary infection. IgG subclass (IgG1, IgG2a, IgG2b, IgG2c) responses to F. hepatica excretory/secretory products (FhESP) differed, depending on the time of  challenge infection, but no difference was observed between the reinfected groups. A predominance of the IgG1 subclass was noted in the group challenged at  4 w.a.p.i., and IgG2b and IgG2c were prominent in the group reinfected at 11 w.a.p.i. These results indicate that the presence of juvenile or adult flukes in  the liver at the time of challenge seems to influence the immune response to a secondary infection.",
    "issueName" : "8-9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Paz",
      "authorRank" : 1,
      "name" : "Paz A",
      "referenceId" : "RGD:A100343"
    }, {
      "firstName" : "R",
      "lastName" : "Sanchez-Andrade",
      "authorRank" : 2,
      "name" : "Sanchez-Andrade R",
      "referenceId" : "RGD:A156081"
    }, {
      "firstName" : "R",
      "lastName" : "Panadero",
      "authorRank" : 3,
      "name" : "Panadero R",
      "referenceId" : "RGD:A156082"
    }, {
      "firstName" : "JL",
      "lastName" : "Suarez",
      "authorRank" : 4,
      "name" : "Suarez JL",
      "referenceId" : "RGD:A156083"
    }, {
      "firstName" : "P",
      "lastName" : "Diez-Banos",
      "authorRank" : 5,
      "name" : "Diez-Banos P",
      "referenceId" : "RGD:A156084"
    }, {
      "firstName" : "P",
      "lastName" : "Morrondo",
      "authorRank" : 6,
      "name" : "Morrondo P",
      "referenceId" : "RGD:A156085"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6484593"
    } ]
  }, {
    "primaryId" : "PMID:10431815",
    "title" : "Characterization of the binding and phosphorylation of cardiac calsequestrin by epsilon protein kinase C.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Rodriguez MM, etal., FEBS Lett 1999 Jul 9;454(3):240-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:04.000-06:00",
    "volume" : "454",
    "pages" : "240-6",
    "abstract" : "In this study, we report the cloning of the rat cardiac isoform of calsequestrin on the basis of its interaction with an epsilonprotein kinase C-unique sequence (epsilonV1) derived form the epsilonprotein kinase C regulatory domain. Calsequestrin binds activated epsilonprotein kinase C holoenzyme better than the inactive enzyme and nearly three times better than other protein kinase C isozymes. The interaction between epsilonprotein kinase C and calsequestrin is mediated by sequences in both the regulatory and kinase domains of the epsilonprotein kinase C. Finally, we show that calsequestrin is an epsilonprotein kinase C substrate in vitro and protein kinase C phosphorylation of calsequestrin leads to a decreased binding of epsilonprotein kinase C to calsequestrin.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Rodriguez",
      "authorRank" : 1,
      "name" : "Rodriguez MM",
      "referenceId" : "RGD:A7182"
    }, {
      "firstName" : "CH",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen CH",
      "referenceId" : "RGD:A5845"
    }, {
      "firstName" : "BL",
      "lastName" : "Smith",
      "authorRank" : 3,
      "name" : "Smith BL",
      "referenceId" : "RGD:A7183"
    }, {
      "firstName" : "D",
      "lastName" : "Mochly-Rosen",
      "authorRank" : 4,
      "name" : "Mochly-Rosen D",
      "referenceId" : "RGD:A5849"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69798"
    } ]
  }, {
    "primaryId" : "PMID:10432312",
    "title" : "Biosynthesis of inositol trisphosphate receptors: selective association with the molecular chaperone calnexin.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Joseph SK, etal., Biochem J. 1999 Aug 15;342 ( Pt 1):153-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-11T11:34:34.000-05:00",
    "volume" : "342 ( Pt 1)",
    "pages" : "153-61",
    "abstract" : "A prominent labelled polypeptide having the same mobility as type-I inositol trisphosphate receptor (IP(3)R) was immunoprecipitated from WB-cell lysates by antibodies to calnexin, an ER integral membrane chaperone. The identity of this polypeptide was confirmed by re-immunoprecipitation of the radioactive polypeptides released from calnexin-antibody immunoprecipitates with type-I IP(3)R antibody. The interaction of calnexin with newly synthesized type-I IP(3)R was transient and inhibited by treatment of the cells with dithiothreitol or the glucosidase inhibitor N-methyldeoxynojirimicin. In similar experiments, there was no evidence for the binding of type-I IP(3)R to calreticulin, an ER luminal chaperone. Calnexin (but not calreticulin) associated with newly synthesized FLAG (DYKDDDDK epitope)-tagged type-III IP(3)R expressed in COS-7 cells. In order to further define the mechanism of interaction of nascent IP(3)R with chaperones, we have utilized an in vitro rabbit reticulocyte translation assay programmed with RNA templates encoding the six putative transmembrane (TM) domains of IP(3)Rs. In accordance with the known preference of calnexin for monoglucosylated oligosaccharide chains, calnexin antibody preferentially immunoprecipitated a proportion of glycosylated type-I translation product. Addition of glucosidase inhibitors prevented the association of calnexin with in vitro translated type-I TM construct. Using truncated RNA templates we found that calnexin did not associate with the first four TM domains but retained affinity for the construct encoding TM domains 5 and 6, which contains the glycosylation sites. We propose that calnexin is a key chaperone involved in the folding, assembly and oligomerization of newly synthesized IP(3) receptors in the ER.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SK",
      "lastName" : "Joseph",
      "authorRank" : 1,
      "name" : "Joseph SK",
      "referenceId" : "RGD:A32186"
    }, {
      "firstName" : "D",
      "lastName" : "Boehning",
      "authorRank" : 2,
      "name" : "Boehning D",
      "referenceId" : "RGD:A111873"
    }, {
      "firstName" : "S",
      "lastName" : "Bokkala",
      "authorRank" : 3,
      "name" : "Bokkala S",
      "referenceId" : "RGD:A111874"
    }, {
      "firstName" : "R",
      "lastName" : "Watkins",
      "authorRank" : 4,
      "name" : "Watkins R",
      "referenceId" : "RGD:A111875"
    }, {
      "firstName" : "J",
      "lastName" : "Widjaja",
      "authorRank" : 5,
      "name" : "Widjaja J",
      "referenceId" : "RGD:A111876"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313157"
    } ]
  }, {
    "primaryId" : "PMID:10432316",
    "title" : "Expression, DNA-binding specificity and transcriptional regulation of nuclear factor 1 family proteins from rat.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Osada S, etal., Biochem J 1999 Aug 15;342 ( Pt 1)(21):189-98.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-10T11:27:24.000-05:00",
    "volume" : "342 ( Pt 1)",
    "pages" : "189-98",
    "abstract" : "Nuclear factor 1 (NF1) family proteins, which are encoded by four different genes (NF1-A, NF1-B, NF1-C and NF1-X), bind to the palindromic sequence and regulate the expression of many viral and cellular genes. We have previously purified NF1-A and NF1-B from rat liver as factors that bind to the silencer in the glutathione transferase P gene, and have also reported the repression domain of NF1-A. In the present study we cloned five cDNA species (NF1-B1, NF1-B2, NF1-B3, NF1-C2 and NF1-X1) and compared their expression profiles and the affinity and specificity of the DNA binding of these NF1 family members. By Northern blot analysis, we found that the expression profiles of the NF1s are indistinguishable in the various tissues of the rat. The DNA-binding affinities of NF1-A and NF1-X are higher than those of NF1-B and NF1-C, whereas all four NF1 proteins showed the same DNA-binding specificity. Transfection analyses revealed that the function of NF1-B on the transcriptional regulation differed between NF1-B isoforms and was affected by the factor(s) that bind to the promoter regions. In addition, we identified the transcriptional regulatory domain of NF1-B, which is enriched with proline and serine residues.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Osada",
      "authorRank" : 1,
      "name" : "Osada S",
      "referenceId" : "RGD:A116137"
    }, {
      "firstName" : "T",
      "lastName" : "Matsubara",
      "authorRank" : 2,
      "name" : "Matsubara T",
      "referenceId" : "RGD:A154566"
    }, {
      "firstName" : "S",
      "lastName" : "Daimon",
      "authorRank" : 3,
      "name" : "Daimon S",
      "referenceId" : "RGD:A31399"
    }, {
      "firstName" : "Y",
      "lastName" : "Terazu",
      "authorRank" : 4,
      "name" : "Terazu Y",
      "referenceId" : "RGD:A3441"
    }, {
      "firstName" : "M",
      "lastName" : "Xu",
      "authorRank" : 5,
      "name" : "Xu M",
      "referenceId" : "RGD:A160330"
    }, {
      "firstName" : "T",
      "lastName" : "Nishihara",
      "authorRank" : 6,
      "name" : "Nishihara T",
      "referenceId" : "RGD:A150090"
    }, {
      "firstName" : "M",
      "lastName" : "Imagawa",
      "authorRank" : 7,
      "name" : "Imagawa M",
      "referenceId" : "RGD:A122922"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61671"
    } ]
  }, {
    "primaryId" : "PMID:10432379",
    "title" : "Genetic mapping of modifier loci affecting malignant hypertension in TGRmRen2 rats.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kantachuvesiri S, etal., Kidney Int 1999 Aug;56(2):414-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-08-05T10:41:12.000-05:00",
    "volume" : "56",
    "pages" : "414-20",
    "abstract" : "BACKGROUND: Genetic background has a major influence on the manifestation of multifactorial diseases such as hypertension in which severe complications may be caused through an interaction with additional factors, which may be genetically determined. We have previously described a genetic model of malignant hypertension (MH) in rats carrying the mouse Ren2 gene (TGRmRen2-27), in which the phenotype is dependent on the genetic background. METHODS: Using a single homozygous TGRmRen2-27 male as transgene donor, we produced two F1 populations with (a) 100% penetrance of MH in progeny heterozygous for the Fischer F344 genetic background and (b) 58.5% penetrance in progeny heterozygous for the Lewis genetic background. To identify the modifier loci affecting the phenotype, a cohort of 252 males was produced by breeding the same single male with Fischer-Lewis F1 females. The progeny were phenotyped for clinical and pathological features of MH. RESULTS: Genome-wide screening and quantitative trait loci (QTL) analysis identified two loci, on chromosome 10 (LOD 4.4) and on chromosome 17 (LOD 3.9) close to the Ace and At1 genes, respectively, which contribute to the lethal MH phenotype. Their influence on mortality was consistent with a multiplicative effect of the two loci. In addition, we found higher plasma angiotensin-converting enzyme activity in progeny receiving the Fischer allele than in progeny receiving the Lewis allele (123.5 +/- 9.5 vs. 91.8 +/- 4.9 U/liter, P < 0.01), suggesting the association of angiotensin-converting enzyme and MH. CONCLUSIONS: Our study demonstrates the application of a transgene as a \"major gene\" to facilitate the identification of modifier loci, which can affect the phenotype of MH, and reveals Ace and At1 as candidate genes involved in the manifestation of the MH phenotype.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kantachuvesiri",
      "authorRank" : 1,
      "name" : "Kantachuvesiri S",
      "referenceId" : "RGD:A10671"
    }, {
      "firstName" : "CS",
      "lastName" : "Haley",
      "authorRank" : 2,
      "name" : "Haley CS",
      "referenceId" : "RGD:A6914"
    }, {
      "firstName" : "S",
      "lastName" : "Fleming",
      "authorRank" : 3,
      "name" : "Fleming S",
      "referenceId" : "RGD:A10834"
    }, {
      "firstName" : "K",
      "lastName" : "Kurian",
      "authorRank" : 4,
      "name" : "Kurian K",
      "referenceId" : "RGD:A10835"
    }, {
      "firstName" : "CE",
      "lastName" : "Whitworth",
      "authorRank" : 5,
      "name" : "Whitworth CE",
      "referenceId" : "RGD:A10836"
    }, {
      "firstName" : "P",
      "lastName" : "Wenham",
      "authorRank" : 6,
      "name" : "Wenham P",
      "referenceId" : "RGD:A10837"
    }, {
      "firstName" : "Y",
      "lastName" : "Kotelevtsev",
      "authorRank" : 7,
      "name" : "Kotelevtsev Y",
      "referenceId" : "RGD:A102148"
    }, {
      "firstName" : "JJ",
      "lastName" : "Mullins",
      "authorRank" : 8,
      "name" : "Mullins JJ",
      "referenceId" : "RGD:A10673"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619627"
    } ]
  }, {
    "primaryId" : "PMID:10432380",
    "title" : "A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Matsunaga A, etal., Kidney Int. 1999 Aug;56(2):421-7. doi: 10.1046/j.1523-1755.1999.00572.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T17:36:51.000-05:00",
    "volume" : "56",
    "pages" : "421-7",
    "abstract" : "<br><b>BACKGROUND: </b>Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG. We detected a novel point mutation in the apo E gene in a patient with LPG, and we characterized the mutant apo E.<br><b>METHODS: </b>The propositus was a 32-year-old male patient on maintenance hemodialysis because of LPG. The mutation was detected by sequencing of genomic DNA from the patient and was confirmed by restriction fragment length polymorphism (RFLP) with Aor51HI. Recombinant apo E2 (Arg25Cys) Kyoto and normal apo E3 were expressed from COS-1 cells. Low-density lipoprotein (LDL) receptor-binding activities of the variants were determined in an in vitro competition assay.<br><b>RESULTS: </b>The propositus had the apo E phenotype E2/E4, as determined by isoelectric focusing, and the genotype epsilon3/epsilon4, as determined by RFLP with HhaI. Sequence analysis of amplified DNA showed a C to T transition, changing the codon for residue 25 from arginine to cysteine. The proband was a heterozygous carrier for apo E2 (Arg25Cys) Kyoto. A family study showed that the mother was a heterozygous carrier of apo E2 Kyoto and had dysbetalipoproteinemia, but no LPG. The pathophysiological effect of this mutation was investigated in vitro by binding studies of recombinant apo E2 Kyoto to LDL receptors on human fibroblasts. The ability of recombinant apo E2 Kyoto to displace LDL was reduced to 10% compared with recombinant apo E3.<br><b>CONCLUSIONS: </b>Apo E2 (Arg25Cys) Kyoto is a novel mutation of apo E that is etiologically related to LPG. However, our case indicates that the development of LPG may involve other genetic or environmental factors. Furthermore, our data suggest that arginine-25 of apo E plays an important functional role by influencing the receptor-binding ability of apo E.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Matsunaga",
      "authorRank" : 1,
      "name" : "Matsunaga A",
      "referenceId" : "RGD:A59009"
    }, {
      "firstName" : "J",
      "lastName" : "Sasaki",
      "authorRank" : 2,
      "name" : "Sasaki J",
      "referenceId" : "RGD:A46939"
    }, {
      "firstName" : "T",
      "lastName" : "Komatsu",
      "authorRank" : 3,
      "name" : "Komatsu T",
      "referenceId" : "RGD:A100403"
    }, {
      "firstName" : "K",
      "lastName" : "Kanatsu",
      "authorRank" : 4,
      "name" : "Kanatsu K",
      "referenceId" : "RGD:A604070"
    }, {
      "firstName" : "E",
      "lastName" : "Tsuji",
      "authorRank" : 5,
      "name" : "Tsuji E",
      "referenceId" : "RGD:A23558"
    }, {
      "firstName" : "K",
      "lastName" : "Moriyama",
      "authorRank" : 6,
      "name" : "Moriyama K",
      "referenceId" : "RGD:A75813"
    }, {
      "firstName" : "T",
      "lastName" : "Koga",
      "authorRank" : 7,
      "name" : "Koga T",
      "referenceId" : "RGD:A15182"
    }, {
      "firstName" : "K",
      "lastName" : "Arakawa",
      "authorRank" : 8,
      "name" : "Arakawa K",
      "referenceId" : "RGD:A23563"
    }, {
      "firstName" : "S",
      "lastName" : "Oikawa",
      "authorRank" : 9,
      "name" : "Oikawa S",
      "referenceId" : "RGD:A12671"
    }, {
      "firstName" : "T",
      "lastName" : "Saito",
      "authorRank" : 10,
      "name" : "Saito T",
      "referenceId" : "RGD:A161595"
    }, {
      "firstName" : "T",
      "lastName" : "Kita",
      "authorRank" : 11,
      "name" : "Kita T",
      "referenceId" : "RGD:A59017"
    }, {
      "firstName" : "T",
      "lastName" : "Doi",
      "authorRank" : 12,
      "name" : "Doi T",
      "referenceId" : "RGD:A21818"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598120143"
    } ]
  }, {
    "primaryId" : "PMID:10432381",
    "title" : "TGF-beta receptor expression and binding in rat mesangial cells: modulation by glucose and cyclic mechanical strain.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Riser BL, etal., Kidney Int. 1999 Aug;56(2):428-39.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-26T09:43:44.000-05:00",
    "volume" : "56",
    "pages" : "428-39",
    "abstract" : "BACKGROUND: Transforming growth factor-beta (TGF-beta) is a causal factor in experimental glomerulosclerosis, and it mediates the increased extracellular matrix (ECM) accumulation that occurs in cultured mesangial cells (MCs) exposed to high glucose concentrations and cyclic mechanical strain. This change is associated with increased levels of TGF-beta, but may also involve alterations in receptor expression and binding. METHODS: Rat MCs cultured in media containing either 8 or 35 mM glucose were seeded into culture plates with elastin-coated flexible bottoms. Thereafter, they were subjected to cyclic stretch or static conditions and then examined for 125I-TGF-beta1 binding and expression of TGF-beta receptors at the gene and protein levels. RESULTS: Kinetic studies showed that MCs bound TGF-beta1 in a time- and concentration-dependent manner, expressing 6800 high-affinity receptors per cell, with an apparent dissociation constant (Kd) of 15.4 pM, while cross-linking analysis identified three TGF-beta receptors (betaR) corresponding to betaRI, betaRII, and betaRIII of 54, 73, and 200 kDa, respectively. Immunocytochemical studies of betaRI and betaRII protein revealed MC expression in a homogeneous, punctate distribution, whereas Northern analysis demonstrated the presence of the corresponding mRNAs. Exposure to cyclic stretching significantly increased (10%) the overall number of TGF-beta receptors, whereas ligands associated with betaRs I, II, and III also increased (25 to 50%). The finding of increased (30 to 40%) betaRI and betaRII transcript levels and immunoreactive protein (163 and 59%, respectively) in the absence of significant changes in the apparent Kd indicated that stretch-induced binding was the result of increased receptor synthesis and expression and not due to a change in binding affinity. In a similar, but more dramatic fashion, exposure to high glucose also elevated (50%) the receptor number, as well as the amount of ligands associated with betaRs I, II, and III (100 to 250%). This same treatment also increased the levels of betaRI and betaRII mRNA (30 to 40%) and the immunoreactive protein (82 and 82%, respectively), without significantly altering the binding affinity of the receptor. A concerted or synergistic effect of both stimuli was not evidenced. CONCLUSION: These results suggest that the modulation of TGF-beta receptors may be an additional control point in mediating the glucose- and mechanical force-induced increase in ECM deposition by MCs.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BL",
      "lastName" : "Riser",
      "authorRank" : 1,
      "name" : "Riser BL",
      "referenceId" : "RGD:A29060"
    }, {
      "firstName" : "S",
      "lastName" : "Ladson-Wofford",
      "authorRank" : 2,
      "name" : "Ladson-Wofford S",
      "referenceId" : "RGD:A81615"
    }, {
      "firstName" : "A",
      "lastName" : "Sharba",
      "authorRank" : 3,
      "name" : "Sharba A",
      "referenceId" : "RGD:A81616"
    }, {
      "firstName" : "P",
      "lastName" : "Cortes",
      "authorRank" : 4,
      "name" : "Cortes P",
      "referenceId" : "RGD:A29057"
    }, {
      "firstName" : "K",
      "lastName" : "Drake",
      "authorRank" : 5,
      "name" : "Drake K",
      "referenceId" : "RGD:A81617"
    }, {
      "firstName" : "CJ",
      "lastName" : "Guerin",
      "authorRank" : 6,
      "name" : "Guerin CJ",
      "referenceId" : "RGD:A52337"
    }, {
      "firstName" : "J",
      "lastName" : "Yee",
      "authorRank" : 7,
      "name" : "Yee J",
      "referenceId" : "RGD:A20063"
    }, {
      "firstName" : "ME",
      "lastName" : "Choi",
      "authorRank" : 8,
      "name" : "Choi ME",
      "referenceId" : "RGD:A68233"
    }, {
      "firstName" : "PR",
      "lastName" : "Segarini",
      "authorRank" : 9,
      "name" : "Segarini PR",
      "referenceId" : "RGD:A81618"
    }, {
      "firstName" : "RG",
      "lastName" : "Narins",
      "authorRank" : 10,
      "name" : "Narins RG",
      "referenceId" : "RGD:A81619"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601616"
    } ]
  }, {
    "primaryId" : "PMID:10432392",
    "title" : "Differential regulation of renal prostaglandin receptor mRNAs by dietary salt intake in the rat.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Jensen BL, etal., Kidney Int. 1999 Aug;56(2):528-37.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-04-06T15:56:19.000-05:00",
    "volume" : "56",
    "pages" : "528-37",
    "abstract" : "BACKGROUND: In this study, we tested the hypothesis that prostaglandin (PG) receptor expression in the rat kidney is subject to physiological regulation by dietary salt intake. METHODS: Rats were fed diets with 0.02 or 4% NaCl for two weeks. PG receptor expression was assayed in kidney regions and cells by ribonuclease protection assay and reverse transcription-polymerase chain reaction analysis. Functional correlates were studied by measurement of PGE2-induced cAMP  formation and renin secretion in juxtaglomerular (JG) cells isolated from animals on various salt intakes. RESULTS: EP1 and EP3 receptors were predominantly expressed, and the EP2 receptor was exclusively expressed in the rat kidney medulla. The EP4 receptor was strongly expressed in glomeruli and in renin-secreting JG granular cells. IP receptor transcripts were found mainly in cortex. Maintaining rats on a low- or high-NaCl diet did not affect the expression of EP1 or IP receptors, whereas EP4 transcripts in glomeruli were increased twofold by salt deprivation. Consistent with this, we found that PGE2-evoked cAMP production and renin secretion by JG cells from salt-deprived animals were significantly higher compared with cells obtained from salt-loaded animals. In the outer medulla, EP3 transcripts correlated directly with salt intake, and mRNA abundance was increased twofold by a high-NaCl diet. CONCLUSIONS: Our results suggest that subtype-specific, regional changes in PG receptor expression are involved in the renal adaptation to changes in salt intake. The results are in accord with the general concept that renocortical PGE2 stimulates renin secretion and maintains renal blood flow during low-salt states, whereas medullary PGE2 promotes salt excretion in response to a high salt intake.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BL",
      "lastName" : "Jensen",
      "authorRank" : 1,
      "name" : "Jensen BL",
      "referenceId" : "RGD:A108223"
    }, {
      "firstName" : "B",
      "lastName" : "Mann",
      "authorRank" : 2,
      "name" : "Mann",
      "referenceId" : "RGD:A200553"
    }, {
      "firstName" : "O",
      "lastName" : "Skott",
      "authorRank" : 3,
      "name" : "Skott O",
      "referenceId" : "RGD:A61312"
    }, {
      "firstName" : "A",
      "lastName" : "Kurtz",
      "authorRank" : 4,
      "name" : "Kurtz A",
      "referenceId" : "RGD:A1134"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9850282"
    } ]
  }, {
    "primaryId" : "PMID:10432394",
    "title" : "Screening for genes up-regulated in 5/6 nephrectomized mouse kidney.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Zhang H, etal., Kidney Int 1999 Aug;56(2):549-58.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T17:22:34.000-05:00",
    "volume" : "56",
    "pages" : "549-58",
    "abstract" : "BACKGROUND: In diabetic and nondiabetic renal diseases, glomerular hyperfiltration is believed to play a central role in the subsequent progression of glomerulosclerosis and interstitial renal scarring. To identify genes involved in the process of hyperfiltration and hypertrophy, a polymerase chain reaction (PCR)-based subtraction method, that is, representational difference analysis of cDNA (cDNA-RDA), was employed. METHODS: Ten-week-old ICR mice were 5/6 nephrectomized and sham operated. After two weeks, mRNAs were isolated from control and remnant kidneys and were subjected to the cDNA-RDA procedure. RESULTS: We identified 10 known and 9 novel genes. Among 19 clones, 12 clones (8 known and 4 novel) showed 1.5- to 6-fold up-regulation by Northern blot analyses. The remaining seven clones were rarely expressed genes and were barely detected by Northern blot analyses, and their up-regulated expression was confirmed by Southern blot analysis using the PCR-amplified representative amplicons. The known genes included kidney androgen-regulated protein, major urinary protein, lysozyme M, metalloproteinase-3 tissue inhibitor, chaperonin 10, cytochrome oxidase I, epsilon-sarcoglycan, ribosomal protein S3a, G-proteingamma10 subunit, and splicing factor 9G8. All of the isolated known genes have not been reported to be up-regulated in the nephrectomized mouse kidney and suggest the possible role of androgen action, mitochondrial functions, matrix metabolism, cell-matrix interactions, and intracellular signaling events in the initiation of the progressive renal injury of the remnant kidney. Furthermore, cDNA-RDA facilitates the discovery of novel genes, including two kidney-specific genes. CONCLUSIONS: The isolated known and novel genes may be involved in the pathobiological process of initial hyperfiltration and hypertrophy of remnant kidney.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Zhang",
      "authorRank" : 1,
      "name" : "Zhang H",
      "referenceId" : "RGD:A6284"
    }, {
      "firstName" : "J",
      "lastName" : "Wada",
      "authorRank" : 2,
      "name" : "Wada J",
      "referenceId" : "RGD:A15598"
    }, {
      "firstName" : "YS",
      "lastName" : "Kanwar",
      "authorRank" : 3,
      "name" : "Kanwar YS",
      "referenceId" : "RGD:A15602"
    }, {
      "firstName" : "Y",
      "lastName" : "Tsuchiyama",
      "authorRank" : 4,
      "name" : "Tsuchiyama Y",
      "referenceId" : "RGD:A11564"
    }, {
      "firstName" : "K",
      "lastName" : "Hiragushi",
      "authorRank" : 5,
      "name" : "Hiragushi K",
      "referenceId" : "RGD:A43154"
    }, {
      "firstName" : "K",
      "lastName" : "Hida",
      "authorRank" : 6,
      "name" : "Hida K",
      "referenceId" : "RGD:A43153"
    }, {
      "firstName" : "K",
      "lastName" : "Shikata",
      "authorRank" : 7,
      "name" : "Shikata K",
      "referenceId" : "RGD:A34042"
    }, {
      "firstName" : "H",
      "lastName" : "Makino",
      "authorRank" : 8,
      "name" : "Makino H",
      "referenceId" : "RGD:A160891"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299473"
    } ]
  }, {
    "primaryId" : "PMID:10432400",
    "title" : "Prevention of crescentic glomerulonephritis by immunoneutralization of the fractalkine receptor CX3CR1 rapid communication.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Feng L, etal., Kidney Int. 1999 Aug;56(2):612-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-01-27T17:46:59.000-06:00",
    "volume" : "56",
    "pages" : "612-20",
    "abstract" : "BACKGROUND: Fractalkine is a newly identified T-cell and monocyte/macrophage (Mphi) chemokine with a transmembrane domain and is a cell-surface protein on activated endothelium. It can mediate adhesion of cells expressing the fractalkine receptor CX3CR1. These unique features make fractalkine well suited for leukocyte recruitment in tissues with high blood flow as in the renal glomerulus. METHODS: Fractalkine expression in glomeruli and response of isolated glomerular inflammatory cells to fractalkine were studied in the Wistar-Kyoto (WKY) crescentic glomerulonephritis model. Antibody was used to confirm the proinflammatory role of fractalkine. RESULTS: Fractalkine was markedly induced in the endothelium of nephritic rat glomeruli, and inflammatory leukocytes infiltrating the glomeruli expressed increased levels of CX3CR1. Anti-CX3CR1 antibody treatment dramatically blocked leukocyte infiltration in the glomeruli, prevented crescent formation, and improved renal function. CONCLUSIONS: Fractalkine plays a central role in leukocyte trafficking at the endothelium in the high-flow glomerular circuit and, in turn, implicates CX3CR1 as a prime drug target for therapeutic intervention of endothelium-related inflammatory diseases.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Feng",
      "authorRank" : 1,
      "name" : "Feng L",
      "referenceId" : "RGD:A7447"
    }, {
      "firstName" : "S",
      "lastName" : "Chen",
      "authorRank" : 2,
      "name" : "Chen S",
      "referenceId" : "RGD:A157966"
    }, {
      "firstName" : "GE",
      "lastName" : "Garcia",
      "authorRank" : 3,
      "name" : "Garcia GE",
      "referenceId" : "RGD:A103216"
    }, {
      "firstName" : "Y",
      "lastName" : "Xia",
      "authorRank" : 4,
      "name" : "Xia Y",
      "referenceId" : "RGD:A7446"
    }, {
      "firstName" : "MA",
      "lastName" : "Siani",
      "authorRank" : 5,
      "name" : "Siani MA",
      "referenceId" : "RGD:A134230"
    }, {
      "firstName" : "P",
      "lastName" : "Botti",
      "authorRank" : 6,
      "name" : "Botti P",
      "referenceId" : "RGD:A28428"
    }, {
      "firstName" : "CB",
      "lastName" : "Wilson",
      "authorRank" : 7,
      "name" : "Wilson CB",
      "referenceId" : "RGD:A16378"
    }, {
      "firstName" : "JK",
      "lastName" : "Harrison",
      "authorRank" : 8,
      "name" : "Harrison JK",
      "referenceId" : "RGD:A134231"
    }, {
      "firstName" : "KB",
      "lastName" : "Bacon",
      "authorRank" : 9,
      "name" : "Bacon KB",
      "referenceId" : "RGD:A28429"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892027"
    } ]
  }, {
    "primaryId" : "PMID:10432437",
    "title" : "The same HLA-DQ alleles determine either susceptibility or resistance to different coxsackievirus-mediated autoimmune diseases.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Luppi P, etal., J Biol Regul Homeost Agents. 1999 Jan-Mar;13(1):14-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-08-25T14:12:45.000-05:00",
    "volume" : "13",
    "pages" : "14-26",
    "abstract" : "An important characteristic of autoimmune diseases is their association with major histocompatibility complex class I and class II alleles. In this study, we compared insulin-dependent diabetes mellitus (IDDM) with idiopathic dilated cardiomyopathy (IDC) from a strictly immunologic perspective. Although the target organs are different, being in one case the insulin-producing beta cells of the pancreas and in the other case the myocytes of the heart, many aspects of the tissue-specific immune destruction are common. Similar yet different Coxsackievirus B strains with either pancreotropic or cardiotropic specificity are able to perpetrate the first injury of the respective target tissue. Their shared capacity of inducing a superantigenic reaction further enhances the damage. Once previously secluded autoantigens are then exposed to the immune system, the tissue injury is completed via a more conventional type of immune response. On the basis of the compounded results we obtained, it is possible to propose that the same HLA-DQ molecules which are able to protect the individuals from IDDM (e.g., HLA-DQA1*0102, DQB1*0602) seem to favour the enteroviral attack to the myocardium, while alleles which confer the strongest susceptibility to IDDM (e.g., DQA1*0301, DQB1*0302), seem unable to sustain the immune attack against the heart.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Luppi",
      "authorRank" : 1,
      "name" : "Luppi P",
      "referenceId" : "RGD:A143819"
    }, {
      "firstName" : "A",
      "lastName" : "Alexander",
      "authorRank" : 2,
      "name" : "Alexander A",
      "referenceId" : "RGD:A143820"
    }, {
      "firstName" : "S",
      "lastName" : "Bertera",
      "authorRank" : 3,
      "name" : "Bertera S",
      "referenceId" : "RGD:A143821"
    }, {
      "firstName" : "K",
      "lastName" : "Noonan",
      "authorRank" : 4,
      "name" : "Noonan K",
      "referenceId" : "RGD:A112828"
    }, {
      "firstName" : "M",
      "lastName" : "Trucco",
      "authorRank" : 5,
      "name" : "Trucco M",
      "referenceId" : "RGD:A30234"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5147858"
    } ]
  }, {
    "primaryId" : "PMID:10432491",
    "title" : "Antibodies and antisense oligonucleotide for probing the distribution and putative functions of central 5-HT6 receptors.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Hamon M, etal., Neuropsychopharmacology. 1999 Aug;21(2 Suppl):68S-76S.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-10T12:48:01.000-06:00",
    "volume" : "21",
    "pages" : "68S-76S",
    "abstract" : "Among the recently cloned serotonin (5-hydroxytryptamine, 5-HT) receptors, the 5-HT6 subtype is of special interest for at least two reasons: 1) it is abundant in limbic areas which participate in the control of mood and emotion; and 2) some antidepressants and antipsychotics are potent 5-HT6 receptor antagonists. Studies using polyclonal anti-5-HT6 receptor antibodies and an antisense oligonucleotide were performed in order to investigate further the function(s) of 5-HT6 receptors in the rat brain. Immunocytochemistry at the light and electron microscope levels showed that 5-HT6 receptors are mainly confined to the dendritic compartment, suggesting that they could mediate 5-HT actions on neuronal firing. In some limbic areas, 5-HT6 receptor-like immunoreactivity is also associated with neuronal cilia with yet unknown functions. Continuous i.c.v. infusion with an antisense oligonucleotide for 3-4 days resulted in decreased 5-HT6 receptor-like immunostaining of the nucleus accumbens and anxiogenic behaviours in the social interaction and elevated plus maze tests. Selective 5-HT6 receptor ligands are eagerly expected to investigate further the potential implication of these receptors in limbic-dependent behaviours.",
    "issueName" : "2 Suppl",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Hamon",
      "authorRank" : 1,
      "name" : "Hamon M",
      "referenceId" : "RGD:A13582"
    }, {
      "firstName" : "E",
      "lastName" : "Doucet",
      "authorRank" : 2,
      "name" : "Doucet E",
      "referenceId" : "RGD:A120156"
    }, {
      "firstName" : "K",
      "lastName" : "Lefevre",
      "authorRank" : 3,
      "name" : "Lefevre K",
      "referenceId" : "RGD:A120202"
    }, {
      "firstName" : "MC",
      "lastName" : "Miquel",
      "authorRank" : 4,
      "name" : "Miquel MC",
      "referenceId" : "RGD:A13583"
    }, {
      "firstName" : "L",
      "lastName" : "Lanfumey",
      "authorRank" : 5,
      "name" : "Lanfumey L",
      "referenceId" : "RGD:A103834"
    }, {
      "firstName" : "R",
      "lastName" : "Insausti",
      "authorRank" : 6,
      "name" : "Insausti R",
      "referenceId" : "RGD:A120203"
    }, {
      "firstName" : "D",
      "lastName" : "Frechilla",
      "authorRank" : 7,
      "name" : "Frechilla D",
      "referenceId" : "RGD:A104270"
    }, {
      "firstName" : "J",
      "lastName" : "Del Rio",
      "authorRank" : 8,
      "name" : "Del Rio J",
      "referenceId" : "RGD:A104269"
    }, {
      "firstName" : "D",
      "lastName" : "Verge",
      "authorRank" : 9,
      "name" : "Verge D",
      "referenceId" : "RGD:A13581"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317011"
    } ]
  }, {
    "primaryId" : "PMID:10433076",
    "title" : "A novel haplotype of the endogenous retrovirus, HRES-1, in patients with multiple sclerosis and healthy individuals.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Rasmussen HB and Clausen J, Autoimmunity. 1999;29(2):141-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T13:57:40.000-05:00",
    "volume" : "29",
    "pages" : "141-5",
    "abstract" : "In this study we searched for genetic variation in a segment of the human endogenous retrovirus, HRES-1, which encodes a potential autoantigen of 28 kDa. The purpose was to further investigate a possible association between this endogenous retrovirus and multiple sclerosis (MS). Fragments amplified from the HRES-1 region in question were subjected to single strand conformational analysis (SSCP analysis) and sequencing if the SSCP migration pattern suggested presence of polymorphisms. Using this approach a synonymous G --> C substitution, creating an NciI site, was found. Our sequence data also revealed an additional nucleotide in the region encoding the 28-kDa protein, i.e. a nucleotide not present in the first published sequence. This finding has implications for future studies of the 28-kDa HRES-1 protein since the additional nucleotide changes the reading frame of this protein. The detection of the Nci polymorphism allowed us to define a novel haplotype of HRES-1 distinct from the three previously known HRES-1 haplotypes. On comparison of the distribution of these four haplotypes in MS patients and healthy individuals we found a statistically significant difference  (P = 0.03) but the contribution from the novel haplotype to this was modest.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HB",
      "lastName" : "Rasmussen",
      "authorRank" : 1,
      "name" : "Rasmussen HB",
      "referenceId" : "RGD:A49118"
    }, {
      "firstName" : "J",
      "lastName" : "Clausen",
      "authorRank" : 2,
      "name" : "Clausen",
      "referenceId" : "RGD:A217064"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11054748"
    } ]
  }, {
    "primaryId" : "PMID:10433093",
    "title" : "Differential expression of p95vav in primary lymphoid tissue of BB rats congenic for the lymphopenia gene.",
    "datePublished" : "1000-03-01T00:00:00.000-06:00",
    "citation" : "Bieg S Autoimmunity. 1999;30(1):37-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-03-17T16:42:08.000-05:00",
    "volume" : "30",
    "pages" : "37-42",
    "abstract" : "Lyp controls lymphopenia and T-cell mediated autoimmune diabetes in the BioBreeding (BB) rat possibly by interacting with T-cell maturation in the thymus. The protooncogene vav (p95) is involved in T-cell activation and in the intrathymic selection of developing T cells. We have previously reported increased production of IFN-gamma of self reactive thymocytes in the thymus medulla of Lyp/Lyp BB rats. Lymphopenia and diabetes may therefore be linked to an increase in thymocyte activation leading to a bias in thymocyte development. The purpose of this study was therefore to investigate whether the expression of p95\"a\" in primary lymphoid tissues from congenic Lyp/Lyp, Lyp/+ and +/+ BB rats was correlated to the Lyp genotype using in situ hybridization and reverse transcription (RT)-PCR. It was found that the expression of vav mRNA in the thymus was increased in Lyp/Lyp compared to Lyp/+ and +/+ rats (p < 0.05). Western blot analysis revealed that the amount of p95 vav protein in Lyp/Lyp thymus was also increased. The results show that vav expression correlates with the lymphopenia phenotype and diabetes development in congenic Lyp/Lyp BB rats. An increase in the availability of p95vav during the development and activation of thymocytes in Lyp/Lyp BB rats may therefore contribute to the generation of islet autoreactivity, lymphopenia or both.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Bieg",
      "authorRank" : 1,
      "name" : "Bieg S",
      "referenceId" : "RGD:A104755"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2306005"
    } ]
  }, {
    "primaryId" : "PMID:10433209",
    "title" : "The rat 17beta-hydroxysteroid dehydrogenase type III: molecular cloning and gonadotropin regulation.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Tsai-Morris CH, etal., Endocrinology 1999 Aug;140(8):3534-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:17.000-05:00",
    "volume" : "140",
    "pages" : "3534-42",
    "abstract" : "17Beta-hydroxysteroid dehydrogenase (17betaHSD), the enzyme that catalyzes the final step of testosterone biosynthesis in the testis, was cloned from a rat Leydig cell complementary DNA library to gain insights into the functional requirements, activation mechanisms, and molecular regulation. The 17betaHSD complementary DNA encoded 306 amino acids (molecular mass of 33.7 kDa) and displayed 75% and 85% amino acid sequence homology to the human and mouse 17betaHSD type III enzymes, respectively. Northern analysis revealed a single 1.4-kb messenger RNA (mRNA) species in rat Leydig cells, whereas ovarian mRNA was detected only by RT-PCR amplification. The cloned 17betaHSD expressed in mammalian cell lines specifically catalyzed the reductive reaction in androgen formation with androstenedione as the preferred substrate. This reaction was significantly reduced in the absence of glucose. Expression of the endogenous 17betaHSD gene in rat Leydig cells was inhibited by a single dose of hCG in vivo, with maximum reduction of steady state mRNA levels at 24 h and recovery at 9 days. Such agonist-induced down-regulation of 17betaHSD expression, which preceded the marked reduction of LH receptors, resulted from changes at the transcriptional level and was accompanied by loss of enzymatic activity. These studies have demonstrated a glucose requirement for optimal activity of the enzyme in vitro and for a role of gonadotropin in regulating the expression of 17betaHSD gene in vivo. Cloning of the 17betaHSD type III enzyme from rat Leydig cells will facilitate further investigation of the molecular regulation of its activity in the testis.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CH",
      "lastName" : "Tsai-Morris",
      "authorRank" : 1,
      "name" : "Tsai-Morris CH",
      "referenceId" : "RGD:A4738"
    }, {
      "firstName" : "A",
      "lastName" : "Khanum",
      "authorRank" : 2,
      "name" : "Khanum A",
      "referenceId" : "RGD:A27206"
    }, {
      "firstName" : "PZ",
      "lastName" : "Tang",
      "authorRank" : 3,
      "name" : "Tang PZ",
      "referenceId" : "RGD:A4737"
    }, {
      "firstName" : "ML",
      "lastName" : "Dufau",
      "authorRank" : 4,
      "name" : "Dufau ML",
      "referenceId" : "RGD:A4739"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727276"
    } ]
  }, {
    "primaryId" : "PMID:10433268",
    "title" : "Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Naisbitt S, etal., Neuron 1999 Jul;23(3):569-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:56.000-05:00",
    "volume" : "23",
    "pages" : "569-82",
    "abstract" : "NMDA receptors are linked to intracellular cytoskeletal and signaling molecules via the PSD-95 protein complex. We report a novel family of postsynaptic density (PSD) proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank/GKAP/PSD-95 assembles in heterologous cells and can be coimmunoprecipitated from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Naisbitt",
      "authorRank" : 1,
      "name" : "Naisbitt S",
      "referenceId" : "RGD:A6131"
    }, {
      "firstName" : "E",
      "lastName" : "Kim",
      "authorRank" : 2,
      "name" : "Kim E",
      "referenceId" : "RGD:A6132"
    }, {
      "firstName" : "JC",
      "lastName" : "Tu",
      "authorRank" : 3,
      "name" : "Tu JC",
      "referenceId" : "RGD:A6133"
    }, {
      "firstName" : "B",
      "lastName" : "Xiao",
      "authorRank" : 4,
      "name" : "Xiao B",
      "referenceId" : "RGD:A6134"
    }, {
      "firstName" : "C",
      "lastName" : "Sala",
      "authorRank" : 5,
      "name" : "Sala C",
      "referenceId" : "RGD:A6135"
    }, {
      "firstName" : "J",
      "lastName" : "Valtschanoff",
      "authorRank" : 6,
      "name" : "Valtschanoff J",
      "referenceId" : "RGD:A6136"
    }, {
      "firstName" : "RJ",
      "lastName" : "Weinberg",
      "authorRank" : 7,
      "name" : "Weinberg RJ",
      "referenceId" : "RGD:A6137"
    }, {
      "firstName" : "PF",
      "lastName" : "Worley",
      "authorRank" : 8,
      "name" : "Worley PF",
      "referenceId" : "RGD:A49791"
    }, {
      "firstName" : "M",
      "lastName" : "Sheng",
      "authorRank" : 9,
      "name" : "Sheng M",
      "referenceId" : "RGD:A6139"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68848"
    } ]
  }, {
    "primaryId" : "PMID:10433269",
    "title" : "Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic  density proteins.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Tu JC, etal., Neuron. 1999 Jul;23(3):583-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:42:50.000-05:00",
    "volume" : "23",
    "pages" : "583-92",
    "abstract" : "Shank is a recently described family of postsynaptic proteins that function as part of the NMDA receptor-associated PSD-95 complex (Naisbitt et al., 1999 [this  issue of Neuron]). Here, we report that Shank proteins also bind to Homer. Homer  proteins form multivalent complexes that bind proline-rich motifs in group 1 metabotropic glutamate receptors and inositol trisphosphate receptors, thereby coupling these receptors in a signaling complex. A single Homer-binding site is identified in Shank, and Shank and Homer coimmunoprecipitate from brain and colocalize at postsynaptic densities. Moreover, Shank clusters mGluR5 in heterologous cells in the presence of Homer and mediates the coclustering of Homer with PSD-95/GKAP. Thus, Shank may cross-link Homer and PSD-95 complexes in  the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JC",
      "lastName" : "Tu",
      "authorRank" : 1,
      "name" : "Tu JC",
      "referenceId" : "RGD:A6133"
    }, {
      "firstName" : "B",
      "lastName" : "Xiao",
      "authorRank" : 2,
      "name" : "Xiao B",
      "referenceId" : "RGD:A6134"
    }, {
      "firstName" : "S",
      "lastName" : "Naisbitt",
      "authorRank" : 3,
      "name" : "Naisbitt S",
      "referenceId" : "RGD:A6131"
    }, {
      "firstName" : "JP",
      "lastName" : "Yuan",
      "authorRank" : 4,
      "name" : "Yuan JP",
      "referenceId" : "RGD:A18818"
    }, {
      "firstName" : "RS",
      "lastName" : "Petralia",
      "authorRank" : 5,
      "name" : "Petralia RS",
      "referenceId" : "RGD:A11936"
    }, {
      "firstName" : "P",
      "lastName" : "Brakeman",
      "authorRank" : 6,
      "name" : "Brakeman",
      "referenceId" : "RGD:A186355"
    }, {
      "firstName" : "A",
      "lastName" : "Doan",
      "authorRank" : 7,
      "name" : "Doan A",
      "referenceId" : "RGD:A19521"
    }, {
      "firstName" : "VK",
      "lastName" : "Aakalu",
      "authorRank" : 8,
      "name" : "Aakalu",
      "referenceId" : "RGD:A186356"
    }, {
      "firstName" : "AA",
      "lastName" : "Lanahan",
      "authorRank" : 9,
      "name" : "Lanahan",
      "referenceId" : "RGD:A186357"
    }, {
      "firstName" : "M",
      "lastName" : "Sheng",
      "authorRank" : 10,
      "name" : "Sheng M",
      "referenceId" : "RGD:A6139"
    }, {
      "firstName" : "PF",
      "lastName" : "Worley",
      "authorRank" : 11,
      "name" : "Worley",
      "referenceId" : "RGD:A372325"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554380"
    } ]
  }, {
    "primaryId" : "PMID:10433620",
    "title" : "Cancer risks in BRCA2 mutation carriers.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "NO_AUTHOR J Natl Cancer Inst. 1999 Aug 4;91(15):1310-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:27:49.000-05:00",
    "volume" : "91",
    "pages" : "1310-6",
    "abstract" : "BACKGROUND: Carriers of germline mutations in the BRCA2 gene are known to be at high risk of breast and ovarian cancers, but the risks of other cancers in mutation carriers are uncertain. We investigated these risks in 173 breast-ovarian cancer families with BRCA2 mutations identified at 20 centers in Europe and North America. METHODS: Other cancer occurrence was determined in a final cohort of 3728 individuals, among whom 681 persons had breast or ovarian cancer and 3047 persons either were known mutation carriers, were first-degree relatives of known mutation carriers, or were first-degree relatives of breast or ovarian cancer patients. Incidence rates were compared with population-specific incidence rates, and relative risks (RRs) to carriers, together with 95% confidence intervals (CIs), were estimated by use of a maximum likelihood approach. Three hundred thirty-three other cancers occurred in this cohort. RESULTS: Statistically significant increases in risks were observed for prostate  cancer (estimated RR = 4.65; 95% CI = 3.48-6.22), pancreatic cancer (RR = 3.51; 95% CI = 1. 87-6.58), gallbladder and bile duct cancer (RR = 4.97; 95% CI = 1. 50-16.52), stomach cancer (RR = 2.59; 95%CI = 1.46-4.61), and malignant melanoma  (RR = 2.58; 95% CI = 1.28-5.17). The RR for prostate cancer for men below the age of 65 years was 7.33 (95% CI = 4.66-11.52). Among women who had already developed breast cancer, the cumulative risks of a second, contralateral breast cancer and  of ovarian cancer by the age of 70 years were estimated to be 52.3% (95% CI = 41.7%-61.0%) and 15.9% (95% CI = 8.8%-22.5%), respectively. CONCLUSIONS: In addition to the large risks of breast and ovarian cancers, BRCA2 mutations may be associated with increased risks of several other cancers.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "1999",
      "authorRank" : 1,
      "name" : "",
      "referenceId" : "RGD:A284409"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073394"
    } ]
  }, {
    "primaryId" : "PMID:10433925",
    "title" : "Increased expression of IP-10, IL-8, MCP-1, and MCP-3 in ulcerative colitis.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Uguccioni M, etal., Am J Pathol. 1999 Aug;155(2):331-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-05-31T14:48:33.000-05:00",
    "volume" : "155",
    "pages" : "331-6",
    "abstract" : "Chemokines are thought to be important for the recruitment of granulocytes and mononuclear cells and thus for the maintenance of inflammation in ulcerative colitis (UC). We have studied the expression of interferon-gamma inducible protein-10 (IP-10), interleukin-8 (IL-8), monocyte chemoattractant protein (MCP)-1, MCP-3, and macrophage inflammatory protein (MIP)-1alpha in UC patients and control individuals to assess the role of these chemokines in disease progression. Colonic biopsies were taken endoscopically from patients and controls, frozen immediately and subsequently stained for IP-10, IL-8, MCP-1, MCP-3, and MIP-1alpha in serial sections. Cells infiltrating the lamina propria but not epithelial cells express the analyzed chemokines. They were differentiated and counted, and chemokine-expressing cells were quantified by image analysis. The percentage of cells expressing IP-10, IL-8, MCP-1, and MCP-3  was significantly enhanced in all UC samples as compared to controls. Expression  in the controls was borderline, except for IP-10. No expression of MIP-1alpha was found in controls and UC. IP-10 was also markedly expressed in the mucosa of control biopsies and therefore could have a role in activated T lymphocytes' recruitment into the healthy mucosa.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Uguccioni",
      "authorRank" : 1,
      "name" : "Uguccioni M",
      "referenceId" : "RGD:A155418"
    }, {
      "firstName" : "P",
      "lastName" : "Gionchetti",
      "authorRank" : 2,
      "name" : "Gionchetti P",
      "referenceId" : "RGD:A134009"
    }, {
      "firstName" : "DF",
      "lastName" : "Robbiani",
      "authorRank" : 3,
      "name" : "Robbiani DF",
      "referenceId" : "RGD:A155419"
    }, {
      "firstName" : "F",
      "lastName" : "Rizzello",
      "authorRank" : 4,
      "name" : "Rizzello F",
      "referenceId" : "RGD:A155420"
    }, {
      "firstName" : "S",
      "lastName" : "Peruzzo",
      "authorRank" : 5,
      "name" : "Peruzzo S",
      "referenceId" : "RGD:A155421"
    }, {
      "firstName" : "M",
      "lastName" : "Campieri",
      "authorRank" : 6,
      "name" : "Campieri M",
      "referenceId" : "RGD:A155422"
    }, {
      "firstName" : "M",
      "lastName" : "Baggiolini",
      "authorRank" : 7,
      "name" : "Baggiolini M",
      "referenceId" : "RGD:A155423"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6483784"
    } ]
  }, {
    "primaryId" : "PMID:10433968",
    "title" : "Cloning and chromosomal mapping of mouse ADAM11, ADAM22 and ADAM23.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Sagane K, etal., Gene 1999 Aug 5;236(1):79-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T12:46:59.000-05:00",
    "volume" : "236",
    "pages" : "79-86",
    "abstract" : "A cellular disintegrin, also called MDC and ADAM is a recently discovered gene family that encodes protein with disintegrin-like and metalloprotease-like domains. We have reported the identification of human cDNAs encoding novel ADAM family proteins that we named MDC2 and MDC3 because of their structural similarity to the MDC (Sagane, K. et al., 1998. Biochem. J. 334, 93-98). The Human Gene Nomenclature Committee assigned the gene symbols ADAM11 for the MDC, ADAM22 for the MDC2 and ADAM23 for the MDC3. Here we report the isolation of three novel murine cDNAs encoding the proteins closely related to the human ADAM11, ADAM22 and ADAM23. Their chromosomal locations in the mouse were identified by interspecies backcross mapping. The loci of these murine ADAM genes were in good accordance with the location of each human ortholog, ADAM11, ADAM22 and ADAM23. These findings suggest that three murine cDNAs that we have isolated are the murine ADAM11, ADAM22 and ADAM23 cDNAs. Northern blot analysis shows that all of these three murine ADAMs were highly expressed in the mouse brain. The structures of these ADAM proteins strongly suggest that they could function as integrin receptors. The implications of the cellular disintegrins in neural development are discussed.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Sagane",
      "authorRank" : 1,
      "name" : "Sagane K",
      "referenceId" : "RGD:A17571"
    }, {
      "firstName" : "K",
      "lastName" : "Yamazaki",
      "authorRank" : 2,
      "name" : "Yamazaki K",
      "referenceId" : "RGD:A161131"
    }, {
      "firstName" : "Y",
      "lastName" : "Mizui",
      "authorRank" : 3,
      "name" : "Mizui Y",
      "referenceId" : "RGD:A17573"
    }, {
      "firstName" : "I",
      "lastName" : "Tanaka",
      "authorRank" : 4,
      "name" : "Tanaka I",
      "referenceId" : "RGD:A158632"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632495"
    } ]
  }, {
    "primaryId" : "PMID:10434477",
    "title" : "Effect of FC43se on endotoxin-induced disseminated intravascular coagulation in rats.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ochikubo H, etal., Hiroshima J Med Sci. 1999 Jun;48(2):71-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-22T16:08:53.000-05:00",
    "volume" : "48",
    "pages" : "71-7",
    "abstract" : "Perfluorotributylamine/Pluronic F68 Stem-Emulsion (FC43se), which is a blood substitute, was assessed for its effectiveness on disseminated intravascular coagulation (DIC) in the rat model. Rats were infused intravenously with 2.5 mg/kg of Escherichia coli lipopolysaccharide (Escherichia coli 055:B5 lipopolysaccharide B) for four hours. At the same time, FC43se or normal physiological saline was infused at 2.5 ml/kg/hr. The white blood cell and platelet counts, prothrombin time (PT), activated partial thromboplastin time (APTT), and the plasma levels of interleukin-1 beta (IL-1 beta), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF alpha) were determined at 4 hr. The infusion of FC43se markedly prevented a decrease in platelet counts (p = 0.0004) and a prolongation of both PT and APTT (p < 0.05 and p < 0.03 each). The serum level of IL-1 beta and IL-4 showed no significant change. The serum level of IL-6, IL-10 and TNF alpha increased significantly (p = 0.0007, p = 0.0004 and p < 0.05 each) with infusion  of FC43se in rats treated with bacterial endotoxin. FC43se has beneficial effects on endotoxin-induced DIC as an anticoagulant and anti-inflammatory cytokine induced agent.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Ochikubo",
      "authorRank" : 1,
      "name" : "Ochikubo",
      "referenceId" : "RGD:A249842"
    }, {
      "firstName" : "S",
      "lastName" : "Wada",
      "authorRank" : 2,
      "name" : "Wada S",
      "referenceId" : "RGD:A31749"
    }, {
      "firstName" : "Y",
      "lastName" : "Sugawara",
      "authorRank" : 3,
      "name" : "Sugawara Y",
      "referenceId" : "RGD:A122935"
    }, {
      "firstName" : "T",
      "lastName" : "Sueda",
      "authorRank" : 4,
      "name" : "Sueda T",
      "referenceId" : "RGD:A61340"
    }, {
      "firstName" : "Y",
      "lastName" : "Matsuura",
      "authorRank" : 5,
      "name" : "Matsuura Y",
      "referenceId" : "RGD:A12330"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11062064"
    } ]
  }, {
    "primaryId" : "PMID:10435007",
    "title" : "Proinflammatory cytokines regulate tissue inhibitors of metalloproteinases and disintegrin metalloproteinase in cardiac cells.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Li YY, etal., Cardiovasc Res. 1999 Apr;42(1):162-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-03-13T14:44:35.000-05:00",
    "volume" : "42",
    "pages" : "162-72",
    "abstract" : "OBJECTIVE: Tissue inhibitors of metalloproteinases (TIMPs) are downregulated in the failing human heart. The objective of the present study was to test the hypothesis that cytokines might be involved in the regulation of TIMPs in cardiac cells. METHODS: Neonatal Sprague-Dawley rat ventricular cells were exposed to 100 units/ml tumor necrosis factor-alpha and/or 5 ng/ml interleukin-1 beta. The mRNA and protein expression of TIMPs-1-4 and disintegrin metalloproteinase was analyzed using Northern blot, ELISA and/or Western blot, respectively. Proteolytic activity and extracellular matrix degradation and turnover were determined using gelatin zymography and pulse-chase experiments. RESULTS: The TIMP-1 mRNA was upregulated in cardiac cells, while TIMP-1 protein levels were unchanged in myocytes but downregulated in non-myocytes. The TIMP-2 expression did not change with the cytokine treatment. TIMP-3 was downregulated at both the mRNA and protein levels in cardiac cells. TIMP-4 protein was transiently increased and then returned to control level. In contrast, disintegrin metalloproteinase mRNA and protein were significantly upregulated in those cells. The gelatinolytic activity and extracellular matrix protein degradation were significantly increased. CONCLUSIONS: Tumor necrosis factor-alpha and interleukin-1 beta regulate the expression of TIMPs and disintegrin metalloproteinase, which may in turn contribute to the increased matrix degradation in cardiac cells. Since heart failure in humans is characterized by both re-expression of myocardial cytokines and remodeling of the extracellular matrix, those in vitro results suggest a potential role for those cytokines in the regulation of extracellular matrix remodeling and therefore in the transition to the end-stage heart failure phenotype.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YY",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li YY",
      "referenceId" : "RGD:A4797"
    }, {
      "firstName" : "CF",
      "lastName" : "McTiernan",
      "authorRank" : 2,
      "name" : "McTiernan CF",
      "referenceId" : "RGD:A4798"
    }, {
      "firstName" : "AM",
      "lastName" : "Feldman",
      "authorRank" : 3,
      "name" : "Feldman AM",
      "referenceId" : "RGD:A4799"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2290469"
    } ]
  }, {
    "primaryId" : "PMID:10435065",
    "title" : "Inhibin forms in serum from postmenopausal women with ovarian cancers.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Robertson DM, etal., Clin Endocrinol (Oxf). 1999 Mar;50(3):381-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-03-11T14:28:05.000-05:00",
    "volume" : "50",
    "pages" : "381-6",
    "abstract" : "BACKGROUND AND OBJECTIVE: Previous studies have shown that serum inhibin as measured by alpha subunit-directed radioimmunoassay (RIA) and inhibin A ELISA was elevated in postmenopausal women with mucinous and granulosa cell cancers, with the RIA showing a more frequent elevation than the inhibin A ELISA. It was thus hypothesised that these cancers may also produce inhibin B or the free alpha subunit. The aim of the study was to identify the forms of inhibin found in a range of ovarian cancers using a range of inhibin assays with varying specificities. DESIGN: Serum samples obtained from women with ovarian cancer were assayed by inhibin B ELISA and Pro-alpha C subunit ELISA and compared with inhibin RIA and inhibin A ELISA. PATIENTS: Blood samples were obtained from 34 postmenopausal women (> 55 years) with no history of endocrine disease and from women with ovarian serous cystadenocarcinomas (n = 66), mucinous cystadenocarcinomas (n = 20), granulosa cell tumours (n = 9-11), miscellaneous ovarian cancers (n = 46) and non ovarian cancers (n = 23). MEASUREMENTS: Inhibin B and inhibin Pro-alpha C subunit levels were determined by ELISA and compared to values obtained by RIA and inhibin A ELISA. Cancers were discriminated from controls based on values obtained 2SD above the geometric mean of the control values. RESULTS: Granulosa cell tumours were detected by RIA and inhibin B ELISA (100%), Pro-alpha C ELISA (90%) and inhibin A ELISA (77%). Mucinous tumours were detected by RIA (70%), inhibin B ELISA (60%), Pro-alpha C ELISA (55%) and inhibin A (20%). Serous tumours were detected by RIA (35%) and the other assays (< 15%). Miscellaneous tumours were detected by RIA (41%) and other assays < 30%. CONCLUSIONS: Ovarian neoplasms may produce a variety of peptides related to the inhibins, including dimeric inhibin A and B. Inhibin B is detected in more ovarian cancers than inhibin A but does not discriminate as well as the alpha subunit directed assays. The higher discrimination index obtained with the RIA compared to the Pro-alpha C ELISA suggests that assays detecting all inhibin forms containing the alpha subunit and not just those detecting the Pro-alpha C subunit will provide the most useful detection method.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DM",
      "lastName" : "Robertson",
      "authorRank" : 1,
      "name" : "Robertson DM",
      "referenceId" : "RGD:A60380"
    }, {
      "firstName" : "N",
      "lastName" : "Cahir",
      "authorRank" : 2,
      "name" : "Cahir N",
      "referenceId" : "RGD:A92866"
    }, {
      "firstName" : "HG",
      "lastName" : "Burger",
      "authorRank" : 3,
      "name" : "Burger HG",
      "referenceId" : "RGD:A90790"
    }, {
      "firstName" : "P",
      "lastName" : "Mamers",
      "authorRank" : 4,
      "name" : "Mamers P",
      "referenceId" : "RGD:A90787"
    }, {
      "firstName" : "N",
      "lastName" : "Groome",
      "authorRank" : 5,
      "name" : "Groome N",
      "referenceId" : "RGD:A15975"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2290383"
    } ]
  }, {
    "primaryId" : "PMID:10435585",
    "title" : "Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Chaturvedi P, etal., Oncogene 1999 Jul 15;18(28):4047-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:45.000-05:00",
    "volume" : "18",
    "pages" : "4047-54",
    "abstract" : "In response to DNA damage and replication blocks, cells activate pathways that arrest the cell cycle and induce the transcription of genes that facilitate repair. In mammals, ATM (ataxia telangiectasia mutated) kinase together with other checkpoint kinases are important components in this response. We have cloned the rat and human homologs of Saccharomyces cerevisiae Rad 53 and Schizosaccharomyces pombe Cds1, called checkpoint kinase 2 (chk2). Complementation studies suggest that Chk2 can partially replace the function of the defective checkpoint kinase in the Cds1 deficient yeast strain. Chk2 was phosphorylated and activated in response to DNA damage in an ATM dependent manner. Its activation in response to replication blocks by hydroxyurea (HU) treatment, however, was independent of ATM. Using mass spectrometry, we found that, similar to Chk1, Chk2 can phosphorylate serine 216 in Cdc25C, a site known to be involved in negative regulation of Cdc25C. These results suggest that Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway. Activation of Chk2 might not only delay mitotic entry, but also increase the capacity of cultured cells to survive after treatment with gamma-radiation or with the topoisomerase-I inhibitor topotecan.",
    "issueName" : "28",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Chaturvedi",
      "authorRank" : 1,
      "name" : "Chaturvedi P",
      "referenceId" : "RGD:A22040"
    }, {
      "firstName" : "WK",
      "lastName" : "Eng",
      "authorRank" : 2,
      "name" : "Eng WK",
      "referenceId" : "RGD:A22041"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhu",
      "authorRank" : 3,
      "name" : "Zhu Y",
      "referenceId" : "RGD:A162476"
    }, {
      "firstName" : "MR",
      "lastName" : "Mattern",
      "authorRank" : 4,
      "name" : "Mattern MR",
      "referenceId" : "RGD:A22042"
    }, {
      "firstName" : "R",
      "lastName" : "Mishra",
      "authorRank" : 5,
      "name" : "Mishra R",
      "referenceId" : "RGD:A22043"
    }, {
      "firstName" : "MR",
      "lastName" : "Hurle",
      "authorRank" : 6,
      "name" : "Hurle MR",
      "referenceId" : "RGD:A22044"
    }, {
      "firstName" : "X",
      "lastName" : "Zhang",
      "authorRank" : 7,
      "name" : "Zhang X",
      "referenceId" : "RGD:A6544"
    }, {
      "firstName" : "RS",
      "lastName" : "Annan",
      "authorRank" : 8,
      "name" : "Annan RS",
      "referenceId" : "RGD:A5757"
    }, {
      "firstName" : "Q",
      "lastName" : "Lu",
      "authorRank" : 9,
      "name" : "Lu Q",
      "referenceId" : "RGD:A5714"
    }, {
      "firstName" : "LF",
      "lastName" : "Faucette",
      "authorRank" : 10,
      "name" : "Faucette LF",
      "referenceId" : "RGD:A22045"
    }, {
      "firstName" : "GF",
      "lastName" : "Scott",
      "authorRank" : 11,
      "name" : "Scott GF",
      "referenceId" : "RGD:A22046"
    }, {
      "firstName" : "X",
      "lastName" : "Li",
      "authorRank" : 12,
      "name" : "Li X",
      "referenceId" : "RGD:A11893"
    }, {
      "firstName" : "SA",
      "lastName" : "Carr",
      "authorRank" : 13,
      "name" : "Carr SA",
      "referenceId" : "RGD:A5758"
    }, {
      "firstName" : "RK",
      "lastName" : "Johnson",
      "authorRank" : 14,
      "name" : "Johnson RK",
      "referenceId" : "RGD:A22047"
    }, {
      "firstName" : "JD",
      "lastName" : "Winkler",
      "authorRank" : 15,
      "name" : "Winkler JD",
      "referenceId" : "RGD:A22048"
    }, {
      "firstName" : "BB",
      "lastName" : "Zhou",
      "authorRank" : 16,
      "name" : "Zhou BB",
      "referenceId" : "RGD:A22049"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633752"
    } ]
  }, {
    "primaryId" : "PMID:10435629",
    "title" : "Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Legoix P, etal., Oncogene 1999 Jul 8;18(27):4044-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T16:08:39.000-06:00",
    "volume" : "18",
    "pages" : "4044-6",
    "abstract" : "To determine the frequency of Wnt/Wingless beta catenin pathway alteration in human hepatocellular carcinoma, a beta catenin and APC gene mutation screening was performed in a series of 119 tumors. An activating beta catenin mutation in exon 3 was found in 18% of the cases. Among tumors lacking beta catenin mutation, no APC mutation has been evidenced in a subset of 30 cases tested. The correlation between beta catenin mutation status and chromosome segment deletions was studied on a set of 48 hyperploid tumors. Chromosome 1p, 4q and 16p deletions were significantly associated with the absence of beta catenin mutation (P<0.05). Furthermore the Fractional Allelic Loss was significantly smaller in the beta catenin mutated tumors than in the non-mutated tumors (0.12 versus 022). Taken together, these results suggest, the existence of two carcinogenesis mechanisms. The first mechanism implies a beta catenin activating mutation associated with a low rate of loss of heterozygosity. The second mechanism, operating in a context of chromosomal instability, would involve tumor suppressor genes.",
    "issueName" : "27",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Legoix",
      "authorRank" : 1,
      "name" : "Legoix P",
      "referenceId" : "RGD:A37654"
    }, {
      "firstName" : "O",
      "lastName" : "Bluteau",
      "authorRank" : 2,
      "name" : "Bluteau O",
      "referenceId" : "RGD:A37655"
    }, {
      "firstName" : "J",
      "lastName" : "Bayer",
      "authorRank" : 3,
      "name" : "Bayer J",
      "referenceId" : "RGD:A37656"
    }, {
      "firstName" : "C",
      "lastName" : "Perret",
      "authorRank" : 4,
      "name" : "Perret C",
      "referenceId" : "RGD:A5702"
    }, {
      "firstName" : "C",
      "lastName" : "Balabaud",
      "authorRank" : 5,
      "name" : "Balabaud C",
      "referenceId" : "RGD:A37657"
    }, {
      "firstName" : "J",
      "lastName" : "Belghiti",
      "authorRank" : 6,
      "name" : "Belghiti J",
      "referenceId" : "RGD:A37658"
    }, {
      "firstName" : "D",
      "lastName" : "Franco",
      "authorRank" : 7,
      "name" : "Franco D",
      "referenceId" : "RGD:A37659"
    }, {
      "firstName" : "G",
      "lastName" : "Thomas",
      "authorRank" : 8,
      "name" : "Thomas G",
      "referenceId" : "RGD:A19995"
    }, {
      "firstName" : "P",
      "lastName" : "Laurent-Puig",
      "authorRank" : 9,
      "name" : "Laurent-Puig P",
      "referenceId" : "RGD:A37660"
    }, {
      "firstName" : "J",
      "lastName" : "Zucman-Rossi",
      "authorRank" : 10,
      "name" : "Zucman-Rossi J",
      "referenceId" : "RGD:A37661"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734850"
    } ]
  }, {
    "primaryId" : "PMID:10435631",
    "title" : "The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "De Valck D, etal., Oncogene 1999 Jul 22;18(29):4182-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:46.000-05:00",
    "volume" : "18",
    "pages" : "4182-90",
    "abstract" : "A20 is a Cys2/Cys2 zinc finger protein which is induced by a variety of inflammatory stimuli and which has been characterized as an inhibitor of cell death by a yet unknown mechanism. In order to clarify its molecular mechanism of action, we used the yeast two-hybrid system to screen for proteins that interact with A20. A cDNA fragment was isolated which encoded a portion of a novel protein (TXBP151), which was recently found to be a human T-cell leukemia virus type-I (HTLV-I) Tax-binding protein. The full-length 2386 bp TXBP151 mRNA encodes a protein of 86 kDa. Like A20, overexpression of TXBP151 could inhibit apoptosis induced by tumour necrosis factor (TNF) in NIH3T3 cells. Moreover, transfection of antisense TXBP151 partially abolished the anti-apoptotic effect of A20. Furthermore, apoptosis induced by TNF or CD95 (Fas/APO-1) was associated with proteolysis of TXBP151. This degradation could be inhibited by the broad-spectrum caspase inhibitor zVAD-fmk or by expression of the cowpox virus-derived inhibitor CrmA, suggesting that TXBP151 is a novel substrate for caspase family members. TXBP151 was indeed found to be specifically cleaved in vitro by members of the caspase-3-like subfamily, viz. caspase-3, caspase-6 and caspase-7. Thus TXBP151 appears to be a novel A20-binding protein which might mediate the anti-apoptotic activity of A20, and which can be processed by specific caspases.",
    "issueName" : "29",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "De Valck",
      "authorRank" : 1,
      "name" : "De Valck D",
      "referenceId" : "RGD:A46628"
    }, {
      "firstName" : "DY",
      "lastName" : "Jin",
      "authorRank" : 2,
      "name" : "Jin DY",
      "referenceId" : "RGD:A46629"
    }, {
      "firstName" : "K",
      "lastName" : "Heyninck",
      "authorRank" : 3,
      "name" : "Heyninck K",
      "referenceId" : "RGD:A46630"
    }, {
      "firstName" : "M",
      "lastName" : "Van de Craen",
      "authorRank" : 4,
      "name" : "Van de Craen M",
      "referenceId" : "RGD:A46631"
    }, {
      "firstName" : "R",
      "lastName" : "Contreras",
      "authorRank" : 5,
      "name" : "Contreras R",
      "referenceId" : "RGD:A46632"
    }, {
      "firstName" : "W",
      "lastName" : "Fiers",
      "authorRank" : 6,
      "name" : "Fiers W",
      "referenceId" : "RGD:A46633"
    }, {
      "firstName" : "KT",
      "lastName" : "Jeang",
      "authorRank" : 7,
      "name" : "Jeang KT",
      "referenceId" : "RGD:A46634"
    }, {
      "firstName" : "R",
      "lastName" : "Beyaert",
      "authorRank" : 8,
      "name" : "Beyaert R",
      "referenceId" : "RGD:A46635"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302506"
    } ]
  }, {
    "primaryId" : "PMID:10435666",
    "title" : "Urinary excretion of intrinsic factor and the receptor for its cobalamin complex  in Grasbeck-Imerslund patients: the disease may have subsets.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Dugue B, etal., J Pediatr Gastroenterol Nutr. 1999 Aug;29(2):227-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-11T11:18:03.000-05:00",
    "volume" : "29",
    "pages" : "227-30",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Dugue",
      "authorRank" : 1,
      "name" : "Dugue",
      "referenceId" : "RGD:A215910"
    }, {
      "firstName" : "E",
      "lastName" : "Ismail",
      "authorRank" : 2,
      "name" : "Ismail",
      "referenceId" : "RGD:A170529"
    }, {
      "firstName" : "F",
      "lastName" : "Sequeira",
      "authorRank" : 3,
      "name" : "Sequeira",
      "referenceId" : "RGD:A215911"
    }, {
      "firstName" : "J",
      "lastName" : "Thakkar",
      "authorRank" : 4,
      "name" : "Thakkar",
      "referenceId" : "RGD:A215912"
    }, {
      "firstName" : "R",
      "lastName" : "Grasbeck",
      "authorRank" : 5,
      "name" : "Grasbeck R",
      "referenceId" : "RGD:A4145"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11049586"
    } ]
  }, {
    "primaryId" : "PMID:10435723",
    "title" : "Genetic analysis of HLA- and HPA-typing in idiopathic (autoimmune) thrombocytopenic purpura patients treated with cepharanthin.",
    "datePublished" : "1000-03-01T00:00:00.000-06:00",
    "citation" : "Nomura S, etal., Autoimmunity. 1999;30(2):99-105.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-28T17:35:32.000-05:00",
    "volume" : "30",
    "pages" : "99-105",
    "abstract" : "We performed genetic analysis of human leukocyte antigen (HLA) and human platelet antigen (HPA) in 45 patients with cepharanthin-treated idiopathic thrombocytopenic purpura. HLA-typing was performed by the polymerase chain reaction-restriction fragment length polymorphism method, and HPA-typing by a polymerase chain reaction-sequence-specific primer method. There were 14 responders and 31 nonresponders. Responders included many patients who had already been treated with prednisolone. HLA-DRB1*0901 was significantly more common in responders than in nonresponders. In contrast, HLA-DRB1*0410 and DQB1*0401 were significantly more common in nonresponders. The a/b genotype of HPA-2a/2a (Ko(b)/Ko(b)) was significantly increased in responders. In contrast, HPA-2a/2b (Ko(b)/Ko(a)) and HPA-3a/3b (Bak(a)/Bak(b)) were significantly more common in nonresponders. These findings suggest that genetic studies of HLA and HPA can predict the response of idiopathic thrombocytopenic purpura to cepharanthin.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Nomura",
      "authorRank" : 1,
      "name" : "Nomura S",
      "referenceId" : "RGD:A10331"
    }, {
      "firstName" : "T",
      "lastName" : "Matsuzaki",
      "authorRank" : 2,
      "name" : "Matsuzaki T",
      "referenceId" : "RGD:A10207"
    }, {
      "firstName" : "M",
      "lastName" : "Yamaoka",
      "authorRank" : 3,
      "name" : "Yamaoka",
      "referenceId" : "RGD:A211557"
    }, {
      "firstName" : "Y",
      "lastName" : "Ozaki",
      "authorRank" : 4,
      "name" : "Ozaki Y",
      "referenceId" : "RGD:A51336"
    }, {
      "firstName" : "M",
      "lastName" : "Nagahama",
      "authorRank" : 5,
      "name" : "Nagahama M",
      "referenceId" : "RGD:A15360"
    }, {
      "firstName" : "C",
      "lastName" : "Yoshimura",
      "authorRank" : 6,
      "name" : "Yoshimura",
      "referenceId" : "RGD:A214873"
    }, {
      "firstName" : "H",
      "lastName" : "Kagawa",
      "authorRank" : 7,
      "name" : "Kagawa H",
      "referenceId" : "RGD:A141581"
    }, {
      "firstName" : "S",
      "lastName" : "Nakayama",
      "authorRank" : 8,
      "name" : "Nakayama S",
      "referenceId" : "RGD:A125700"
    }, {
      "firstName" : "S",
      "lastName" : "Fukuhara",
      "authorRank" : 9,
      "name" : "Fukuhara S",
      "referenceId" : "RGD:A21562"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041758"
    } ]
  }, {
    "primaryId" : "PMID:10435724",
    "title" : "Detection of anti-LKM-1(anti-CYP2D6) by an enzyme-linked immunosorbent assay in adult patients with chronic liver diseases.",
    "datePublished" : "1000-07-01T00:00:00.000-06:00",
    "citation" : "Miyakawa H, etal., Autoimmunity. 1999;30(2):107-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-07-21T11:23:17.000-05:00",
    "volume" : "30",
    "pages" : "107-14",
    "abstract" : "Anti-liver kidney microsome-1 (LKM-1) autoantibody, which is a serological marker for autoimmune hepatitis type II, recognizes Cytochrome P450 IID6 (CYP2D6). This  autoantibody is also detected in a portion of patients with chronic hepatitis C.  Anti-LKM-1 has been measured by indirect immunofluorescence (IF) using rat liver  and kidney sections. However, this method has some problems in specificity and is so laborious to handle with many samples. In this study, in order to determine anti-LKM-1, we established an enzyme-linked immunosorbent assay (ELISA) for anti-CYP2D6 using a recombinant CYP2D6 fusion protein. We studied sera from 29 patients positive for anti-LKM-1 by the new ELISA. We further studied sera from a total of 301 patients with various liver diseases and 100 sera from normal controls negative for anti-LKM-1 by the new ELISA. The specificity of the ELISA was ascertained by absorption tests using sera positive for anti-LKM-1. In 29 sera from patients positive for anti-LKM-1 by IF, we found a good correlation between the logarithms of the antibody titers determined by IF and ELISA indexes  obtained by our new method. Anti-CYP2D6 was positive in 12 of 12 (100%) patient with autoimmune hepatitis type II and 16 of 17(94.1%) with chronic hepatitis C positive for anti-LKM-1 by IF. In other 401 sera negative for anti-LKM-1 by IF, anti-CYP2D6 was all negative except a few sera. We established a new ELISA for anti-LKM-1 (anti-CYP2D6). This ELISA system is sensitive, antigen-specific and easy to be done. Therefore, this assay allows a routine test of many serum samples, especially for diagnosing autoimmune hepatitis type II.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Miyakawa",
      "authorRank" : 1,
      "name" : "Miyakawa H",
      "referenceId" : "RGD:A149212"
    }, {
      "firstName" : "E",
      "lastName" : "Kikazawa",
      "authorRank" : 2,
      "name" : "Kikazawa",
      "referenceId" : "RGD:A349864"
    }, {
      "firstName" : "K",
      "lastName" : "Abe",
      "authorRank" : 3,
      "name" : "Abe K",
      "referenceId" : "RGD:A9795"
    }, {
      "firstName" : "K",
      "lastName" : "Kikuchi",
      "authorRank" : 4,
      "name" : "Kikuchi",
      "referenceId" : "RGD:A371806"
    }, {
      "firstName" : "H",
      "lastName" : "Fujikawa",
      "authorRank" : 5,
      "name" : "Fujikawa",
      "referenceId" : "RGD:A251151"
    }, {
      "firstName" : "M",
      "lastName" : "Matsushita",
      "authorRank" : 6,
      "name" : "Matsushita M",
      "referenceId" : "RGD:A5979"
    }, {
      "firstName" : "N",
      "lastName" : "Kawaguchi",
      "authorRank" : 7,
      "name" : "Kawaguchi N",
      "referenceId" : "RGD:A32176"
    }, {
      "firstName" : "T",
      "lastName" : "Morizane",
      "authorRank" : 8,
      "name" : "Morizane",
      "referenceId" : "RGD:A349866"
    }, {
      "firstName" : "K",
      "lastName" : "Ohya",
      "authorRank" : 9,
      "name" : "Ohya K",
      "referenceId" : "RGD:A15176"
    }, {
      "firstName" : "M",
      "lastName" : "Kako",
      "authorRank" : 10,
      "name" : "Kako",
      "referenceId" : "RGD:A349867"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11353781"
    } ]
  }, {
    "primaryId" : "PMID:10435922",
    "title" : "Expression of intercellular adhesion molecule-1 in rat inner ear due to bacterial otitis media.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Sone M, etal., Ann Otol Rhinol Laryngol. 1999 Jul;108(7 Pt 1):648-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-18T17:16:57.000-06:00",
    "volume" : "108",
    "pages" : "648-52",
    "abstract" : "Expressions of anti-Streptococcus pneumoniae antibody and anti-intercellular adhesion molecule-1 (ICAM-1) antibody in the inner ear were studied immunohistochemically in rats following inoculation of S pneumoniae type 6A into  the middle ear cavity. Positive staining with anti-S pneumoniae antibody was detected in the marginal cells of the stria vascularis of rats sacrificed 3 days  after S pneumoniae inoculation, but almost no staining was detected in those sacrificed at 14 days. Strong ICAM-1 expression was detected in the basal cell layer of the stria vascularis of rats sacrificed 3 days after inoculation, but the intensity of the staining had decreased by 14 days. These results suggest that the stria vascularis may be a site of the inner ear damage that follows bacterial inoculation into the middle ear cavity. The up-regulated expression of  ICAM-1 in the basal cell layer may represent a reaction of the inner ear to the bacterial otitis media.",
    "issueName" : "7 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Sone",
      "authorRank" : 1,
      "name" : "Sone M",
      "referenceId" : "RGD:A42138"
    }, {
      "firstName" : "HQ",
      "lastName" : "Russlie",
      "authorRank" : 2,
      "name" : "Russlie",
      "referenceId" : "RGD:A179578"
    }, {
      "firstName" : "DM",
      "lastName" : "Canafax",
      "authorRank" : 3,
      "name" : "Canafax",
      "referenceId" : "RGD:A179579"
    }, {
      "firstName" : "MM",
      "lastName" : "Paparella",
      "authorRank" : 4,
      "name" : "Paparella MM",
      "referenceId" : "RGD:A103966"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547588"
    } ]
  }, {
    "primaryId" : "PMID:10436048",
    "title" : "Embryonic lethal abnormal vision-like RNA-binding proteins regulate neurite outgrowth and tau expression in PC12 cells.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Aranda-Abreu GE, etal., J Neurosci. 1999 Aug 15;19(16):6907-17.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-12-31T15:51:00.000-06:00",
    "volume" : "19",
    "pages" : "6907-17",
    "abstract" : "The embryonic lethal abnormal vision (ELAV)-like proteins are mRNA-binding proteins that regulate mRNA stability. The neuronal members of this family are required for neuronal differentiation. We identified the binding region of purified HuD protein to a target neuronal mRNA encoding for the tau microtubule-associated protein and demonstrated an in vivo interaction between the ELAV-like protein and its target tau mRNA. We show that treatment of neuronal cells with antisense oligodeoxynucleotides directed against HuD blocks the induction of neurite outgrowth and decreases the levels of tau mRNAs, indicating  that the ELAV-like proteins are required for neuronal differentiation.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GE",
      "lastName" : "Aranda-Abreu",
      "authorRank" : 1,
      "name" : "Aranda-Abreu",
      "referenceId" : "RGD:A197934"
    }, {
      "firstName" : "L",
      "lastName" : "Behar",
      "authorRank" : 2,
      "name" : "Behar L",
      "referenceId" : "RGD:A5975"
    }, {
      "firstName" : "S",
      "lastName" : "Chung",
      "authorRank" : 3,
      "name" : "Chung S",
      "referenceId" : "RGD:A7825"
    }, {
      "firstName" : "H",
      "lastName" : "Furneaux",
      "authorRank" : 4,
      "name" : "Furneaux H",
      "referenceId" : "RGD:A13951"
    }, {
      "firstName" : "I",
      "lastName" : "Ginzburg",
      "authorRank" : 5,
      "name" : "Ginzburg I",
      "referenceId" : "RGD:A5976"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685302"
    } ]
  }, {
    "primaryId" : "PMID:10436050",
    "title" : "Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Dong H, etal., J Neurosci 1999 Aug 15;19(16):6930-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:29.000-05:00",
    "volume" : "19",
    "pages" : "6930-41",
    "abstract" : "The molecular mechanisms underlying the targeting and localization of glutamate receptors at postsynaptic sites is poorly understood. Recently, we have identified a PDZ domain-containing protein, glutamate receptor-interacting protein 1 (GRIP1), which specifically binds to the C termini of AMPA receptor subunits and may be involved in the synaptic targeting of these receptors. Here, we report the cloning of GRIP2, a homolog of GRIP1, and the characterization of the GRIP1 and GRIP2 proteins in the rat CNS. GRIP1 and GRIP2 are approximately 130 kDa proteins that are highly enriched in brain. GRIP1 and GRIP2 are widely expressed in brain, with the highest levels found in the cerebral cortex, hippocampus, and olfactory bulb. Biochemical studies show that GRIP1 and GRIP2 are enriched in synaptic plasma membrane and postsynaptic density fractions. GRIP1 is expressed early in embryonic development before the expression of AMPA receptors and peaks in expression at postnatal day 8-10. In contrast, GRIP2 is expressed relatively late in development and parallels the expression of AMPA receptors. Immunohistochemistry using the GRIP1 antibodies demonstrated that GRIP1 is expressed in neurons in a somatodendritic staining pattern. At the ultrastructural level, DAB and immunogold electromicroscopy studies showed that GRIP1 was enriched in dendritic spines near the postsynaptic density and was expressed in dendritic shafts and in peri-Golgi regions in the neuronal soma. GRIP1 appeared to be clustered at both glutamatergic and GABAergic synapses. These results suggest that GRIP1 and GRIP2 are AMPA receptor binding proteins potentially involved in the targeting of AMPA receptors to synapses. GRIP1 also may play functional roles at both excitatory and inhibitory synapses, as well as in early neuronal development.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Dong",
      "authorRank" : 1,
      "name" : "Dong H",
      "referenceId" : "RGD:A6157"
    }, {
      "firstName" : "P",
      "lastName" : "Zhang",
      "authorRank" : 2,
      "name" : "Zhang P",
      "referenceId" : "RGD:A8872"
    }, {
      "firstName" : "I",
      "lastName" : "Song",
      "authorRank" : 3,
      "name" : "Song I",
      "referenceId" : "RGD:A5443"
    }, {
      "firstName" : "RS",
      "lastName" : "Petralia",
      "authorRank" : 4,
      "name" : "Petralia RS",
      "referenceId" : "RGD:A11936"
    }, {
      "firstName" : "D",
      "lastName" : "Liao",
      "authorRank" : 5,
      "name" : "Liao D",
      "referenceId" : "RGD:A19056"
    }, {
      "firstName" : "RL",
      "lastName" : "Huganir",
      "authorRank" : 6,
      "name" : "Huganir RL",
      "referenceId" : "RGD:A6546"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632957"
    } ]
  }, {
    "primaryId" : "PMID:10436054",
    "title" : "Thyroid hormone regulates reelin and dab1 expression during brain development.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Alvarez-Dolado M, etal., J Neurosci 1999 Aug 15;19(16):6979-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-09T14:28:45.000-05:00",
    "volume" : "19",
    "pages" : "6979-93",
    "abstract" : "The reelin and dab1 genes are necessary for appropriate neuronal migration and lamination during brain development. Since these processes are controlled by thyroid hormone, we studied the effect of thyroid hormone deprivation and administration on the expression of reelin and dab1. As shown by Northern analysis, in situ hybridization, and immunohistochemistry studies, hypothyroid rats expressed decreased levels of reelin RNA and protein during the perinatal period [embryonic day 18 (E18) and postnatal day 0 (P0)]. The effect was evident in Cajal-Retzius cells of cortex layer I, as well as in layers V/VI, hippocampus, and granular neurons of the cerebellum. At later ages, however, Reelin was more abundant in the cortex, hippocampus, cerebellum, and olfactory bulb of hypothyroid rats (P5), and no differences were detected at P15. Conversely, Dab1 levels were higher at P0, and lower at P5 in hypothyroid animals. In line with these results, reelin RNA and protein levels were higher in cultured hippocampal slices from P0 control rats compared to those from hypothyroid animals. Significantly, thyroid-dependent regulation of reelin and dab1 was confirmed in vivo and in vitro by hormone treatment of hypothyroid rats and organotypic cultures, respectively. In both cases, thyroid hormone led to an increase in reelin expression. Our data suggest that the effects of thyroid hormone on neuronal migration may be in part mediated through the control of reelin and dab1 expression during brain ontogenesis.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Alvarez-Dolado",
      "authorRank" : 1,
      "name" : "Alvarez-Dolado M",
      "referenceId" : "RGD:A24868"
    }, {
      "firstName" : "M",
      "lastName" : "Ruiz",
      "authorRank" : 2,
      "name" : "Ruiz M",
      "referenceId" : "RGD:A24869"
    }, {
      "firstName" : "JA",
      "lastName" : "Del Rio",
      "authorRank" : 3,
      "name" : "Del Rio JA",
      "referenceId" : "RGD:A24870"
    }, {
      "firstName" : "S",
      "lastName" : "Alcantara",
      "authorRank" : 4,
      "name" : "Alcantara S",
      "referenceId" : "RGD:A24871"
    }, {
      "firstName" : "F",
      "lastName" : "Burgaya",
      "authorRank" : 5,
      "name" : "Burgaya F",
      "referenceId" : "RGD:A24872"
    }, {
      "firstName" : "M",
      "lastName" : "Sheldon",
      "authorRank" : 6,
      "name" : "Sheldon M",
      "referenceId" : "RGD:A24873"
    }, {
      "firstName" : "K",
      "lastName" : "Nakajima",
      "authorRank" : 7,
      "name" : "Nakajima K",
      "referenceId" : "RGD:A5501"
    }, {
      "firstName" : "J",
      "lastName" : "Bernal",
      "authorRank" : 8,
      "name" : "Bernal J",
      "referenceId" : "RGD:A18020"
    }, {
      "firstName" : "BW",
      "lastName" : "Howell",
      "authorRank" : 9,
      "name" : "Howell BW",
      "referenceId" : "RGD:A24874"
    }, {
      "firstName" : "T",
      "lastName" : "Curran",
      "authorRank" : 10,
      "name" : "Curran T",
      "referenceId" : "RGD:A18201"
    }, {
      "firstName" : "E",
      "lastName" : "Soriano",
      "authorRank" : 11,
      "name" : "Soriano E",
      "referenceId" : "RGD:A24875"
    }, {
      "firstName" : "A",
      "lastName" : "Munoz",
      "authorRank" : 12,
      "name" : "Munoz A",
      "referenceId" : "RGD:A24876"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634730"
    } ]
  }, {
    "primaryId" : "PMID:10436160",
    "title" : "Fas ligand: a sensor for DNA damage critical in skin cancer etiology.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hill LL, etal., Science 1999 Aug 6;285(5429):898-900.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:43:14.000-06:00",
    "volume" : "285",
    "pages" : "898-900",
    "abstract" : "DNA-damaged cells can either repair the DNA or be eliminated through a homeostatic control mechanism termed \"cellular proofreading.\" Elimination of DNA-damaged cells after ultraviolet radiation (UVR) through sunburn cell (apoptotic keratinocyte) formation is thought to be pivotal for the removal of precancerous skin cells. Sunburn cell formation was found to be dependent on Fas ligand (FasL), a pro-apoptotic protein induced by DNA damage. Chronic exposure to UVR caused 14 of 20 (70 percent) FasL-deficient mice and 1 of 20 (5 percent) wild-type mice to accumulate p53 mutations in the epidermis. Thus, FasL-mediated apoptosis is important for skin homeostasis, suggesting that the dysregulation of Fas-FasL interactions may be central to the development of skin cancer.",
    "issueName" : "5429",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LL",
      "lastName" : "Hill",
      "authorRank" : 1,
      "name" : "Hill LL",
      "referenceId" : "RGD:A36046"
    }, {
      "firstName" : "A",
      "lastName" : "Ouhtit",
      "authorRank" : 2,
      "name" : "Ouhtit A",
      "referenceId" : "RGD:A36047"
    }, {
      "firstName" : "SM",
      "lastName" : "Loughlin",
      "authorRank" : 3,
      "name" : "Loughlin SM",
      "referenceId" : "RGD:A36048"
    }, {
      "firstName" : "ML",
      "lastName" : "Kripke",
      "authorRank" : 4,
      "name" : "Kripke ML",
      "referenceId" : "RGD:A36049"
    }, {
      "firstName" : "HN",
      "lastName" : "Ananthaswamy",
      "authorRank" : 5,
      "name" : "Ananthaswamy HN",
      "referenceId" : "RGD:A12259"
    }, {
      "firstName" : "LB",
      "lastName" : "Owen-Schaub",
      "authorRank" : 6,
      "name" : "Owen-Schaub LB",
      "referenceId" : "RGD:A36050"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734594"
    } ]
  }, {
    "primaryId" : "PMID:10436175",
    "title" : "Polymorphic genotypes of the HRES-1 human endogenous retrovirus locus correlate with systemic lupus erythematosus and autoreactivity.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Magistrelli C, etal., Immunogenetics. 1999 Sep;49(10):829-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:32:57.000-05:00",
    "volume" : "49",
    "pages" : "829-34",
    "abstract" : "Antinuclear autoantibodies are a hallmark of systemic lupus erythematosus (SLE).  Autoantibodies to HRES-1/p28, a 28 000 M(r) nuclear protein, commonly occur in patients with SLE. HRES-1 is a single-copy endogenous retroviral element mapped to human Chromosome 1 at q42. A polymorphic Hin dIII site defines two different allelic forms of the genomic locus. The HRES-1/1 probe [5.5 kilobases (kb)] anneals to three polymorphic fragments and three genotypes can be differentiated: I, 5.5 kb fragment only; II, 3.7 kb and 1.8 kb fragments only; and III, all three polymorphic fragments. By cloning of the HRES-1 locus from homozygous type I and  type II human DNA samples, the polymorphic Hin dIII site was identified as a G to C transition at position 653 of the long terminal repeat region. Family studies showed that Hin dIII genotypes of the HRES-1 locus are inherited in a Mendelian pattern. The relative frequency of genotype I with respect to genotype III was 3.1-fold lower in patients with SLE (14:40=0.35) in comparison to 100 ethnically  matched control donors (47:43=1.09; P=0.0084). Frequency of genotype I vs genotype II alleles was lower in SLE (68/52) than in normal donors (137/63; P=0.033), suggesting that a genotype I allele of the HRES-1 locus may be protective against SLE. Western blot seroreactivity with recombinant HRES-1/p28 was noted in 4/14 (29%) of genotype I patients and 13/19 (68%) of genotype III patients (P<0.025). These data raise the possibility that the HRES-1 element or a gene in linkage disequilibrium with this genomic locus may influence autoimmunity in SLE.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Magistrelli",
      "authorRank" : 1,
      "name" : "Magistrelli",
      "referenceId" : "RGD:A235417"
    }, {
      "firstName" : "E",
      "lastName" : "Samoilova",
      "authorRank" : 2,
      "name" : "Samoilova",
      "referenceId" : "RGD:A235418"
    }, {
      "firstName" : "RK",
      "lastName" : "Agarwal",
      "authorRank" : 3,
      "name" : "Agarwal",
      "referenceId" : "RGD:A174201"
    }, {
      "firstName" : "K",
      "lastName" : "Banki",
      "authorRank" : 4,
      "name" : "Banki K",
      "referenceId" : "RGD:A38846"
    }, {
      "firstName" : "P",
      "lastName" : "Ferrante",
      "authorRank" : 5,
      "name" : "Ferrante",
      "referenceId" : "RGD:A235419"
    }, {
      "firstName" : "A",
      "lastName" : "Vladutiu",
      "authorRank" : 6,
      "name" : "Vladutiu",
      "referenceId" : "RGD:A235420"
    }, {
      "firstName" : "PE",
      "lastName" : "Phillips",
      "authorRank" : 7,
      "name" : "Phillips",
      "referenceId" : "RGD:A199909"
    }, {
      "firstName" : "A",
      "lastName" : "Perl",
      "authorRank" : 8,
      "name" : "Perl A",
      "referenceId" : "RGD:A38850"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11056771"
    } ]
  }, {
    "primaryId" : "PMID:10436176",
    "title" : "The complete primary structure of mouse 20S proteasomes.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Elenich LA, etal., Immunogenetics 1999 Sep;49(10):835-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-08-23T15:25:31.000-05:00",
    "volume" : "49",
    "pages" : "835-42",
    "abstract" : "The proteasome is a large multicatalytic proteinase that plays a role in the generation of peptides for presentation by major histocompatibility complex class I molecules. The 20S proteolytic core of mammalian proteasomes is assembled from a group of 17 protein subunits that generate a distinctive pattern of spots upon two-dimensional gel electrophoresis. The genes for most of these subunits have been cloned from humans and rats. We isolated cDNA clones for the mouse orthologues of ten of the subunits [PSMA1 (C2), PSMA2 (C3), PSMA3 (C8), PSMA4 (C9), PSMA5 (ZETA), PSMA6 (IOTA), PSMA7 (C6-I), PSMB2 (C7-I), PSMB3 (C10-II), and PSMB5 (X)] to complete the cloning of all of the mouse subunits. Using antisera raised against these subunits or their orthologues, we verified the identity of these proteins by two-dimensional NEPHGE-PAGE.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LA",
      "lastName" : "Elenich",
      "authorRank" : 1,
      "name" : "Elenich LA",
      "referenceId" : "RGD:A54822"
    }, {
      "firstName" : "D",
      "lastName" : "Nandi",
      "authorRank" : 2,
      "name" : "Nandi D",
      "referenceId" : "RGD:A54823"
    }, {
      "firstName" : "AE",
      "lastName" : "Kent",
      "authorRank" : 3,
      "name" : "Kent AE",
      "referenceId" : "RGD:A54824"
    }, {
      "firstName" : "TS",
      "lastName" : "McCluskey",
      "authorRank" : 4,
      "name" : "McCluskey TS",
      "referenceId" : "RGD:A54825"
    }, {
      "firstName" : "M",
      "lastName" : "Cruz",
      "authorRank" : 5,
      "name" : "Cruz M",
      "referenceId" : "RGD:A54826"
    }, {
      "firstName" : "MN",
      "lastName" : "Iyer",
      "authorRank" : 6,
      "name" : "Iyer MN",
      "referenceId" : "RGD:A54827"
    }, {
      "firstName" : "EC",
      "lastName" : "Woodward",
      "authorRank" : 7,
      "name" : "Woodward EC",
      "referenceId" : "RGD:A54828"
    }, {
      "firstName" : "CW",
      "lastName" : "Conn",
      "authorRank" : 8,
      "name" : "Conn CW",
      "referenceId" : "RGD:A54829"
    }, {
      "firstName" : "AL",
      "lastName" : "Ochoa",
      "authorRank" : 9,
      "name" : "Ochoa AL",
      "referenceId" : "RGD:A54830"
    }, {
      "firstName" : "DB",
      "lastName" : "Ginsburg",
      "authorRank" : 10,
      "name" : "Ginsburg DB",
      "referenceId" : "RGD:A54831"
    }, {
      "firstName" : "JJ",
      "lastName" : "Monaco",
      "authorRank" : 11,
      "name" : "Monaco JJ",
      "referenceId" : "RGD:A23046"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1547882"
    } ]
  }, {
    "primaryId" : "PMID:10436316",
    "title" : "Targeted deletion of the cytosolic Cu/Zn-superoxide dismutase gene (Sod1) increases susceptibility to noise-induced hearing loss.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Ohlemiller KK, etal., Audiol Neurootol. 1999 Sep-Oct;4(5):237-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-27T11:19:59.000-05:00",
    "volume" : "4",
    "pages" : "237-46",
    "abstract" : "Reactive oxygen species (ROS) such as superoxide, peroxide and hydroxyl radicals  are generated during normal cellular metabolism and are increased in acute injury and in many chronic disease states. When their production is inadequately regulated, ROS accumulate and irreversibly damage cell components, causing impaired cellular function and death. Antioxidant enzymes such as superoxide dismutase (SOD) play a vital role in minimizing ROS levels and ROS-mediated damage. The cytosolic form of Cu/Zn-SOD appears specialized to remove superoxide  produced as a result of injury. 'Knockout' mice with targeted deletion of Sod1, the gene that codes for Cu/Zn-SOD, develop normally but show enhanced susceptibility to central nervous system injury. Since loud noise is injurious to the cochlea and is associated with elevated cochlear ROS, we hypothesized that Sod1 knockout mice would be more susceptible to noise-induced permanent threshold shifts (PTS) than wild-type and heterozygous control mice. Fifty-nine mice (15 knockout, 29 heterozygous and 15 wild type for Sod1) were exposed to broad-band noise (4.0-45.0 kHz) at 110 dB SPL for 1 h. Hearing sensitivity was evaluated at  5, 10, 20 and 40 kHz using auditory brainstem responses before exposure and 1, 14 and 28 days afterward. Cu/Zn-SOD deficiency led to minor (0-7 dB) threshold elevations prior to noise exposure, and about 10 dB of additional noise-induced PTS at all test frequencies, compared to controls. The distribution of thresholds at 10 and 20 kHz at 28 days following exposure contained three modes, each showing an effect of Cu/Zn-SOD deficiency. Thus another factor, possibly an additional unlinked gene, may account for the majority of the observed PTS. Our results indicate that genes involved in ROS regulation can impact the vulnerability of the cochlea to noise-induced hearing loss.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KK",
      "lastName" : "Ohlemiller",
      "authorRank" : 1,
      "name" : "Ohlemiller",
      "referenceId" : "RGD:A188182"
    }, {
      "firstName" : "SL",
      "lastName" : "McFadden",
      "authorRank" : 2,
      "name" : "McFadden",
      "referenceId" : "RGD:A188139"
    }, {
      "firstName" : "DL",
      "lastName" : "Ding",
      "authorRank" : 3,
      "name" : "Ding",
      "referenceId" : "RGD:A188439"
    }, {
      "firstName" : "DG",
      "lastName" : "Flood",
      "authorRank" : 4,
      "name" : "Flood DG",
      "referenceId" : "RGD:A96326"
    }, {
      "firstName" : "AG",
      "lastName" : "Reaume",
      "authorRank" : 5,
      "name" : "Reaume",
      "referenceId" : "RGD:A188141"
    }, {
      "firstName" : "EK",
      "lastName" : "Hoffman",
      "authorRank" : 6,
      "name" : "Hoffman",
      "referenceId" : "RGD:A188440"
    }, {
      "firstName" : "RW",
      "lastName" : "Scott",
      "authorRank" : 7,
      "name" : "Scott",
      "referenceId" : "RGD:A188441"
    }, {
      "firstName" : "JS",
      "lastName" : "Wright",
      "authorRank" : 8,
      "name" : "Wright",
      "referenceId" : "RGD:A188442"
    }, {
      "firstName" : "GV",
      "lastName" : "Putcha",
      "authorRank" : 9,
      "name" : "Putcha",
      "referenceId" : "RGD:A188443"
    }, {
      "firstName" : "RJ",
      "lastName" : "Salvi",
      "authorRank" : 10,
      "name" : "Salvi",
      "referenceId" : "RGD:A188142"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8655966"
    } ]
  }, {
    "primaryId" : "PMID:10436391",
    "title" : "Topical CTLA4-Ig suppresses ongoing mucosal immune response in presensitized murine model of allergic rhinitis.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Sato J, etal., Int Arch Allergy Immunol. 1999 Jul;119(3):197-204.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-07-08T15:19:25.000-05:00",
    "volume" : "119",
    "pages" : "197-204",
    "abstract" : "Allergic rhinitis is thought to be mediated by CD4+ T cells producing Th2-associated cytokines. Optimal Ag-specific T-cell activation requires the engagement of T-cell receptor with antigen (Ag) in the context of MHC, and the engagement of appropriate costimulatory molecules. One of the most well-characterized costimulatory pathways is the interaction of B7/CD28-CTLA4 molecules. Recent studies have suggested that the costimulatory pathway may influence the development of Th2 immune responses. The objective of this study was the examination of the role of B7/CD28-CTLA4 costimulatory pathway in the pathogenesis of ovalbumin (OVA)-induced immune response in presensitized murine model of allergic rhinitis. Systemically presensitized BALB/c mice significantly  developed Ag-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine, nasal eosinophilia, serum levels of OVA- specific IgE and Th2-associated cytokines following repeated topical Ag challenges. Topical administration of CTLA4-Ig during nasal challenges inhibited Ag-induced nasal symptoms and histamine hyperresponsiveness. We also found a significant reduction in nasal lavage eosinophilia and serum levels of OVA-specific IgE. Furthermore, CTLA4-Ig treatment significantly decreased interleukin (IL)-4 content in nasal tissue, while there was no significant change in IL-5 or IFN-gamma levels. These  results suggest that B7/CD28-CTLA4 costimulatory pathway mediates the development of ongoing Th2 immune responses and plays a major role in regulating allergic disease, such as allergic rhinitis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Sato",
      "authorRank" : 1,
      "name" : "Sato J",
      "referenceId" : "RGD:A23911"
    }, {
      "firstName" : "K",
      "lastName" : "Asakura",
      "authorRank" : 2,
      "name" : "Asakura K",
      "referenceId" : "RGD:A11955"
    }, {
      "firstName" : "M",
      "lastName" : "Murakami",
      "authorRank" : 3,
      "name" : "Murakami",
      "referenceId" : "RGD:A383271"
    }, {
      "firstName" : "T",
      "lastName" : "Uede",
      "authorRank" : 4,
      "name" : "Uede T",
      "referenceId" : "RGD:A65537"
    }, {
      "firstName" : "A",
      "lastName" : "Kataura",
      "authorRank" : 5,
      "name" : "Kataura",
      "referenceId" : "RGD:A344100"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11344920"
    } ]
  }, {
    "primaryId" : "PMID:10437118",
    "title" : "Neuronal ERCC6 mRNA expression in rat brain induced by a transient focal cerebral ischemia.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Ling X, etal., Zhongguo Yao Li Xue Bao. 1999 Jan;20(1):15-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-09-25T15:26:59.000-05:00",
    "volume" : "20",
    "pages" : "15-20",
    "abstract" : "AIM: To study whether the excision repair cross-complementing group 6 (ERCC6) is  involved in the neuronal pathophysiological process following cerebral ischemia-reperfusion injury. METHODS: A transient middle cerebral artery occlusion (MCAO) was used to induce cerebral ischemia-reperfusion injury in rat brain. Northern blot was used to check a specific signal for oligonucleotide probe. The expression of ERCC6 mRNA in the rat brain was observed by in situ hybridization. The specific cellular distribution of ERCC6 mRNA in the neuron or  glia of the rat brain was analyzed by double staining combined with confocal laser scanning microscopic analysis. RESULT: The expression of ERCC6 mRNA in the  penumbra area increased following ischemia and reperfusion with a time-dependent  manner. ERCC6 was expressed on d 2, reached peak values on d 3, and kept high level even on d 14 of reperfusion following ischemia. Number of ERCC6 mRNA expressive cell in the penumbra area on d 1, d 2, d 3, d 7, d 14 of reperfusion following ischemia were (0 +/- 0), (253 +/- 56), (816 +/- 355), (341 +/- 185), (128 +/- 95) x 10(6) cells/m2, respectively. Confocal microscopic analysis showed that ERCC6 mRNA coexpressed with phosphopyruvate hydratase in the neurons and with glial fibrillary acidic protein (GFAP) in a few proliferation astrocyte glia. CONCLUSION: The expression of transcription-repair coupling factor ERCC6 mRNA in the neuron and glia was induced by ischemia-reperfusion injury.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Ling",
      "authorRank" : 1,
      "name" : "Ling X",
      "referenceId" : "RGD:A93846"
    }, {
      "firstName" : "LM",
      "lastName" : "Zhang",
      "authorRank" : 2,
      "name" : "Zhang LM",
      "referenceId" : "RGD:A113267"
    }, {
      "firstName" : "YL",
      "lastName" : "Huang",
      "authorRank" : 3,
      "name" : "Huang YL",
      "referenceId" : "RGD:A141314"
    }, {
      "firstName" : "WL",
      "lastName" : "Bao",
      "authorRank" : 4,
      "name" : "Bao WL",
      "referenceId" : "RGD:A124511"
    }, {
      "firstName" : "FY",
      "lastName" : "Sun",
      "authorRank" : 5,
      "name" : "Sun FY",
      "referenceId" : "RGD:A113269"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10401104"
    } ]
  }, {
    "primaryId" : "PMID:10437794",
    "title" : "p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Sanchez-Margalet V and Najib S, FEBS Lett. 1999 Jul 23;455(3):307-10.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:34:45.000-05:00",
    "volume" : "455",
    "pages" : "307-10",
    "abstract" : "The 68 kDa Src substrate associated during mitosis is an RNA binding protein with Src homology 2 and 3 domain binding sites. A role for Src associated in mitosis 68 as an adaptor protein in signaling transduction has been proposed in different systems such as T-cell receptors. In the present work, we have sought to assess the possible role of Src associated in mitosis 68 in insulin receptor signaling.  We performed in vivo studies in HTC-IR cells and in vitro studies using recombinant Src associated in mitosis 68, purified insulin receptor and fusion proteins containing either the N-terminal or the C-terminal Src homology 2 domain of p85 phosphatidylinositol-3-kinase. We have found that Src associated in mitosis 68 is a substrate of the insulin receptor both in vivo and in vitro. Moreover, tyrosine-phosphorylated Src associated in mitosis 68 was found to associate with p85 phosphatidylinositol-3-kinase in response to insulin, as assessed by co-immunoprecipitation studies. Therefore, Src associated in mitosis  68 may be part of the signaling complexes of insulin receptor along with p85. In  vitro studies demonstrate that Src associated in mitosis 68 associates with the Src homology 2 domains of p85 after tyrosine phosphorylation by the activated insulin receptor. Moreover, tyr-phosphorylated Src associated in mitosis 68 binds with a higher affinity to the N-terminal Src homology 2 domain of p85 compared to the C-terminal Src homology 2 domain of p85, suggesting a preferential association of Src associated in mitosis 68 with the N-terminal Src homology 2 domain of p85. This association may be important for the link of the signaling with RNA metabolism.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Sanchez-Margalet",
      "authorRank" : 1,
      "name" : "Sanchez-Margalet V",
      "referenceId" : "RGD:A14062"
    }, {
      "firstName" : "S",
      "lastName" : "Najib",
      "authorRank" : 2,
      "name" : "Najib S",
      "referenceId" : "RGD:A23016"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553603"
    } ]
  }, {
    "primaryId" : "PMID:10438475",
    "title" : "Requirement for a negative charge at threonine 60 of the FcRgamma for complete activation of Syk.",
    "datePublished" : "1999-08-13T00:00:00.000-05:00",
    "citation" : "Swann PG, etal., J Biol Chem. 1999 Aug 13;274(33):23068-77. doi: 10.1074/jbc.274.33.23068.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-12-29T15:41:20.000-06:00",
    "volume" : "274",
    "pages" : "23068-77",
    "abstract" : "Aggregation of FcepsilonRI on mast cells results in the phosphorylation of the FcepsilonRIgamma chain on tyrosine and threonine residues within the immunoreceptor tyrosine-based activation motif. In the present study we sought to identify the site of threonine phosphorylation in FcepsilonRIgamma and investigate its functional importance. We found that threonine 60 was phosphorylated in vitro and in vivo. Expression of a mutated FcepsilonRIgamma (T60A), in either FcepsilonRIgamma-deficient or gamma-null mast cells, resulted in a delay of FcepsilonRI endocytosis, inhibition of TNF-alpha mRNA production, and inhibition of degranulation but did not affect FcepsilonRI-induced cell adhesion. Tyrosine phosphorylation of the T60A mutant gamma chain was normal, but Syk phosphorylation was dramatically reduced in these transfectants. This correlated with reduced co-immunoprecipitation of FcepsilonRIgamma with Syk. Substitution of an aspartic residue for threonine 60 of the FcepsilonRIgamma reconstituted complete activation of Syk and co-immunoprecipitation of FcepsilonRIgamma with Syk. We conclude that the negative charge provided by phosphorylation of threonine 60 of the FcepsilonRIgamma is required for the appropriate interaction and activation of Syk. This is a likely requirement for immunoreceptor tyrosine-based activation motifs involved in Syk activation.",
    "issueName" : "33",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P G",
      "lastName" : "Swann",
      "authorRank" : 1,
      "name" : "Swann PG",
      "referenceId" : "RGD:A613004"
    }, {
      "firstName" : "S",
      "lastName" : "Odom",
      "authorRank" : 2,
      "name" : "Odom S",
      "referenceId" : "RGD:A613005"
    }, {
      "firstName" : "Y J",
      "lastName" : "Zhou",
      "authorRank" : 3,
      "name" : "Zhou YJ",
      "referenceId" : "RGD:A613006"
    }, {
      "firstName" : "Z",
      "lastName" : "Szallasi",
      "authorRank" : 4,
      "name" : "Szallasi Z",
      "referenceId" : "RGD:A103912"
    }, {
      "firstName" : "P M",
      "lastName" : "Blumberg",
      "authorRank" : 5,
      "name" : "Blumberg PM",
      "referenceId" : "RGD:A613007"
    }, {
      "firstName" : "P",
      "lastName" : "Draber",
      "authorRank" : 6,
      "name" : "Draber P",
      "referenceId" : "RGD:A24146"
    }, {
      "firstName" : "J",
      "lastName" : "Rivera",
      "authorRank" : 7,
      "name" : "Rivera J",
      "referenceId" : "RGD:A27197"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:629142771"
    } ]
  }, {
    "primaryId" : "PMID:10438514",
    "title" : "Rat peroxisome proliferator-activated receptors and brown adipose tissue function during cold acclimatization.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Guardiola-Diaz HM, etal., J Biol Chem 1999 Aug 13;274(33):23368-77.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:50.000-05:00",
    "volume" : "274",
    "pages" : "23368-77",
    "abstract" : "Brown adipose tissue (BAT) hyperplasia is a fundamental physiological response to cold; it involves an acute phase of mitotic cell growth followed by a prolonged differentiation phase. Peroxisome proliferator-activated receptors (PPARs) are key regulators of fatty acid metabolism and adipocyte differentiation and may therefore mediate important metabolic changes during non-shivering thermogenesis. In the present study we have investigated PPAR mRNA expression in relation to peroxisome proliferation in rat BAT during cold acclimatization. By immunoelectron microscopy we show that the number of peroxisomes per cytoplasmic volume and acyl-CoA oxidase immunolabeling density remained constant (thus increasing in parallel with tissue mass and cell number) during the initial proliferative phase and the acute thermogenic response but increased after 14 days of cold exposure, correlating with terminal differentiation of BAT. A pronounced decrease in BAT PPARalpha and PPARgamma mRNA levels was found within hours of exposure to cold, which was reversed after 14 days, suggesting a role for either or both of these subtypes in the proliferation and induction of peroxisomes and peroxisomal beta-oxidation enzymes. In contrast, PPARdelta mRNA levels increased progressively during cold exposure. Transactivation assays in HIB 1B and HEK-293 cells demonstrated an adrenergic stimulation of peroxisome proliferator response element reporter activity via PPAR, establishing a role for these nuclear receptors in hormonal regulation of gene transcription in BAT.",
    "issueName" : "33",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HM",
      "lastName" : "Guardiola-Diaz",
      "authorRank" : 1,
      "name" : "Guardiola-Diaz HM",
      "referenceId" : "RGD:A27207"
    }, {
      "firstName" : "S",
      "lastName" : "Rehnmark",
      "authorRank" : 2,
      "name" : "Rehnmark S",
      "referenceId" : "RGD:A27208"
    }, {
      "firstName" : "N",
      "lastName" : "Usuda",
      "authorRank" : 3,
      "name" : "Usuda N",
      "referenceId" : "RGD:A25933"
    }, {
      "firstName" : "T",
      "lastName" : "Albrektsen",
      "authorRank" : 4,
      "name" : "Albrektsen T",
      "referenceId" : "RGD:A27209"
    }, {
      "firstName" : "D",
      "lastName" : "Feltkamp",
      "authorRank" : 5,
      "name" : "Feltkamp D",
      "referenceId" : "RGD:A27210"
    }, {
      "firstName" : "JA",
      "lastName" : "Gustafsson",
      "authorRank" : 6,
      "name" : "Gustafsson JA",
      "referenceId" : "RGD:A5567"
    }, {
      "firstName" : "SE",
      "lastName" : "Alexson",
      "authorRank" : 7,
      "name" : "Alexson SE",
      "referenceId" : "RGD:A9862"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727277"
    } ]
  }, {
    "primaryId" : "PMID:10438530",
    "title" : "Identification of residues in the CH2/CH3 domain interface of IgA essential for interaction with the human fcalpha receptor (FcalphaR) CD89.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Pleass RJ, etal., J Biol Chem. 1999 Aug 13;274(33):23508-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:58:50.000-05:00",
    "volume" : "274",
    "pages" : "23508-14",
    "abstract" : "Cellular receptors for IgA (FcalphaR) mediate important protective functions. An  extensive panel of site-directed mutant IgAs was used to identify IgA residues critical for FcalphaR (CD89) binding and triggering. Although a tailpiece-deleted IgA1 was able to bind and trigger CD89, antibodies featuring CH3 domain exchanges between human IgA1 and IgG1 could not, indicating that both domains but not the tailpiece are required for FcalphaR recognition. To further investigate the role  of the interdomain region, numerous IgA1s, each with a point substitution in either of two interdomain loops (Leu-257-Gly-259 in Calpha2; Pro-440-Phe-443 in Calpha3), were generated. With only one exception (G259R), substitutions produced either ablation (L257R, P440A, A442R, F443R) or marked reduction (P440R) in CD89  binding and triggering. Further support for involvement of these interdomain loops was provided by interspecies comparisons of IgA. Thus a human IgA1 mutant,  LA441-442MN, which mimicked the mouse IgA loop sequence through substitution of two adjacent residues in the Calpha3 loop, was found, like mouse IgA, not to bind CD89. In contrast, bovine IgA1, identical to human IgA1 within these interdomain  loops despite numerous differences elsewhere in the Fc region, did bind CD89. We  have thus identified motifs in the interdomain region of IgA Fc critical for FcalphaR binding and triggering, significantly enhancing present understanding of the molecular basis of the IgA-FcalphaR interaction.",
    "issueName" : "33",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RJ",
      "lastName" : "Pleass",
      "authorRank" : 1,
      "name" : "Pleass",
      "referenceId" : "RGD:A239213"
    }, {
      "firstName" : "JI",
      "lastName" : "Dunlop",
      "authorRank" : 2,
      "name" : "Dunlop",
      "referenceId" : "RGD:A239214"
    }, {
      "firstName" : "CM",
      "lastName" : "Anderson",
      "authorRank" : 3,
      "name" : "Anderson CM",
      "referenceId" : "RGD:A23523"
    }, {
      "firstName" : "JM",
      "lastName" : "Woof",
      "authorRank" : 4,
      "name" : "Woof",
      "referenceId" : "RGD:A218619"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11057791"
    } ]
  }, {
    "primaryId" : "PMID:10438538",
    "title" : "Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Conrad PW, etal., J Biol Chem. 1999 Aug 13;274(33):23570-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:33:01.000-05:00",
    "volume" : "274",
    "pages" : "23570-6",
    "abstract" : "Hypoxic/ischemic trauma is a primary factor in the pathology of a multitude of disease states. The effects of hypoxia on the stress- and mitogen-activated protein kinase signaling pathways were studied in PC12 cells. Exposure to moderate hypoxia (5% O(2)) progressively stimulated phosphorylation and activation of p38gamma in particular, and also p38alpha, two stress-activated protein kinases. In contrast, hypoxia had no effect on enzyme activity of p38beta, p38beta(2), p38delta, or on c-Jun N-terminal kinase, another stress-activated protein kinase. Prolonged hypoxia also induced phosphorylation and activation of p42/p44 mitogen-activated protein kinase, although this activation was modest compared with nerve growth factor- and ultraviolet light-induced activation. Hypoxia also dramatically down-regulated immunoreactivity of cyclin D1, a gene that is known to be regulated negatively by p38 at the level of gene expression (Lavoie, J. N., L'Allemain, G., Brunet, A., Muller, R., and Pouyssegur, J. (1996) J. Biol. Chem. 271, 20608-20616). This effect was partially blocked by SB203580, an inhibitor of p38alpha but not p38gamma. Overexpression of a kinase-inactive form of p38gamma was also able to reverse in part the effect of hypoxia on cyclin D1 levels, suggesting that p38alpha and p38gamma converge to regulate cyclin D1 during hypoxia. These studies demonstrate that an extremely typical physiological stress (hypoxia) causes selective activation of specific p38 signaling elements; and they also identify a downstream target of these pathways.",
    "issueName" : "33",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "PW",
      "lastName" : "Conrad",
      "authorRank" : 1,
      "name" : "Conrad",
      "referenceId" : "RGD:A183973"
    }, {
      "firstName" : "RT",
      "lastName" : "Rust",
      "authorRank" : 2,
      "name" : "Rust RT",
      "referenceId" : "RGD:A88641"
    }, {
      "firstName" : "J",
      "lastName" : "Han",
      "authorRank" : 3,
      "name" : "Han J",
      "referenceId" : "RGD:A20082"
    }, {
      "firstName" : "DE",
      "lastName" : "Millhorn",
      "authorRank" : 4,
      "name" : "Millhorn DE",
      "referenceId" : "RGD:A49737"
    }, {
      "firstName" : "D",
      "lastName" : "Beitner-Johnson",
      "authorRank" : 5,
      "name" : "Beitner-Johnson D",
      "referenceId" : "RGD:A88639"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553435"
    } ]
  }, {
    "primaryId" : "PMID:104388",
    "title" : "Eye malformations in rats: induction by prenatal exposure to nickel carbonyl.",
    "datePublished" : "1979-09-01T00:00:00.000-05:00",
    "citation" : "Sunderman FW Jr, etal., Science 1979 Feb 9;203(4380):550-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-26T11:04:46.000-05:00",
    "volume" : "203",
    "pages" : "550-3",
    "abstract" : "Exposure of pregnant rats to inhalation of nickel carbonyl on days 7 or 8 of gestation frequently causes the progeny to develop ocular anomalies, including anophthalmia and microphthalmia. The incidence of extraocular anomalies is very low. The specificity of nickel carbonyl for induction of ocular anomalies in rats appears to be unique among known teratogenic agents.",
    "issueName" : "4380",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JR",
      "lastName" : "Sunderman FW",
      "authorRank" : 1,
      "name" : "Sunderman FW JR",
      "referenceId" : "RGD:A25197"
    }, {
      "firstName" : "PR",
      "lastName" : "Allpass",
      "authorRank" : 2,
      "name" : "Allpass PR",
      "referenceId" : "RGD:A25198"
    }, {
      "firstName" : "JM",
      "lastName" : "Mitchell",
      "authorRank" : 3,
      "name" : "Mitchell JM",
      "referenceId" : "RGD:A25199"
    }, {
      "firstName" : "RC",
      "lastName" : "Baselt",
      "authorRank" : 4,
      "name" : "Baselt RC",
      "referenceId" : "RGD:A25200"
    }, {
      "firstName" : "DM",
      "lastName" : "Albert",
      "authorRank" : 5,
      "name" : "Albert DM",
      "referenceId" : "RGD:A25201"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634838"
    } ]
  }, {
    "primaryId" : "PMID:10438864",
    "title" : "Adenovirus-mediated expression of a ribozyme to c-myb mRNA inhibits smooth muscle cell proliferation and neointima formation in vivo.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Macejak DG, etal., J Virol. 1999 Sep;73(9):7745-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-09-06T11:10:02.000-05:00",
    "volume" : "73",
    "pages" : "7745-51",
    "abstract" : "Smooth muscle cell (SMC) proliferation is an important component of restenosis in response to injury after balloon angioplasty. Inhibition of proliferation in vivo can limit neointima hyperplasia in animal models of restenosis. Ribozymes against c-myb mRNA have been shown to be effective inhibitors of SMC proliferation in vitro. The effectiveness of adenovirus as a gene therapy vector in animal models  of restenosis is well documented. In order to test the utility of ribozymes to inhibit SMC proliferation by a gene therapy approach, recombinant adenovirus expressing ribozymes against c-myb mRNA was generated and tested both in vitro and in vivo. This adenovirus ribozyme vector is shown to inhibit SMC proliferation in culture and neointima formation in a rat carotid artery balloon  injury model of restenosis.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DG",
      "lastName" : "Macejak",
      "authorRank" : 1,
      "name" : "Macejak",
      "referenceId" : "RGD:A378373"
    }, {
      "firstName" : "H",
      "lastName" : "Lin",
      "authorRank" : 2,
      "name" : "Lin H",
      "referenceId" : "RGD:A23648"
    }, {
      "firstName" : "S",
      "lastName" : "Webb",
      "authorRank" : 3,
      "name" : "Webb S",
      "referenceId" : "RGD:A37121"
    }, {
      "firstName" : "J",
      "lastName" : "Chase",
      "authorRank" : 4,
      "name" : "Chase",
      "referenceId" : "RGD:A300937"
    }, {
      "firstName" : "K",
      "lastName" : "Jensen",
      "authorRank" : 5,
      "name" : "Jensen",
      "referenceId" : "RGD:A227145"
    }, {
      "firstName" : "TC",
      "lastName" : "Jarvis",
      "authorRank" : 6,
      "name" : "Jarvis",
      "referenceId" : "RGD:A378355"
    }, {
      "firstName" : "JM",
      "lastName" : "Leiden",
      "authorRank" : 7,
      "name" : "Leiden JM",
      "referenceId" : "RGD:A37430"
    }, {
      "firstName" : "L",
      "lastName" : "Couture",
      "authorRank" : 8,
      "name" : "Couture",
      "referenceId" : "RGD:A378374"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11532744"
    } ]
  }, {
    "primaryId" : "PMID:10438867",
    "title" : "Nuclear export factor CRM1 interacts with nonstructural proteins NS2 from parvovirus minute virus of mice.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Bodendorf U, etal., J Virol 1999 Sep;73(9):7769-79.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:44:02.000-05:00",
    "volume" : "73",
    "pages" : "7769-79",
    "abstract" : "The nonstructural NS2 proteins of autonomous parvoviruses are known to act in a host cell-dependent manner and to play a role in viral DNA replication, efficient translation of viral mRNA, and/or encapsidation. Their exact function during the parvovirus life cycle remains, however, still obscure. We report here the characterization of the interaction with the NS2 proteins from the parvovirus minute virus of mice (MVM) and rat as well as mouse homologues of the human CRM1 protein, a member of the importin-beta family recently identified as an essential nuclear export factor. Using the two-hybrid system, we could detect the interaction between the carboxy-terminal region of rat CRM1 and each of the three isoforms of NS2 (P [or major], Y [or minor], and L [or rare]). NS2 proteins were further shown to interact with the full-length CRM1 by coimmunoprecipitation experiments using extracts from both mouse and rat cell lines. Our data show that CRM1 preferentially binds to the nonphosphorylated isoforms of NS2. Moreover, we observed that the treatment of MVM-infected cells with leptomycin B, a drug that specifically inhibits the CRM1-dependent nuclear export pathway, leads to a drastic accumulation of NS2 proteins in the nucleus. Both NS2 interaction with CRM1 and nuclear accumulation upon leptomycin B treatment strongly suggest that these nonstructural viral proteins are actively exported out of the nuclei of infected cells via a CRM1-mediated nuclear export pathway.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "U",
      "lastName" : "Bodendorf",
      "authorRank" : 1,
      "name" : "Bodendorf U",
      "referenceId" : "RGD:A24244"
    }, {
      "firstName" : "C",
      "lastName" : "Cziepluch",
      "authorRank" : 2,
      "name" : "Cziepluch C",
      "referenceId" : "RGD:A23060"
    }, {
      "firstName" : "JC",
      "lastName" : "Jauniaux",
      "authorRank" : 3,
      "name" : "Jauniaux JC",
      "referenceId" : "RGD:A23065"
    }, {
      "firstName" : "J",
      "lastName" : "Rommelaere",
      "authorRank" : 4,
      "name" : "Rommelaere J",
      "referenceId" : "RGD:A23064"
    }, {
      "firstName" : "N",
      "lastName" : "Salome",
      "authorRank" : 5,
      "name" : "Salome N",
      "referenceId" : "RGD:A24245"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634528"
    } ]
  }, {
    "primaryId" : "PMID:10438957",
    "title" : "Monocyte chemoattractant protein-1 mediates cockroach allergen-induced bronchial hyperreactivity in normal but not CCR2-/- mice: the role of mast cells.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Campbell EM, etal., J Immunol. 1999 Aug 15;163(4):2160-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-10-26T14:19:03.000-05:00",
    "volume" : "163",
    "pages" : "2160-7",
    "abstract" : "Bronchial eosinophil and mononuclear cell infiltrates are a hallmark of the asthmatic lung and are associated with the induction of reversible airway hyperreactivity. In these studies, we have found that monocyte chemotactic protein-1 (MCP-1), a CC (beta) chemokine, mediates airway hyperreactivity in normal and allergic mice. Using a murine model of cockroach Ag-induced allergic airway inflammation, we have demonstrated that anti-MCP-1 Abs inhibit changes in airway resistance and attenuate histamine release into the bronchoalveolar lavage, suggesting a role for MCP-1 in mast cell degranulation. In normal mice, instillation of MCP-1 induced prolonged airway hyperreactivity and histamine release. In addition, MCP-1 directly induced pulmonary mast cell degranulation in vitro. These latter effects would appear to be selective because no changes were observed when macrophage-inflammatory protein-1alpha, eotaxin, or MCP-3 were instilled into the airways of normal mice or when mast cells were treated in vitro. Airway hyperreactivity was mediated by MCP-1 through CCR2 because allergen-induced as well as direct MCP-1 instilled-induced changes in airway hyperreactivity were significantly attenuated in CCR2 -/- mice. The neutralization of MCP-1 in allergic animals and instillation of MCP-1 in normal animals was related to leukotriene C4 levels in the bronchoalveolar lavage and was directly induced in pulmonary mast cells by MCP-1. Thus, these data identify MCP-1 and CCR2 as potentially important therapeutic targets for the treatment of hyperreactive airway disease.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EM",
      "lastName" : "Campbell",
      "authorRank" : 1,
      "name" : "Campbell EM",
      "referenceId" : "RGD:A129665"
    }, {
      "firstName" : "IF",
      "lastName" : "Charo",
      "authorRank" : 2,
      "name" : "Charo IF",
      "referenceId" : "RGD:A36859"
    }, {
      "firstName" : "SL",
      "lastName" : "Kunkel",
      "authorRank" : 3,
      "name" : "Kunkel SL",
      "referenceId" : "RGD:A69785"
    }, {
      "firstName" : "RM",
      "lastName" : "Strieter",
      "authorRank" : 4,
      "name" : "Strieter RM",
      "referenceId" : "RGD:A49755"
    }, {
      "firstName" : "L",
      "lastName" : "Boring",
      "authorRank" : 5,
      "name" : "Boring L",
      "referenceId" : "RGD:A36856"
    }, {
      "firstName" : "J",
      "lastName" : "Gosling",
      "authorRank" : 6,
      "name" : "Gosling J",
      "referenceId" : "RGD:A36857"
    }, {
      "firstName" : "NW",
      "lastName" : "Lukacs",
      "authorRank" : 7,
      "name" : "Lukacs NW",
      "referenceId" : "RGD:A126569"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4145126"
    } ]
  }, {
    "primaryId" : "PMID:10439047",
    "title" : "The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Klugbauer S and Rabes HM, Oncogene. 1999 Jul 29;18(30):4388-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-09T15:19:21.000-06:00",
    "volume" : "18",
    "pages" : "4388-93",
    "abstract" : "Children exposed to radioactive iodine as a consequence of the Chernobyl reactor accident have an increased risk of papillary thyroid carcinomas (PTC). The predominant molecular lesions in these tumors are rearrangements of the RET receptor tyrosine kinase (tk). Here we report on two novel types of RET rearrangement, PTC6 and 7, and describe the fusion products and the ret fused gene (rfg) proteins. Like the other rfg proteins identified so far they are ubiquitously expressed, not membrane-bound and contain coiled coil domains required for constitutive activation of the ret tk domain. In the PTC6 rearrangement the ret tk domain is fused to the aminoterminal part of the human transcription intermediary factor htif 1. In the PTC7 rearrangement the ret tk domain is fused to a novel protein that is strongly related to htif1. Like htif1 it contains a RBCC motif (ring finger, B boxes, coiled coil domain) located in the aminoterminal part and a phd finger and a bromodomain in the carboxyterminal part. Htif1 and related proteins are transcription coactivators for nuclear receptors, thus participating in controlling cellular development, differentiation and homeostasis. This is the first report on their involvement in human thyroid carcinogenesis.",
    "issueName" : "30",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Klugbauer",
      "authorRank" : 1,
      "name" : "Klugbauer S",
      "referenceId" : "RGD:A43127"
    }, {
      "firstName" : "HM",
      "lastName" : "Rabes",
      "authorRank" : 2,
      "name" : "Rabes HM",
      "referenceId" : "RGD:A43131"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599658"
    } ]
  }, {
    "primaryId" : "PMID:10439464",
    "title" : "Regulation of neurofilament gene expression by thyroid hormone in the developing  rat brain.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Ghosh S, etal., Neuroreport. 1999 Aug 2;10(11):2361-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-02-23T14:05:30.000-06:00",
    "volume" : "10",
    "pages" : "2361-5",
    "abstract" : "The role of thyroid hormone (TH) in the expression of neurofilament (NF) genes during the first 3-4 postnatal weeks of rat brain development has been examined.  I.p. administration of TH to 2-day-old hypothyroid rats resulted in a 2-fold increase in cerebral NF-M and NF-L mRNAs, while administration to 15-day-old hypothyroid rats led to a 1.5- to 3-fold increase in NF-H mRNA within 2-4 h of hormone injection. Comparison of the level of these mRNAs in cerebra from 5, 10,  15 and 20-day-old normal and hypothyroid rats by Northern blot analysis revealed  that hypothyroidism declined the expression of all three mRNAs by 50-70% at all ages examined. Western blot analysis of total protein and cytoskeletal proteins isolated from cerebras of 5, 10, 15, 20 and 25-day-old normal and hypothyroid rats demonstrated an even greater reduction (60-90%) in the expression of NF proteins in the hypothyroid cerebra during the period examined. The overall results show that TH plays an important role in regulating the expression of all  three NF genes during rat brain development.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Ghosh",
      "authorRank" : 1,
      "name" : "Ghosh S",
      "referenceId" : "RGD:A6884"
    }, {
      "firstName" : "SO",
      "lastName" : "Rahaman",
      "authorRank" : 2,
      "name" : "Rahaman",
      "referenceId" : "RGD:A199384"
    }, {
      "firstName" : "PK",
      "lastName" : "Sarkar",
      "authorRank" : 3,
      "name" : "Sarkar",
      "referenceId" : "RGD:A199385"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9743942"
    } ]
  }, {
    "primaryId" : "PMID:10439967",
    "title" : "Two buffer PAGE system-based SSCP/HD analysis: a general protocol for rapid and sensitive mutation screening in cystic fibrosis and any other human genetic disease.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Liechti-Gallati S, etal., Eur J Hum Genet. 1999 Jul;7(5):590-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:24:27.000-05:00",
    "volume" : "7",
    "pages" : "590-8",
    "abstract" : "The large size of many disease genes and the multiplicity of mutations complicate the design of an adequate assay for the identification of disease-causing variants. One of the most successful methods for mutation detection is the single strand conformation polymorphism (SSCP) technique. By varying temperature, gel composition, ionic strength and additives, we optimised the sensitivity of SSCP for all 27 exons of the CFTR gene. Using simultaneously SSCP and heteroduplex (HD) analysis, a total of 80 known CF mutations (28 missense, 22 frameshift, 17 nonsense, 13 splicesite) and 20 polymorphisms was analysed resulting in a detection rate of 97.5% including the 24 most common mutations worldwide. The ability of this technique to detect mutations independent of their nature, frequency, and population specificity was confirmed by the identification of five novel mutations (420del9, 1199delG, R560S, A613T, T1299I) in Swiss CF patients, as well as by the detection of 41 different mutations in 198 patients experimentally analysed. We present a three-stage screening strategy allowing analysis of seven exons within 5 hours and analysis of the entire coding region within 1 week, including sequence analysis of the variants. Additionally, our protocol represents a general model for point mutation analysis in other genetic  disorders and has already been successfully established for OTC deficiency, collagene deficiency, X-linked myotubular myopathy (XLMTM), Duchenne and Becker muscular dystrophy (DMD, BMD), Wilson disease (WD), Neurofibromatosis I and II, Charcot-Marie-Tooth disease, hereditary neuropathy with liability to pressure palsies, and defects in mitochondrial DNA. No other protocol published so far presents standard SSCP/HD conditions for mutation screening in different disease  genes.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Liechti-Gallati",
      "authorRank" : 1,
      "name" : "Liechti-Gallati S",
      "referenceId" : "RGD:A79216"
    }, {
      "firstName" : "V",
      "lastName" : "Schneider",
      "authorRank" : 2,
      "name" : "Schneider V",
      "referenceId" : "RGD:A89286"
    }, {
      "firstName" : "D",
      "lastName" : "Neeser",
      "authorRank" : 3,
      "name" : "Neeser",
      "referenceId" : "RGD:A267788"
    }, {
      "firstName" : "R",
      "lastName" : "Kraemer",
      "authorRank" : 4,
      "name" : "Kraemer",
      "referenceId" : "RGD:A200478"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067334"
    } ]
  }, {
    "primaryId" : "PMID:10440069",
    "title" : "Complement haemolytic activity, circulating immune complexes and the morbidity of sickle cell anaemia.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Anyaegbu CC, etal., APMIS. 1999 Jul;107(7):699-702.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-23T09:46:56.000-05:00",
    "volume" : "107",
    "pages" : "699-702",
    "abstract" : "The aim of this study was to find out if the number of crises and complications of sickle cell anaemia (SCA) relate to complement function, or the levels of circulating immune complexes (CIC), complement factor B (Bf), C3 and C4. In 73 steady-state HbSS patients and 50 HbAA control subjects, we determined the haemolytic activity of the alternative pathway of complement (AP50), of the classical pathway (CH50); and the serum concentrations of Bf, C3, C4 and CIC. By  clinical examination of each patient and review of the medical records, we determined the number of complications of SCA which had occurred and the mean number of crises per year over a minimum period of 3 years. The mean+/-SD AP50 for the patients (14+/-2 U/ml) was significantly lower than the control value of  16+/-3 U/ml (p<0.001). AP50 had a significant inverse correlation with the number of crises (r=-0.30, p<0.02). Mean+/-SD CIC in patients (0.45+/-0.38 g/l) was significantly higher than in controls: 0.24+/-0.15 g/l (p<0.002). CIC showed a significant direct correlation with the number of complications of SCA (r=+/-0.28, p<0.02). Mean+/-SD Bf in SCA patients (0.19+/-0.09) was higher than in controls (0.17+/-0.05). The difference reached marginal statistical significance (p=0.049). SCA patients and controls had no significant differences  in CH50, C3 and C4. These parameters and Bf did not correlate with either the number of crises or complications. The mechanisms underlying the correlations observed in this study are yet to be fully elucidated.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CC",
      "lastName" : "Anyaegbu",
      "authorRank" : 1,
      "name" : "Anyaegbu",
      "referenceId" : "RGD:A214285"
    }, {
      "firstName" : "IE",
      "lastName" : "Okpala",
      "authorRank" : 2,
      "name" : "Okpala",
      "referenceId" : "RGD:A214286"
    }, {
      "firstName" : "AY",
      "lastName" : "Aken'ova",
      "authorRank" : 3,
      "name" : "Aken'ova",
      "referenceId" : "RGD:A214287"
    }, {
      "firstName" : "LS",
      "lastName" : "Salimonu",
      "authorRank" : 4,
      "name" : "Salimonu",
      "referenceId" : "RGD:A214288"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041159"
    } ]
  }, {
    "primaryId" : "PMID:10440485",
    "title" : "Prenatal ethanol effects on NGF level, NPY and ChAT immunoreactivity in mouse entorhinal cortex: a preliminary study.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Angelucci F, etal., Neurotoxicol Teratol. 1999 Jul-Aug;21(4):415-25. doi: 10.1016/s0892-0362(99)00005-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-02-29T13:33:41.000-06:00",
    "volume" : "21",
    "pages" : "415-25",
    "abstract" : "It has been reported that maternal ethanol consumption leads to deficits in the limbic areas involved in cognitive functions and interferes with synthesis and utilization of neurotrophins. In the present study, it was hypothesized that prenatal alcohol intake might induce neuroanatomical alterations in the entorhinal cortex (EC). We also investigated the possible EC involvement of brain nerve growth factor (NGF), the first neurotrophin to be isolated, during such pathological events. To test this hypothesis, we used pregnant mice exposed to ethanol during EC neurogenesis (starting about gestational day 8). Our data show that prenatal alcohol intake in male mice alters the EC neuronal growth and differentiation. These morphological alterations are accompanied by an altered NGF level in the EC of prenatal alcohol-treated mice. We also found a decrease in choline acetyltransferase- and neuropeptide Y-immunopositive neurons in the EC of alcohol-exposed mice. However, the relationship between neuronal damage induced in the EC by ethanol, low presence of NGF, and the possible functional and behavioral consequences remains to be elucidated.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Angelucci",
      "authorRank" : 1,
      "name" : "Angelucci F",
      "referenceId" : "RGD:A64766"
    }, {
      "firstName" : "M",
      "lastName" : "Fiore",
      "authorRank" : 2,
      "name" : "Fiore M",
      "referenceId" : "RGD:A64760"
    }, {
      "firstName" : "C",
      "lastName" : "Cozzari",
      "authorRank" : 3,
      "name" : "Cozzari C",
      "referenceId" : "RGD:A539464"
    }, {
      "firstName" : "L",
      "lastName" : "Aloe",
      "authorRank" : 4,
      "name" : "Aloe L",
      "referenceId" : "RGD:A64767"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401976542"
    } ]
  }, {
    "primaryId" : "PMID:10440754",
    "title" : "Expression of tumour necrosis factor (TNF) receptor/ligand superfamily co-stimulatory molecules CD40, CD30L, CD27L, and OX40L in murine hearts with chronic ongoing myocarditis caused by coxsackie virus B3.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Seko Y, etal., J Pathol. 1999 Aug;188(4):423-30. doi: 10.1002/(SICI)1096-9896(199908)188:4<423::AID-PATH373>3.0.CO;2-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-23T12:35:15.000-05:00",
    "volume" : "188",
    "pages" : "423-30",
    "abstract" : "T-cell-mediated myocardial damage has been shown to be involved in acute myocarditis and dilated cardiomyopathy. It is necessary for T-cells to receive a co-stimulatory signal as well as the main signal through the T-cell receptor for antigen-specific T-cell activation to occur. To investigate the roles of the co-stimulatory molecules CD40/CD40L, CD30/CD30L, CD27/CD27L, and OX40/OX40L, which belong to the tumour necrosis factor (TNF) receptor/ligand superfamily, in the development of chronic ongoing myocarditis, the expression of CD40, CD30L, CD27L, and OX40L was analysed in the hearts of A/J mice with myocarditis induced by Coxsackie virus B3 (CVB3). The expression of CD40L, CD30, CD27, and OX40 was also examined on the infiltrating cells. Furthermore, the induction of CD40, CD30L, CD27L, and OX40L was evaluated on cultured cardiac myocytes treated with interferon (IFN)-gamma. CVB3-induced myocarditis resulted in the induction of CD40 and CD30L on the surface of cardiac myocytes. Induction of CD40 and CD30L on cardiac myocytes was confirmed by treatment with IFN-gamma in vitro. CD27L and OX40L were expressed on cardiac myocytes in vivo and in vitro. The expression of CD27L and OX40L on cardiac myocytes was increased, at least partly, by CVB3-induced myocarditis in vivo. Many infiltrating cells expressed CD27 and OX40, whereas much smaller numbers expressed CD40L and CD30. The induction of these molecules, especially CD40 and CD30L, on cardiac myocytes strongly suggests that cardiac myocytes may co-stimulate T-cells and induce cytokine production by T-cells and humoral immune responses. This may play an important role in the pathogenesis of the resulting myocardial damage.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Seko",
      "authorRank" : 1,
      "name" : "Seko Y",
      "referenceId" : "RGD:A63525"
    }, {
      "firstName" : "N",
      "lastName" : "Takahashi",
      "authorRank" : 2,
      "name" : "Takahashi N",
      "referenceId" : "RGD:A16701"
    }, {
      "firstName" : "H",
      "lastName" : "Oshima",
      "authorRank" : 3,
      "name" : "Oshima H",
      "referenceId" : "RGD:A83842"
    }, {
      "firstName" : "O",
      "lastName" : "Shimozato",
      "authorRank" : 4,
      "name" : "Shimozato O",
      "referenceId" : "RGD:A461743"
    }, {
      "firstName" : "H",
      "lastName" : "Akiba",
      "authorRank" : 5,
      "name" : "Akiba H",
      "referenceId" : "RGD:A24189"
    }, {
      "firstName" : "T",
      "lastName" : "Kobata",
      "authorRank" : 6,
      "name" : "Kobata T",
      "referenceId" : "RGD:A461744"
    }, {
      "firstName" : "H",
      "lastName" : "Yagita",
      "authorRank" : 7,
      "name" : "Yagita H",
      "referenceId" : "RGD:A17485"
    }, {
      "firstName" : "K",
      "lastName" : "Okumura",
      "authorRank" : 8,
      "name" : "Okumura K",
      "referenceId" : "RGD:A11657"
    }, {
      "firstName" : "M",
      "lastName" : "Azuma",
      "authorRank" : 9,
      "name" : "Azuma M",
      "referenceId" : "RGD:A5699"
    }, {
      "firstName" : "Y",
      "lastName" : "Yazaki",
      "authorRank" : 10,
      "name" : "Yazaki Y",
      "referenceId" : "RGD:A161904"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702887"
    } ]
  }, {
    "primaryId" : "PMID:10440820",
    "title" : "Partial monosomy of distal 10q: three new cases and a review.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Waggoner DJ, etal., Am J Med Genet. 1999 Sep 3;86(1):1-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:53:36.000-05:00",
    "volume" : "86",
    "pages" : "1-5",
    "abstract" : "We report on 3 patients with partial deletions of the long arm of chromosome 10-46,XY,del (10)(q26.2), 46,XX,del(10) (q25.3q26.3) or 46,XX,del(10)(q26.1), and 46,XX,del (10)(q26.1). They are compared with other known cases with interstitial or terminal deletions involving chromosome bands 10q25 or q26. Unique manifestations are identified, including scoliosis and a severe behavior disorder with attention deficit and hyperactivity in a 12-year-old boy as well as patchy alopecia in a 6-year-old patient.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Waggoner",
      "authorRank" : 1,
      "name" : "Waggoner",
      "referenceId" : "RGD:A262786"
    }, {
      "firstName" : "CK",
      "lastName" : "Chow",
      "authorRank" : 2,
      "name" : "Chow",
      "referenceId" : "RGD:A273904"
    }, {
      "firstName" : "SB",
      "lastName" : "Dowton",
      "authorRank" : 3,
      "name" : "Dowton SB",
      "referenceId" : "RGD:A4642"
    }, {
      "firstName" : "MS",
      "lastName" : "Watson",
      "authorRank" : 4,
      "name" : "Watson",
      "referenceId" : "RGD:A273905"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069442"
    } ]
  }, {
    "primaryId" : "PMID:10441006",
    "title" : "SMAD genes in juvenile polyposis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Roth S, etal., Genes Chromosomes Cancer. 1999 Sep;26(1):54-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:33:13.000-05:00",
    "volume" : "26",
    "pages" : "54-61",
    "abstract" : "Juvenile polyposis (JP) is a dominantly inherited condition characterized by the  development of multiple hamartomatous tumors, juvenile polyps, in the gastrointestinal tract. The aim of this study was to clarify the role of SMAD4 in JP. DNA from four unrelated JP kindreds and three sporadic JP cases was available for mutation screening. Two truncating defects (one in a familial and one in a sporadic case) and one missense change (in a familial case) that was absent in 55 control samples were detected. To study the possibility that germline mutations in other genes encoding different components of the TGF-beta signaling pathway may be present in these JP patients, mutation analyses of the SMAD2, SMAD3, and SMAD7 genes were also performed. No mutations of these genes were detected in any of the patients. Our results confirm that SMAD4 is a gene predisposing to JP and  suggest the existence of further JP loci other than the SMAD2, SMAD3, or SMAD7 genes. Genes Chromosomes Cancer 26:54-61, 1999.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Roth",
      "authorRank" : 1,
      "name" : "Roth",
      "referenceId" : "RGD:A400446"
    }, {
      "firstName" : "P",
      "lastName" : "Sistonen",
      "authorRank" : 2,
      "name" : "Sistonen P",
      "referenceId" : "RGD:A51406"
    }, {
      "firstName" : "R",
      "lastName" : "Salovaara",
      "authorRank" : 3,
      "name" : "Salovaara R",
      "referenceId" : "RGD:A36409"
    }, {
      "firstName" : "A",
      "lastName" : "Hemminki",
      "authorRank" : 4,
      "name" : "Hemminki A",
      "referenceId" : "RGD:A100127"
    }, {
      "firstName" : "A",
      "lastName" : "Loukola",
      "authorRank" : 5,
      "name" : "Loukola A",
      "referenceId" : "RGD:A75502"
    }, {
      "firstName" : "M",
      "lastName" : "Johansson",
      "authorRank" : 6,
      "name" : "Johansson M",
      "referenceId" : "RGD:A75501"
    }, {
      "firstName" : "E",
      "lastName" : "Avizienyte",
      "authorRank" : 7,
      "name" : "Avizienyte",
      "referenceId" : "RGD:A248482"
    }, {
      "firstName" : "KA",
      "lastName" : "Cleary",
      "authorRank" : 8,
      "name" : "Cleary",
      "referenceId" : "RGD:A258455"
    }, {
      "firstName" : "P",
      "lastName" : "Lynch",
      "authorRank" : 9,
      "name" : "Lynch",
      "referenceId" : "RGD:A258456"
    }, {
      "firstName" : "CI",
      "lastName" : "Amos",
      "authorRank" : 10,
      "name" : "Amos CI",
      "referenceId" : "RGD:A39955"
    }, {
      "firstName" : "P",
      "lastName" : "Kristo",
      "authorRank" : 11,
      "name" : "Kristo",
      "referenceId" : "RGD:A258457"
    }, {
      "firstName" : "JP",
      "lastName" : "Mecklin",
      "authorRank" : 12,
      "name" : "Mecklin JP",
      "referenceId" : "RGD:A36419"
    }, {
      "firstName" : "I",
      "lastName" : "Kellokumpu",
      "authorRank" : 13,
      "name" : "Kellokumpu I",
      "referenceId" : "RGD:A36415"
    }, {
      "firstName" : "H",
      "lastName" : "Jarvinen",
      "authorRank" : 14,
      "name" : "Jarvinen H",
      "referenceId" : "RGD:A36414"
    }, {
      "firstName" : "LA",
      "lastName" : "Aaltonen",
      "authorRank" : 15,
      "name" : "Aaltonen LA",
      "referenceId" : "RGD:A36425"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064398"
    } ]
  }, {
    "primaryId" : "PMID:10441197",
    "title" : "Intronic mutations at splice junctions in the low-density lipoprotein receptor gene.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Peeters AV, etal., Mol Cell Probes. 1999 Aug;13(4):257-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T20:14:50.000-05:00",
    "volume" : "13",
    "pages" : "257-60",
    "abstract" : "Most of the low-density lipoprotein receptor (LDLR) gene mutations causing familial hypercholesterolemia (FH) have been identified in the coding region of the gene. We have screened 180 patients for disease-related gene defects and report the identification of three previously described (IVS3+1G-->A, IVS9-1G-->A and IVS16-2A-->G) and two novel mutations (IVS2+1G-->A and IVS14+1G-->T) at splice junctions. Approximately 9% (38/404) of LDLR gene point mutations identified to date in FH patients occur in introns and may affect splicing. The severe consequences of these mutations make them an important target for the molecular analysis of FH.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AV",
      "lastName" : "Peeters",
      "authorRank" : 1,
      "name" : "Peeters",
      "referenceId" : "RGD:A320462"
    }, {
      "firstName" : "R",
      "lastName" : "Thiart",
      "authorRank" : 2,
      "name" : "Thiart",
      "referenceId" : "RGD:A282254"
    }, {
      "firstName" : "JN",
      "lastName" : "De Villiers",
      "authorRank" : 3,
      "name" : "De Villiers",
      "referenceId" : "RGD:A282258"
    }, {
      "firstName" : "HK",
      "lastName" : "Jensen",
      "authorRank" : 4,
      "name" : "Jensen HK",
      "referenceId" : "RGD:A57707"
    }, {
      "firstName" : "LF",
      "lastName" : "Van Gaal",
      "authorRank" : 5,
      "name" : "Van Gaal LF",
      "referenceId" : "RGD:A84833"
    }, {
      "firstName" : "MJ",
      "lastName" : "Kotze",
      "authorRank" : 6,
      "name" : "Kotze MJ",
      "referenceId" : "RGD:A148949"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11098233"
    } ]
  }, {
    "primaryId" : "PMID:10441236",
    "title" : "Pigment epithelium-derived factor promotes the survival and differentiation of developing spinal motor neurons.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Houenou LJ, etal., J Comp Neurol. 1999 Sep 27;412(3):506-14.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-12T13:47:55.000-05:00",
    "volume" : "412",
    "pages" : "506-14",
    "abstract" : "Pigment epithelium-derived factor (PEDF) is a member of the serine protease inhibitor (serpin) superfamily that has been shown previously to promote the survival and/or differentiation of rat cerebellar granule neurons and human retinoblastoma cells in vitro. However, in contrast to most serpins, PEDF has no  inhibitory activity against any known proteases, and its described biological activities do not appear to require the serpin-reactive loop located toward the carboxy end of the polypeptide. Because another serpin, protease nexin-1, has been shown to promote the in vivo survival and growth of motor neurons, the authors investigated the potential neurotrophic effects of PEDF on spinal cord motor neurons in highly enriched cultures and in vivo after injury. Here, it is shown that native bovine and recombinant human PEDF promoted the survival and differentiation (neurite outgrowth) of embryonic chick spinal cord motor neurons  in vitro in a dose-dependent manner. A truncated form of PEDF that lacks approximately 62% of the carboxy end of the polypeptide comprising the homologous serpin-reactive loop also exhibited neurotrophic activities similar to those of the full-length protein. Furthermore, the data here showed that PEDF was transported retrogradely and prevented the death and atrophy of spinal motor neurons in the developing neonatal mouse after axotomy. These results indicate that PEDF exerts trophic effects on motor neurons, and, together with previous reports, these findings suggest that this protein may be useful as a pharmacologic agent to promote the development and maintenance of motor neurons.  J. Comp. Neurol. 412:506-514, 1999. Published 1999 Wiley-Liss, Inc.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LJ",
      "lastName" : "Houenou",
      "authorRank" : 1,
      "name" : "Houenou",
      "referenceId" : "RGD:A187762"
    }, {
      "firstName" : "AP",
      "lastName" : "D'Costa",
      "authorRank" : 2,
      "name" : "D'Costa",
      "referenceId" : "RGD:A187763"
    }, {
      "firstName" : "L",
      "lastName" : "Li",
      "authorRank" : 3,
      "name" : "Li L",
      "referenceId" : "RGD:A4356"
    }, {
      "firstName" : "VL",
      "lastName" : "Turgeon",
      "authorRank" : 4,
      "name" : "Turgeon",
      "referenceId" : "RGD:A187764"
    }, {
      "firstName" : "C",
      "lastName" : "Enyadike",
      "authorRank" : 5,
      "name" : "Enyadike",
      "referenceId" : "RGD:A187765"
    }, {
      "firstName" : "E",
      "lastName" : "Alberdi",
      "authorRank" : 6,
      "name" : "Alberdi",
      "referenceId" : "RGD:A177193"
    }, {
      "firstName" : "SP",
      "lastName" : "Becerra",
      "authorRank" : 7,
      "name" : "Becerra",
      "referenceId" : "RGD:A187766"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554886"
    } ]
  }, {
    "primaryId" : "PMID:10441327",
    "title" : "Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Boutell JM, etal., Hum Mol Genet. 1999 Sep;8(9):1647-55.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-02-28T11:18:39.000-06:00",
    "volume" : "8",
    "pages" : "1647-55",
    "abstract" : "We detected an interaction of the N-terminus of huntingtin (htt171) with the C-terminal region of the nuclear receptor co-repressor (N-CoR) using the yeast two-hybrid system. This interaction was repeat length dependent and specific to htt171; the co-repressor did not interact with the repeat carrying a section of atrophin 1 nor with the androgen receptor or polyglutamine alone. The interaction was confirmed using His-tagged Escherichia coli -expressed C-terminal human and rat co-repressor protein which pulled full-length huntingtin out of homogenized rat brain and in pull-down assays. The N-CoR represses transcription from sequence-specific ligand-activated receptors such as the retinoid X-thyroid hormone receptor dimers and other nuclear receptors including Mad-Max receptor dimers. The mechanism of this repression appears to be through the formation of a complex of repressor proteins including the N-CoR, mSin3 and histone deacetylases. We have used N-CoR and mSin3A antibodies in immunohistochemical studies and find that in Huntington's disease (HD) cortex and caudate, the cellular localization of these proteins is exclusively cytoplasmic whilst in control brain they are localized in the nucleus as well as the cytoplasm; mSin3A  immunoreactivity also occurred in a subset of huntingtin positive intranuclear inclusions. The relocalization of repressor proteins in HD brain may alter transcription and be involved in the pathology of the disease.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JM",
      "lastName" : "Boutell",
      "authorRank" : 1,
      "name" : "Boutell JM",
      "referenceId" : "RGD:A151404"
    }, {
      "firstName" : "P",
      "lastName" : "Thomas",
      "authorRank" : 2,
      "name" : "Thomas P",
      "referenceId" : "RGD:A12091"
    }, {
      "firstName" : "JW",
      "lastName" : "Neal",
      "authorRank" : 3,
      "name" : "Neal JW",
      "referenceId" : "RGD:A78067"
    }, {
      "firstName" : "VJ",
      "lastName" : "Weston",
      "authorRank" : 4,
      "name" : "Weston VJ",
      "referenceId" : "RGD:A151405"
    }, {
      "firstName" : "J",
      "lastName" : "Duce",
      "authorRank" : 5,
      "name" : "Duce J",
      "referenceId" : "RGD:A151406"
    }, {
      "firstName" : "PS",
      "lastName" : "Harper",
      "authorRank" : 6,
      "name" : "Harper PS",
      "referenceId" : "RGD:A64390"
    }, {
      "firstName" : "AL",
      "lastName" : "Jones",
      "authorRank" : 7,
      "name" : "Jones AL",
      "referenceId" : "RGD:A33015"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5688338"
    } ]
  }, {
    "primaryId" : "PMID:10441331",
    "title" : "Expression of the Sonic hedgehog (SHH ) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Odent S, etal., Hum Mol Genet. 1999 Sep;8(9):1683-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-03-28T13:31:51.000-05:00",
    "volume" : "8",
    "pages" : "1683-9",
    "abstract" : "Holoprosencephaly (HPE), the most common developmental defect of the forebrain and the face, is genetically heterogeneous. One of the genes involved, Sonic hedgehog ( SHH ), on 7q36, has been identified as the first HPE-causing gene both in mouse and humans. In order to delineate the phenotype of specific SHH mutations, we described the expression of the SHH gene during early human embryogenesis and investigated the phenotype of novel SHH mutations. In situ hybridization studies were performed on paraffin-embedded human embryo sections at three different development stages. These studies show that SHH is expressed in the notochord, the floorplate, the brain, the zone of polarizing activity and the gut. We also report on the phenotype of four novel mutations identified in 40 HPE families (two in isolated HPE and two in familial HPE). Expressivity ranged from alobar HPE to microcephaly and hypoplasia of the pituitary gland in one family, and from HPE to an asymptomatic form in another family. No SHH mutation was found in six polymalformed cases combining HPE with other defects, such as skeletal, limb, cardiac, anal and/or renal anomalies. This study confirms the genetic heterogeneity of HPE, and further demonstrates that SHH mutations are associated with a broad spectrum of cerebral midline defects.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Odent",
      "authorRank" : 1,
      "name" : "Odent S",
      "referenceId" : "RGD:A44749"
    }, {
      "firstName" : "T",
      "lastName" : "Atti-Bitach",
      "authorRank" : 2,
      "name" : "Atti-Bitach T",
      "referenceId" : "RGD:A441351"
    }, {
      "firstName" : "M",
      "lastName" : "Blayau",
      "authorRank" : 3,
      "name" : "Blayau M",
      "referenceId" : "RGD:A52616"
    }, {
      "firstName" : "M",
      "lastName" : "Mathieu",
      "authorRank" : 4,
      "name" : "Mathieu M",
      "referenceId" : "RGD:A71744"
    }, {
      "firstName" : "J",
      "lastName" : "Aug",
      "authorRank" : 5,
      "name" : "Aug J",
      "referenceId" : "RGD:A441352"
    }, {
      "firstName" : "A L",
      "lastName" : "Delezo de",
      "authorRank" : 6,
      "name" : "Delezo de AL",
      "referenceId" : "RGD:A441353"
    }, {
      "firstName" : "J Y",
      "lastName" : "Gall",
      "authorRank" : 7,
      "name" : "Gall JY",
      "referenceId" : "RGD:A441354"
    }, {
      "firstName" : "B",
      "lastName" : "Le Marec",
      "authorRank" : 8,
      "name" : "Le Marec B",
      "referenceId" : "RGD:A57376"
    }, {
      "firstName" : "A",
      "lastName" : "Munnich",
      "authorRank" : 9,
      "name" : "Munnich A",
      "referenceId" : "RGD:A26324"
    }, {
      "firstName" : "V",
      "lastName" : "David",
      "authorRank" : 10,
      "name" : "David V",
      "referenceId" : "RGD:A52619"
    }, {
      "firstName" : "M",
      "lastName" : "Vekemans",
      "authorRank" : 11,
      "name" : "Vekemans M",
      "referenceId" : "RGD:A39418"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12798570"
    } ]
  }, {
    "primaryId" : "PMID:10441334",
    "title" : "Combined sib-TDT and TDT provide evidence for linkage of the interleukin-1 gene cluster to erosive rheumatoid arthritis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Cox A, etal., Hum Mol Genet 1999 Sep;8(9):1707-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-04-23T09:26:25.000-05:00",
    "volume" : "8",
    "pages" : "1707-13",
    "abstract" : "Rheumatoid arthritis (RA) is a common disease of unknown aetiology which usually causes progressive destruction of the joints. Familial aggregation, twin studies and segregation analyses suggest that there is a genetic component to RA and the HLA-DRB1 locus in the major histocompatibility complex on chromosome 6 has been shown to be linked to, and associated with, RA susceptibility. It is likely that other genes with weaker effects are also involved, which may be difficult to detect using conventional parametric and non-parametric linkage methods. We have implemented the combined sib-TDT and TDT, in addition to parametric and non-parametric linkage methods, to investigate the candidate genes of the interleukin-1 (IL-1) gene cluster on chromosome region 2q13, since IL-1 is an important cytokine in the control of the inflammatory response that is central to RA pathology. Several tightly linked IL-1 cluster markers yielded suggestive evidence for linkage in the combined TDT in those families in which affected siblings did not share two HLA-DRB1 alleles identical by descent. The evidence was significant in those with severe disease, as assessed by the presence of bone erosions. In contrast, there was no evidence of linkage using non-parametric linkage analysis, but parametric analysis revealed weak evidence of linkage when marker-trait disequilibrium was incorporated into the analysis. The data provide preliminary evidence for linkage of genes of the IL-1 cluster to RA and suggest a possible role for this region in severe erosive disease.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Cox",
      "authorRank" : 1,
      "name" : "Cox A",
      "referenceId" : "RGD:A40058"
    }, {
      "firstName" : "NJ",
      "lastName" : "Camp",
      "authorRank" : 2,
      "name" : "Camp NJ",
      "referenceId" : "RGD:A38160"
    }, {
      "firstName" : "C",
      "lastName" : "Cannings",
      "authorRank" : 3,
      "name" : "Cannings C",
      "referenceId" : "RGD:A40059"
    }, {
      "firstName" : "FS",
      "lastName" : "Di Giovine",
      "authorRank" : 4,
      "name" : "Di Giovine FS",
      "referenceId" : "RGD:A40060"
    }, {
      "firstName" : "M",
      "lastName" : "Dale",
      "authorRank" : 5,
      "name" : "Dale M",
      "referenceId" : "RGD:A40061"
    }, {
      "firstName" : "J",
      "lastName" : "Worthington",
      "authorRank" : 6,
      "name" : "Worthington J",
      "referenceId" : "RGD:A183442"
    }, {
      "firstName" : "S",
      "lastName" : "John",
      "authorRank" : 7,
      "name" : "John S",
      "referenceId" : "RGD:A164798"
    }, {
      "firstName" : "WE",
      "lastName" : "Ollier",
      "authorRank" : 8,
      "name" : "Ollier WE",
      "referenceId" : "RGD:A14494"
    }, {
      "firstName" : "AJ",
      "lastName" : "Silman",
      "authorRank" : 9,
      "name" : "Silman AJ",
      "referenceId" : "RGD:A40062"
    }, {
      "firstName" : "GW",
      "lastName" : "Duff",
      "authorRank" : 10,
      "name" : "Duff GW",
      "referenceId" : "RGD:A40063"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1298028"
    } ]
  }, {
    "primaryId" : "PMID:10441342",
    "title" : "Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Kalff-Suske M, etal., Hum Mol Genet. 1999 Sep;8(9):1769-77.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-01-30T12:47:16.000-06:00",
    "volume" : "8",
    "pages" : "1769-77",
    "abstract" : "Greig cephalopolysyndactyly syndrome, characterized by craniofacial and limb anomalies (GCPS; MIM 175700), previously has been demonstrated to be associated with translocations as well as point mutations affecting one allele of the zinc finger gene GLI3. In addition to GCPS, Pallister-Hall syndrome (PHS; MIM 146510) and post-axial polydactyly type A (PAP-A; MIM 174200), two other disorders of human development, are caused by GLI3 mutations. In order to gain more insight into the mutational spectrum associated with a single phenotype, we report here the extension of the GLI3 mutation analysis to 24 new GCPS cases. We report the identification of 15 novel mutations present in one of the patient's GLI3 alleles. The mutations map throughout the coding gene regions. The majority are truncating mutations (nine of 15) that engender prematurely terminated protein products mostly but not exclusively N-terminally to or within the central region encoding the DNA-binding domain. Two missense and two splicing mutations mapping within the zinc finger motifs presumably also interfere with DNA binding. The five mutations identified within the protein regions C-terminal to the zinc fingers putatively affect additional functional properties of GLI3. In cell transfection experiments using fusions of the DNA-binding domain of yeast GAL4 to different segments of GLI3, transactivating capacity was assigned to two adjacent independent domains (TA(1)and TA(2)) in the C-terminal third of GLI3. Since these are the only functional domains affected by three C-terminally truncating mutations, we postulate that GCPS may be due either to haploinsufficiency resulting from the complete loss of one gene copy or to functional haploinsufficiency related to compromised properties of this transcription factor such as DNA binding and transactivation.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Kalff-Suske",
      "authorRank" : 1,
      "name" : "Kalff-Suske M",
      "referenceId" : "RGD:A438419"
    }, {
      "firstName" : "A",
      "lastName" : "Wild",
      "authorRank" : 2,
      "name" : "Wild A",
      "referenceId" : "RGD:A438420"
    }, {
      "firstName" : "J",
      "lastName" : "Topp",
      "authorRank" : 3,
      "name" : "Topp J",
      "referenceId" : "RGD:A438421"
    }, {
      "firstName" : "M",
      "lastName" : "Wessling",
      "authorRank" : 4,
      "name" : "Wessling M",
      "referenceId" : "RGD:A438422"
    }, {
      "firstName" : "E M",
      "lastName" : "Jacobsen",
      "authorRank" : 5,
      "name" : "Jacobsen EM",
      "referenceId" : "RGD:A438423"
    }, {
      "firstName" : "D",
      "lastName" : "Bornholdt",
      "authorRank" : 6,
      "name" : "Bornholdt D",
      "referenceId" : "RGD:A56305"
    }, {
      "firstName" : "H",
      "lastName" : "Engel",
      "authorRank" : 7,
      "name" : "Engel H",
      "referenceId" : "RGD:A27109"
    }, {
      "firstName" : "H",
      "lastName" : "Heuer",
      "authorRank" : 8,
      "name" : "Heuer H",
      "referenceId" : "RGD:A65539"
    }, {
      "firstName" : "C M",
      "lastName" : "Aalfs",
      "authorRank" : 9,
      "name" : "Aalfs CM",
      "referenceId" : "RGD:A438424"
    }, {
      "firstName" : "M G",
      "lastName" : "Ausems",
      "authorRank" : 10,
      "name" : "Ausems MG",
      "referenceId" : "RGD:A438425"
    }, {
      "firstName" : "R",
      "lastName" : "Barone",
      "authorRank" : 11,
      "name" : "Barone R",
      "referenceId" : "RGD:A438426"
    }, {
      "firstName" : "A",
      "lastName" : "Herzog",
      "authorRank" : 12,
      "name" : "Herzog A",
      "referenceId" : "RGD:A438427"
    }, {
      "firstName" : "P",
      "lastName" : "Heutink",
      "authorRank" : 13,
      "name" : "Heutink P",
      "referenceId" : "RGD:A381289"
    }, {
      "firstName" : "T",
      "lastName" : "Homfray",
      "authorRank" : 14,
      "name" : "Homfray T",
      "referenceId" : "RGD:A438428"
    }, {
      "firstName" : "G",
      "lastName" : "Gillessen-Kaesbach",
      "authorRank" : 15,
      "name" : "Gillessen-Kaesbach G",
      "referenceId" : "RGD:A57947"
    }, {
      "firstName" : "R",
      "lastName" : "König",
      "authorRank" : 16,
      "name" : "König R",
      "referenceId" : "RGD:A433160"
    }, {
      "firstName" : "J",
      "lastName" : "Kunze",
      "authorRank" : 17,
      "name" : "Kunze J",
      "referenceId" : "RGD:A51339"
    }, {
      "firstName" : "P",
      "lastName" : "Meinecke",
      "authorRank" : 18,
      "name" : "Meinecke P",
      "referenceId" : "RGD:A73709"
    }, {
      "firstName" : "D",
      "lastName" : "Müller",
      "authorRank" : 19,
      "name" : "Müller D",
      "referenceId" : "RGD:A438429"
    }, {
      "firstName" : "R",
      "lastName" : "Rizzo",
      "authorRank" : 20,
      "name" : "Rizzo R",
      "referenceId" : "RGD:A430698"
    }, {
      "firstName" : "S",
      "lastName" : "Strenge",
      "authorRank" : 21,
      "name" : "Strenge S",
      "referenceId" : "RGD:A438430"
    }, {
      "firstName" : "A",
      "lastName" : "Superti-Furga",
      "authorRank" : 22,
      "name" : "Superti-Furga A",
      "referenceId" : "RGD:A35248"
    }, {
      "firstName" : "K H",
      "lastName" : "Grzeschik",
      "authorRank" : 23,
      "name" : "Grzeschik KH",
      "referenceId" : "RGD:A438431"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12738208"
    } ]
  }, {
    "primaryId" : "PMID:10441346",
    "title" : "A genome-wide scan reveals a maternal susceptibility locus for pre-eclampsia on chromosome 2p13.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Arngrimsson R, etal., Hum Mol Genet 1999 Sep;8(9):1799-805.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:50:44.000-05:00",
    "volume" : "8",
    "pages" : "1799-805",
    "abstract" : "Pre-eclampsia is a common and serious disease and a major cause of maternal and infant mortality. Antenatal care systems world-wide screen for signs of the disease such as hypertension and proteinuria. Unlike most other human disorders it impacts two individuals, the mother and the child, both of whom can be severely affected. The pathophysiology of the disorder is incompletely understood, but familial clustering of the disease is apparent. Here we report the results of a genome-wide screen of Icelandic families representing 343 affected women. Including those patients with non-proteinuric pre-eclampsia (gestational hypertension), proteinuric pre-eclampsia and eclampsia, we detected a significant locus on 2p13 with a lod score of 4.70 (single point P < 3.49 x 10(-6)). This is the first reported locus for pre-eclampsia meeting the criteria for genome-wide significance.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Arngrimsson",
      "authorRank" : 1,
      "name" : "Arngrimsson R",
      "referenceId" : "RGD:A39984"
    }, {
      "firstName" : "S",
      "lastName" : "Sigurard ttir",
      "authorRank" : 2,
      "name" : "Sigurard ttir S",
      "referenceId" : "RGD:A39985"
    }, {
      "firstName" : "ML",
      "lastName" : "Frigge",
      "authorRank" : 3,
      "name" : "Frigge ML",
      "referenceId" : "RGD:A39885"
    }, {
      "firstName" : "RI",
      "lastName" : "Bjarnad ttir",
      "authorRank" : 4,
      "name" : "Bjarnad ttir RI",
      "referenceId" : "RGD:A39986"
    }, {
      "firstName" : "T",
      "lastName" : "Jonsson",
      "authorRank" : 5,
      "name" : "Jonsson T",
      "referenceId" : "RGD:A39987"
    }, {
      "firstName" : "H",
      "lastName" : "Stefansson",
      "authorRank" : 6,
      "name" : "Stefansson H",
      "referenceId" : "RGD:A39988"
    }, {
      "firstName" : "A",
      "lastName" : "Baldursdottir",
      "authorRank" : 7,
      "name" : "Baldursdottir A",
      "referenceId" : "RGD:A39989"
    }, {
      "firstName" : "AS",
      "lastName" : "Einarsdottir",
      "authorRank" : 8,
      "name" : "Einarsdottir AS",
      "referenceId" : "RGD:A39990"
    }, {
      "firstName" : "B",
      "lastName" : "Palsson",
      "authorRank" : 9,
      "name" : "Palsson B",
      "referenceId" : "RGD:A39991"
    }, {
      "firstName" : "S",
      "lastName" : "Snorradottir",
      "authorRank" : 10,
      "name" : "Snorradottir S",
      "referenceId" : "RGD:A39992"
    }, {
      "firstName" : "AM",
      "lastName" : "Lachmeijer",
      "authorRank" : 11,
      "name" : "Lachmeijer AM",
      "referenceId" : "RGD:A39993"
    }, {
      "firstName" : "D",
      "lastName" : "Nicolae",
      "authorRank" : 12,
      "name" : "Nicolae D",
      "referenceId" : "RGD:A39994"
    }, {
      "firstName" : "A",
      "lastName" : "Kong",
      "authorRank" : 13,
      "name" : "Kong A",
      "referenceId" : "RGD:A39886"
    }, {
      "firstName" : "BT",
      "lastName" : "Bragason",
      "authorRank" : 14,
      "name" : "Bragason BT",
      "referenceId" : "RGD:A39995"
    }, {
      "firstName" : "JR",
      "lastName" : "Gulcher",
      "authorRank" : 15,
      "name" : "Gulcher JR",
      "referenceId" : "RGD:A39889"
    }, {
      "firstName" : "RT",
      "lastName" : "Geirsson",
      "authorRank" : 16,
      "name" : "Geirsson RT",
      "referenceId" : "RGD:A39996"
    }, {
      "firstName" : "K",
      "lastName" : "Stefansson",
      "authorRank" : 17,
      "name" : "Stefansson K",
      "referenceId" : "RGD:A39887"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:738129"
    } ]
  }, {
    "primaryId" : "PMID:10441480",
    "title" : "hnRNP A2 and hnRNP L bind the 3'UTR of glucose transporter 1 mRNA and exist as a  complex in vivo.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hamilton BJ, etal., Biochem Biophys Res Commun. 1999 Aug 11;261(3):646-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-04-20T13:48:05.000-05:00",
    "volume" : "261",
    "pages" : "646-51",
    "abstract" : "Recent work identified an RNA binding protein whose presence in brain tumors correlated with translational repression of Glut1 expression. RNase T1 mapping demonstrated that this protein bound an AU-rich response element (AURE) in the Glut1 3'UTR. Facilitated by its differential expression in brain tumor cytosols,  we identified this Glut1 RNA binding protein as hnRNP A2. Studies further demonstrated that hnRNP A2 was the major Glut1 RNA binding activity in other cell lines. Recombinant hnRNP A2 exhibited equivalent Glut1 RNA binding specificity, quite distinct from the related AURE binding protein hnRNP A1. These data indicate that hnRNP A2 is the Glut1 AURE binding protein whose cytoplasmic expression in gliomas is associated with translational repression and mRNA instability. Using this approach, we also identified the other major Glut1 3'UTR  RNA binding activity as hnRNP L. Stimuli (hypoxia and hypoglycemia) which increase Glut1 mRNA stability selectively decreased polysomal levels of hnRNP A2  and L. Immunoprecipitation demonstrated that hnRNP A2 and L exist as a complex in vivo. As a result of these and other studies, we conclude that hnRNP A2 and L associate in vivo and independently bind the 3'UTR of Glut1 mRNA.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BJ",
      "lastName" : "Hamilton",
      "authorRank" : 1,
      "name" : "Hamilton",
      "referenceId" : "RGD:A200987"
    }, {
      "firstName" : "RC",
      "lastName" : "Nichols",
      "authorRank" : 2,
      "name" : "Nichols RC",
      "referenceId" : "RGD:A40670"
    }, {
      "firstName" : "H",
      "lastName" : "Tsukamoto",
      "authorRank" : 3,
      "name" : "Tsukamoto H",
      "referenceId" : "RGD:A12791"
    }, {
      "firstName" : "RJ",
      "lastName" : "Boado",
      "authorRank" : 4,
      "name" : "Boado RJ",
      "referenceId" : "RGD:A21189"
    }, {
      "firstName" : "WM",
      "lastName" : "Pardridge",
      "authorRank" : 5,
      "name" : "Pardridge WM",
      "referenceId" : "RGD:A23516"
    }, {
      "firstName" : "WF",
      "lastName" : "Rigby",
      "authorRank" : 6,
      "name" : "Rigby WF",
      "referenceId" : "RGD:A151202"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9999432"
    } ]
  }, {
    "primaryId" : "PMID:10441524",
    "title" : "TIP120B: a novel TIP120-family protein that is expressed specifically in muscle tissues.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Aoki T, etal., Biochem Biophys Res Commun 1999 Aug 11;261(3):911-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:36:50.000-05:00",
    "volume" : "261",
    "pages" : "911-6",
    "abstract" : "TATA-binding protein (TBP) forms complexes with various nuclear proteins and plays roles in all eukaryotic transcription. We previously identified TBP-interacting protein 120 (TIP120) from rat liver. TIP120 stimulates in vitro transcription generally. Homologs of TIP120 exist in various higher eukaryotes including D. melanogaster, C. elegans, and A. thaliana. Here, we isolated cDNA of a novel rat TIP120-like protein, named TIP120B. Rat TIP120B was composed of 1,235 amino acids and was 60% identical to the original TIP120 (re-named TIP120A). However, TIP120B gene was expressed specifically in the muscle tissues, which was contrary to the ubiquitous expression of TIP120A. Moreover, TIP120B protein was observed exclusively in the muscle tissues. TIP120B is therefore suggested to be a muscle-specific protein. Northern blot analysis of the mouse embryo revealed that the expression of TIP120B was temporarily increased during the embryogenesis, whereas TIP120A maintained a constant expression level. Pull-down assay using GST-fused TBP demonstrated that TBP specifically associated with TIP120B in the nuclear extract. These results indicate that TIP120B is a muscle-specific TIP120 family protein and can also interact with TBP. TIP120B is supposed to have a specific role in muscle tissues, which may be diffrerent from that of TIP120A.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Aoki",
      "authorRank" : 1,
      "name" : "Aoki T",
      "referenceId" : "RGD:A9876"
    }, {
      "firstName" : "N",
      "lastName" : "Okada",
      "authorRank" : 2,
      "name" : "Okada N",
      "referenceId" : "RGD:A7541"
    }, {
      "firstName" : "M",
      "lastName" : "Ishida",
      "authorRank" : 3,
      "name" : "Ishida M",
      "referenceId" : "RGD:A24138"
    }, {
      "firstName" : "S",
      "lastName" : "Yogosawa",
      "authorRank" : 4,
      "name" : "Yogosawa S",
      "referenceId" : "RGD:A24110"
    }, {
      "firstName" : "Y",
      "lastName" : "Makino",
      "authorRank" : 5,
      "name" : "Makino Y",
      "referenceId" : "RGD:A5103"
    }, {
      "firstName" : "TA",
      "lastName" : "Tamura",
      "authorRank" : 6,
      "name" : "Tamura TA",
      "referenceId" : "RGD:A24139"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634488"
    } ]
  }, {
    "primaryId" : "PMID:10441568",
    "title" : "PEX13 is mutated in complementation group 13 of the peroxisome-biogenesis disorders.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Liu Y, etal., Am J Hum Genet. 1999 Sep;65(3):621-34. doi: 10.1086/302534.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:25:34.000-05:00",
    "volume" : "65",
    "pages" : "621-34",
    "abstract" : "The peroxisome-biogenesis disorders (PBDs) are a genetically and phenotypically diverse group of diseases caused by defects in peroxisome assembly. One of the milder clinical variants within the PBDs is neonatal adrenoleukodystrophy (NALD), a disease that is usually associated with partial defects in the import of peroxisomal matrix proteins that carry the type 1 or type 2 peroxisomal targeting signals. Here, we characterize the sole representative of complementation group 13 of the PBDs, a patient with NALD (patient PBD222). Skin fibroblasts from patient PBD222 display defects in the import of multiple peroxisomal matrix proteins. However, residual matrix-protein import can be detected in cells from patient PBD222, consistent with the relatively mild phenotypes of the patient. PEX13 encodes a peroxisomal membrane protein with a cytoplasmically exposed SH3 domain, and we find that expression of human PEX13 restores peroxisomal matrix-protein import in cells from patient PBD222. Furthermore, these cells are homozygous for a missense mutation at a conserved position in the PEX13 SH3 domain. This mutation attenuated the activity of human PEX13, and an analogous mutation in yeast PEX13 also reduced its activity. The mutation was absent in >100 control alleles, indicating that it is not a common polymorphism. Previous studies have demonstrated extragenic suppression in the PBDs, but the phenotypes of patient PBD222 cells could not be rescued by expression of any other human PEX genes. Taken together, these results provide strong evidence that mutations in PEX13 are responsible for disease in patient PBD222 and, by extension, in complementation group 13 of the PBDs.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu Y",
      "referenceId" : "RGD:A6576"
    }, {
      "firstName" : "J",
      "lastName" : "Björkman",
      "authorRank" : 2,
      "name" : "Björkman J",
      "referenceId" : "RGD:A565148"
    }, {
      "firstName" : "A",
      "lastName" : "Urquhart",
      "authorRank" : 3,
      "name" : "Urquhart A",
      "referenceId" : "RGD:A565149"
    }, {
      "firstName" : "R J",
      "lastName" : "Wanders",
      "authorRank" : 4,
      "name" : "Wanders RJ",
      "referenceId" : "RGD:A466958"
    }, {
      "firstName" : "D I",
      "lastName" : "Crane",
      "authorRank" : 5,
      "name" : "Crane DI",
      "referenceId" : "RGD:A565150"
    }, {
      "firstName" : "S J",
      "lastName" : "Gould",
      "authorRank" : 6,
      "name" : "Gould SJ",
      "referenceId" : "RGD:A472198"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598114567"
    } ]
  }, {
    "primaryId" : "PMID:10441570",
    "title" : "The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; No phenotype prediction from the position of GLI3 mutations.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Radhakrishna U, etal., Am J Hum Genet. 1999 Sep;65(3):645-55. doi: 10.1086/302557.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:35:58.000-05:00",
    "volume" : "65",
    "pages" : "645-55",
    "abstract" : "Functional characterization of a gene often requires the discovery of the full spectrum of its associated phenotypes. Mutations in the human GLI3 gene have been identified in Greig cepalopolysyndactyly, Pallister-Hall syndrome (PHS), and postaxial polydactyly type-A (PAP-A). We studied the involvement of GLI3 in additional phenotypes of digital abnormalities in one family (UR003) with preaxial polydactyly type-IV (PPD-IV), three families (UR014, UR015, and UR016) with dominant PAP-A/B (with PPD-A and -B in the same family), and one family with PHS. Linkage analysis showed no recombination with GLI3-linked polymorphisms. Family UR003 had a 1-nt frameshift insertion, resulting in a truncated protein of 1,245 amino acids. A frameshift mutation due to a 1-nt deletion was found in family UR014, resulting in a truncated protein of 1,280 amino acids. Family UR015 had a nonsense mutation, R643X, and family UR016 had a missense mutation, G727R, in a highly conserved amino acid of domain 3. The patient with PHS had a nonsense mutation, E1147X. These results add two phenotypes to the phenotypic spectrum caused by GLI3 mutations: the combined PAP-A/B and PPD-IV. These mutations do not support the suggested association between the mutations in GLI3 and the resulting phenotypes. We propose that all phenotypes associated with GLI3 mutations be called \"GLI3 morphopathies,\" since the phenotypic borders of the resulting syndromes are not well defined and there is no apparent genotype-phenotype correlation.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "U",
      "lastName" : "Radhakrishna",
      "authorRank" : 1,
      "name" : "Radhakrishna U",
      "referenceId" : "RGD:A73874"
    }, {
      "firstName" : "D",
      "lastName" : "Bornholdt",
      "authorRank" : 2,
      "name" : "Bornholdt D",
      "referenceId" : "RGD:A56305"
    }, {
      "firstName" : "H S",
      "lastName" : "Scott",
      "authorRank" : 3,
      "name" : "Scott HS",
      "referenceId" : "RGD:A581849"
    }, {
      "firstName" : "U C",
      "lastName" : "Patel",
      "authorRank" : 4,
      "name" : "Patel UC",
      "referenceId" : "RGD:A577596"
    }, {
      "firstName" : "C",
      "lastName" : "Rossier",
      "authorRank" : 5,
      "name" : "Rossier C",
      "referenceId" : "RGD:A37941"
    }, {
      "firstName" : "H",
      "lastName" : "Engel",
      "authorRank" : 6,
      "name" : "Engel H",
      "referenceId" : "RGD:A27109"
    }, {
      "firstName" : "A",
      "lastName" : "Bottani",
      "authorRank" : 7,
      "name" : "Bottani A",
      "referenceId" : "RGD:A116854"
    }, {
      "firstName" : "D",
      "lastName" : "Chandal",
      "authorRank" : 8,
      "name" : "Chandal D",
      "referenceId" : "RGD:A581850"
    }, {
      "firstName" : "J L",
      "lastName" : "Blouin",
      "authorRank" : 9,
      "name" : "Blouin JL",
      "referenceId" : "RGD:A577594"
    }, {
      "firstName" : "J V",
      "lastName" : "Solanki",
      "authorRank" : 10,
      "name" : "Solanki JV",
      "referenceId" : "RGD:A577598"
    }, {
      "firstName" : "K H",
      "lastName" : "Grzeschik",
      "authorRank" : 11,
      "name" : "Grzeschik KH",
      "referenceId" : "RGD:A438431"
    }, {
      "firstName" : "S E",
      "lastName" : "Antonarakis",
      "authorRank" : 12,
      "name" : "Antonarakis SE",
      "referenceId" : "RGD:A438508"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598116630"
    } ]
  }, {
    "primaryId" : "PMID:10441571",
    "title" : "Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Azuma N, etal., Am J Hum Genet. 1999 Sep;65(3):656-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-10T16:08:07.000-05:00",
    "volume" : "65",
    "pages" : "656-63",
    "abstract" : "The PAX6 gene is involved in ocular morphogenesis, and PAX6 mutations have been detected in various types of ocular anomalies, including aniridia, Peters anomaly, corneal dystrophy, congenital cataract, and foveal hypoplasia. The gene encodes a transcriptional regulator that recognizes target genes through its paired-type DNA-binding domain. The paired domain is composed of two distinct DNA-binding subdomains, the N-terminal subdomain (NTS) and the C-terminal subdomain (CTS), which bind respective consensus DNA sequences. The human PAX6 gene produces two alternative splice isoforms that have the distinct structure of the paired domain. The insertion, into the NTS, of 14 additional amino acids encoded by exon 5a abolishes the DNA-binding activity of the NTS and unmasks the DNA-binding ability of the CTS. Thus, exon 5a appears to function as a molecular switch that specifies target genes. We ascertained a novel missense mutation in four pedigrees with Peters anomaly, congenital cataract, Axenfeldt anomaly, and/or foveal hypoplasia, which, to our knowledge, is the first mutation identified in the splice-variant region. A T-->A transition at the 20th nucleotide position of exon 5a results in a Val-->Asp (GTC-->GAC) substitution at the 7th codon of the alternative splice region. Functional analyses demonstrated that the V54D mutation slightly increased NTS binding and decreased CTS transactivation activity to almost half.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Azuma",
      "authorRank" : 1,
      "name" : "Azuma N",
      "referenceId" : "RGD:A61891"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamaguchi",
      "authorRank" : 2,
      "name" : "Yamaguchi Y",
      "referenceId" : "RGD:A5502"
    }, {
      "firstName" : "H",
      "lastName" : "Handa",
      "authorRank" : 3,
      "name" : "Handa H",
      "referenceId" : "RGD:A80119"
    }, {
      "firstName" : "M",
      "lastName" : "Hayakawa",
      "authorRank" : 4,
      "name" : "Hayakawa M",
      "referenceId" : "RGD:A80120"
    }, {
      "firstName" : "A",
      "lastName" : "Kanai",
      "authorRank" : 5,
      "name" : "Kanai A",
      "referenceId" : "RGD:A162421"
    }, {
      "firstName" : "M",
      "lastName" : "Yamada",
      "authorRank" : 6,
      "name" : "Yamada M",
      "referenceId" : "RGD:A161371"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601210"
    } ]
  }, {
    "primaryId" : "PMID:10441584",
    "title" : "Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease).",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Geschwind DH, etal., Am J Hum Genet. 1999 Sep;65(3):764-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-15T20:07:48.000-05:00",
    "volume" : "65",
    "pages" : "764-72",
    "abstract" : "Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative syndrome that is associated with a variety of movement disorders and neurobehavioral and cognitive manifestations. Despite numerous clinical, pathological, and biochemical investigations, its etiology remains unknown. We have identified a multigenerational family with dominantly inherited IBGC and, in 24 members of this family, performed a whole-genome scan using polymorphic microsatellite markers to identify the first chromosomal locus for this disorder (IBGC1). A maximum two-point LOD score of 3.37 was obtained at marker D14S1014, and a maximum multipoint LOD score of 4.95 was obtained between D14S75 and D14S306. The minimal haplotype shared by affected patients extended over a 17.1-cM region bounded by D14S70 and D14S66, which is potentially further narrowed to a 13.3-cM  region by a recombination observed in a patient with probable affected status. The age at onset appeared to be decreasing by an average of >20 years with each transmission, which is consistent with genetic anticipation.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DH",
      "lastName" : "Geschwind",
      "authorRank" : 1,
      "name" : "Geschwind DH",
      "referenceId" : "RGD:A17477"
    }, {
      "firstName" : "M",
      "lastName" : "Loginov",
      "authorRank" : 2,
      "name" : "Loginov",
      "referenceId" : "RGD:A328278"
    }, {
      "firstName" : "JM",
      "lastName" : "Stern",
      "authorRank" : 3,
      "name" : "Stern",
      "referenceId" : "RGD:A171526"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11251606"
    } ]
  }, {
    "primaryId" : "PMID:10441618",
    "title" : "Immunolocalization of transforming growth factor alpha and epidermal growth factor receptor in lungs of patients with cystic fibrosis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Hardie WD, etal., Pediatr Dev Pathol. 1999 Sep-Oct;2(5):415-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-13T10:57:31.000-05:00",
    "volume" : "2",
    "pages" : "415-23",
    "abstract" : "Transforming growth factor alpha (TGF-alpha) is expressed in respiratory epithelial cells and alveolar macrophages during development and following lung injury. In the present study, the presence and sites of synthesis of TGF-alpha and its receptor, the epidermal growth factor receptor (EGF-R), were assessed in lung tissue from patients with severe lung disease caused by cystic fibrosis (CF). Lung sections from 24 individuals with CF, obtained at the time of lung transplantation, were compared to lung sections from five lung donors without CF. Cellular sites of TGF-alpha, EGF-R, and cellular sites of proliferation were assessed by immunohistochemistry. All CF lung sections contained multiple cell types with detectable TGF-alpha. Compared to control sections, intensity of TGF-alpha immunostaining in macrophages, airway epithelial cells, and peribronchial submucosal cells was increased. EGF-R was detected in respiratory epithelial and peribronchial stromal cells but not in alveolar macrophages. The intensity of EGF-R staining in CF lung tissue did not differ from that of controls. An increased number of cells expressing Ki-67 nuclear antigen was detected in peribronchial submucosal cells but not bronchiolar epithelial cells in the CF lungs. The increased expression of TGF-alpha in CF lung tissue supports the concept that TGF-alpha plays a role in paracrine/autocrine regulation of lung remodeling associated with injury and repair in the lungs of individuals with cystic fibrosis.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WD",
      "lastName" : "Hardie",
      "authorRank" : 1,
      "name" : "Hardie WD",
      "referenceId" : "RGD:A59427"
    }, {
      "firstName" : "PA",
      "lastName" : "Bejarano",
      "authorRank" : 2,
      "name" : "Bejarano PA",
      "referenceId" : "RGD:A59498"
    }, {
      "firstName" : "MA",
      "lastName" : "Miller",
      "authorRank" : 3,
      "name" : "Miller MA",
      "referenceId" : "RGD:A59497"
    }, {
      "firstName" : "JR",
      "lastName" : "Yankaskas",
      "authorRank" : 4,
      "name" : "Yankaskas JR",
      "referenceId" : "RGD:A59500"
    }, {
      "firstName" : "JH",
      "lastName" : "Ritter",
      "authorRank" : 5,
      "name" : "Ritter JH",
      "referenceId" : "RGD:A59501"
    }, {
      "firstName" : "JA",
      "lastName" : "Whitsett",
      "authorRank" : 6,
      "name" : "Whitsett JA",
      "referenceId" : "RGD:A33764"
    }, {
      "firstName" : "TR",
      "lastName" : "Korfhagen",
      "authorRank" : 7,
      "name" : "Korfhagen TR",
      "referenceId" : "RGD:A33763"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578629"
    } ]
  }, {
    "primaryId" : "PMID:10441679",
    "title" : "Phylogenetic analysis of the homologous proteins of the terminal complement complex supports the emergence of C6 and C7 followed by C8 and C9.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Mondragon-Palomino M, etal., J Mol Evol 1999 Aug;49(2):282-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-10T15:50:59.000-05:00",
    "volume" : "49",
    "pages" : "282-9",
    "abstract" : "The plasma complement system comprises several activation pathways that share a common terminal route involving the assembly of the terminal complement complex (TCC), formed by C5b-C9. The order of emergence of the homologous components of TCC (C6, C7, C8alpha, C8beta, and C9) has been determined by phylogenetic analyses of their amino acid sequences. Using all the sequence data available for C6-C9 proteins, as well as for perforins, the results suggested that these TCC components originated from a single ancestral gene and that C6 and C7 were the earliest to emerge. Our evidence supports the notion that the ancestral gene had a complex modular composition. A series of gene duplications in combination with a tendency to lose modules resulted in successive complement proteins with decreasing modular complexity. C9 and perforin apparently are the result of different selective conditions to acquire pore-forming function. Thus C9 and perforin are examples of evolutionary parallelism.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Mondragon-Palomino",
      "authorRank" : 1,
      "name" : "Mondragon-Palomino M",
      "referenceId" : "RGD:A24982"
    }, {
      "firstName" : "D",
      "lastName" : "Pinero",
      "authorRank" : 2,
      "name" : "Pinero D",
      "referenceId" : "RGD:A24983"
    }, {
      "firstName" : "A",
      "lastName" : "Nicholson-Weller",
      "authorRank" : 3,
      "name" : "Nicholson-Weller A",
      "referenceId" : "RGD:A24984"
    }, {
      "firstName" : "JP",
      "lastName" : "Laclette",
      "authorRank" : 4,
      "name" : "Laclette JP",
      "referenceId" : "RGD:A24985"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634755"
    } ]
  }, {
    "primaryId" : "PMID:10441734",
    "title" : "Identification and genetic mapping of differentially expressed genes in mice differing at the If1 interferon regulatory locus.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kozak CA, etal., Mamm Genome. 1999 Sep;10(9):853-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:02:15.000-05:00",
    "volume" : "10",
    "pages" : "853-7",
    "abstract" : "A subtractive cDNA library was used to identify differentially expressed genes in mouse strains that differ at If1, a locus that regulates response to interferon induction by Newcastle Disease Virus infection. Among the isolated clones, sequence analysis identified the ribosomal proteins L37a and S8 as well as cDNAs  for thymosine beta4, the QM transcriptional factor, and a novel genetic sequence. Analysis of two multilocus mouse crosses showed that the thymosine beta4 gene, Ptmb4, is present as a single-copy gene that maps to distal Chr X. The L37a, S8,  and QM clones are all members of large multilocus families. These five clones were used to determine the map locations for 37 loci, of which 31 had not previously been described. The novel genetic sequence, D3Ppr1, mapped to distal Chr 3 near the position of the If1 locus, suggesting it may be a candidate for this regulatory gene.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CA",
      "lastName" : "Kozak",
      "authorRank" : 1,
      "name" : "Kozak",
      "referenceId" : "RGD:A416993"
    }, {
      "firstName" : "Y",
      "lastName" : "Su",
      "authorRank" : 2,
      "name" : "Su Y",
      "referenceId" : "RGD:A22655"
    }, {
      "firstName" : "NB",
      "lastName" : "Raj",
      "authorRank" : 3,
      "name" : "Raj",
      "referenceId" : "RGD:A229330"
    }, {
      "firstName" : "PM",
      "lastName" : "Pitha",
      "authorRank" : 4,
      "name" : "Pitha",
      "referenceId" : "RGD:A229331"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11055135"
    } ]
  }, {
    "primaryId" : "PMID:10441739",
    "title" : "BB rat diabetes susceptibility and body weight regulation genes colocalize on chromosome 2.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Klaff LS, etal., Mamm Genome 1999 Sep;10(9):883-7",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-01-22T14:47:00.000-06:00",
    "volume" : "10",
    "pages" : "883-7",
    "abstract" : "The genetic etiology of Type 1 (insulin-dependent) diabetes mellitus is complicated by the apparent presence of several diabetes susceptibility genetic regions. Type 1 diabetes in the inbred BioBreeding (BB) rat closely resembles the human disorder and was previously shown to involve two genes: the lymphopenia (lyp) region on Chromosome (Chr) 4 and RT1(u) in the major histocompatibility complex (MHC) on Chr 20. In addition, a segregation analysis of an F(2) intercross between the diabetes-prone congenic BB DR(lyp/lyp, u/u) and F344(+/+,)(lv/lv) rats indicated that at least one more genetic factor was responsible for Type 1 diabetes. In this study, we generated F(2)N(2) progeny in a cross between non-diabetic F(2)(DR(lyp/lyp,u/u) x F344)(lyp/lyp,u/u) and diabetic DR(lyp/lyp, u/u) rats. In a subsequent total genome scan, a third factor was mapped to the 21.3-cM region on Chr 2 between D2Mit14 and D2Mit15 (peak LOD score 4.7 with 67% penetrance). Interestingly, the homozygosity of the BB allele (b/b) for the Chr 2 region was significantly associated with a greater weight reduction after fasting than the homozygosity of the F344 allele (f/f, p < 0.008). In conclusion, the development of Type 1 diabetes in the congenic DR(lyp/lyp) rat is controlled by at least three genes: lymphopenia, MHC, and a third factor that may play a role in metabolism and body weight regulation.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LS",
      "lastName" : "Klaff",
      "authorRank" : 1,
      "name" : "Klaff LS",
      "referenceId" : "RGD:A958"
    }, {
      "firstName" : "G",
      "lastName" : "Koike",
      "authorRank" : 2,
      "name" : "Koike G",
      "referenceId" : "RGD:A51179"
    }, {
      "firstName" : "J",
      "lastName" : "Iang J",
      "authorRank" : 3,
      "name" : "Iang J J",
      "referenceId" : "RGD:A960"
    }, {
      "firstName" : "Y",
      "lastName" : "Wang",
      "authorRank" : 4,
      "name" : "Wang Y",
      "referenceId" : "RGD:A381280"
    }, {
      "firstName" : "S",
      "lastName" : "Bieg",
      "authorRank" : 5,
      "name" : "Bieg S",
      "referenceId" : "RGD:A104755"
    }, {
      "firstName" : "A",
      "lastName" : "Pettersson",
      "authorRank" : 6,
      "name" : "Pettersson A",
      "referenceId" : "RGD:A51183"
    }, {
      "firstName" : "E",
      "lastName" : "Lander",
      "authorRank" : 7,
      "name" : "Lander E",
      "referenceId" : "RGD:A964"
    }, {
      "firstName" : "H",
      "lastName" : "Jacob",
      "authorRank" : 8,
      "name" : "Jacob H",
      "referenceId" : "RGD:A59492"
    }, {
      "firstName" : "A",
      "lastName" : "Lernmark",
      "authorRank" : 9,
      "name" : "Lernmark A",
      "referenceId" : "RGD:A163556"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61481"
    } ]
  }, {
    "primaryId" : "PMID:10442317",
    "title" : "Denaturing gradient gel electrophoresis screening of the BRCA1 gene in cells from precancerous cervical lesions.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Park SJ, etal., J Reprod Med. 1999 Jul;44(7):575-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-08-04T14:13:22.000-05:00",
    "volume" : "44",
    "pages" : "575-80",
    "abstract" : "OBJECTIVE: To determine the integrity of the BRCA1 gene in archival, paraffin-embedded tissues from precancerous lesions of the uterine cervix. STUDY DESIGN: DNA was extracted from histologically documented precancerous cervical lesions (17 cases). Polymerase chain reactions were performed targeting exon 11 of BRCA1 (434-bp), the L1 consensus human papillomavirus (HPV) gene common to > 25 HPV types, as well as the beta-globin gene. The amplified products were analyzed using denaturing gradient gel electrophoresis. RESULTS: Mutation of the BRCA1 exon 11 gene was detected in > 76% of cases with precancerous lesions of the cervix. The mutations were either complete deletions or deletions of one or more nucleotides, leading to frame shifts. There were no significant differences in frequency of BRCA1 mutations among precancerous cervical tissues positive for the HPV L1 consensus gene (n = 9) when compared with HPV-negative tissues. CONCLUSION: The mutated BRCA1 gene was associated with 76% of 17 precancerous lesions of the cervix. The type of cervical intraepithelial neoplasia and the presence or absence of HPV were not related to the mutations. The role of BRCA1 mutation in the genesis of precancerous cervical lesions needs to be explored further.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SJ",
      "lastName" : "Park",
      "authorRank" : 1,
      "name" : "Park SJ",
      "referenceId" : "RGD:A30387"
    }, {
      "firstName" : "PJ",
      "lastName" : "Chan",
      "authorRank" : 2,
      "name" : "Chan PJ",
      "referenceId" : "RGD:A98686"
    }, {
      "firstName" : "IM",
      "lastName" : "Seraj",
      "authorRank" : 3,
      "name" : "Seraj IM",
      "referenceId" : "RGD:A98687"
    }, {
      "firstName" : "A",
      "lastName" : "King",
      "authorRank" : 4,
      "name" : "King A",
      "referenceId" : "RGD:A57326"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2298942"
    } ]
  }, {
    "primaryId" : "PMID:10444029",
    "title" : "Glomerular ultrafiltration of IGF-I may contribute to increased renal sodium retention in diabetic nephropathy.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wang SN, etal., J Lab Clin Med. 1999 Aug;134(2):154-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-05-30T15:22:53.000-05:00",
    "volume" : "134",
    "pages" : "154-60",
    "abstract" : "Insulin-like growth factor-I (IGF-I) is found in plasma at relatively high levels (approximately 40 nmol/L) but <1% is present in the free form and >99% is bound to specific binding proteins to form high-molecular-weight complexes of approximately 50 and approximately 150 kd. We hypothesized that in rats with diabetic nephropathy but not in normal animals, IGF-I-containing binding protein complexes undergo glomerular ultrafiltration, allowing the peptide to interact with IGF-I receptors in apical tubular membranes. By this route, ultrafiltered IGF-I may increase tubular epithelial cell sodium absorption in overt diabetic nephropathy. In serum samples from diabetic rats, IGF-I levels (227 +/- 34 ng/mL) were reduced as compared with control levels (319 +/- 33 ng/mL, P = .05), and IGF-binding protein-2 (IGFBP-2) is increased about 2-fold. In diabetic rats, IGF-I undergoes glomerular ultrafiltration and is present in proximal tubular fluid that was collected by nephron micropuncture at 2.54 +/- 0.54 nmol/L but is below the detection limit in tubular fluid from normal rats. IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4 are all present in diabetic rat glomerular ultrafiltrate, but IGFBP-2 levels are greater than those of each of the other three IGFBPs. Neither recombinant human IGF-I (1 nmol/L) nor diabetic rat glomerular ultrafiltrate affect sodium transport in cultured mouse proximal tubular cells. In contrast, rhIGF-I and diabetic rat glomerular ultrafiltrate increase the apical-to-basolateral transport of 22Na+ in distal tubule-like A6 cells through mechanisms involving apical IGF-I receptors. In normal rats, luminal infusion with rhIGF-I or with diabetic rat glomerular ultrafiltrate into late proximal tubules increases distal tubular Na+ absorption. These findings indicate that diabetic glomerular sclerosis causes glomerular ultrafiltration of IGF-I, and they suggest that tubular fluid IGF-I may contribute to sodium (and fluid) retention that is commonly observed in patients with severe diabetic nephropathy.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S N",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang SN",
      "referenceId" : "RGD:A444687"
    }, {
      "firstName" : "J",
      "lastName" : "Lapage",
      "authorRank" : 2,
      "name" : "Lapage J",
      "referenceId" : "RGD:A113652"
    }, {
      "firstName" : "R",
      "lastName" : "Hirschberg",
      "authorRank" : 3,
      "name" : "Hirschberg R",
      "referenceId" : "RGD:A113653"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12904967"
    } ]
  }, {
    "primaryId" : "PMID:10444339",
    "title" : "Mutations of CTNS causing intermediate cystinosis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Thoene J, etal., Mol Genet Metab. 1999 Aug;67(4):283-93. doi: 10.1006/mgme.1999.2876.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:51:22.000-05:00",
    "volume" : "67",
    "pages" : "283-93",
    "abstract" : "Six patients with the intermediate form of cystinosis are described. Two have new mutations not previously described. The disease occurs due either to the combination of one mild mutation and one which is known to cause nephropathic cystinosis or to homozygosity for a predicted mild mutation. Partial phenotypic correction of cystinotic fibroblasts by transfection with normal cDNA or a cDNA derived from a mutation causing intermediate cystinosis is demonstrated.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Thoene",
      "authorRank" : 1,
      "name" : "Thoene J",
      "referenceId" : "RGD:A446242"
    }, {
      "firstName" : "R",
      "lastName" : "Lemons",
      "authorRank" : 2,
      "name" : "Lemons R",
      "referenceId" : "RGD:A584970"
    }, {
      "firstName" : "Y",
      "lastName" : "Anikster",
      "authorRank" : 3,
      "name" : "Anikster Y",
      "referenceId" : "RGD:A74242"
    }, {
      "firstName" : "J",
      "lastName" : "Mullet",
      "authorRank" : 4,
      "name" : "Mullet J",
      "referenceId" : "RGD:A596581"
    }, {
      "firstName" : "K",
      "lastName" : "Paelicke",
      "authorRank" : 5,
      "name" : "Paelicke K",
      "referenceId" : "RGD:A596582"
    }, {
      "firstName" : "C",
      "lastName" : "Lucero",
      "authorRank" : 6,
      "name" : "Lucero C",
      "referenceId" : "RGD:A446160"
    }, {
      "firstName" : "W",
      "lastName" : "Gahl",
      "authorRank" : 7,
      "name" : "Gahl W",
      "referenceId" : "RGD:A596583"
    }, {
      "firstName" : "J",
      "lastName" : "Schneider",
      "authorRank" : 8,
      "name" : "Schneider J",
      "referenceId" : "RGD:A56620"
    }, {
      "firstName" : "S G",
      "lastName" : "Shu",
      "authorRank" : 9,
      "name" : "Shu SG",
      "referenceId" : "RGD:A596584"
    }, {
      "firstName" : "H T",
      "lastName" : "Campbell",
      "authorRank" : 10,
      "name" : "Campbell HT",
      "referenceId" : "RGD:A596585"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118839"
    } ]
  }, {
    "primaryId" : "PMID:10444419",
    "title" : "Changes in the circulating IGF system during short-term fasting and refeeding in rats.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Frystyk J, etal., Am J Physiol. 1999 Aug;277(2 Pt 1):E245-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-06-28T18:16:06.000-05:00",
    "volume" : "277",
    "pages" : "E245-52",
    "abstract" : "There is little information on free insulin-like growth factor I (IGF-I) and its regulatory proteins during fasting and refeeding. Therefore, we examined rats during fasting (0, 1, 2, and 3 days) and refeeding (3, 6, and 12 h and 1, 2, 3, and 7 days) (n = 6-9). Serum was analyzed for insulin, C-peptide, growth hormone (GH), free and total IGF-I, IGF-binding protein (IGFBP)-1 and -3, and the acid-labile subunit (ALS). Additionally, liver mRNA for IGF-I, IGFBP-1, and ALS was determined. Fasting reduced serum levels of GH, free and total IGF-I, IGFBP-3, and ALS, whereas IGFBP-1 was increased (P < 0.0001). Refeeding normalized IGFBP-1 at 3 h and GH at 12 h. Free IGF-I changed in parallel with total IGF-I, ALS, and IGFBP-3, being normalized at 48 h of refeeding. IGFBP-1 (peptide and mRNA) correlated inversely with insulin and C-peptide (P < 0.001). The correlation between peptide and mRNA was relatively strong for IGFBP-1 (r(2) = 0.36; P < 0.0001), moderate for IGF-I (r(2) = 0.18; P < 0.0005), and insignificant for ALS. In conclusion, insulin appears to regulate IGFBP-1 in fasted and refed rats. However, the normal inverse relationship between free IGF-I and IGFBP-1 was absent, and free IGF-I changed in parallel with total IGF-I and thus ALS and IGFBP-3. Finally, the regulation of the hepatic synthesis of IGF-I, IGFBP-1, and ALS seems to differ substantially.",
    "issueName" : "2 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Frystyk",
      "authorRank" : 1,
      "name" : "Frystyk J",
      "referenceId" : "RGD:A109638"
    }, {
      "firstName" : "P J",
      "lastName" : "Delhanty",
      "authorRank" : 2,
      "name" : "Delhanty PJ",
      "referenceId" : "RGD:A446256"
    }, {
      "firstName" : "C",
      "lastName" : "Skjaerbaek",
      "authorRank" : 3,
      "name" : "Skjaerbaek C",
      "referenceId" : "RGD:A446257"
    }, {
      "firstName" : "R C",
      "lastName" : "Baxter",
      "authorRank" : 4,
      "name" : "Baxter RC",
      "referenceId" : "RGD:A446258"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:12910943"
    } ]
  }, {
    "primaryId" : "PMID:10444590",
    "title" : "Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Michaelson JS, etal., Genes Dev. 1999 Aug 1;13(15):1918-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-05-18T19:14:02.000-05:00",
    "volume" : "13",
    "pages" : "1918-23",
    "abstract" : "The mammalian Daxx gene has been identified in a diverse set of yeast interaction trap experiments. Although a facilitating role for Daxx in Fas-induced apoptosis  has been suggested, Daxx's physiologic function remains unknown. To elucidate the in vivo role of Daxx, we have generated Daxx-deficient mice. Surprisingly, rather than a hyperproliferative disorder expected from the loss of a pro-apoptotic gene, mutation of Daxx results in extensive apoptosis and embryonic lethality. These findings argue against a role for Daxx in promoting Fas-induced cell death  and suggest that Daxx either directly or indirectly suppresses apoptosis in the early embryo.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JS",
      "lastName" : "Michaelson",
      "authorRank" : 1,
      "name" : "Michaelson JS",
      "referenceId" : "RGD:A45995"
    }, {
      "firstName" : "D",
      "lastName" : "Bader",
      "authorRank" : 2,
      "name" : "Bader D",
      "referenceId" : "RGD:A54315"
    }, {
      "firstName" : "F",
      "lastName" : "Kuo",
      "authorRank" : 3,
      "name" : "Kuo F",
      "referenceId" : "RGD:A44547"
    }, {
      "firstName" : "C",
      "lastName" : "Kozak",
      "authorRank" : 4,
      "name" : "Kozak C",
      "referenceId" : "RGD:A19095"
    }, {
      "firstName" : "P",
      "lastName" : "Leder",
      "authorRank" : 5,
      "name" : "Leder P",
      "referenceId" : "RGD:A20577"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11079315"
    } ]
  }, {
    "primaryId" : "PMID:10445390",
    "title" : "Polymorphism of GSTM1 gene in patients with colorectal cancer and colonic polyps.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Gawrońska-Szklarz B, etal., Exp Toxicol Pathol. 1999 Jul;51(4-5):321-5. doi: 10.1016/S0940-2993(99)80014-1.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-08-29T15:55:38.000-05:00",
    "volume" : "51",
    "pages" : "321-5",
    "abstract" : "The frequency of the GSTM1 gene in patients with nonpolyposis colorectal cancer (CRC) (n = 70) and in subjects with colonic polyps (n = 27) was evaluated and compared with healthy individuals (n = 145). Patients with CRC were divided into the three groups: patients coming from the families with hereditary nonpolyposis colorectal cancer (HNPCC) (n = 17); patients with a high risk of HNPCC who were referred to as suspected of HNPCC (n = 25); patients with sporadic colorectal cancer without clinical features of hereditary tumours (n = 28). A simple polymerase chain reaction (PCR) - based assay to identify GSTM1 nulled and positive (non-nulled) genotype was used. No significant differences in frequency of nulled individuals were observed in both patients with HNPCC and patients suspected of HNPCC as well as in subjects with colonic polyps. The most interesting observation was made in the group of patients with sporadic CRC. Twenty individuals (71.4 %) of the group were GSTM 1 deficient which was significantly different from the control population (p < 0.04). The above data indicate that the absence of the GSTM1 gene is associated with a greater risk of sporadic colorectal cancer. There is an increase in the overall risk of approximately 2.5 as compared with the control population.",
    "issueName" : "4-5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Gawrońska-Szklarz",
      "authorRank" : 1,
      "name" : "Gawrońska-Szklarz B",
      "referenceId" : "RGD:A473236"
    }, {
      "firstName" : "J",
      "lastName" : "Lubiński",
      "authorRank" : 2,
      "name" : "Lubiński J",
      "referenceId" : "RGD:A473237"
    }, {
      "firstName" : "J",
      "lastName" : "Kladny",
      "authorRank" : 3,
      "name" : "Kladny J",
      "referenceId" : "RGD:A473238"
    }, {
      "firstName" : "G",
      "lastName" : "Kurzawski",
      "authorRank" : 4,
      "name" : "Kurzawski G",
      "referenceId" : "RGD:A139801"
    }, {
      "firstName" : "D",
      "lastName" : "Bielicki",
      "authorRank" : 5,
      "name" : "Bielicki D",
      "referenceId" : "RGD:A473239"
    }, {
      "firstName" : "M",
      "lastName" : "Wójcicki",
      "authorRank" : 6,
      "name" : "Wójcicki M",
      "referenceId" : "RGD:A473240"
    }, {
      "firstName" : "Z",
      "lastName" : "Sych",
      "authorRank" : 7,
      "name" : "Sych Z",
      "referenceId" : "RGD:A44211"
    }, {
      "firstName" : "H D",
      "lastName" : "Musial",
      "authorRank" : 8,
      "name" : "Musial HD",
      "referenceId" : "RGD:A473241"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14700958"
    } ]
  }, {
    "primaryId" : "PMID:10445602",
    "title" : "Increased frequency of cystic fibrosis deltaF508 mutation in bronchiectasis associated with rheumatoid arthritis.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Puechal X, etal., Eur Respir J. 1999 Jun;13(6):1281-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:03:18.000-05:00",
    "volume" : "13",
    "pages" : "1281-7",
    "abstract" : "This study investigated the clinical characteristics and the possible involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients with symptomatic diffuse bronchiectasis (DB) associated with rheumatoid  arthritis (RA). Twenty-six patients with both RA and DB (group RA+DB) and control groups of 29 consecutive patients with RA but no bronchiectasis (group RA) and 29 patients with symptomatic DB of unknown origin (group DB) were prospectively studied. Among the patients of the RA+DB group, four (15.4%) were heterozygous for the CFTR gene deltaF508 mutation, whereas no deltaF508 mutation was found in  patients of the RA and the DB groups (both, p<0.05). This frequency of deltaF508  mutation was also higher than the expected frequency (2.8%) in the general European population (p<0.04). Sweat chloride values and nasal potential differences were normal in three out of four patients carrying the deltaF508 mutation. In the RA+DB group, those with deltaF508 mutation had more frequent chronic sinusitis (p<0.05), a trend toward a more severe pulmonary involvement, and a lower value of nasal potential differences (p<0.01) whereas their rheumatic features had no particularity. In the RA+DB group, patients with adult-onset bronchiectasis (including two with deltaF508 mutation) had a greater reduction in total lung capacity (p<0.05) and lower nasal potential differences (p<0.005) than those with childhood-onset bronchiectasis. This study suggests a possible deleterious effect of the cystic fibrosis transmembrane conductance regulator mutated protein in the airways which may predispose to the development and severity of bronchiectasis in patients suffering from rheumatoid arthritis.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Puechal",
      "authorRank" : 1,
      "name" : "Puechal",
      "referenceId" : "RGD:A189579"
    }, {
      "firstName" : "I",
      "lastName" : "Fajac",
      "authorRank" : 2,
      "name" : "Fajac I",
      "referenceId" : "RGD:A126301"
    }, {
      "firstName" : "T",
      "lastName" : "Bienvenu",
      "authorRank" : 3,
      "name" : "Bienvenu",
      "referenceId" : "RGD:A415997"
    }, {
      "firstName" : "N",
      "lastName" : "Desmazes-Dufeu",
      "authorRank" : 4,
      "name" : "Desmazes-Dufeu",
      "referenceId" : "RGD:A272357"
    }, {
      "firstName" : "D",
      "lastName" : "Hubert",
      "authorRank" : 5,
      "name" : "Hubert",
      "referenceId" : "RGD:A277692"
    }, {
      "firstName" : "JC",
      "lastName" : "Kaplan",
      "authorRank" : 6,
      "name" : "Kaplan JC",
      "referenceId" : "RGD:A30780"
    }, {
      "firstName" : "CJ",
      "lastName" : "Menkes",
      "authorRank" : 7,
      "name" : "Menkes",
      "referenceId" : "RGD:A277693"
    }, {
      "firstName" : "DJ",
      "lastName" : "Dusser",
      "authorRank" : 8,
      "name" : "Dusser DJ",
      "referenceId" : "RGD:A140554"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070748"
    } ]
  }, {
    "primaryId" : "PMID:10445603",
    "title" : "Sputum endothelin-1 is increased in cystic fibrosis and chronic obstructive pulmonary disease.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Chalmers GW, etal., Eur Respir J. 1999 Jun;13(6):1288-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-10-21T15:54:52.000-05:00",
    "volume" : "13",
    "pages" : "1288-92",
    "abstract" : "Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GW",
      "lastName" : "Chalmers",
      "authorRank" : 1,
      "name" : "Chalmers GW",
      "referenceId" : "RGD:A129456"
    }, {
      "firstName" : "KJ",
      "lastName" : "Macleod",
      "authorRank" : 2,
      "name" : "Macleod KJ",
      "referenceId" : "RGD:A129457"
    }, {
      "firstName" : "S",
      "lastName" : "Sriram",
      "authorRank" : 3,
      "name" : "Sriram S",
      "referenceId" : "RGD:A47573"
    }, {
      "firstName" : "LJ",
      "lastName" : "Thomson",
      "authorRank" : 4,
      "name" : "Thomson LJ",
      "referenceId" : "RGD:A129458"
    }, {
      "firstName" : "C",
      "lastName" : "McSharry",
      "authorRank" : 5,
      "name" : "McSharry C",
      "referenceId" : "RGD:A129459"
    }, {
      "firstName" : "BH",
      "lastName" : "Stack",
      "authorRank" : 6,
      "name" : "Stack BH",
      "referenceId" : "RGD:A129460"
    }, {
      "firstName" : "NC",
      "lastName" : "Thomson",
      "authorRank" : 7,
      "name" : "Thomson NC",
      "referenceId" : "RGD:A21598"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4145062"
    } ]
  }, {
    "primaryId" : "PMID:10445750",
    "title" : "Soluble epoxide hydrolase in rat inflammatory cells is indistinguishable from soluble epoxide hydrolase in rat liver.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Draper AJ and Hammock BD, Toxicol Sci. 1999 Jul;50(1):30-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-10-31T17:21:59.000-06:00",
    "volume" : "50",
    "pages" : "30-5",
    "abstract" : "Soluble epoxide hydrolase (sEH) is a ubiquitous mammalian enzyme for which liver and kidney are reported to have the highest activity. We have shown that the soluble epoxide hydrolase (sEH) activity present in rat neutrophils and macrophages is kinetically, immunologically, and physically indistinguishable from rat liver cytosolic sEH. Cytosol from rat liver or inflammatory cells and recombinant rat sEH were incubated with trans-diphenylpropene oxide (tDPPO), a selective substrate for sEH. The tDPPO hydration activity we observed in inflammatory cell cytosol was lower than that from liver. The Km for tDPPO hydration observed in rat inflammatory cell cytosol was the same as the Km for rat liver cytosol (10 microM). Recombinant rat sEH and cytosol from rat liver or inflammatory cells were incubated with the sEH inhibitors, chalcone oxide, 4-fluorochalcone oxide, and 4-phenylchalcone oxide. The IC50 values were 40, 8, and 0.4 microM, respectively, in all samples. Furthermore, sEH activity could be completely immunoprecipitated out of the samples, and the amount of antibody required to do so was apparently identical, regardless of the source of enzyme. SDS-polyacrylamide gel electrophoresis followed by Western blot analysis revealed a single sEH band with a molecular weight of 62 kDa. Isoelectric focusing followed by Western blot analysis revealed multiple bands containing tDPPO-hydrating activity. Although the inflammatory cell bands had the same pattern as those from liver cytosol, the recombinant sEH showed a different banding pattern. These multiple bands were not an artifact of the IEF gel selected. Furthermore, in a 2-dimensional IEF gel, the bands re-migrated to the same position. The presence of sEH in inflammatory cells suggests that this enzyme may have an important endogenous function.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AJ",
      "lastName" : "Draper",
      "authorRank" : 1,
      "name" : "Draper AJ",
      "referenceId" : "RGD:A67967"
    }, {
      "firstName" : "BD",
      "lastName" : "Hammock",
      "authorRank" : 2,
      "name" : "Hammock BD",
      "referenceId" : "RGD:A12912"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581957"
    } ]
  }, {
    "primaryId" : "PMID:10446064",
    "title" : "LDL stimulates mitogen-activated protein kinase phosphatase-1 expression, independent of LDL receptors, in vascular smooth muscle cells.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Metzler B, etal., Arterioscler Thromb Vasc Biol. 1999 Aug;19(8):1862-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-12-19T15:28:24.000-06:00",
    "volume" : "19",
    "pages" : "1862-71",
    "abstract" : "Low density lipoprotein (LDL) is a well-established risk factor for atherosclerosis, stimulating vascular smooth muscle cell (SMC) differentiation and proliferation, but the signal transduction pathways between LDL stimulation and cell proliferation are poorly understood. Because mitogen-activated protein kinases (MAPKs) play a crucial role in mediating cell growth, we studied the effect of LDL on the induction of MAPK phosphatase-1 (MKP-1) in human SMCs and found that LDL stimulated induction of MKP-1 mRNA and proteins in a time- and dose-dependent manner. Heparin, inhibiting LDL-receptor binding, did not influence LDL-stimulated MKP-1 mRNA expression, and human LDL also induced MKP-1  expression in rat SMCs and fibroblasts derived from LDL receptor-deficient mice,  indicating an LDL receptor-independent process. Pretreatment of SMCs with pertussis toxin markedly inhibited LDL-induced MKP-1 expression. Depletion of protein kinase C (PKC) by phorbol 12-myristate 13 acetate or inhibition of PKC by calphostin C blocked MKP-1 induction, but the phospholipase C inhibitor U73122 had no effect. Pretreatment of SMCs with genistein or herbimycin A abrogated LDL-stimulated MKP-1 induction. The MAPK kinase inhibitor PD98059 abolished LDL-stimulated activation of extracellular signal-regulated protein kinases (ERKs) but not MKP-1 induction. Furthermore, constitutive expression of MKP-1 in  vivo reduced LDL-induced expression of Elk-1-dependent reporter genes, and SMC lines overexpressing recombinant MKP-1 exhibited decreased ERK activities and retarded proliferation in response to LDL. Our findings demonstrate that LDL induces MKP-1 expression in SMCs via activation of PKC and tyrosine kinases, independent of LDL receptors and ERK-MAPKs, and that MKP-1 plays an important role in the regulation of LDL-initiated signal transductions leading to SMC proliferation.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Metzler",
      "authorRank" : 1,
      "name" : "Metzler B",
      "referenceId" : "RGD:A153664"
    }, {
      "firstName" : "C",
      "lastName" : "Li",
      "authorRank" : 2,
      "name" : "Li",
      "referenceId" : "RGD:A416968"
    }, {
      "firstName" : "Y",
      "lastName" : "Hu",
      "authorRank" : 3,
      "name" : "Hu Y",
      "referenceId" : "RGD:A21657"
    }, {
      "firstName" : "G",
      "lastName" : "Sturm",
      "authorRank" : 4,
      "name" : "Sturm",
      "referenceId" : "RGD:A177150"
    }, {
      "firstName" : "N",
      "lastName" : "Ghaffari-Tabrizi",
      "authorRank" : 5,
      "name" : "Ghaffari-Tabrizi",
      "referenceId" : "RGD:A177151"
    }, {
      "firstName" : "Q",
      "lastName" : "Xu",
      "authorRank" : 6,
      "name" : "Xu",
      "referenceId" : "RGD:A416817"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7771571"
    } ]
  }, {
    "primaryId" : "PMID:10446087",
    "title" : "Plasma glutathione peroxidase deficiency and platelet insensitivity to nitric oxide in children with familial stroke.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kenet G, etal., Arterioscler Thromb Vasc Biol. 1999 Aug;19(8):2017-23. doi: 10.1161/01.atv.19.8.2017.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2023-09-28T14:54:59.000-05:00",
    "volume" : "19",
    "pages" : "2017-23",
    "abstract" : "In a previous report by Freedman et al (J Clin Invest. 1996;97:979-987), plasma from 2 brothers with stroke or transient ischemic attack inactivated the antiplatelet effects of nitric oxide (NO), and this effect was found to be a consequence of a deficiency of plasma glutathione peroxidase (GSH-Px). In this study, we attempted to define the generalizability of this deficiency by studying NO-mediated antiplatelet effects in 7 families with familial childhood stroke. Seven families with familial childhood stroke that consecutively presented to a large referral center were included in the study. We monitored ADP-induced aggregation of normal gel-filtered platelets (GFP) in platelet-poor plasma (PPP) from normal individuals and from patients in the presence or absence of an NO donor (S-nitroso-glutathione). Surface P-selectin expression of normal GFP in patients' PPP was analyzed by flow cytometry after incubation with a P-selectin-specific monoclonal antibody in the presence or absence of the NO donor. We also measured GSH-Px activity in plasmas from family members and normal controls using standard methods. In 6 of 7 families, NO failed to inhibit platelet P-selectin expression and platelet aggregation in PPP from the affected family members and some of their relatives. Of 4 families studied, 3 probands and their corresponding affected parent had 50% decrease in plasma GSH-Px activity. In some patients with childhood stroke, impaired metabolism of reactive oxygen species as a result of reduced GSH-Px activity results in NO insufficiency that affects normal platelet inhibitory mechanisms and predisposes to arterial thrombosis.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Kenet",
      "authorRank" : 1,
      "name" : "Kenet G",
      "referenceId" : "RGD:A533187"
    }, {
      "firstName" : "J",
      "lastName" : "Freedman",
      "authorRank" : 2,
      "name" : "Freedman J",
      "referenceId" : "RGD:A533188"
    }, {
      "firstName" : "B",
      "lastName" : "Shenkman",
      "authorRank" : 3,
      "name" : "Shenkman B",
      "referenceId" : "RGD:A533189"
    }, {
      "firstName" : "E",
      "lastName" : "Regina",
      "authorRank" : 4,
      "name" : "Regina E",
      "referenceId" : "RGD:A533190"
    }, {
      "firstName" : "F",
      "lastName" : "Brok-Simoni",
      "authorRank" : 5,
      "name" : "Brok-Simoni F",
      "referenceId" : "RGD:A533191"
    }, {
      "firstName" : "F",
      "lastName" : "Holzman",
      "authorRank" : 6,
      "name" : "Holzman F",
      "referenceId" : "RGD:A533192"
    }, {
      "firstName" : "F",
      "lastName" : "Vavva",
      "authorRank" : 7,
      "name" : "Vavva F",
      "referenceId" : "RGD:A533193"
    }, {
      "firstName" : "N",
      "lastName" : "Brand",
      "authorRank" : 8,
      "name" : "Brand N",
      "referenceId" : "RGD:A533194"
    }, {
      "firstName" : "A",
      "lastName" : "Michelson",
      "authorRank" : 9,
      "name" : "Michelson A",
      "referenceId" : "RGD:A533195"
    }, {
      "firstName" : "M",
      "lastName" : "Trolliet",
      "authorRank" : 10,
      "name" : "Trolliet M",
      "referenceId" : "RGD:A533196"
    }, {
      "firstName" : "J",
      "lastName" : "Loscalzo",
      "authorRank" : 11,
      "name" : "Loscalzo J",
      "referenceId" : "RGD:A132738"
    }, {
      "firstName" : "A",
      "lastName" : "Inbal",
      "authorRank" : 12,
      "name" : "Inbal A",
      "referenceId" : "RGD:A533197"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401827831"
    } ]
  }, {
    "primaryId" : "PMID:10446112",
    "title" : "Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha in alcoholic liver disease.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Fisher NC, etal., Gut. 1999 Sep;45(3):416-20. doi: 10.1136/gut.45.3.416.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-10-25T11:42:13.000-05:00",
    "volume" : "45",
    "pages" : "416-20",
    "abstract" : "<br><b>BACKGROUND: </b>Alcoholic liver disease is associated with increased hepatic expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP-1alpha).<br><b>AIMS: </b>To determine whether concentrations of chemokines in the peripheral circulation reflect disease activity, and whether chemokine secretion is restricted to the liver or is part of a systemic inflammatory response in alcoholic liver disease.<br><b>PATIENTS: </b>Fifty one patients with alcoholic liver disease and 12 healthy controls.<br><b>METHODS: </b>Peripheral vein (and hepatic vein in patients undergoing transjugular liver biopsy) chemokine concentrations were measured by ELISA. Chemokine secretion and transcription in isolated peripheral mononuclear cells were assessed using ELISA and in situ hybridisation in patients with severe alcoholic hepatitis.<br><b>RESULTS: </b>Serum MCP-1 concentrations were higher in alcoholic hepatitis compared with cirrhosis or healthy controls. MIP-1alpha concentrations were below the assay sensitivity in most patients. Serum MCP-1 concentrations correlated significantly with serum aspartate aminotransferase and creatinine. In severe alcoholic hepatitis, MCP-1 concentrations were higher in hepatic compared with peripheral veins; in mild alcoholic hepatitis there was no difference. Mononuclear cell secretion of both MCP-1 and MIP-1alpha was higher in severe alcoholic hepatitis compared with healthy controls, and chemokine mRNA was identified in monocytes.<br><b>CONCLUSIONS: </b>Serum MCP-1 concentrations are raised in alcoholic liver disease and reflect severity of hepatic inflammation. Monocyte secretion of both MCP-1 and MIP-1alpha is increased in severe alcoholic hepatitis. Both intrahepatic sources and peripheral mononuclear cells contribute to the raised serum MCP-1 concentrations.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N C",
      "lastName" : "Fisher",
      "authorRank" : 1,
      "name" : "Fisher NC",
      "referenceId" : "RGD:A475986"
    }, {
      "firstName" : "D A",
      "lastName" : "Neil",
      "authorRank" : 2,
      "name" : "Neil DA",
      "referenceId" : "RGD:A475987"
    }, {
      "firstName" : "A",
      "lastName" : "Williams",
      "authorRank" : 3,
      "name" : "Williams A",
      "referenceId" : "RGD:A47558"
    }, {
      "firstName" : "D H",
      "lastName" : "Adams",
      "authorRank" : 4,
      "name" : "Adams DH",
      "referenceId" : "RGD:A470187"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14995467"
    } ]
  }, {
    "primaryId" : "PMID:10446192",
    "title" : "Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3'-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Jilani A, etal., J Biol Chem 1999 Aug 20;274(34):24176-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-02-02T09:42:35.000-06:00",
    "volume" : "274",
    "pages" : "24176-86",
    "abstract" : "Mammalian polynucleotide kinases catalyze the 5'-phosphorylation of nucleic acids and can have associated 3'-phosphatase activity, predictive of an important function in DNA repair following ionizing radiation or oxidative damage. The sequences of three tryptic peptides from a bovine 60-kDa polypeptide that correlated with 5'-DNA kinase and 3'-phosphatase activities identified human and murine dbEST clones. The 57.1-kDa conceptual translation product of this gene, polynucleotide kinase 3'-phosphatase (PNKP), contained a putative ATP binding site and a potential 3'-phosphatase domain with similarity to L-2-haloacid dehalogenases. BLAST searches identified possible homologs in Caenorhabditis elegans, Schizosaccharomyces pombe, and Drosophila melanogaster. The gene was localized to chromosome 19q13.3-13.4. Northern analysis indicated a 2-kilobase mRNA in eight human tissues. A glutathione S-transferase-PNKP fusion protein displayed 5'-DNA kinase and 3'-phosphatase activities. PNKP is the first gene for a DNA-specific kinase from any organism. PNKP expression partially rescued the sensitivity to oxidative damaging agents of the Escherichia coli DNA repair-deficient xth nfo double mutant. PNKP gene function restored termini suitable for DNA polymerase, consistent with in vivo removal of 3'-phosphate groups, facilitating DNA repair.",
    "issueName" : "34",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Jilani",
      "authorRank" : 1,
      "name" : "Jilani A",
      "referenceId" : "RGD:A50642"
    }, {
      "firstName" : "D",
      "lastName" : "Ramotar",
      "authorRank" : 2,
      "name" : "Ramotar D",
      "referenceId" : "RGD:A50643"
    }, {
      "firstName" : "C",
      "lastName" : "Slack",
      "authorRank" : 3,
      "name" : "Slack C",
      "referenceId" : "RGD:A50644"
    }, {
      "firstName" : "C",
      "lastName" : "Ong",
      "authorRank" : 4,
      "name" : "Ong C",
      "referenceId" : "RGD:A50645"
    }, {
      "firstName" : "XM",
      "lastName" : "Yang",
      "authorRank" : 5,
      "name" : "Yang XM",
      "referenceId" : "RGD:A50646"
    }, {
      "firstName" : "SW",
      "lastName" : "Scherer",
      "authorRank" : 6,
      "name" : "Scherer SW",
      "referenceId" : "RGD:A37723"
    }, {
      "firstName" : "DD",
      "lastName" : "Lasko",
      "authorRank" : 7,
      "name" : "Lasko DD",
      "referenceId" : "RGD:A50647"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1332584"
    } ]
  }, {
    "primaryId" : "PMID:10446335",
    "title" : "C1-esterase inhibitor reduces infarct volume after cortical vein occlusion.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Heimann A, etal., Brain Res. 1999 Aug 14;838(1-2):210-3.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-11T14:52:59.000-05:00",
    "volume" : "838",
    "pages" : "210-3",
    "abstract" : "In order to clarify the role of complement as a mediator of cerebral infarct growth, we inhibited the classical complement activation pathway in a photochemical cortical vein occlusion model. Immediately after occlusion, rats were infused with either 0.9% saline (vehicle), or C1-esterase inhibitor (C1-INH) over 30 min. Regional cerebral blood flow (rCBF) decreased after occlusion, and was about 50% of baseline after 2 h. No difference was noted between experimental groups. Mean arterial blood pressure (MABP) and arterial blood gases were likewise unaffected by the treatment. However, administration of C1-INH had significantly reduced infarct volume by 72%, as evaluated after 5 days survival.  Thus, the neuroprotective effect cannot be explained by an improvement of cerebral perfusion but rather by protection of the parenchyma in the penumbra.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Heimann",
      "authorRank" : 1,
      "name" : "Heimann",
      "referenceId" : "RGD:A189446"
    }, {
      "firstName" : "T",
      "lastName" : "Takeshima",
      "authorRank" : 2,
      "name" : "Takeshima",
      "referenceId" : "RGD:A189447"
    }, {
      "firstName" : "G",
      "lastName" : "Horstick",
      "authorRank" : 3,
      "name" : "Horstick",
      "referenceId" : "RGD:A189448"
    }, {
      "firstName" : "O",
      "lastName" : "Kempski",
      "authorRank" : 4,
      "name" : "Kempski",
      "referenceId" : "RGD:A189449"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8661653"
    } ]
  }, {
    "primaryId" : "PMID:10446380",
    "title" : "Albumin banks peninsula: a new termination variant characterised by electrospray  mass spectrometry.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Brennan SO, etal., Biochim Biophys Acta. 1999 Aug 17;1433(1-2):321-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:44:48.000-05:00",
    "volume" : "1433",
    "pages" : "321-6",
    "abstract" : "Albumin Banks Peninsula is an electrophoretically fast variant that is expressed  at only 2% of the total serum albumin. Electrospray ionisation analysis indicated a mass decrease of 755 Da relative to normal albumin and carboxypeptidase A digestion, together with CNBr peptide mapping, indicated a C-terminal truncation. This was confirmed by PCR and DNA sequence analysis which showed the introduction of a new AG acceptor splice site near the 3' end of intron 13. Predictably this results in the replacement of the C-terminal GKKLVAASQAALGL sequence by SLCSG and would be associated with an 861 Da decrease in molecular mass. We surmised that the new Cys was most probably cysteinylated as this albumin species would have a  mass decrease of 742 Da and be very close to the measured value of 755 Da. Cysteinylation was confirmed when a mass decrease of 863 Da was measured between  the proteins after reduction of their disulfide bonds.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SO",
      "lastName" : "Brennan",
      "authorRank" : 1,
      "name" : "Brennan SO",
      "referenceId" : "RGD:A78805"
    }, {
      "firstName" : "AP",
      "lastName" : "Fellowes",
      "authorRank" : 2,
      "name" : "Fellowes",
      "referenceId" : "RGD:A279685"
    }, {
      "firstName" : "PM",
      "lastName" : "George",
      "authorRank" : 3,
      "name" : "George PM",
      "referenceId" : "RGD:A78808"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071514"
    } ]
  }, {
    "primaryId" : "PMID:10446428",
    "title" : "Rat sn-glycerol-3-phosphate acyltransferase: molecular cloning and characterization of the cDNA and expressed protein.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ganesh Bhat B, etal., Biochim Biophys Acta 1999 Aug 18;1439(3):415-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-10T11:27:24.000-05:00",
    "volume" : "1439",
    "pages" : "415-23",
    "abstract" : "Rat mitochondrial glycerol-3-phosphate acyltransferase (GPAT) cDNA was cloned and characterized. We identified a cDNA containing an open reading frame of 828 amino acids that had an 89% homology with the coding region of the previously characterized mouse mitochondrial GPAT and a predicted amino acid sequence that was 96% identical. The rat 5' UTR was only 159 nucleotides, in contrast to the 926 nucleotide 5' UTR of the mouse cDNA and had an internal deletion of 167 nucleotides. GPAT was expressed in Sf21 insect cells, and specific inhibitors strongly suggest that, like the Escherichia coli GPAT, the recombinant mitochondrial GPAT and the mitochondrial GPAT isoform in rat liver contain critical serine, histidine, and arginine residues.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Ganesh Bhat",
      "authorRank" : 1,
      "name" : "Ganesh Bhat B",
      "referenceId" : "RGD:A3110"
    }, {
      "firstName" : "P",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang P",
      "referenceId" : "RGD:A160054"
    }, {
      "firstName" : "JH",
      "lastName" : "Kim",
      "authorRank" : 3,
      "name" : "Kim JH",
      "referenceId" : "RGD:A157311"
    }, {
      "firstName" : "TM",
      "lastName" : "Black",
      "authorRank" : 4,
      "name" : "Black TM",
      "referenceId" : "RGD:A3113"
    }, {
      "firstName" : "TM",
      "lastName" : "Lewin",
      "authorRank" : 5,
      "name" : "Lewin TM",
      "referenceId" : "RGD:A113252"
    }, {
      "firstName" : "FT",
      "lastName" : "Fiedorek",
      "authorRank" : 6,
      "name" : "Fiedorek FT",
      "referenceId" : "RGD:A3115"
    }, {
      "firstName" : "RA",
      "lastName" : "Coleman",
      "authorRank" : 7,
      "name" : "Coleman RA",
      "referenceId" : "RGD:A113254"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61613"
    } ]
  }, {
    "primaryId" : "PMID:10446905",
    "title" : "Mutations to the third cytoplasmic domain of the glucagon-like peptide 1 (GLP-1) receptor can functionally uncouple GLP-1-stimulated insulin secretion in HIT-T15 cells.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Salapatek AM, etal., Mol Endocrinol. 1999 Aug;13(8):1305-17.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-11-29T11:10:08.000-06:00",
    "volume" : "13",
    "pages" : "1305-17",
    "abstract" : "Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone with powerful antidiabetogenic effects that are thought to be mediated by adenylyl cyclase (AC). Recently, we generated two GLP-1 receptor mutant isoforms (IC3-1 and DM-1) that displayed efficient ligand binding and the ability to promote Ca2+ mobilization from intracellular stores but lacked the ability to couple to AC. In the present study, the wild-type rat GLP-1 receptor (WT-GLP-1 R) or the IC3-1 and DM-1 mutant forms were expressed for the first time in the insulin-producing HIT-T15 cells. Only cells expressing WT-GLP-1 R displayed dramatically elevated GLP-1-induced cAMP responses and elevated insulin secretion. The increase in GLP-1-stimulated secretion in cells expressing WT-GLP-1 R, however, was not accompanied by differences in glucose-stimulated insulin release. Prolonged exposure to GLP-1 (10 nM, 17 h), not only led to an increase in insulin secretion but also increased insulin mRNA levels, but only in cells expressing the WT-GLP-1 R and not the mutant isoforms. Electrophysiological analyses revealed that GLP-1 application enhanced L-type voltage-dependent Ca2+ channel (VDCC) currents > 2-fold and caused a positive shift in VDCC voltage-dependent inactivation in WT-GLP-1R cells only, not control or mutant (DM-1) cells. This action on the Ca2+ current was further enhanced by the VDCC agonist, BAYK8644, suggesting GLP-1 acts via a distinct mechanism dependent on cAMP. These studies demonstrate that the GLP-1 receptor efficiently couples to AC to stimulate insulin secretion and that receptors lacking critical residues in the proximal region of the third intracellular loop can effectively uncouple the receptor from cAMP production, VDCC activity, insulin secretion, and insulin biosynthesis.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AM",
      "lastName" : "Salapatek",
      "authorRank" : 1,
      "name" : "Salapatek AM",
      "referenceId" : "RGD:A41900"
    }, {
      "firstName" : "PE",
      "lastName" : "MacDonald",
      "authorRank" : 2,
      "name" : "MacDonald PE",
      "referenceId" : "RGD:A70330"
    }, {
      "firstName" : "HY",
      "lastName" : "Gaisano",
      "authorRank" : 3,
      "name" : "Gaisano HY",
      "referenceId" : "RGD:A41908"
    }, {
      "firstName" : "MB",
      "lastName" : "Wheeler",
      "authorRank" : 4,
      "name" : "Wheeler MB",
      "referenceId" : "RGD:A33991"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598448"
    } ]
  }, {
    "primaryId" : "PMID:10446908",
    "title" : "Induction of max by adrenomedullin and calcitonin gene-related peptide antagonizes endothelial apoptosis.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Shichiri M, etal., Mol Endocrinol. 1999 Aug;13(8):1353-63.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-25T15:49:58.000-06:00",
    "volume" : "13",
    "pages" : "1353-63",
    "abstract" : "Adrenomedullin is a novel vasodilatory peptide originally isolated from pheochromocytoma. Recently, we found that adrenomedullin acts as an autocrine/paracrine apoptosis survival factor for rat endothelial cells. In the present study, we show that adrenomedullin induces the expression of Max, a heterodimeric partner of c-Myc, which may contribute to its ability to rescue endothelial cells from apoptosis. Max is a basic-helix-loop-helix-leucine zipper protein that forms heterodimers with its alternative partners, Mad and Mxi-1, to behave as an antagonist for Myc-Max heterodimer through competition for common DNA targets. The expression of Max is reported to be constitutive and more stable than c-Myc, and serum induces immediate c-Myc stimulation followed by modest Max up-regulation. In quiescent rat endothelial cells, adrenomedullin stimulated the expression of Max without affecting c-Myc. Quantitation with real-time quantitative PCR detected on the ABI Prism 7700 Sequence Detection System revealed that adrenomedullin and calcitonin gene-related peptide (CGRP), as well as serum, up-regulated Max mRNA levels and that down-regulation of Max mRNA after serum deprivation was prevented by adrenomedullin. Neither adrenomedullin nor CGRP affected c-Myc expression. Transfection of a Max-expressing plasmid into endothelial cells rescued the apoptosis induced by serum deprivation. Neutralization with anti-adrenomedullin antiserum or blockade with a CGRP receptor antagonist, CGRP(8-37), reduced Max mRNA levels in growing endothelial cells and enhanced apoptosis after serum starvation. Introduction of an antisense oligodeoxynucleotide against Max mRNA using transferrin receptor-operated transfer led to inhibition of both adrenomedullin-induced up-regulation of Max transcripts and its cell survival effect, whereas random, sense, or missense oligonucleotides were without effect. The negative regulation of E-box-driven transcription by adrenomedullin was demonstrated by using preproendothelin-1 promoter containing c-Myc-Max binding consensus sequence; the promoter activity of preproendothelin-1 was reduced by cotransfecting Max- and Mad-expressing plasmids as well as addition of adrenomedullin and CGRP. The present results demonstrate that adrenomedullin antagonizes serum deprivation-induced endothelial apoptosis by up-regulation of the max gene in an autocrine/ paracrine manner.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Shichiri",
      "authorRank" : 1,
      "name" : "Shichiri M",
      "referenceId" : "RGD:A35024"
    }, {
      "firstName" : "H",
      "lastName" : "Kato",
      "authorRank" : 2,
      "name" : "Kato H",
      "referenceId" : "RGD:A158249"
    }, {
      "firstName" : "M",
      "lastName" : "Doi",
      "authorRank" : 3,
      "name" : "Doi M",
      "referenceId" : "RGD:A119807"
    }, {
      "firstName" : "F",
      "lastName" : "Marumo",
      "authorRank" : 4,
      "name" : "Marumo F",
      "referenceId" : "RGD:A4690"
    }, {
      "firstName" : "Y",
      "lastName" : "Hirata",
      "authorRank" : 5,
      "name" : "Hirata Y",
      "referenceId" : "RGD:A4689"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316822"
    } ]
  }, {
    "primaryId" : "PMID:10446938",
    "title" : "Quantitative trait loci for blood pressure exist near the IGF-1, the Liddle syndrome, the angiotensin II-receptor gene and the renin loci in man.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Nagy Z, etal., J Am Soc Nephrol 1999 Aug;10(8):1709-16.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-01-29T14:13:54.000-06:00",
    "volume" : "10",
    "pages" : "1709-16",
    "abstract" : "Blood pressure (BP) is heritable and finding quantitative trait loci that influence BP is an important step in identifying genes responsible for BP regulation. Sixty-six pairs of dizygotic (DZ) twin subjects and their parents were used in a sib-pair analysis to look for linkage of selected candidate genes to the quantitative trait BP. Microsatellite markers were tested in the vicinity of the gene loci for insulin-like growth factor-1 (IGF-1), Liddle syndrome, autosomal-dominant hypertension with brachydactyly, angiotensinogen, angiotensin II type 1 receptor, angiotensin-converting enzyme, renin, and lipoprotein lipase. BP was measured in a standardized manner. Heart size was determined echocardiographically. Significant linkage was found at the IGF-1, Liddle syndrome, and AT1 receptor gene for systolic BP. Linkage for diastolic BP was found at the autosomal-dominant hypertension with brachydactyly locus. Both systolic and diastolic BP were linked to the renin gene locus. The linkage was most consistent for the IGF-1 gene locus and systolic BP. Linkage was also found between the IGF-1 gene locus and posterior cardiac wall thickness, septal thickness, and left ventricular mass index. It is suggested that these quantitative trait loci may be important for the subsequent detection of allelic variants for elevated BP. Furthermore, these results linking the IGF-1 gene locus to both BP and cardiac dimensions underscore the importance of the IGF-1 gene as a candidate gene for cardiovascular disease.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Nagy",
      "authorRank" : 1,
      "name" : "Nagy Z",
      "referenceId" : "RGD:A35687"
    }, {
      "firstName" : "A",
      "lastName" : "Busjahn",
      "authorRank" : 2,
      "name" : "Busjahn A",
      "referenceId" : "RGD:A35688"
    }, {
      "firstName" : "S",
      "lastName" : "Bahring",
      "authorRank" : 3,
      "name" : "Bahring S",
      "referenceId" : "RGD:A35689"
    }, {
      "firstName" : "HD",
      "lastName" : "Faulhaber",
      "authorRank" : 4,
      "name" : "Faulhaber HD",
      "referenceId" : "RGD:A35690"
    }, {
      "firstName" : "HR",
      "lastName" : "Gohlke",
      "authorRank" : 5,
      "name" : "Gohlke HR",
      "referenceId" : "RGD:A35691"
    }, {
      "firstName" : "H",
      "lastName" : "Knoblauch",
      "authorRank" : 6,
      "name" : "Knoblauch H",
      "referenceId" : "RGD:A35692"
    }, {
      "firstName" : "M",
      "lastName" : "Rosenthal",
      "authorRank" : 7,
      "name" : "Rosenthal M",
      "referenceId" : "RGD:A35693"
    }, {
      "firstName" : "B",
      "lastName" : "Muller-Myhsok",
      "authorRank" : 8,
      "name" : "Muller-Myhsok B",
      "referenceId" : "RGD:A35694"
    }, {
      "firstName" : "H",
      "lastName" : "Schuster",
      "authorRank" : 9,
      "name" : "Schuster H",
      "referenceId" : "RGD:A35695"
    }, {
      "firstName" : "FC",
      "lastName" : "Luft",
      "authorRank" : 10,
      "name" : "Luft FC",
      "referenceId" : "RGD:A15968"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734529"
    } ]
  }, {
    "primaryId" : "PMID:10446963",
    "title" : "Unbalanced germ-line expression of hMLH1 and hMSH2 alleles in hereditary nonpolyposis colorectal cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Curia MC, etal., Cancer Res. 1999 Aug 1;59(15):3570-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:19:43.000-05:00",
    "volume" : "59",
    "pages" : "3570-5",
    "abstract" : "We analyzed the hMLH1 and hMSH2 genes in 30 unrelated hereditary nonpolyposis colorectal cancer (HNPCC) patients using mutational and immunohistochemical analyses combined whenever possible with primer extension assays, designed to estimate hMLH1 and hMSH2 transcript expression in peripheral blood lymphocytes. Single-strand conformational polymorphism screening and PCR-direct sequencing revealed seven hMLH1 and five hMSH2 sequence variants in 14 unrelated HNPCC patients, including three definite pathogenic mutations, four amino acid substitutions of uncertain pathogenic significance, and five polymorphisms. Immunohistochemistry indicated the lack of either hMLH1 or hMSH2 protein expression in tumors from 13 patients, and the absence of both hMLH1 and hMSH2 immunostaining was observed in the tumor from one additional case. The lack of hMLH1 or hMSH2 immunostaining was associated with the presence of microsatellite  instability in the corresponding tumor and was also observed in tumors from patients negative for pathogenic mutations by mutational screening. There was a marked unbalance in the allelic expression of either hMLH1 or hMSH2 transcripts in three of eight unrelated HNPCC patients that could be analyzed, although a less marked unbalance was detected in two additional patients. Tumors from patients with germ-line unbalance in hMLH1 or hMSH2 transcript expression did not express the corresponding mismatch repair protein and displayed microsatellite instability. Our results indicate that constitutional alterations in hMLH1 and hMSH2 transcript expression may represent genetic markers for HNPCC carrier status also in cases in which mutational analysis did not detect a definite pathogenic variant. This suggests that transcript deregulation may represent a relevant mode of germ-line inactivation for mismatch repair genes.",
    "issueName" : "15",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MC",
      "lastName" : "Curia",
      "authorRank" : 1,
      "name" : "Curia",
      "referenceId" : "RGD:A258424"
    }, {
      "firstName" : "R",
      "lastName" : "Palmirotta",
      "authorRank" : 2,
      "name" : "Palmirotta R",
      "referenceId" : "RGD:A82949"
    }, {
      "firstName" : "G",
      "lastName" : "Aceto",
      "authorRank" : 3,
      "name" : "Aceto",
      "referenceId" : "RGD:A257188"
    }, {
      "firstName" : "L",
      "lastName" : "Messerini",
      "authorRank" : 4,
      "name" : "Messerini L",
      "referenceId" : "RGD:A153683"
    }, {
      "firstName" : "MC",
      "lastName" : "Veri",
      "authorRank" : 5,
      "name" : "Veri",
      "referenceId" : "RGD:A271941"
    }, {
      "firstName" : "S",
      "lastName" : "Crognale",
      "authorRank" : 6,
      "name" : "Crognale",
      "referenceId" : "RGD:A271942"
    }, {
      "firstName" : "R",
      "lastName" : "Valanzano",
      "authorRank" : 7,
      "name" : "Valanzano",
      "referenceId" : "RGD:A258427"
    }, {
      "firstName" : "F",
      "lastName" : "Ficari",
      "authorRank" : 8,
      "name" : "Ficari",
      "referenceId" : "RGD:A271943"
    }, {
      "firstName" : "P",
      "lastName" : "Fracasso",
      "authorRank" : 9,
      "name" : "Fracasso",
      "referenceId" : "RGD:A271944"
    }, {
      "firstName" : "V",
      "lastName" : "Stigliano",
      "authorRank" : 10,
      "name" : "Stigliano V",
      "referenceId" : "RGD:A45806"
    }, {
      "firstName" : "F",
      "lastName" : "Tonelli",
      "authorRank" : 11,
      "name" : "Tonelli",
      "referenceId" : "RGD:A215121"
    }, {
      "firstName" : "V",
      "lastName" : "Casale",
      "authorRank" : 12,
      "name" : "Casale V",
      "referenceId" : "RGD:A45808"
    }, {
      "firstName" : "F",
      "lastName" : "Guadagni",
      "authorRank" : 13,
      "name" : "Guadagni",
      "referenceId" : "RGD:A271945"
    }, {
      "firstName" : "P",
      "lastName" : "Battista",
      "authorRank" : 14,
      "name" : "Battista P",
      "referenceId" : "RGD:A82784"
    }, {
      "firstName" : "R",
      "lastName" : "Mariani-Costantini",
      "authorRank" : 15,
      "name" : "Mariani-Costantini R",
      "referenceId" : "RGD:A82783"
    }, {
      "firstName" : "A",
      "lastName" : "Cama",
      "authorRank" : 16,
      "name" : "Cama A",
      "referenceId" : "RGD:A76456"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068737"
    } ]
  }, {
    "primaryId" : "PMID:10447243",
    "title" : "Immunoelectron microscopic localization of the M6a antigen in rat brain.",
    "datePublished" : "1998-09-01T00:00:00.000-05:00",
    "citation" : "Roussel G, etal., J Neurocytol. 1998 Sep;27(9):695-703. doi: 10.1023/a:1006924400768.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-09-21T01:55:36.000-05:00",
    "volume" : "27",
    "pages" : "695-703",
    "abstract" : "The monoclonal antibody M6-7, which recognizes both native and denatured immunopurified M6a antigen, was used in the present immunocytochemical study to localize its corresponding antigen in young rat brain. Strong labelling was observed in the cerebellar molecular layer, which corresponds to heavily stained axon terminals originating from granule cells. The immunodeposit, as observed by electron microscopy, is present only on the cytoplasmic side of the presynaptic membrane and on the membrane of synaptic vesicles. In contrast, the Purkinje cells and their processes are unstained. Stained synapses are also found, although less frequently, in several other cerebral areas. The pattern of staining at these synapses is similar to that observed in the cerebellar molecular layer. It is hypothesized, on the basis of its restricted distribution in certain neuronal endings and its high homology with myelin proteolipids, that the M6a antigen revealed by the M6-7 antibody is probably involved in a specific biological function in these structures.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Roussel",
      "authorRank" : 1,
      "name" : "Roussel G",
      "referenceId" : "RGD:A32436"
    }, {
      "firstName" : "E",
      "lastName" : "Trifilieff",
      "authorRank" : 2,
      "name" : "Trifilieff E",
      "referenceId" : "RGD:A520885"
    }, {
      "firstName" : "C",
      "lastName" : "Lagenaur",
      "authorRank" : 3,
      "name" : "Lagenaur C",
      "referenceId" : "RGD:A25790"
    }, {
      "firstName" : "J L",
      "lastName" : "Nussbaum",
      "authorRank" : 4,
      "name" : "Nussbaum JL",
      "referenceId" : "RGD:A520886"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:155230692"
    } ]
  }, {
    "primaryId" : "PMID:10447258",
    "title" : "Identification of a common PEX1 mutation in Zellweger syndrome.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Collins CS and Gould SJ, Hum Mutat. 1999;14(1):45-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:17:07.000-05:00",
    "volume" : "14",
    "pages" : "45-53",
    "abstract" : "The Zellweger spectrum of disease, encompassing Zellweger syndrome and the progressively milder phenotypes of neonatal adrenoleukodystrophy and infantile Refsum disease, is due to a failure to form functional peroxisomes. Cell fusion complementation studies demonstrated that these diseases are genetically heterogeneous, with two-thirds of all patients lying within a single complementation group, CG1. Molecular genetic and cell biology studies have shown that PEX1 is deficient in many CG1 patients. However, previous studies have focused on mildly affected patients and there is still no report of two mutant PEX1 alleles in any Zellweger syndrome patient. Furthermore, mutations in the PMP70 gene have also been identified in two Zellweger syndrome patients from CG1, raising the possibility that CG1 patients may represent a mixture of PEX1-deficient and PMP70-deficient individuals. To address the molecular basis of disease in Zellweger syndrome patients from CG1, we examined all 24 PEX1 exons in four patients, including both patients that have mutations in PMP70. PEX1 mutations were detected in all four patients, including a 1-bp insertion (c.2097insT) in exon 13 that was present in three of the four patients. Subsequent studies demonstrated that this mutation is present in one-half of all  CG1 patients and correlates with the Zellweger syndrome phenotype. As this mutation leads to a loss of protein function its frequency makes it the most common cause of Zellweger syndrome, helping to explain the high percentage of patients that belong to CG1.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CS",
      "lastName" : "Collins",
      "authorRank" : 1,
      "name" : "Collins",
      "referenceId" : "RGD:A270871"
    }, {
      "firstName" : "SJ",
      "lastName" : "Gould",
      "authorRank" : 2,
      "name" : "Gould SJ",
      "referenceId" : "RGD:A27102"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11070984"
    } ]
  }, {
    "primaryId" : "PMID:10447263",
    "title" : "Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia. Mutation in brief no. 248. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Hattori H, etal., Hum Mutat. 1999;14(1):87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:50:47.000-05:00",
    "volume" : "14",
    "pages" : "87",
    "abstract" : "We used the denaturing gradient gel electrophoresis (DGGE) method to investigate  120 Japanese patients with familial hypercholesterolemia (FH) for mutations in the promoter region and the 18 exons and their flanking intron sequence of the low density lipoprotein (LDL) receptor gene. Fourteen aberrant DGGE patterns were found, and the underlying mutations were characterized by DNA sequencing. Five novel missense mutations (C317S, F382L A410T, L547V, and E693K), two nonsense mutations (W512X and K790X), four frameshift mutation (355del7, 1246ins5, 1687ins1, and 2035ins1), one splicing mutation (1845+2 T-->C), and two inframe mutations (661ins21 and 1115del9/ins6) were identified. Six of these mutations (L547V, E693K, W512X, 355del7, 1687ins1, and 20354ins1) have not been described before in FH. These newly identified mutations cosegregated in their family members with defective LDL receptor activity and hypercholesterolemia, and are thought to be causal for the FH phenotype. These results demonstrate that there is a broad spectrum of mutations in the LDL receptor gene in the Japanese population.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Hattori",
      "authorRank" : 1,
      "name" : "Hattori H",
      "referenceId" : "RGD:A11691"
    }, {
      "firstName" : "M",
      "lastName" : "Nagano",
      "authorRank" : 2,
      "name" : "Nagano M",
      "referenceId" : "RGD:A28390"
    }, {
      "firstName" : "F",
      "lastName" : "Iwata",
      "authorRank" : 3,
      "name" : "Iwata F",
      "referenceId" : "RGD:A77389"
    }, {
      "firstName" : "Y",
      "lastName" : "Homma",
      "authorRank" : 4,
      "name" : "Homma Y",
      "referenceId" : "RGD:A4656"
    }, {
      "firstName" : "T",
      "lastName" : "Egashira",
      "authorRank" : 5,
      "name" : "Egashira T",
      "referenceId" : "RGD:A65031"
    }, {
      "firstName" : "T",
      "lastName" : "Okada",
      "authorRank" : 6,
      "name" : "Okada",
      "referenceId" : "RGD:A415574"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064998"
    } ]
  }, {
    "primaryId" : "PMID:10447265",
    "title" : "Mutation analysis in patients with Wilson disease: identification of 4 novel mutations. Mutation in brief no. 250. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Haas R, etal., Hum Mutat. 1999;14(1):88.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:33:59.000-05:00",
    "volume" : "14",
    "pages" : "88",
    "abstract" : "In order to obtain novel mutations in the recently discovered Wilson disease gene, we screened 5 unrelated German individuals for mutations in the 21 exons and their flanking intronic sequences. We detected 9 mutations affecting the Wilson disease gene. Four of those, designated 802-808delTGTAAGT, 2008-2013delTATATG, Cys985Thr, and Ile1148Thr have not yet been reported. One patient had a homozygous mutation whereas the remaining four subjects were compound heterozygous. Therefore these data confirm, that mutations causing Wilson disease are frequently found in affected subjects and they are very heterogenous.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Haas",
      "authorRank" : 1,
      "name" : "Haas R",
      "referenceId" : "RGD:A35987"
    }, {
      "firstName" : "B",
      "lastName" : "Gutierrez-Rivero",
      "authorRank" : 2,
      "name" : "Gutierrez-Rivero",
      "referenceId" : "RGD:A279208"
    }, {
      "firstName" : "J",
      "lastName" : "Knoche",
      "authorRank" : 3,
      "name" : "Knoche",
      "referenceId" : "RGD:A279209"
    }, {
      "firstName" : "K",
      "lastName" : "Boker",
      "authorRank" : 4,
      "name" : "Boker",
      "referenceId" : "RGD:A279210"
    }, {
      "firstName" : "MP",
      "lastName" : "Manns",
      "authorRank" : 5,
      "name" : "Manns MP",
      "referenceId" : "RGD:A35335"
    }, {
      "firstName" : "HH",
      "lastName" : "Schmidt",
      "authorRank" : 6,
      "name" : "Schmidt HH",
      "referenceId" : "RGD:A35989"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071309"
    } ]
  }, {
    "primaryId" : "PMID:10447272",
    "title" : "Direct detection of common mutations in the familial Mediterranean fever gene (MEFV) using naturally occurring and primer mediated restriction fragment analysis. Mutation in brief no. 257. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Gershoni-Baruch R, etal., Hum Mutat. 1999;14(1):91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:19:00.000-05:00",
    "volume" : "14",
    "pages" : "91",
    "abstract" : "The MEFV gene involved in familial Mediterranean fever was recently cloned and four distinct sequence alterations (M680I, M694V, M6941 and V726A) were identified at the 3'-most exon. We genotyped 170 unrelated FMF patients from various ethnic groups in Israel and found that mutation M694V predominates in North African Jews, that mutation V726A is common in Jewish patients other than North African Jews and that all four mutations occur in patients of Arabian origin, namely, Moslems, Christians and Druze. Since these four distinct sequence alterations seem to account for the majority of mutations identified in FMF patients from the middle east, we have devised a simple protocol using PCR mediated site directed mutagenesis or naturally occurring recognition sites to scan for these mutations.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Gershoni-Baruch",
      "authorRank" : 1,
      "name" : "Gershoni-Baruch R",
      "referenceId" : "RGD:A95551"
    }, {
      "firstName" : "I",
      "lastName" : "Kepten",
      "authorRank" : 2,
      "name" : "Kepten",
      "referenceId" : "RGD:A271882"
    }, {
      "firstName" : "M",
      "lastName" : "Shinawi",
      "authorRank" : 3,
      "name" : "Shinawi M",
      "referenceId" : "RGD:A137056"
    }, {
      "firstName" : "R",
      "lastName" : "Brik",
      "authorRank" : 4,
      "name" : "Brik R",
      "referenceId" : "RGD:A137055"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068715"
    } ]
  }, {
    "primaryId" : "PMID:10447273",
    "title" : "Strong founder effects in BRCA1 mutation carrier breast cancer patients from Latvia. Mutation in brief no. 258. Online.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Csokay B, etal., Hum Mutat. 1999;14(1):92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:07:07.000-05:00",
    "volume" : "14",
    "pages" : "92",
    "abstract" : "Germ-line mutations of the BRCA1 gene account for approximately half of the cases of hereditary breast/ovarian cancers. We have screened index patients from 15 breast cancer families and 8 sporadic breast cancer patients from Latvia for mutations in all coding exons of the BRCA1 gene, using combined Heteroduplex Analysis/SSCP followed by direct sequencing of the variants. BRCA1 germ-line mutations proved to be frequent in Latvian breast cancer patients, also in moderate-risk families and sporadic patients. Out of 23 cases a total of 8 patients (35%) exhibited three different mutations (5382insC, C61G, 4153delA). Interestingly, these three recurrent mutations accounted for all mutations in our sample set and no unique mutation was found. The 5382insC and C61G mutations accounted for 63% (5/8) and 25% (2/8) of all mutations, respectively. Allelotyping suggested a common founder in each recurrent mutation. Additional one-hundred hospital-based incident breast cancer patients were screened for the  three mutations and 4 other 5382insC mutation carriers were identified (4%). Patients with C61G and 4153delA mutations were all Latvians, whilst the majority  of 5382insC carriers (7/9=78%) were of Russian ethnicity, which is intriguing for the supposed Baltic origin of this mutation.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "B",
      "lastName" : "Csokay",
      "authorRank" : 1,
      "name" : "Csokay",
      "referenceId" : "RGD:A265189"
    }, {
      "firstName" : "L",
      "lastName" : "Tihomirova",
      "authorRank" : 2,
      "name" : "Tihomirova",
      "referenceId" : "RGD:A239423"
    }, {
      "firstName" : "A",
      "lastName" : "Stengrevics",
      "authorRank" : 3,
      "name" : "Stengrevics",
      "referenceId" : "RGD:A196537"
    }, {
      "firstName" : "O",
      "lastName" : "Sinicka",
      "authorRank" : 4,
      "name" : "Sinicka",
      "referenceId" : "RGD:A268204"
    }, {
      "firstName" : "E",
      "lastName" : "Olah",
      "authorRank" : 5,
      "name" : "Olah E",
      "referenceId" : "RGD:A63268"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068445"
    } ]
  }, {
    "primaryId" : "PMID:10447460",
    "title" : "The expression of several mitochondrial and nuclear genes encoding the subunits of electron transport chain enzyme complexes, cytochrome c oxidase, and NADH dehydrogenase, in different brain regions in Alzheimer's disease.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Aksenov MY, etal., Neurochem Res. 1999 Jun;24(6):767-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-10-20T12:11:58.000-05:00",
    "volume" : "24",
    "pages" : "767-74",
    "abstract" : "In this study, changes of the expression of two mitochondrial and two nuclear genes encoding the subunits of cytochrome c oxidase (CO) and NADH dehydrogenase (ND) were studied in the hippocampus, inferior parietal lobule, and cerebellum of 10 Alzheimer's disease (AD) and 10 age-matched control subjects. The altered proportion between CO II and CO IV mRNAs was observed in the AD brain. Changes of the proportion between CO II and CO IV transcripts may contribute to the kinetic perturbation of CO documented in AD. A coordinated decrease of ND4 and ND15 mRNAs was found in the AD hippocampus and inferior parietal lobule, but not in cerebellum. The decrease of ND4 gene expression may lead to the inhibition of normal ubiquinone oxidoreductase activity of ND. This study suggests that changes of the expression of mitochondrial and nuclear genes, encoding parts of ND and CO enzyme complexes, may contribute to alterations of oxidative metabolism in AD.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MY",
      "lastName" : "Aksenov",
      "authorRank" : 1,
      "name" : "Aksenov MY",
      "referenceId" : "RGD:A42685"
    }, {
      "firstName" : "HM",
      "lastName" : "Tucker",
      "authorRank" : 2,
      "name" : "Tucker HM",
      "referenceId" : "RGD:A146122"
    }, {
      "firstName" : "P",
      "lastName" : "Nair",
      "authorRank" : 3,
      "name" : "Nair P",
      "referenceId" : "RGD:A76699"
    }, {
      "firstName" : "MV",
      "lastName" : "Aksenova",
      "authorRank" : 4,
      "name" : "Aksenova MV",
      "referenceId" : "RGD:A146123"
    }, {
      "firstName" : "DA",
      "lastName" : "Butterfield",
      "authorRank" : 5,
      "name" : "Butterfield DA",
      "referenceId" : "RGD:A82148"
    }, {
      "firstName" : "S",
      "lastName" : "Estus",
      "authorRank" : 6,
      "name" : "Estus S",
      "referenceId" : "RGD:A78008"
    }, {
      "firstName" : "WR",
      "lastName" : "Markesbery",
      "authorRank" : 7,
      "name" : "Markesbery WR",
      "referenceId" : "RGD:A63353"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5508713"
    } ]
  }, {
    "primaryId" : "PMID:10447463",
    "title" : "Expression of GDNF and GDNFR-alpha mRNAs in muscles of patients with motor neuron diseases.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Yamamoto M, etal., Neurochem Res. 1999 Jun;24(6):785-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-03-07T16:23:05.000-06:00",
    "volume" : "24",
    "pages" : "785-90",
    "abstract" : "The mRNA expression levels of GDNF, GDNFR-alpha and RET were examined in the muscles of amyotrophic lateral screlosis (ALS) and X-linked spinal and bulbar muscular atrophy (SBMA). GDNF mRNA levels were significantly elevated to variable extent in the diseased muscles compared to control muscles, although they were not specific to the type of the diseases. The diseased muscles also have a different expression pattern of GDNF mRNA isoforms from controls. GDNF mRNA expression, however, tended to reduce in advanced muscle pathology. On the other  hand, GDNFR-alpha mRNA levels were not changed significantly on expression levels in the diseased muscles. In situ hybridization study revealed that GDNF and GDNFR-alpha mRNAs were localized in subsarcolemmal space of muscle cells. RET mRNA was not detected in control nor diseased muscles. These results suggest that the elevated muscle GDNF acts as a trophic signal for motor neurons of motor neuron diseases, implying a possible therapeutic implication of GDNF to this type of diseases.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Yamamoto",
      "authorRank" : 1,
      "name" : "Yamamoto M",
      "referenceId" : "RGD:A5108"
    }, {
      "firstName" : "N",
      "lastName" : "Mitsuma",
      "authorRank" : 2,
      "name" : "Mitsuma N",
      "referenceId" : "RGD:A151961"
    }, {
      "firstName" : "A",
      "lastName" : "Inukai",
      "authorRank" : 3,
      "name" : "Inukai A",
      "referenceId" : "RGD:A151962"
    }, {
      "firstName" : "Y",
      "lastName" : "Ito",
      "authorRank" : 4,
      "name" : "Ito Y",
      "referenceId" : "RGD:A13854"
    }, {
      "firstName" : "M",
      "lastName" : "Li",
      "authorRank" : 5,
      "name" : "Li M",
      "referenceId" : "RGD:A5679"
    }, {
      "firstName" : "T",
      "lastName" : "Mitsuma",
      "authorRank" : 6,
      "name" : "Mitsuma T",
      "referenceId" : "RGD:A7742"
    }, {
      "firstName" : "G",
      "lastName" : "Sobue",
      "authorRank" : 7,
      "name" : "Sobue G",
      "referenceId" : "RGD:A7739"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6218978"
    } ]
  }, {
    "primaryId" : "PMID:10447648",
    "title" : "REP-1 gene mutations in Japanese patients with choroideremia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Fujiki K, etal., Graefes Arch Clin Exp Ophthalmol. 1999 Sep;237(9):735-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:19:14.000-05:00",
    "volume" : "237",
    "pages" : "735-40",
    "abstract" : "BACKGROUND: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. METHODS: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1-15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. RESULTS: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. CONCLUSIONS: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no  hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Fujiki",
      "authorRank" : 1,
      "name" : "Fujiki",
      "referenceId" : "RGD:A183458"
    }, {
      "firstName" : "Y",
      "lastName" : "Hotta",
      "authorRank" : 2,
      "name" : "Hotta Y",
      "referenceId" : "RGD:A90204"
    }, {
      "firstName" : "M",
      "lastName" : "Hayakawa",
      "authorRank" : 3,
      "name" : "Hayakawa M",
      "referenceId" : "RGD:A80120"
    }, {
      "firstName" : "A",
      "lastName" : "Saito",
      "authorRank" : 4,
      "name" : "Saito A",
      "referenceId" : "RGD:A4969"
    }, {
      "firstName" : "Y",
      "lastName" : "Mashima",
      "authorRank" : 5,
      "name" : "Mashima Y",
      "referenceId" : "RGD:A113715"
    }, {
      "firstName" : "M",
      "lastName" : "Mori",
      "authorRank" : 6,
      "name" : "Mori M",
      "referenceId" : "RGD:A7028"
    }, {
      "firstName" : "M",
      "lastName" : "Yoshii",
      "authorRank" : 7,
      "name" : "Yoshii M",
      "referenceId" : "RGD:A63173"
    }, {
      "firstName" : "A",
      "lastName" : "Murakami",
      "authorRank" : 8,
      "name" : "Murakami A",
      "referenceId" : "RGD:A8173"
    }, {
      "firstName" : "M",
      "lastName" : "Matsumoto",
      "authorRank" : 9,
      "name" : "Matsumoto M",
      "referenceId" : "RGD:A9603"
    }, {
      "firstName" : "S",
      "lastName" : "Hayasaka",
      "authorRank" : 10,
      "name" : "Hayasaka S",
      "referenceId" : "RGD:A5341"
    }, {
      "firstName" : "N",
      "lastName" : "Tagami",
      "authorRank" : 11,
      "name" : "Tagami",
      "referenceId" : "RGD:A271903"
    }, {
      "firstName" : "Y",
      "lastName" : "Isashiki",
      "authorRank" : 12,
      "name" : "Isashiki",
      "referenceId" : "RGD:A183459"
    }, {
      "firstName" : "N",
      "lastName" : "Ohba",
      "authorRank" : 13,
      "name" : "Ohba N",
      "referenceId" : "RGD:A119284"
    }, {
      "firstName" : "A",
      "lastName" : "Kanai",
      "authorRank" : 14,
      "name" : "Kanai",
      "referenceId" : "RGD:A416187"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068727"
    } ]
  }, {
    "primaryId" : "PMID:10447691",
    "title" : "The mature size of rat 4-aminobutyrate aminotransferase is different in liver and brain.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kontani Y, etal., Eur J Biochem 1999 Aug;264(1):218-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-21T16:23:44.000-05:00",
    "volume" : "264",
    "pages" : "218-22",
    "abstract" : "The amino acid sequence predicted from a rat liver cDNA library indicated that the precursor of beta-AlaAT I (4-aminobutyrate aminotransferase, beta-alanine-oxoglutarate aminotransferase) consists of a mature enzyme of 466 amino acid residues and a 34-amino acid terminal segment, with amino acids attributed to the leader peptide. However, the mass of beta-AlaAT I from rat brain was larger than that from rat liver and kidney, as assessed by Western-blot analysis, mass spectroscopy and N-terminal sequencing. The mature form of beta-AlaAT I from the brain had an ISQAAAK- peptide on the N-terminus of the liver mature beta-AlaAT I. Brain beta-AlaAT I was cleaved to liver beta-AlaAT I when incubated with fresh mitochondrial extract from rat liver. These results imply that mature rat liver beta-AlaAT I is proteolytically cleaved in two steps. The first cleavage of the motif XRX( downward arrow)XS is performed by a mitochondrial processing peptidase, yielding an intermediate-sized protein which is the mature brain beta-AlaAT I. The second cleavage, which generates the mature liver beta-AlaAT I, is also carried out by a mitochondrial endopeptidase. The second peptidase is active in liver but lacking in brain.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Kontani",
      "authorRank" : 1,
      "name" : "Kontani Y",
      "referenceId" : "RGD:A16000"
    }, {
      "firstName" : "SF",
      "lastName" : "Sakata",
      "authorRank" : 2,
      "name" : "Sakata SF",
      "referenceId" : "RGD:A16001"
    }, {
      "firstName" : "K",
      "lastName" : "Matsuda",
      "authorRank" : 3,
      "name" : "Matsuda K",
      "referenceId" : "RGD:A4784"
    }, {
      "firstName" : "T",
      "lastName" : "Ohyama",
      "authorRank" : 4,
      "name" : "Ohyama T",
      "referenceId" : "RGD:A16002"
    }, {
      "firstName" : "K",
      "lastName" : "Sano",
      "authorRank" : 5,
      "name" : "Sano K",
      "referenceId" : "RGD:A150110"
    }, {
      "firstName" : "N",
      "lastName" : "Tamaki",
      "authorRank" : 6,
      "name" : "Tamaki N",
      "referenceId" : "RGD:A4790"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:631980"
    } ]
  }, {
    "primaryId" : "PMID:10447766",
    "title" : "Platelet-activating factor receptor mRNA is localized in eosinophils and epithelial cells in rat small intestine: regulation by dexamethasone and gut flora.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wang H, etal., Immunology. 1999 Jul;97(3):447-54.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-04-13T11:36:36.000-05:00",
    "volume" : "97",
    "pages" : "447-54",
    "abstract" : "Platelet-activating factor (PAF) is a potent mediator involved in bowel injury. We investigated PAF receptor transcription and its mRNA localization in the small intestine of normal (conventionally fed) and germ-free rats, by competitive polymerase chain reaction (PCR) and in situ hybridization. A dose of PAF (1.5 microg/kg, i.v.) insufficient to cause gross bowel injury was injected into rats. Some rats were pretreated with dexamethasone (1 mg/kg). We found: (1) PAF receptor (PAF-R) mRNA localized predominantly in lamina propria eosinophils and in epithelial cells; (2) PAF increased PAF-receptor signals in the epithelial cells; (3) Dexamethasone depleted eosinophils in the intestine and markedly decreased PAF-receptor transcripts; the response to PAF was also weaker than control rats; (4) Germ-free rats had less PAF-R mRNA than normal rats, and showed a weaker response to PAF than conventionally fed rats. Thus, we conclude: (1) PAF receptor mRNA is constitutively expressed in the epithelium and in lamina propria eosinophils in the intestine. (2) PAF-R transcription is up-regulated by PAF and  gut flora, mostly in the epithelium. (3) PAF-R transcription is down-regulated by glucocorticoids, mainly as a result of eosinophil depletion. These results suggest a functional role for PAF receptors both in host defence and the inflammatory response in the small intestine.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang",
      "referenceId" : "RGD:A416760"
    }, {
      "firstName" : "X",
      "lastName" : "Tan",
      "authorRank" : 2,
      "name" : "Tan X",
      "referenceId" : "RGD:A67552"
    }, {
      "firstName" : "H",
      "lastName" : "Chang",
      "authorRank" : 3,
      "name" : "Chang H",
      "referenceId" : "RGD:A19390"
    }, {
      "firstName" : "W",
      "lastName" : "Huang",
      "authorRank" : 4,
      "name" : "Huang W",
      "referenceId" : "RGD:A5009"
    }, {
      "firstName" : "F",
      "lastName" : "Gonzalez-Crussi",
      "authorRank" : 5,
      "name" : "Gonzalez-Crussi F",
      "referenceId" : "RGD:A35105"
    }, {
      "firstName" : "W",
      "lastName" : "Hsueh",
      "authorRank" : 6,
      "name" : "Hsueh W",
      "referenceId" : "RGD:A35103"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9999199"
    } ]
  }, {
    "primaryId" : "PMID:10448056",
    "title" : "Regulation of calcium channel alpha(1A) subunit splice variant mRNAs in kainate-induced temporal lobe epilepsy.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Vigues S, etal., Neurobiol Dis. 1999 Aug;6(4):288-301.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-08-06T13:58:57.000-05:00",
    "volume" : "6",
    "pages" : "288-301",
    "abstract" : "P/Q-type voltage-gated Ca(2+) channels (VGCC) regulate neurotransmitter release in the hippocampus and molecular alterations of their alpha(1A) pore-forming subunits are involved in various animal and human CNS diseases. We evaluated, using RT-PCR and in situ hybridization, the spatio-temporal activation of two alpha(1A) subunits splice variants (alpha(1A-a) and alpha(1A-b)) in control and kainic acid (KA)-treated rats. Six hours after KA treatment, alpha(1A-a) and alpha(1A-b) mRNAs increased, decreased or remained unchanged with area specific patterns. These changes were evidenced in the hippocampus and the dentatus gyrus  and absent in the cerebellum. The alpha(1A) mRNA upregulation lasted for at least 7 days after KA treatment. Altogether, these results indicate that alpha(1A-a) and alpha(1A-b) mRNAs following seizure onset exhibit a complex and specific spatio-temporal pattern. The long-lasting changes in alpha(1A) subunit mRNA contents suggests that VGCC may be involved in the mechanisms generating chronic  focal hyperexcitability and/or cellular damage in temporal lobe epilepsy.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Vigues",
      "authorRank" : 1,
      "name" : "Vigues S",
      "referenceId" : "RGD:A19815"
    }, {
      "firstName" : "M",
      "lastName" : "Gastaldi",
      "authorRank" : 2,
      "name" : "Gastaldi M",
      "referenceId" : "RGD:A120983"
    }, {
      "firstName" : "C",
      "lastName" : "Chabret",
      "authorRank" : 3,
      "name" : "Chabret C",
      "referenceId" : "RGD:A53748"
    }, {
      "firstName" : "A",
      "lastName" : "Massacrier",
      "authorRank" : 4,
      "name" : "Massacrier A",
      "referenceId" : "RGD:A120985"
    }, {
      "firstName" : "P",
      "lastName" : "Cau",
      "authorRank" : 5,
      "name" : "Cau P",
      "referenceId" : "RGD:A120987"
    }, {
      "firstName" : "J",
      "lastName" : "Valmier",
      "authorRank" : 6,
      "name" : "Valmier J",
      "referenceId" : "RGD:A74237"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10054441"
    } ]
  }, {
    "primaryId" : "PMID:10448073",
    "title" : "Developmental expression of sarcoglycan gene products in cultured myocytes.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Noguchi S, etal., Biochem Biophys Res Commun 1999 Aug 19;262(1):88-93.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-02T11:43:37.000-05:00",
    "volume" : "262",
    "pages" : "88-93",
    "abstract" : "The sarcoglycan complex consists of four membrane-spanning proteins and was shown to be exclusively distributed in striated muscles. In this study, we analyzed the pattern of expression of the mRNAs and proteins of the sarcoglycan subunits during cell differentiation in a culture of myocytes. All four sarcoglycan mRNAs were detectable in proliferating cells, and expression of the alpha- and gamma-subunits was up-regulated by 20- and 50-fold following muscle cell fusion. However, sarcoglycan proteins were scarcely detectable in proliferating cells and were first detected 2 days after the induction to be differentiated. The accumulation of the sarcoglycan protein subunits was accompanied by cell differentiation. The discrepancy between the expression of the mRNAs and proteins of the sarcoglycan subunits in proliferating cells may be ascribed to rapid degradation of the protein.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Noguchi",
      "authorRank" : 1,
      "name" : "Noguchi S",
      "referenceId" : "RGD:A15613"
    }, {
      "firstName" : "E",
      "lastName" : "Wakabayashi",
      "authorRank" : 2,
      "name" : "Wakabayashi E",
      "referenceId" : "RGD:A55402"
    }, {
      "firstName" : "M",
      "lastName" : "Imamura",
      "authorRank" : 3,
      "name" : "Imamura M",
      "referenceId" : "RGD:A7058"
    }, {
      "firstName" : "M",
      "lastName" : "Yoshida",
      "authorRank" : 4,
      "name" : "Yoshida M",
      "referenceId" : "RGD:A15115"
    }, {
      "firstName" : "E",
      "lastName" : "Ozawa",
      "authorRank" : 5,
      "name" : "Ozawa E",
      "referenceId" : "RGD:A24016"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549557"
    } ]
  }, {
    "primaryId" : "PMID:10448096",
    "title" : "Molecular cloning and genomic organization of mouse homologue of Drosophila germ cell-less and its expression in germ lineage cells.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Kimura T, etal., Biochem Biophys Res Commun 1999 Aug 19;262(1):223-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-09-01T15:11:54.000-05:00",
    "volume" : "262",
    "pages" : "223-30",
    "abstract" : "Primordial germ cells (PGCs) are founder cells of all gametes. A number of genes which control PGCs development have been identified in invertebrates, whereas such genes are by and large unelucidated in mammals. Here we describe cloning, genomic structure and expression of mouse homologue of germ cell-less (gcl) gene which is required for PGCs formation in Drosophila. The mouse gcl shows 34% identity compared with Drosophila gcl protein and contains BTB/POZ domain. The gcl gene consists of 14 exons and spans more than 50 kb. The CpG islands are found around exon 1 of the gene. Putative promoter region contains potential binding sites for various transcription factors. Northern blot analysis showed that its mRNA is highly expressed in adult testis with lower expression in ovary, ES (embryonic stem) cells, and various other organs. In situ hybridization analysis revealed strong expression of the gcl gene in the pachytene stage spermatocytes. The expression was also observed in post-migratory PGCs, but was not apparent in migratory and pre-migratory PGCs. Further studies including gene disruption analysis would provide an important insight into mammalian germ lineage development.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kimura",
      "authorRank" : 1,
      "name" : "Kimura T",
      "referenceId" : "RGD:A6130"
    }, {
      "firstName" : "K",
      "lastName" : "Yomogida",
      "authorRank" : 2,
      "name" : "Yomogida K",
      "referenceId" : "RGD:A19336"
    }, {
      "firstName" : "N",
      "lastName" : "Iwai",
      "authorRank" : 3,
      "name" : "Iwai N",
      "referenceId" : "RGD:A109702"
    }, {
      "firstName" : "Y",
      "lastName" : "Kato",
      "authorRank" : 4,
      "name" : "Kato Y",
      "referenceId" : "RGD:A12978"
    }, {
      "firstName" : "T",
      "lastName" : "Nakano",
      "authorRank" : 5,
      "name" : "Nakano T",
      "referenceId" : "RGD:A158778"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1549526"
    } ]
  }, {
    "primaryId" : "PMID:10448273",
    "title" : "Evaluation of the replication error phenotype in relation to molecular and clinicopathological features in hereditary and early onset colorectal cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Capozzi E, etal., Eur J Cancer. 1999 Feb;35(2):289-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:12:31.000-05:00",
    "volume" : "35",
    "pages" : "289-95",
    "abstract" : "Mutations affecting human mismatch repair (MMR) genes (MLH1, MSH2, PMS1, PMS2, and MSH6) cause tumour predisposition in hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, and an association has been demonstrated with the replication error (RER) phenotype in most colorectal and some extracolonic neoplasms. A pathogenetic model for RER+ tumours through inactivation of suppressor genes has been hypothesised, and TGF beta RII, BAX and IGFIIR genes have recently been proposed as targets of such inactivating mutations. In this study, a series of 47 tumours developed in patients with known MLH1/MSH2 status and a family history of HNPCC and/or early onset colorectal cancer were characterised for the RER phenotype through microsatellite analysis. The RER phenotype, displayed by 17 tumours, was then correlated with the presence of insertions/deletions at the TGF beta RII, IGFIIR and BAX gene stretches, confirming that the TGF beta RII inactivation may be particularly critical for the RER-associated tumorigenesis. RER+ colorectal cancers (CRCs) developed more frequently in patients from HNPCC families (72.7%) than in those from families not fulfilling the Amsterdam criteria (33.3% in suspected HNPCC and 20.8% in early onset CRC patients). A consistent fraction of either Amsterdam and non-Amsterdam patients developed RER- CRCs, pointing to the involvement of other  genes not related to the MMR system. The RER phenotype was associated with younger age at diagnosis in familial cases, and there was a trend for an association with proximal CRC localisation and early Dukes' stages. The RER status was also correlated with the presence and type of MLH1 and MSH2 alteration.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Capozzi",
      "authorRank" : 1,
      "name" : "Capozzi",
      "referenceId" : "RGD:A256730"
    }, {
      "firstName" : "L",
      "lastName" : "Della Puppa",
      "authorRank" : 2,
      "name" : "Della Puppa",
      "referenceId" : "RGD:A256733"
    }, {
      "firstName" : "M",
      "lastName" : "Fornasarig",
      "authorRank" : 3,
      "name" : "Fornasarig",
      "referenceId" : "RGD:A251065"
    }, {
      "firstName" : "M",
      "lastName" : "Pedroni",
      "authorRank" : 4,
      "name" : "Pedroni",
      "referenceId" : "RGD:A251063"
    }, {
      "firstName" : "M",
      "lastName" : "Boiocchi",
      "authorRank" : 5,
      "name" : "Boiocchi M",
      "referenceId" : "RGD:A116643"
    }, {
      "firstName" : "A",
      "lastName" : "Viel",
      "authorRank" : 6,
      "name" : "Viel A",
      "referenceId" : "RGD:A122297"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065683"
    } ]
  }, {
    "primaryId" : "PMID:10448858",
    "title" : "Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Clancy CE and Rudy Y, Nature. 1999 Aug 5;400(6744):566-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-05-11T18:10:45.000-05:00",
    "volume" : "400",
    "pages" : "566-9",
    "abstract" : "Advances in genetics and molecular biology have provided an extensive body of information on the structure and function of the elementary building blocks of living systems. Genetic defects in membrane ion channels can disrupt the delicate balance of dynamic interactions between the ion channels and the cellular environment, leading to altered cell function. As ion-channel defects are typically studied in isolated expression systems, away from the cellular environment where they function physiologically, a connection between molecular findings and the physiology and pathophysiology of the cell is rarely established. Here we describe a single-channel-based Markovian modelling approach that bridges this gap. We achieve this by determining the cellular arrhythmogenic consequences of a mutation in the cardiac sodium channel that can lead to a clinical arrhythmogenic disorder (the long-QT syndrome) and sudden cardiac death.",
    "issueName" : "6744",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CE",
      "lastName" : "Clancy",
      "authorRank" : 1,
      "name" : "Clancy",
      "referenceId" : "RGD:A258884"
    }, {
      "firstName" : "Y",
      "lastName" : "Rudy",
      "authorRank" : 2,
      "name" : "Rudy",
      "referenceId" : "RGD:A251792"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11076928"
    } ]
  }, {
    "primaryId" : "PMID:10448933",
    "title" : "A novel biological role for prostaglandin D2 is suggested by distribution studies of the rat DP prostanoid receptor.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wright DH, etal., Eur J Pharmacol 1999 Jul 14;377(1):101-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T16:33:36.000-05:00",
    "volume" : "377",
    "pages" : "101-15",
    "abstract" : "We report the cloning, functional expression and cell-specific localization of the rat homologue of the prostaglandin D2 receptor (DP). In situ hybridization, utilizing multiple digoxigenin-labelled riboprobes and their complementary sense controls, was performed to determine the detailed distribution of DP receptor mRNA in the central nervous system and the gastrointestinal tract. Within the brain, the leptomeninges and choroid plexus expressed DP receptor mRNA. Transcripts detected in the spinal cord were localized to the sensory and motor neurons of the dorsal and ventral horns, respectively, suggesting a role for the DP receptor in the modulation of central nervous system processes, including pain transmission. Within the gastrointestinal tract (stomach, duodenum, ileum and colon) signals were highly localized to the mucous-secreting goblet cells and the columnar epithelium. These findings suggest a novel biological role for prostaglandin D2-mediated activity at the DP receptor, namely mucous secretion. In addition, radioligand binding assays (saturation analyses and equilibrium competition assays) and functional assays (measuring cAMP accumulation) were performed to characterize the recombinant rat DP receptor expressed in human embryonic kidney (HEK) 293(EBNA) cells. A single site of binding (K(D) = 14 nM, Bmax = 115 fmol/mg protein) was measured for prostaglandin D2-specific binding to the rat DP receptor. Prostaglandin D2 proved to be a potent agonist at the rat DP receptor (EC50 = 5 nM). The rank order of efficacy for DP receptor specific agonists [prostaglandin D2 = prostaglandin J2 = BW 245C (5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropylhydantoin)) > L-644,698 ((4-(3-(3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl) propyl) benzoic acid) (racemate)] reflected the affinity with which the ligands bound to the receptor.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DH",
      "lastName" : "Wright",
      "authorRank" : 1,
      "name" : "Wright DH",
      "referenceId" : "RGD:A22366"
    }, {
      "firstName" : "F",
      "lastName" : "Nantel",
      "authorRank" : 2,
      "name" : "Nantel F",
      "referenceId" : "RGD:A22367"
    }, {
      "firstName" : "KM",
      "lastName" : "Metters",
      "authorRank" : 3,
      "name" : "Metters KM",
      "referenceId" : "RGD:A22368"
    }, {
      "firstName" : "AW",
      "lastName" : "Ford-Hutchinson",
      "authorRank" : 4,
      "name" : "Ford-Hutchinson AW",
      "referenceId" : "RGD:A22369"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633864"
    } ]
  }, {
    "primaryId" : "PMID:10449435",
    "title" : "Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Garred P, etal., J Clin Invest. 1999 Aug;104(4):431-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-12-02T09:18:02.000-06:00",
    "volume" : "104",
    "pages" : "431-7",
    "abstract" : "Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Accordingly, we investigated whether MBL variant alleles, which are associated with recurrent infections, might be risk factors for CF patients. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology, and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers of MBL variant alleles when compared with normal homozygotes. The negative impact of variant alleles on lung function was especially confined to patients with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infection was significantly more frequent in carriers of variant alleles than in homozygotes. The risk of end-stage CF among carriers of variant alleles increased 3-fold, and the survival time decreased over a 10-year follow-up period. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes. Presence of MBL variant alleles is therefore associated with poor prognosis and early death in patients with CF.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Garred",
      "authorRank" : 1,
      "name" : "Garred P",
      "referenceId" : "RGD:A68178"
    }, {
      "firstName" : "T",
      "lastName" : "Pressler",
      "authorRank" : 2,
      "name" : "Pressler T",
      "referenceId" : "RGD:A131545"
    }, {
      "firstName" : "HO",
      "lastName" : "Madsen",
      "authorRank" : 3,
      "name" : "Madsen HO",
      "referenceId" : "RGD:A68169"
    }, {
      "firstName" : "B",
      "lastName" : "Frederiksen",
      "authorRank" : 4,
      "name" : "Frederiksen B",
      "referenceId" : "RGD:A131546"
    }, {
      "firstName" : "A",
      "lastName" : "Svejgaard",
      "authorRank" : 5,
      "name" : "Svejgaard A",
      "referenceId" : "RGD:A53118"
    }, {
      "firstName" : "N",
      "lastName" : "Hoiby",
      "authorRank" : 6,
      "name" : "Hoiby N",
      "referenceId" : "RGD:A127544"
    }, {
      "firstName" : "M",
      "lastName" : "Schwartz",
      "authorRank" : 7,
      "name" : "Schwartz M",
      "referenceId" : "RGD:A37268"
    }, {
      "firstName" : "C",
      "lastName" : "Koch",
      "authorRank" : 8,
      "name" : "Koch C",
      "referenceId" : "RGD:A16363"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4889447"
    } ]
  }, {
    "primaryId" : "PMID:10449440",
    "title" : "Rapid downregulation of rat renal Na/P(i) cotransporter in response to parathyroid hormone involves microtubule rearrangement.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Lotscher M, etal., J Clin Invest. 1999 Aug;104(4):483-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-05-10T16:09:07.000-05:00",
    "volume" : "104",
    "pages" : "483-94",
    "abstract" : "Renal proximal tubule cells express in their apical brush border membrane (BBM) a Na/P(i) cotransporter type IIa that is rapidly downregulated in response to parathyroid hormone (PTH). We used the rat renal Na/P(i) cotransporter type IIa (NaPi-2) as an in vivo model to assess early cellular events in the rapid downregulation of this transporter. When rats were treated with PTH for 15 minutes, NaPi-2 abundance in the BBM was decreased. In parallel, transporter accumulated in intracellular vesicles. Concomitantly, microtubules (MTs) were found to form dense bundles of apical-to-basal orientation. After 60 minutes of PTH action, the cells were vastly depleted of NaPi-2, whereas their microtubular  cytoskeleton had returned to its normal appearance. Prevention of MT rearrangement by taxol resulted in accumulation of NaPi-2 in the subapical cell portion after 15 minutes and a strong delay in depletion of intracellular transporter after 60 minutes of PTH action. Furthermore, the subapical accumulation of NaPi-2 was associated with the expansion of dense apical tubules  of the subapical endocytic apparatus (SEA). Depolymerization of MTs by colchicine likewise caused a retardation of intracellular NaPi-2 depletion. These results suggest that NaPi-2 is downregulated in response to PTH through a rapid endocytic process in 2 separate steps: (a) internalization of the transporter into the SEA, and (b) its delivery to degradative organelles by a trafficking mechanism whose efficiency depends on a taxol-sensitive rearrangement of MTs.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Lotscher",
      "authorRank" : 1,
      "name" : "Lotscher",
      "referenceId" : "RGD:A169473"
    }, {
      "firstName" : "Y",
      "lastName" : "Scarpetta",
      "authorRank" : 2,
      "name" : "Scarpetta",
      "referenceId" : "RGD:A169742"
    }, {
      "firstName" : "M",
      "lastName" : "Levi",
      "authorRank" : 3,
      "name" : "Levi M",
      "referenceId" : "RGD:A11989"
    }, {
      "firstName" : "N",
      "lastName" : "Halaihel",
      "authorRank" : 4,
      "name" : "Halaihel N",
      "referenceId" : "RGD:A11987"
    }, {
      "firstName" : "H",
      "lastName" : "Wang",
      "authorRank" : 5,
      "name" : "Wang",
      "referenceId" : "RGD:A416760"
    }, {
      "firstName" : "HK",
      "lastName" : "Zajicek",
      "authorRank" : 6,
      "name" : "Zajicek",
      "referenceId" : "RGD:A169744"
    }, {
      "firstName" : "J",
      "lastName" : "Biber",
      "authorRank" : 7,
      "name" : "Biber",
      "referenceId" : "RGD:A403617"
    }, {
      "firstName" : "H",
      "lastName" : "Murer",
      "authorRank" : 8,
      "name" : "Murer",
      "referenceId" : "RGD:A341576"
    }, {
      "firstName" : "B",
      "lastName" : "Kaissling",
      "authorRank" : 9,
      "name" : "Kaissling B",
      "referenceId" : "RGD:A89473"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7243174"
    } ]
  }, {
    "primaryId" : "PMID:10449524",
    "title" : "Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Song X, etal., J Exp Med 1999 Aug 16;190(4):535-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:39.000-05:00",
    "volume" : "190",
    "pages" : "535-42",
    "abstract" : "Disruption of the balance between proteases and protease inhibitors is often associated with pathologic tissue destruction. To explore the therapeutic potential of secretory leukocyte protease inhibitor (SLPI) in erosive joint diseases, we cloned, sequenced, and expressed active rat SLPI, which shares the protease-reactive site found in human SLPI. In a rat streptococcal cell wall (SCW)-induced model of inflammatory erosive polyarthritis, endogenous SLPI was unexpectedly upregulated at both mRNA and protein levels in inflamed joint tissues. Systemic delivery of purified recombinant rat SLPI inhibited joint inflammation and cartilage and bone destruction. Inflammatory pathways as reflected by circulating tumor necrosis factor alpha and nuclear factor kappaB activation and cartilage resorption detected by circulating levels of type II collagen collagenase-generated cleavage products were all diminished by SLPI treatment in acute and chronic arthritis, indicating that the action of SLPI may extend beyond inhibition of serine proteases.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Song",
      "authorRank" : 1,
      "name" : "Song X",
      "referenceId" : "RGD:A23508"
    }, {
      "firstName" : "L",
      "lastName" : "Zeng",
      "authorRank" : 2,
      "name" : "Zeng L",
      "referenceId" : "RGD:A23509"
    }, {
      "firstName" : "W",
      "lastName" : "Jin",
      "authorRank" : 3,
      "name" : "Jin W",
      "referenceId" : "RGD:A21800"
    }, {
      "firstName" : "J",
      "lastName" : "Thompson",
      "authorRank" : 4,
      "name" : "Thompson J",
      "referenceId" : "RGD:A23510"
    }, {
      "firstName" : "DE",
      "lastName" : "Mizel",
      "authorRank" : 5,
      "name" : "Mizel DE",
      "referenceId" : "RGD:A23511"
    }, {
      "firstName" : "K",
      "lastName" : "Lei",
      "authorRank" : 6,
      "name" : "Lei K",
      "referenceId" : "RGD:A23512"
    }, {
      "firstName" : "RC",
      "lastName" : "Billinghurst",
      "authorRank" : 7,
      "name" : "Billinghurst RC",
      "referenceId" : "RGD:A23513"
    }, {
      "firstName" : "AR",
      "lastName" : "Poole",
      "authorRank" : 8,
      "name" : "Poole AR",
      "referenceId" : "RGD:A23514"
    }, {
      "firstName" : "SM",
      "lastName" : "Wahl",
      "authorRank" : 9,
      "name" : "Wahl SM",
      "referenceId" : "RGD:A22559"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634208"
    } ]
  }, {
    "primaryId" : "PMID:10449650",
    "title" : "Mitochondrial DNA mutations in patients with orthostatic hypotension.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Schwartz F, etal., Am J Med Genet. 1999 Sep 10;86(2):145-50.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-09-13T10:01:39.000-05:00",
    "volume" : "86",
    "pages" : "145-50",
    "abstract" : "We determined the entire sequence of the mitochondrial genome in affected individuals from three families with idiopathic orthostatic hypotension. The disorder in two of these families was recently linked to chromosome arm 18q, while the third family remains unlinked. In all three families, orthostatic hypotension is inherited through the females, suggesting the existence of additional contributing factors, such as genomic imprinting or a mitochondrial modifier. We now report the presence of multiple point mutations in the mitochondrial DNA (mtDNA) in all three families. While most of the changes are common polymorphisms, several novel mutations were found that merit further consideration. In one individual, we detected a T-to-C transition at position 1243 in the 12SrRNA, a change from threonine to alanine at position 67 of the ND1 protein, and from valine to isoleucine at position 197 of the ND2 protein. A second individual harbored a novel substitution of threonine with serine at position 536 of the ND5 protein. Two previously unreported amino acid replacements were detected in a third individual: amino acid 193 of cytochrome b was changed from alanine to threonine, and amino acid 88 of COIII was changed from threonine to alanine. Further studies are required to assess the role of these mutations in blood pressure homeostasis.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Schwartz",
      "authorRank" : 1,
      "name" : "Schwartz F",
      "referenceId" : "RGD:A10809"
    }, {
      "firstName" : "CT",
      "lastName" : "Baldwin",
      "authorRank" : 2,
      "name" : "Baldwin CT",
      "referenceId" : "RGD:A10816"
    }, {
      "firstName" : "J",
      "lastName" : "Baima",
      "authorRank" : 3,
      "name" : "Baima J",
      "referenceId" : "RGD:A10807"
    }, {
      "firstName" : "H",
      "lastName" : "Gavras",
      "authorRank" : 4,
      "name" : "Gavras H",
      "referenceId" : "RGD:A10817"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1581056"
    } ]
  }, {
    "primaryId" : "PMID:10449762",
    "title" : "Expression pattern of the mouse ortholog of the Pendred's syndrome gene (Pds) suggests a key role for pendrin in the inner ear.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Everett LA, etal., Proc Natl Acad Sci U S A 1999 Aug 17;96(17):9727-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-09T15:42:06.000-06:00",
    "volume" : "96",
    "pages" : "9727-32",
    "abstract" : "Pendred's syndrome is an autosomal-recessive disorder characterized by deafness and goiter. After our recent identification of the human gene mutated in Pendred's syndrome (PDS), we sought to investigate in greater detail the expression of the gene and the function of its encoded protein (pendrin). Toward that end, we isolated the corresponding mouse ortholog (Pds) and performed RNA in situ hybridization on mouse inner ears (from 8 days postcoitum to postnatal day 5) to establish the expression pattern of Pds in the developing auditory and vestibular systems. Pds expression was detected throughout the endolymphatic duct and sac, in distinct areas of the utricle and saccule, and in the external sulcus region within the cochlea. This highly discrete expression pattern is unlike that of any other known gene and involves several regions thought to be important for endolymphatic fluid resorption in the inner ear, consistent with the putative functioning of pendrin as an anion transporter. These studies provide key first steps toward defining the precise role of pendrin in inner ear development and elucidating the pathogenic mechanism for the deafness seen in Pendred's syndrome.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LA",
      "lastName" : "Everett",
      "authorRank" : 1,
      "name" : "Everett LA",
      "referenceId" : "RGD:A7694"
    }, {
      "firstName" : "H",
      "lastName" : "Morsli",
      "authorRank" : 2,
      "name" : "Morsli H",
      "referenceId" : "RGD:A7695"
    }, {
      "firstName" : "DK",
      "lastName" : "Wu",
      "authorRank" : 3,
      "name" : "Wu DK",
      "referenceId" : "RGD:A7696"
    }, {
      "firstName" : "ED",
      "lastName" : "Green",
      "authorRank" : 4,
      "name" : "Green ED",
      "referenceId" : "RGD:A7697"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:69928"
    } ]
  }, {
    "primaryId" : "PMID:10450019",
    "title" : "Regulation of dopamine-induced natriuresisby the dopamine-metabolizing enzyme catechol-O-methyltransferase.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Odlind C, etal., Exp Nephrol. 1999 Jul-Aug;7(4):314-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-19T18:11:04.000-05:00",
    "volume" : "7",
    "pages" : "314-22",
    "abstract" : "Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis. A study was performed to elucidate two possible regulatory pathways  of DA-induced natriuresis, i.e., metabolism and precursor delivery. This was done by use of an intraperitoneal injection of a catechol-O-methyltransferase (COMT) inhibitor, entacapone, or intravenous infusion of the DA precursor, L-dopa. Entacapone (30 mg/kg i.p.) induced a more than fivefold increase in renal sodium  excretion which occurred without changes in renal haemodynamics. The natriuretic  response was highly dependent on DA D(1)-like receptor activation, since the selective D(1)-like receptor antagonist SCH23390 attenuated the natriuretic response by 61%, while the selective D(2)-like receptor antagonist sulpiride was  ineffective. The urinary excretion of DA did not increase. Infusion of L-dopa (60 microg/h/kg) only induced a twofold increase in sodium excretion, but the urinary excretion of DA increased more than 17-fold. The L-dopa-induced natriuretic response occurred without increments in glomerular filtration rate and could be blocked with the D(1)-like receptor antagonist SCH23390. It is concluded that the DA-metabolizing enzyme COMT is involved in the regulation of the natriuretic effect of intrarenal DA. It may be speculated that intrarenal DA activity is not  primarily determined on the basis of delivered precursor, but on that of the level of DA metabolism.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Odlind",
      "authorRank" : 1,
      "name" : "Odlind",
      "referenceId" : "RGD:A190164"
    }, {
      "firstName" : "V",
      "lastName" : "Goransson",
      "authorRank" : 2,
      "name" : "Goransson",
      "referenceId" : "RGD:A190165"
    }, {
      "firstName" : "I",
      "lastName" : "Reenila",
      "authorRank" : 3,
      "name" : "Reenila I",
      "referenceId" : "RGD:A91671"
    }, {
      "firstName" : "P",
      "lastName" : "Hansell",
      "authorRank" : 4,
      "name" : "Hansell P",
      "referenceId" : "RGD:A48549"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8662342"
    } ]
  }, {
    "primaryId" : "PMID:10450036",
    "title" : "Expression of the molecule detectable by anti-propolypeptide of von Willebrand factor antibody in rat mesangial cells in anti-Thy 1.1 mAb 1-22-3 induced glomerulonephritis: A marker of injured mesangial cells.",
    "datePublished" : "1000-05-01T00:00:00.000-06:00",
    "citation" : "Wakasugi M, etal., Nephron. 1999;82(4):338-47.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-05-17T16:03:05.000-05:00",
    "volume" : "82",
    "pages" : "338-47",
    "abstract" : "We have previously reported that propolypeptide of von Willebrand factor (pp-vWF) binds to collagen with an affinity comparable to that of mature vWF, inhibits collagen-induced platelet aggregation, is cross-linked with laminin, and also serves as a ligand for very-late antigen 4 integrin. These observations from in vitro experiments suggest that pp-vWF is incorporated in the extracellular matrix and affects the cell-matrix interaction and that pp-vWF functions in leukocyte recruitment to inflammatory and vascular injury sites. We, therefore, hypothesize that pp-vWF might be involved in the induction and/or progression of mesangial proliferative glomerulonephritis. To test this hypothesis, we examined the kinetics of the immunostaining of the molecule detectable by an affinity-purified anti-pp-vWF antibody in rat glomeruli in monoclonal antibody 1-22-3 induced glomerulonephritis. Immunostaining by pp-vWF antibody was observed in the nuclear rim of mesangial cells in monoclonal antibody 1-22-3 induced glomerulonephritis.  Positive staining first appeared on day 10 after monoclonal antibody injection, when mesangial cell proliferation and mesangial matrix expansion had already begun. Staining was still detected on day 56, when morphologic alterations observed by light microscopy had been normalized. The pp-vWF antibody recognized  molecule appeared later than alpha-smooth muscle actin or collagen type I. Positive staining was not detected in cultured mesangial cells. It should be noted that the positive staining by pp-vWF antibody in mesangial cells was still  detected in previously injured glomeruli that have almost recovered normal morphology. These observations indicate that positive staining by pp-vWF antibody could be a very useful marker for identifying a past episode of injury in mesangial cells.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Wakasugi",
      "authorRank" : 1,
      "name" : "Wakasugi M",
      "referenceId" : "RGD:A24426"
    }, {
      "firstName" : "H",
      "lastName" : "Kawachi",
      "authorRank" : 2,
      "name" : "Kawachi H",
      "referenceId" : "RGD:A20997"
    }, {
      "firstName" : "S",
      "lastName" : "Omori",
      "authorRank" : 3,
      "name" : "Omori",
      "referenceId" : "RGD:A295108"
    }, {
      "firstName" : "J",
      "lastName" : "Takagi",
      "authorRank" : 4,
      "name" : "Takagi",
      "referenceId" : "RGD:A290497"
    }, {
      "firstName" : "S",
      "lastName" : "Nishi",
      "authorRank" : 5,
      "name" : "Nishi S",
      "referenceId" : "RGD:A7496"
    }, {
      "firstName" : "M",
      "lastName" : "Arakawa",
      "authorRank" : 6,
      "name" : "Arakawa M",
      "referenceId" : "RGD:A90118"
    }, {
      "firstName" : "F",
      "lastName" : "Shimizu",
      "authorRank" : 7,
      "name" : "Shimizu F",
      "referenceId" : "RGD:A21005"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11079208"
    } ]
  }, {
    "primaryId" : "PMID:10450379",
    "title" : "Lipid peroxidation in proliferative vitreoretinopathies.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Verdejo C, etal., Eye (Lond). 1999 Apr;13 ( Pt 2):183-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-08-25T10:28:33.000-05:00",
    "volume" : "13 ( Pt 2)",
    "pages" : "183-8",
    "abstract" : "PURPOSE: To study the lipid hydroperoxide activity in vasoproliferative and fibroproliferative retinal disorders. METHODS: Vitreous body samples from patients undergoing vitrectomy because of proliferative vitreoretinopathy (PVR; n = 12) or proliferative diabetic retinopathy (PDR; n = 15), and rhegmatogenous retinal detachment/macular hole/epiretinal membranes as the comparison group (CG; n = 14), were analysed for protein content and basal and induced lipid peroxidation (LPO), as determined by the thiobarbituric acid reactive substances  (TBARS) test and LPO 586 commercial kit. The antioxidant activity for superoxide  dismutase (SOD) and catalase (CAT) was also assayed. RESULTS: Malondialdehyde (MDA)-like metabolites and 4-hydroxynonenal (4-HNE) mean values were first measured to assess basal LPO, and found to be significantly higher in the PVR and PDR cases than in the CG (p < or = 0.0001). LPO induced by nicotine adenine dinucleotide phosphate iron (NADPH-Fe) was then assayed and the data showed that  MDA mean values were 5-fold greater for the PVR and PDR eyes than in the case of  basal LPO (p < or = 0.0001). SOD activity was significantly smaller in the PVR (p = 0.0010) and PDR (p < or = 0.0001) groups than in the CG. CAT levels displayed significantly lower values in the PVR and PDR cases than in the CG (p < or = 0.0001). No significant differences in free radical (FR) formation and antioxidant status between PVR and PDR patients were observed. CONCLUSIONS: Fibrovascular proliferative vitreoretinopathies correlate with increased FR formation and decreased antioxidant activity in the human vitreous body.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Verdejo",
      "authorRank" : 1,
      "name" : "Verdejo",
      "referenceId" : "RGD:A193400"
    }, {
      "firstName" : "P",
      "lastName" : "Marco",
      "authorRank" : 2,
      "name" : "Marco P",
      "referenceId" : "RGD:A121747"
    }, {
      "firstName" : "J",
      "lastName" : "Renau-Piqueras",
      "authorRank" : 3,
      "name" : "Renau-Piqueras J",
      "referenceId" : "RGD:A51309"
    }, {
      "firstName" : "MD",
      "lastName" : "Pinazo-Duran",
      "authorRank" : 4,
      "name" : "Pinazo-Duran",
      "referenceId" : "RGD:A193401"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9068932"
    } ]
  }, {
    "primaryId" : "PMID:10450519",
    "title" : "Inflammatory disease in HLA-B27 transgenic rats.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Taurog JD, etal., Immunol Rev 1999 Jun;169:209-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T10:07:31.000-05:00",
    "volume" : "169",
    "pages" : "209-23",
    "abstract" : "A spontaneous inflammatory disease in rats transgenic for HLA-B27 resembles the B27-associated human spondyloarthropathies. Colitis and arthritis, the two most important features, require T cells, gut bacteria, and high expression of B27 in bone marrow-derived cells. Control rats with HLA-B7 remain healthy. Most rats with HLA-Cw6 (associated with psoriasis vulgaris) remain healthy; a minority develop mild and transient disease. Rats with a mutant B27 with a Cys67-->Ser substitution resemble wild-type B27 transgenics, but with a lower prevalence of arthritis. A similar phenotype is seen in B27 rats co-expressing a viral peptide that binds B27. Disease-prone LEW but not F344 B27 rats develop high serum IgA levels concurrent with disease progression. Colitis is associated with high interferon-gamma, arthritis with high interleukin-6. Disease is similar in B27 LEW, F344, and PVG rats, but the DA background is protective. Conclusions: The spondyloarthropathy-like disease in rats is specific for HLA-B27 but does not require Cys67. Arthritis but not colitis is particularly sensitive to B27 peptide-binding specificity. Genetic background exerts a strong influence, but some phenotypic differences exist between permissive strains that do not influence disease susceptibility. The data favor a role for B27 peptide presentation in arthritis, but other mechanisms to explain the role of B27 have not been excluded.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JD",
      "lastName" : "Taurog",
      "authorRank" : 1,
      "name" : "Taurog JD",
      "referenceId" : "RGD:A35298"
    }, {
      "firstName" : "SD",
      "lastName" : "Maika",
      "authorRank" : 2,
      "name" : "Maika SD",
      "referenceId" : "RGD:A35299"
    }, {
      "firstName" : "N",
      "lastName" : "Satumtira",
      "authorRank" : 3,
      "name" : "Satumtira N",
      "referenceId" : "RGD:A35300"
    }, {
      "firstName" : "ML",
      "lastName" : "Dorris",
      "authorRank" : 4,
      "name" : "Dorris ML",
      "referenceId" : "RGD:A35301"
    }, {
      "firstName" : "IL",
      "lastName" : "McLean",
      "authorRank" : 5,
      "name" : "McLean IL",
      "referenceId" : "RGD:A35302"
    }, {
      "firstName" : "H",
      "lastName" : "Yanagisawa",
      "authorRank" : 6,
      "name" : "Yanagisawa H",
      "referenceId" : "RGD:A35303"
    }, {
      "firstName" : "A",
      "lastName" : "Sayad",
      "authorRank" : 7,
      "name" : "Sayad A",
      "referenceId" : "RGD:A35304"
    }, {
      "firstName" : "AJ",
      "lastName" : "Stagg",
      "authorRank" : 8,
      "name" : "Stagg AJ",
      "referenceId" : "RGD:A35305"
    }, {
      "firstName" : "GM",
      "lastName" : "Fox",
      "authorRank" : 9,
      "name" : "Fox GM",
      "referenceId" : "RGD:A30910"
    }, {
      "firstName" : "A",
      "lastName" : "Le O'Brien",
      "authorRank" : 10,
      "name" : "Le O'Brien A",
      "referenceId" : "RGD:A35306"
    }, {
      "firstName" : "M",
      "lastName" : "Rehman",
      "authorRank" : 11,
      "name" : "Rehman M",
      "referenceId" : "RGD:A35307"
    }, {
      "firstName" : "M",
      "lastName" : "Zhou",
      "authorRank" : 12,
      "name" : "Zhou M",
      "referenceId" : "RGD:A13022"
    }, {
      "firstName" : "AL",
      "lastName" : "Weiner",
      "authorRank" : 13,
      "name" : "Weiner AL",
      "referenceId" : "RGD:A35308"
    }, {
      "firstName" : "JB",
      "lastName" : "Splawski",
      "authorRank" : 14,
      "name" : "Splawski JB",
      "referenceId" : "RGD:A35309"
    }, {
      "firstName" : "JA",
      "lastName" : "Richardson",
      "authorRank" : 15,
      "name" : "Richardson JA",
      "referenceId" : "RGD:A14041"
    }, {
      "firstName" : "RE",
      "lastName" : "Hammer",
      "authorRank" : 16,
      "name" : "Hammer RE",
      "referenceId" : "RGD:A14042"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:731214"
    } ]
  }, {
    "primaryId" : "PMID:10450539",
    "title" : "Etofibrate decreases factor VII and fibrinogen levels in patients with polymetabolic syndrome.",
    "datePublished" : "1000-08-01T00:00:00.000-06:00",
    "citation" : "Jastrzebska M, etal., Int J Clin Pharmacol Res. 1999;19(1):19-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-08-11T12:55:10.000-05:00",
    "volume" : "19",
    "pages" : "19-25",
    "abstract" : "Etofibrate is a hypolipemic drug belonging to the fibrate class. By improving the lipid profile, these drugs often exert a favorable influence on hemostatic risk factors of ischemic heart disease. We present a pilot study on the influence of etofibrate on lipids and lipoproteins in serum, as well as on factor VII and fibrinogen. The study group was comprised of 18 males, aged 52.5 +/- 7.3 years, with hypertriglyceridemia or mixed hyperlipoproteinemia and other risk factors of atherosclerosis, particularly insulin-dependent diabetes and arterial hypertension. The group was further divided into two subgroups depending on the coexistence of arterial hypertension. All patients received etofibrate 500 mg daily for 3 months. In comparison with initial values, a decrease in the following was noted for the whole study group: triglyceride level (226.0 +/- 27.1 vs. 288.0 +/- 51.9 mg/dl; p < 0.05), percent LDL-cholesterol (72.4 +/- 1.8 vs. 75.8 +/- 1.7; p < 0.05), apolipoprotein B (111.2 +/- 4.6 vs. 115.3 +/- 5.4 mg/dl; p < 0.05), atherogenic indices: LDL/HDL (5.06 +/- 0.58 vs. 5.95 +/- 0.50; p < 0.02) and apolipoprotein B and A (apoB/apoA) (0.92 +/- 0.04 vs. 1.02 +/- 0.06; p < 0.05). There was an increase in percent HDL-cholesterol (14.7 +/- 1.1 vs. 12.8 +/- 0.7; p < 0.05) and apoA (121.0 +/- 4.8 vs. 111.2 +/- 2.4 mg/dl; p < 0.05). A marked decrease in the level of factor VII (FVIIc) (114 +/- 5.9 vs. 136 +/- 5.3%; p < 0.001) and fibrinogen (2.95 +/- 0.17 vs. 3.58 +/- 0.17 g/l; p < 0.01) was found. Fibrinogen levels fell notably (3.09 +/- 0.30 vs. 3.87 +/- 0.34 g/l; p < 0.05) in the subgroup with arterial hypertension, and F1 + 2 markers tended to decline (2.32 +/- 0.53 vs. 2.74 +/- 0.37 nmol/l; NS). Patients with normals arterial pressure maintained their fibrinogen levels (3.23 +/- 0.24 vs. 3.36 +/- 0.26 g/l; NS). A positive correlation between FVIIc and F1 + 2 was observed during treatment. All results were expressed as arithmetic means +/- SE. The present study has demonstrated that etofibrate has hypolipemic, antithrombotic and antiatherosclerotic properties in patients with polymetabolic syndrome.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Jastrzebska",
      "authorRank" : 1,
      "name" : "Jastrzebska M",
      "referenceId" : "RGD:A110643"
    }, {
      "firstName" : "B",
      "lastName" : "Torbus-Lisiecka",
      "authorRank" : 2,
      "name" : "Torbus-Lisiecka B",
      "referenceId" : "RGD:A110644"
    }, {
      "firstName" : "J",
      "lastName" : "Pieczul-Mroz",
      "authorRank" : 3,
      "name" : "Pieczul-Mroz J",
      "referenceId" : "RGD:A110645"
    }, {
      "firstName" : "K",
      "lastName" : "Chelstowski",
      "authorRank" : 4,
      "name" : "Chelstowski K",
      "referenceId" : "RGD:A110646"
    }, {
      "firstName" : "J",
      "lastName" : "Kopciewicz",
      "authorRank" : 5,
      "name" : "Kopciewicz J",
      "referenceId" : "RGD:A110647"
    }, {
      "firstName" : "M",
      "lastName" : "Naruszewicz",
      "authorRank" : 6,
      "name" : "Naruszewicz M",
      "referenceId" : "RGD:A110648"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2312402"
    } ]
  }, {
    "primaryId" : "PMID:10450801",
    "title" : "The expression of CD59 in experimental allergic neuritis.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Vedeler CA, etal., J Neurol Sci. 1999 Jun 1;165(2):154-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-09T16:22:44.000-06:00",
    "volume" : "165",
    "pages" : "154-9",
    "abstract" : "Complement is implicated as an effector in inflammatory demyelination occurring in Guillain-Barre syndrome (GBS) and in experimental allergic neuritis (EAN). CD59, a potent complement regulatory protein that inhibits the formation of the terminal cytolytic membrane attack complex (MAC), is expressed on human and rat Schwann cells. In EAN the expression of CD59 was increased on Schwann cells during demyelination and axonal degeneration, evaluated by immunostaining of nerve sections and teased fibres. Mac-1 (CD11b) positive leukocytes were localized close to the Schwann cells showing enhanced CD59 staining. The increased CD59 expression in EAN could therefore be due to the release of cytokines or other immunoregulatory molecules from the inflammatory cells. However, interferon gamma (IFN-gamma) or tumor necrosis factor alfa (TNF-alpha) did not upregulate the expression of CD59 on rat Schwann cells in culture. The increased expression of CD59 in EAN is likely to be important in the protection of Schwann cells from MAC.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CA",
      "lastName" : "Vedeler",
      "authorRank" : 1,
      "name" : "Vedeler CA",
      "referenceId" : "RGD:A77390"
    }, {
      "firstName" : "G",
      "lastName" : "Conti",
      "authorRank" : 2,
      "name" : "Conti G",
      "referenceId" : "RGD:A61821"
    }, {
      "firstName" : "T",
      "lastName" : "Fujioka",
      "authorRank" : 3,
      "name" : "Fujioka T",
      "referenceId" : "RGD:A71204"
    }, {
      "firstName" : "E",
      "lastName" : "Scarpini",
      "authorRank" : 4,
      "name" : "Scarpini E",
      "referenceId" : "RGD:A61822"
    }, {
      "firstName" : "A",
      "lastName" : "Rostami",
      "authorRank" : 5,
      "name" : "Rostami A",
      "referenceId" : "RGD:A26183"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600494"
    } ]
  }, {
    "primaryId" : "PMID:10450867",
    "title" : "Dysmorphic phenotype and neurological impairment in 22 retinoblastoma patients with constitutional cytogenetic 13q deletion.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Baud O, etal., Clin Genet. 1999 Jun;55(6):478-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-12-07T20:14:04.000-06:00",
    "volume" : "55",
    "pages" : "478-82",
    "abstract" : "We describe the facial dysmorphic phenotype and the neurological development of a series of 22 retinoblastoma patients sharing a cytogenetically detectable 13q deletion in a retrospective and longitudinal study. In most of the cases, high-resolution banding analysis, morphological analysis, and assessment for neurodevelopmental outcome, as well for organ malformations, were performed. Chromosomal rearrangement involving the RB1 gene included 20 13q interstitial deletions (including 16 de novo deletions) and two (de novo translocations. The most prominent dysmorphic abnormalities were anteverted ear lobes (90%), a high and broad forehead (85%), and a prominent philtrum (65%). This phenotype was associated with severe mental retardation and/or motor impairment at age 2 years  in 69% of patients and correlated with the size and the location of the 13q deletion. The survival rate of our series (91%) was not different from that usually seen in retinoblastoma patients.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "O",
      "lastName" : "Baud",
      "authorRank" : 1,
      "name" : "Baud O",
      "referenceId" : "RGD:A46952"
    }, {
      "firstName" : "V",
      "lastName" : "Cormier-Daire",
      "authorRank" : 2,
      "name" : "Cormier-Daire V",
      "referenceId" : "RGD:A57109"
    }, {
      "firstName" : "S",
      "lastName" : "Lyonnet",
      "authorRank" : 3,
      "name" : "Lyonnet S",
      "referenceId" : "RGD:A72674"
    }, {
      "firstName" : "L",
      "lastName" : "Desjardins",
      "authorRank" : 4,
      "name" : "Desjardins",
      "referenceId" : "RGD:A180486"
    }, {
      "firstName" : "C",
      "lastName" : "Turleau",
      "authorRank" : 5,
      "name" : "Turleau",
      "referenceId" : "RGD:A278587"
    }, {
      "firstName" : "F",
      "lastName" : "Doz",
      "authorRank" : 6,
      "name" : "Doz",
      "referenceId" : "RGD:A180487"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11568322"
    } ]
  }, {
    "primaryId" : "PMID:10451024",
    "title" : "Biochemical characterization of recombinant serotonin N-acetyltransferase.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Zhan-Poe X and Craft CM, J Pineal Res. 1999 Aug;27(1):49-58.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-09-23T16:42:52.000-05:00",
    "volume" : "27",
    "pages" : "49-58",
    "abstract" : "Pineal and retinal melatonin synthesis is controlled by the enzymatic activity of arylalkylamine N-acetyltransferase (AA-NAT, EC 2.3.1.87), which is regulated by light/dark signals and circadian factors. This enzyme converts serotonin to N-acetylserotonin by the transfer of an acetyl group from acetyl coenzyme A. Endogenous AA-NAT instability during routine purification has made enzyme characterization difficult, but now a stable recombinant protein for AA-NAT has been synthesized to investigate the intrinsic biochemical properties of AA-NAT from a rat pineal cDNA encoding a 205 amino acid, 23 kilodalton protein, by using a glutathione-S-transferase (GST) fusion protein system. Recombinant GST-AA-NAT showed substrate specificity for arylalkylamines and stability at 4 degrees C; however, the enzyme activity was reduced by 40% upon preincubation at 37 degrees C for 2 hr. GST-AA-NAT is preferentially phosphorylated by either cyclic AMP- or cyclic GMP-dependent kinases in vitro, but no detrimental effect was observed on AA-NAT enzymatic activity. Among the metal cations tested in this study, Ca2+, Mg2+, Mn2+, Fe2+, and Co2 showed little or no inhibitory potency, while either 1 mM Zn2+ or 0.1 mM Cu2+ nearly abolished the enzymatic activity. GST-AA-NAT enzyme activity is also inhibited by reagents that are known biochemically to modify thiol groups (N-ethylmaleimide, NEM) and histidine residues (p-chloromercuribenzoate, NBS and diethyl pyrocarbonate, DEPC), suggesting the presence of essential cysteine and histidine moieties. Moreover, preincubation of acetyl CoA completely protects the recombinant AA-NAT from inactivation by NEM and DEPC, indicating that specific cysteine and histidine residues may be at the acetylation site. The conclusion is that the biochemical properties of rat recombinant AA-NAT is similar to the endogenous pineal and retinal AA-NAT with respect to the sensitivity to temperature, metal cations, as well as the thiol modification reagents. These data also suggest that the phosphorylation status of the AA-NAT does not affect enzymatic activity directly, and histidine residues are potentially important residues required for high catalytic activity.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Zhan-Poe",
      "authorRank" : 1,
      "name" : "Zhan-Poe X",
      "referenceId" : "RGD:A100302"
    }, {
      "firstName" : "CM",
      "lastName" : "Craft",
      "authorRank" : 2,
      "name" : "Craft CM",
      "referenceId" : "RGD:A10128"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301041"
    } ]
  }, {
    "primaryId" : "PMID:10451362",
    "title" : "The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Newberry EP, etal., Biochemistry. 1999 Aug 17;38(33):10678-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-06-20T13:33:18.000-05:00",
    "volume" : "38",
    "pages" : "10678-90",
    "abstract" : "Msx2 is a homeodomain transcriptional repressor that exerts tissue-specific actions during craniofacial skeletal and neural development. To identify coregulatory molecules that participate in transcriptional repression by Msx2, we applied a Farwestern expression cloning strategy to identify transcripts encoding proteins that bind Msx2. A lambdagt11 expression library from mouse brain was screened with radiolabeled GST-Msx2 fusion protein encompassing the core suppressor domain of Msx2. A cDNA was isolated that encodes a novel protein fragment that binds radiolabeled Msx2. Homeoprotein binding activity was confirmed by Farwestern analysis of the T7-epitope-tagged recombinant protein fragment, and interactions in vitro require Msx2 residues necessary for transcriptional suppression in vivo. On the basis of biochemical analyses, this novel protein was named MINT, an acronym for Msx2-interacting nuclear target protein. The original clone is part of a 12.6 kb transcript expressed at high levels in testis and at lower levels in calvarial osteoblasts and brain. Multiple clones isolated from a mouse testis library were sequenced to construct a MINT cDNA contig of 11 kb. Starting from an initiator Met in good Kozak context, a large nascent polypeptide of 3576 amino acids is predicted, in contiguous open reading frame with the Msx2 interaction domain residues 2070-2394. Protein sequence analysis reveals that MINT has three N-terminal RNA recognition motifs (RRMs) and four nuclear localization signals. Western blot analysis of fractionated cell extracts reveals that mature approximately 110 kDa (N-terminal) and approximately 250 kDa (C-terminal) MINT protein fragments accumulate in chromatin and nuclear matrix fractions, cosegregating with Msx2 and topoisomerase II. In gel shift assays, the MINT RRM domain selectively binds T- and G-rich DNA sequences; this includes a large G/T-rich inverted repeat element present in the proximal rat osteocalcin (OC) promoter, overlapping three cognates that support OC expression in osteoblasts. MINT and OC mRNAs are reciprocally regulated during differentiation of MC3T3E1 calvarial osteoblasts. Consistent with its proposed role as a nuclear transcriptional factor, transient expression of MINT(1-812) suppresses the FGF/forskolin-activated OC promoter, does not significantly regulate CMV promoter activity, but markedly upregulates the HSV thymidine kinase promoter in MC3T3E1 cells. In toto, these data indicate that the novel nuclear protein MINT binds the homeoprotein Msx2 and coregulates OC during craniofacial development. Msx2 and MINT both target an information-dense, osteoblast-specific regulatory region of the OC proximal promoter, nucleotides -141 to -111. The N-terminal MINT RRM domain represents an authentic dsDNA binding module for this novel vertebrate nuclear matrix protein. Acting as a scaffold protein, MINT potentially exerts both positive and negative regulatory actions by organizing transcriptional complexes in the nuclear matrix.",
    "issueName" : "33",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "EP",
      "lastName" : "Newberry",
      "authorRank" : 1,
      "name" : "Newberry EP",
      "referenceId" : "RGD:A60752"
    }, {
      "firstName" : "T",
      "lastName" : "Latifi",
      "authorRank" : 2,
      "name" : "Latifi T",
      "referenceId" : "RGD:A60753"
    }, {
      "firstName" : "DA",
      "lastName" : "Towler",
      "authorRank" : 3,
      "name" : "Towler DA",
      "referenceId" : "RGD:A23589"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580033"
    } ]
  }, {
    "primaryId" : "PMID:10451498",
    "title" : "DNA damage and p21(WAF1/CIP1/SDI1) in experimental injury of the rat adrenal cortex and trauma-associated damage of the human adrenal cortex.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Didenko VV, etal., J Pathol. 1999 Sep;189(1):119-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-05-28T15:16:18.000-05:00",
    "volume" : "189",
    "pages" : "119-26",
    "abstract" : "In vivo models are needed to study the reactions of tissues to DNA damage, such as the induction of the cyclin-dependent kinase inhibitor p21, indicating potential repair of the damage, versus apoptosis, indicating the elimination of the damaged cells. Damage to DNA occurs in tissues during shock, sepsis, and other critical medical conditions. Previous studies have found evidence of damage to the cortex of adrenal glands from organ donors who had undergone severe trauma prior to death. The present experiment studied rats under experimental interventions of clinical relevance to patients with conditions that put them at  risk for damage to the adrenal glands. These interventions comprised ischaemia and reperfusion injury, sepsis following caecal ligation and puncture, acute pancreatitis, and administration of chemical agents (zymosan and acrylonitrile).  All the interventions caused an increase in p21 mRNA as assessed by northern blotting and in situ hybridization. Increased nuclear p21 protein was shown by immunohistochemistry. All the interventions caused damage to DNA, as shown by labelling of available 3' termini of single-strand breaks with terminal transferase. The number of cells undergoing apoptosis, visualized by ligation of  a hairpin oligonucleotide probe to double-strand breaks in DNA, was much lower. In rat adrenal glands, apoptotic cells were infrequent under all the conditions studied. They were more abundant in human organ donor adrenal glands that were previously shown to have extensive DNA damage accompanied by induction of p21. The similarity of the effects of a wide variety of surgical interventions and chemical agents suggest a common pathophysiological mechanism which is not specific to the initiating injury. Experimental injury of the rat adrenal cortex  provides a model for investigating the role of organ DNA damage and of mediators  of the response to DNA damage, such as p21.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "VV",
      "lastName" : "Didenko",
      "authorRank" : 1,
      "name" : "Didenko",
      "referenceId" : "RGD:A202447"
    }, {
      "firstName" : "X",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang",
      "referenceId" : "RGD:A416757"
    }, {
      "firstName" : "L",
      "lastName" : "Yang",
      "authorRank" : 3,
      "name" : "Yang",
      "referenceId" : "RGD:A415820"
    }, {
      "firstName" : "PJ",
      "lastName" : "Hornsby",
      "authorRank" : 4,
      "name" : "Hornsby",
      "referenceId" : "RGD:A202450"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10043817"
    } ]
  }, {
    "primaryId" : "PMID:10451700",
    "title" : "A somatic BRCA2 mutation in RER+ endometrial carcinomas that specifically deletes the amino-terminal transactivation domain.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Koul A, etal., Genes Chromosomes Cancer. 1999 Mar;24(3):207-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-06-23T17:38:02.000-05:00",
    "volume" : "24",
    "pages" : "207-12",
    "abstract" : "Mismatch repair deficiency and replication errors (RERs) occur in approximately 20% of sporadic endometrial carcinomas. Frameshift mutations in several cancer predisposing genes, especially in their mononucleotide repeats, are seen in RER+ tumors. In a survey of hereditary breast cancer genes in gynecological cancer, we analyzed the entire coding sequence of BRCA1 and BRCA2 in 51 endometrial tumors, of which 12 were RER+. Seven somatic mutations were identified in six (50%) of the RER+ tumors, but none in RER- tumors. A novel base pair deletion at a (T)10 tract in BRCA2 intron 2, causing an in-frame splice deletion of exon 3, was observed in four tumors, one of which contained a second, truncating BRCA2 mutation. Two tumors exhibited frameshift mutations at polyA tracts in BRCA1 and BRCA2 exon 11, both predicted to result in premature translation termination. Whereas most mutations in BRCA1 and BRCA2 are known to affect the more carboxy-terminal regions interacting with RAD51, and the transactivating BRCT domains of BRCA1, this is the first demonstration of a recurrent BRCA2 mutation that specifically deletes the amino-terminal transactivation domain. Moreover, our results suggest that somatic mutations in BRCA2(and to some extent BRCA1) may confer a growth advantage in RER+ endometrial carcinomas.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Koul",
      "authorRank" : 1,
      "name" : "Koul A",
      "referenceId" : "RGD:A97495"
    }, {
      "firstName" : "M",
      "lastName" : "Nilbert",
      "authorRank" : 2,
      "name" : "Nilbert M",
      "referenceId" : "RGD:A97496"
    }, {
      "firstName" : "A",
      "lastName" : "Borg",
      "authorRank" : 3,
      "name" : "Borg A",
      "referenceId" : "RGD:A36538"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2296027"
    } ]
  }, {
    "primaryId" : "PMID:10451707",
    "title" : "Allelic imbalance in chromosome band 18q21 and SMAD4 mutations in ovarian cancers.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Takakura S, etal., Genes Chromosomes Cancer. 1999 Mar;24(3):264-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-08-22T17:05:28.000-05:00",
    "volume" : "24",
    "pages" : "264-71",
    "abstract" : "Recently, three candidate tumor suppressor genes, SMAD2 (MADR2/JV18-1), SMAD4 (DPC4), and DCC, were identified in chromosome band 18q21. We examined allelic imbalance (AI) in 18q21 using six polymorphic microsatellite markers in 38 primary ovarian cancers and four ovarian borderline tumors. AI at one or more loci was detected in 15 of 37 (41%) informative ovarian cancers and in none of the four borderline tumors. Frequent AI was detected at the D18S46 (31%) and D18S474 (36%) loci, which were adjacent to the SMAD4 gene, and at the D18S69 (33%) locus, which was telomeric to the DCC gene. Therefore, we searched for mutations of the SMAD4 gene in 42 primary tumors and eight cell lines by PCR-SSCP and sequencing analyses. Missense mutations were detected in two ovarian tumors and three ovarian cancer cell lines, whereas silent mutation was detected in a primary ovarian cancer. These results suggest that there are at least two tumor suppressor genes on chromosome arm 18q and that SMAD4 is of importance in ovarian tumorigenesis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Takakura",
      "authorRank" : 1,
      "name" : "Takakura S",
      "referenceId" : "RGD:A83994"
    }, {
      "firstName" : "A",
      "lastName" : "Okamoto",
      "authorRank" : 2,
      "name" : "Okamoto A",
      "referenceId" : "RGD:A97501"
    }, {
      "firstName" : "M",
      "lastName" : "Saito",
      "authorRank" : 3,
      "name" : "Saito M",
      "referenceId" : "RGD:A24865"
    }, {
      "firstName" : "T",
      "lastName" : "Yasuhara",
      "authorRank" : 4,
      "name" : "Yasuhara T",
      "referenceId" : "RGD:A99391"
    }, {
      "firstName" : "H",
      "lastName" : "Shinozaki",
      "authorRank" : 5,
      "name" : "Shinozaki H",
      "referenceId" : "RGD:A99392"
    }, {
      "firstName" : "S",
      "lastName" : "Isonishi",
      "authorRank" : 6,
      "name" : "Isonishi S",
      "referenceId" : "RGD:A99393"
    }, {
      "firstName" : "T",
      "lastName" : "Yoshimura",
      "authorRank" : 7,
      "name" : "Yoshimura T",
      "referenceId" : "RGD:A99394"
    }, {
      "firstName" : "Y",
      "lastName" : "Ohtake",
      "authorRank" : 8,
      "name" : "Ohtake Y",
      "referenceId" : "RGD:A17916"
    }, {
      "firstName" : "K",
      "lastName" : "Ochiai",
      "authorRank" : 9,
      "name" : "Ochiai K",
      "referenceId" : "RGD:A99395"
    }, {
      "firstName" : "T",
      "lastName" : "Tanaka",
      "authorRank" : 10,
      "name" : "Tanaka T",
      "referenceId" : "RGD:A404001"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2299976"
    } ]
  }, {
    "primaryId" : "PMID:10452877",
    "title" : "Acute portal hypertension increases ileal vulnerability to platelet-activating factor in rats.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Sakaguchi T, etal., J Surg Res. 1999 Sep;86(1):116-22. doi: 10.1006/jsre.1999.5697.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-08-19T10:50:14.000-05:00",
    "volume" : "86",
    "pages" : "116-22",
    "abstract" : "<br><b>BACKGROUND: </b>Patients with portal hypertension can easily develop sepsis of enteric origin after suffering severe trauma and hemorrhagic shock. Platelet-activating factor (PAF) is one of the key mediators of such stress. The aim of this study was to investigate whether portal hypertension increases the vulnerability of the ileum to PAF.<br><b>MATERIALS AND METHODS: </b>Seven days after surgery, PAF (1.5 microg/kg) was intravenously injected into portal stenosis (PS) rats and sham-operated rats. The levels of tumor necrosis factor-alpha (TNF-alpha), cytokine-induced neutrophil chemoattractant (CINC), and endotoxin in portal plasma were determined. The levels of PAF receptor (PAFR), TNF-alpha, and CINC mRNA in the ileum were also investigated.<br><b>RESULTS: </b>After PAF administration, PS rats showed (1) significantly higher portal plasma levels of TNF-alpha, CINC, and endotoxin; (2) higher histological damage scores in the ileum; (3) more infiltrating neutrophils in the ileum; and (4) a significantly higher mortality rate than sham-operated rats (P < 0.01). However, PAFR mRNA levels were similar in the two groups. The CINC mRNA level in the ileum of PS rats was increased from 1 to 4 h after PAF administration, while that of the sham-operated rats was transiently increased at 1 h.<br><b>CONCLUSIONS: </b>Portal hypertension increases the vulnerability of the ileum to PAF. These findings suggest that conditions which causes PAF production may be dangerous in patients with portal hypertension.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Sakaguchi",
      "authorRank" : 1,
      "name" : "Sakaguchi T",
      "referenceId" : "RGD:A136384"
    }, {
      "firstName" : "S",
      "lastName" : "Nakamura",
      "authorRank" : 2,
      "name" : "Nakamura S",
      "referenceId" : "RGD:A161688"
    }, {
      "firstName" : "S",
      "lastName" : "Suzuki",
      "authorRank" : 3,
      "name" : "Suzuki S",
      "referenceId" : "RGD:A9090"
    }, {
      "firstName" : "T",
      "lastName" : "Oda",
      "authorRank" : 4,
      "name" : "Oda T",
      "referenceId" : "RGD:A16565"
    }, {
      "firstName" : "A",
      "lastName" : "Ichiyama",
      "authorRank" : 5,
      "name" : "Ichiyama A",
      "referenceId" : "RGD:A16568"
    }, {
      "firstName" : "S",
      "lastName" : "Baba",
      "authorRank" : 6,
      "name" : "Baba S",
      "referenceId" : "RGD:A35966"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:38508900"
    } ]
  }, {
    "primaryId" : "PMID:10452880",
    "title" : "Early detection of apoptosis and fas ligand expression in hepatic graft-versus-host disease after rat small bowel transplantation.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Shiraishi M, etal., J Surg Res. 1999 Sep;86(1):136-44. doi: 10.1006/jsre.1999.5706.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-08-09T14:40:37.000-05:00",
    "volume" : "86",
    "pages" : "136-44",
    "abstract" : "<br><b>BACKGROUND: </b>The liver is one of the primary targets of acute graft-versus-host disease (GVHD), which is the principal complication that occurs after allogeneic intestinal transplantation. The purpose of this study is to investigate the involvement of the Fas/Fas ligand system in hepatic GVHD after rat semiallogeneic intestinal transplantation.<br><b>MATERIALS AND METHODS: </b>Liver samples were serially harvested from LEW x BN F(1) (LBNF(1)) recipients of either LEW heterotopic intestinal allografts (group 1) or LBNF(1) isografts (group 2), on Days 1, 3, 5, 9, and 13 posttransplant.<br><b>RESULTS: </b>In group 1, hepatic injuries as assessed by either serum aspartate aminotransferase (AST) level, alanine aminotransferase (ALT) level, or cellular infiltration on HE staining became apparent after Day 13. The incidence of apoptosis, examined by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL), was observed to steadily increase in the liver from Day 5 accompanied by a progression of GVHD: 17.5 +/- 3.1 and 3.1 +/- 0.4 cells/field (200x) in groups 1 and 2, respectively. In an immunohistochemical study, Fas was constitutively expressed in the liver in both groups, while Fas ligand was expressed most extensively on Day 13 in group 1. Immunoreactivity of both Fas and Fas ligand was observed in hepatocytes, in addition to leukocytes. Analysis by reverse transcription polymerase chain reaction also revealed the expression of Fas mRNA to be constitutive in both groups, while that of Fas ligand mRNA increased significantly from Day 5 and peaked on Day 13 in group 1, and the expression was 10 times stronger than that for isogeneic combination (group 2).<br><b>CONCLUSION: </b>Early detection of upregulated Fas ligand and increased apoptosis is thus considered to be potentially a useful tool for the diagnosis of hepatic GVHD.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Shiraishi",
      "authorRank" : 1,
      "name" : "Shiraishi M",
      "referenceId" : "RGD:A74907"
    }, {
      "firstName" : "S",
      "lastName" : "Hiroyasu",
      "authorRank" : 2,
      "name" : "Hiroyasu S",
      "referenceId" : "RGD:A472517"
    }, {
      "firstName" : "T",
      "lastName" : "Oshiro",
      "authorRank" : 3,
      "name" : "Oshiro T",
      "referenceId" : "RGD:A472518"
    }, {
      "firstName" : "M",
      "lastName" : "Nagahama",
      "authorRank" : 4,
      "name" : "Nagahama M",
      "referenceId" : "RGD:A15360"
    }, {
      "firstName" : "H",
      "lastName" : "Tomori",
      "authorRank" : 5,
      "name" : "Tomori H",
      "referenceId" : "RGD:A472519"
    }, {
      "firstName" : "T",
      "lastName" : "Mamadi",
      "authorRank" : 6,
      "name" : "Mamadi T",
      "referenceId" : "RGD:A472520"
    }, {
      "firstName" : "Y",
      "lastName" : "Muto",
      "authorRank" : 7,
      "name" : "Muto Y",
      "referenceId" : "RGD:A17509"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14700681"
    } ]
  }, {
    "primaryId" : "PMID:10453035",
    "title" : "Inducible expression and regulation of the alpha 1-acid glycoprotein gene by alveolar macrophages: prostaglandin E2 and cyclic AMP act as new positive stimuli.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Fournier T, etal., J Immunol. 1999 Sep 1;163(5):2883-90.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-02-18T17:12:36.000-06:00",
    "volume" : "163",
    "pages" : "2883-90",
    "abstract" : "We have reported that alpha 1-acid glycoprotein (AGP) gene expression was induced in lung tissue and in alveolar type II cells during pulmonary inflammatory processes, suggesting that local production of this immunomodulatory protein might contribute to the modulation of inflammation within the alveolar space. Because AGP may also be secreted by other cell types in the alveolus, we have investigated the expression and the regulation of the AGP gene in human and rat alveolar macrophages. Spontaneous AGP secretion by alveolar macrophages was increased 4-fold in patients with interstitial lung involvement compared with that in controls. In the rat, immunoprecipitation of [35S]methionine-labeled cell lysates showed that alveolar macrophages synthesize and secrete AGP. IL-1 beta had no effect by itself, but potentiated the dexamethasone-induced increase in AGP production. RNase protection assay demonstrated that AGP mRNA, undetectable in unstimulated cells, was induced by dexamethasone. Conditioned medium from LPS-stimulated macrophages as well as IL-1 beta had no effect by themselves, but potentiated the dexamethasone-induced increase in AGP mRNA levels. In addition to cytokines, PGE2 as well as dibutyryl cAMP increased AGP mRNA levels in the presence of dexamethasone. When AGP expression in other cells of the monocyte/macrophage lineage was examined, weak and no AGP production by human blood monocytes and by rat peritoneal macrophages, respectively, were observed. Our data showed that 1) AGP expression is inducible specifically in alveolar macrophages in vivo and in vitro; and 2) PGE2 and cAMP act as new positive stimuli for AGP gene expression.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Fournier",
      "authorRank" : 1,
      "name" : "Fournier T",
      "referenceId" : "RGD:A13228"
    }, {
      "firstName" : "N",
      "lastName" : "Bouach",
      "authorRank" : 2,
      "name" : "Bouach N",
      "referenceId" : "RGD:A119489"
    }, {
      "firstName" : "C",
      "lastName" : "Delafosse",
      "authorRank" : 3,
      "name" : "Delafosse C",
      "referenceId" : "RGD:A119490"
    }, {
      "firstName" : "B",
      "lastName" : "Crestani",
      "authorRank" : 4,
      "name" : "Crestani B",
      "referenceId" : "RGD:A119491"
    }, {
      "firstName" : "M",
      "lastName" : "Aubier",
      "authorRank" : 5,
      "name" : "Aubier M",
      "referenceId" : "RGD:A13231"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316645"
    } ]
  }, {
    "primaryId" : "PMID:10453039",
    "title" : "Identification of genes controlling collagen-induced arthritis in mice: striking homology with susceptibility loci previously identified in the rat.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Yang HT, etal., J Immunol 1999 Sep 1;163(5):2916-21.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-07-30T15:23:36.000-05:00",
    "volume" : "163",
    "pages" : "2916-21",
    "abstract" : "The susceptibility to collagen-induced arthritis in the highly susceptible DBA/1 mouse has earlier been shown to be partly controlled by the MHC class II gene Aq. To identify susceptibility loci outside of MHC, we have made crosses between DBA/1 and the less susceptible B10.Q strain, both expressing the MHC class II gene Aq. Analysis of 224 F2 intercross mice with 170 microsatellite markers in a genome-wide scan suggested 4 quantitative trait loci controlling arthritis susceptibility located on chromosomes 6, 7, 8, and 10. The locus on chromosome 6 (Cia6), which was associated with arthritis onset, yielded a logarithm of odds score of 4.7 in the F2 intercross experiment and was reproduced in serial backcross experiments. Surprisingly, the DBA/1 allele had a recessive effect leading to a delay in arthritis onset. The suggestive loci on chromosomes 7 and 10 were associated with arthritis severity rather than onset, and another suggestive locus on chromosome 8 was most closely associated with arthritis incidence. The loci on chromosomes 7, 8, and 10 all appeared to contain disease-promoting alleles derived from the DBA/1 strain. Interestingly, most of the identified loci were situated in chromosomal regions that are homologous to regions in the rat genome containing susceptibility genes for arthritis; the mouse Cia6 locus is homologous with the rat Cia3, Pia5, Pia2, and Aia3; the locus on chromosome 7 (Cia7) is homologous with the rat Cia2; and the locus on chromosome 10 (Cia8) is homologous with the rat Cia4.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HT",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang HT",
      "referenceId" : "RGD:A121048"
    }, {
      "firstName" : "J",
      "lastName" : "Jirholt",
      "authorRank" : 2,
      "name" : "Jirholt J",
      "referenceId" : "RGD:A10733"
    }, {
      "firstName" : "L",
      "lastName" : "Svensson",
      "authorRank" : 3,
      "name" : "Svensson L",
      "referenceId" : "RGD:A10734"
    }, {
      "firstName" : "M",
      "lastName" : "Sundvall",
      "authorRank" : 4,
      "name" : "Sundvall M",
      "referenceId" : "RGD:A19773"
    }, {
      "firstName" : "L",
      "lastName" : "Jansson",
      "authorRank" : 5,
      "name" : "Jansson L",
      "referenceId" : "RGD:A10736"
    }, {
      "firstName" : "U",
      "lastName" : "Pettersson",
      "authorRank" : 6,
      "name" : "Pettersson U",
      "referenceId" : "RGD:A68710"
    }, {
      "firstName" : "R",
      "lastName" : "Holmdahl",
      "authorRank" : 7,
      "name" : "Holmdahl R",
      "referenceId" : "RGD:A144746"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:619595"
    } ]
  }, {
    "primaryId" : "PMID:10453196",
    "title" : "Molecular analysis and diagnosis in Japanese patients with Wilson's disease.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Shimizu N, etal., Pediatr Int. 1999 Aug;41(4):409-13.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:25:40.000-05:00",
    "volume" : "41",
    "pages" : "409-13",
    "abstract" : "BACKGROUND: Wilson's disease is characterized by the toxic accumulation of copper in the liver, brain, cornea and other organs. It is caused by both impaired excretion via the bile and impaired incorporation of copper into ceruloplasmin in the liver. The Wilson's disease gene (ATP7B) has been cloned as a putative copper-transporting P-type ATPase gene. We therefore analysed mutations of ATP7B  in Japanese patients with Wilson's disease. METHODS: Twenty-three Japanese patients with Wilson's disease were investigated. In all patients, the ATP7B coding sequence, including exon-intron junctions, was analysed by restriction endonuclease digestion, mutation detected enhancement gel electrophoresis and/or  direct sequencing analysis of amplified fragments. RESULTS: Thirteen mutations were identified, including seven missense mutations, four detections, one insertion and one exon skipping in the coding region. The most common mutations were 2874deletion(del)C in exon 13 and arginine (Arg)778 leucine (Leu) in exon 8. DISCUSSION: None of the observed mutations, except for 2302insertion(ins)C, have  been previously detected in either European or North American patients. We conclude that the mutation spectrum of Wilson's disease may thus indicate a population-dependent pattern. Based on the population-dependent manner of the occurrence of ATP7B gene mutations, it may be possible to establish a molecular diagnosis system. A molecular diagnosis system is considered to be very effective for making a definitive diagnosis in very young patients and for also detecting carriers.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Shimizu",
      "authorRank" : 1,
      "name" : "Shimizu N",
      "referenceId" : "RGD:A5024"
    }, {
      "firstName" : "H",
      "lastName" : "Nakazono",
      "authorRank" : 2,
      "name" : "Nakazono",
      "referenceId" : "RGD:A272233"
    }, {
      "firstName" : "Y",
      "lastName" : "Takeshita",
      "authorRank" : 3,
      "name" : "Takeshita",
      "referenceId" : "RGD:A206220"
    }, {
      "firstName" : "C",
      "lastName" : "Ikeda",
      "authorRank" : 4,
      "name" : "Ikeda",
      "referenceId" : "RGD:A272234"
    }, {
      "firstName" : "H",
      "lastName" : "Fujii",
      "authorRank" : 5,
      "name" : "Fujii H",
      "referenceId" : "RGD:A19044"
    }, {
      "firstName" : "A",
      "lastName" : "Watanabe",
      "authorRank" : 6,
      "name" : "Watanabe A",
      "referenceId" : "RGD:A78981"
    }, {
      "firstName" : "Y",
      "lastName" : "Yamaguchi",
      "authorRank" : 7,
      "name" : "Yamaguchi Y",
      "referenceId" : "RGD:A5502"
    }, {
      "firstName" : "H",
      "lastName" : "Hemmi",
      "authorRank" : 8,
      "name" : "Hemmi",
      "referenceId" : "RGD:A272235"
    }, {
      "firstName" : "H",
      "lastName" : "Shimatake",
      "authorRank" : 9,
      "name" : "Shimatake",
      "referenceId" : "RGD:A272236"
    }, {
      "firstName" : "T",
      "lastName" : "Aoki",
      "authorRank" : 10,
      "name" : "Aoki T",
      "referenceId" : "RGD:A9876"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068860"
    } ]
  }, {
    "primaryId" : "PMID:10453197",
    "title" : "The Long-Evans Cinnamon rat: an animal model for Wilson's disease.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Terada K and Sugiyama T, Pediatr Int. 1999 Aug;41(4):414-8. doi: 10.1046/j.1442-200x.1999.01089.x.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-05-01T10:39:36.000-05:00",
    "volume" : "41",
    "pages" : "414-8",
    "abstract" : "The Long-Evans Cinnamon (LEC) rat is known to develop hepatitis and liver cancer spontaneously, phenomena attributed to abnormal copper metabolism. This mutant strain of rat shows some clinical features that are similar to those of Wilson's disease, including excessive copper in the liver, reduced excretion of copper into bile, a reduced level of serum copper and a remarkable decrease in serum ceruloplasmin activity. Molecular studies have revealed that the copper transporting P-type ATPase, atp7b, which is the rat gene homologous to human ATP7B, was found to be defective in the LEC rat. These observations have confirmed that the LEC rat is a rodent model for Wilson's disease. In addition, recent studies have suggested that the ATP7B protein is involved in the intracellular transport of hepatic copper. The absence or diminution of ATP7B function results in abnormal copper metabolism in the LEC rat and in patients with Wilson's disease.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Terada",
      "authorRank" : 1,
      "name" : "Terada K",
      "referenceId" : "RGD:A46176"
    }, {
      "firstName" : "T",
      "lastName" : "Sugiyama",
      "authorRank" : 2,
      "name" : "Sugiyama T",
      "referenceId" : "RGD:A16566"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:25823146"
    } ]
  }, {
    "primaryId" : "PMID:10453732",
    "title" : "NME6: a new member of the nm23/nucleoside diphosphate kinase gene family located on human chromosome 3p21.3.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Mehus JG, etal., Hum Genet 1999 Jun;104(6):454-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-04-10T11:27:24.000-05:00",
    "volume" : "104",
    "pages" : "454-9",
    "abstract" : "The NME (nm23/nucleoside diphosphate kinase) gene family in human is involved in the phosphorylation of nucleoside diphosphates and a variety of regulatory phenomena associated with development, oncogenic transformation, and metastasis. Here we report the cDNA sequence for a sixth member of this family, NME6. The cDNA sequence predicts a 186-residue protein that includes the characteristic active site motif of a nucleoside diphosphate (NDP) kinase, as well as the other residues previously identified as crucial for nucleotide binding and catalysis. The NME6 protein sequence is only 34-41% identical to the five previously reported human NME proteins, and is similarly related to prokaryotic and primitive eukaryotic NDP kinases. Compared to typical proteins of this family such as NME1 and NME2, NME6 has three additional residues located in the Kpn loop, and a 22-residue extension at the COOH-terminal. Using radiation hybrid mapping, the NME6 gene was localized to chromosome 3p21.3. The 1.3-kb transcript of NME6 is expressed at a moderately low level in many human tissues, and is most abundant in kidney, prostate, ovary, intestine, and spleen. Homologous cDNAs were also cloned and sequenced for rat and mouse. The sequence of the first 171 residues of the mouse homologue (Nm23-M6) is 94% identical to the deduced human NME6 protein.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JG",
      "lastName" : "Mehus",
      "authorRank" : 1,
      "name" : "Mehus JG",
      "referenceId" : "RGD:A141162"
    }, {
      "firstName" : "P",
      "lastName" : "Deloukas",
      "authorRank" : 2,
      "name" : "Deloukas P",
      "referenceId" : "RGD:A298695"
    }, {
      "firstName" : "DO",
      "lastName" : "Lambeth",
      "authorRank" : 3,
      "name" : "Lambeth DO",
      "referenceId" : "RGD:A141163"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:61672"
    } ]
  }, {
    "primaryId" : "PMID:10453738",
    "title" : "Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL).",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Nakamura I, etal., Hum Genet. 1999 Jun;104(6):492-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-04T13:14:27.000-05:00",
    "volume" : "104",
    "pages" : "492-7",
    "abstract" : "OPLL (ossification of the posterior longitudinal ligament of the spine) is a common form of human myelopathy with a prevalence of as much as 4% in a variety of ethnic groups. To clarify the genetic factors that predispose to OPLL, we have studied ttw (tiptoe walking), a mouse model that presents ectopic ossification of the spinal ligaments similar to OPLL and have found that the ttw phenotype is caused by the nonsense mutation of the gene encoding nucleotide pyrophosphatase (NPPS), a membrane-bound glycoprotein thought to produce inorganic pyrophosphate, a major inhibitor of calcification and mineralization. To investigate a possible role of NPPS in the etiology of OPLL, we have examined its genetic variations in OPLL patients. A total of 323 OPLL patients was screened by means of polymerase chain reaction/single-strand conformation polymorphism analysis covering all the exons and their surrounding introns, plus about 1.5-kb of the promoter region. We identified ten nucleotide variations in the NPPS gene; five of the alterations caused amino-acid substitutions, and two of them were found specifically in OPLL patients. Subsequently, we performed an association study using these variations and found a significant association of an allele, viz., a deletion of T at a position 11 nucleotides upstream from the splice acceptor site of intron 20 (IVS20-11delT), with OPLL; the proportion of the individuals having this deletion was significantly higher (P = 0.0029) in OPLL patients than in controls, indicating that those who have this variation may be more susceptible to the abnormal ossification of the spinal ligaments. Thus, our study suggests that NPPS plays an important role in the etiology of human OPLL.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Nakamura",
      "authorRank" : 1,
      "name" : "Nakamura I",
      "referenceId" : "RGD:A38176"
    }, {
      "firstName" : "S",
      "lastName" : "Ikegawa",
      "authorRank" : 2,
      "name" : "Ikegawa S",
      "referenceId" : "RGD:A38179"
    }, {
      "firstName" : "A",
      "lastName" : "Okawa",
      "authorRank" : 3,
      "name" : "Okawa A",
      "referenceId" : "RGD:A38175"
    }, {
      "firstName" : "S",
      "lastName" : "Okuda",
      "authorRank" : 4,
      "name" : "Okuda S",
      "referenceId" : "RGD:A79368"
    }, {
      "firstName" : "Y",
      "lastName" : "Koshizuka",
      "authorRank" : 5,
      "name" : "Koshizuka Y",
      "referenceId" : "RGD:A79369"
    }, {
      "firstName" : "H",
      "lastName" : "Kawaguchi",
      "authorRank" : 6,
      "name" : "Kawaguchi H",
      "referenceId" : "RGD:A55604"
    }, {
      "firstName" : "K",
      "lastName" : "Nakamura",
      "authorRank" : 7,
      "name" : "Nakamura K",
      "referenceId" : "RGD:A14458"
    }, {
      "firstName" : "T",
      "lastName" : "Koyama",
      "authorRank" : 8,
      "name" : "Koyama T",
      "referenceId" : "RGD:A33043"
    }, {
      "firstName" : "S",
      "lastName" : "Goto",
      "authorRank" : 9,
      "name" : "Goto S",
      "referenceId" : "RGD:A22148"
    }, {
      "firstName" : "J",
      "lastName" : "Toguchida",
      "authorRank" : 10,
      "name" : "Toguchida J",
      "referenceId" : "RGD:A79370"
    }, {
      "firstName" : "M",
      "lastName" : "Matsushita",
      "authorRank" : 11,
      "name" : "Matsushita M",
      "referenceId" : "RGD:A5979"
    }, {
      "firstName" : "T",
      "lastName" : "Ochi",
      "authorRank" : 12,
      "name" : "Ochi T",
      "referenceId" : "RGD:A23067"
    }, {
      "firstName" : "K",
      "lastName" : "Takaoka",
      "authorRank" : 13,
      "name" : "Takaoka K",
      "referenceId" : "RGD:A17449"
    }, {
      "firstName" : "Y",
      "lastName" : "Nakamura",
      "authorRank" : 14,
      "name" : "Nakamura Y",
      "referenceId" : "RGD:A161073"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601041"
    } ]
  }, {
    "primaryId" : "PMID:10453740",
    "title" : "Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Whatley SD, etal., Hum Genet. 1999 Jun;104(6):505-10. doi: 10.1007/s004390050995.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2020-02-18T11:45:43.000-06:00",
    "volume" : "104",
    "pages" : "505-10",
    "abstract" : "Acute intermittent porphyria (AIP) is a low-penetrant autosomal dominant disorder caused by mutations in the hydroxymethylbilane synthase (HMBS) gene. Direct detection of mutations is becoming the method of choice for the accurate identification of asymptomatic affected individuals within AIP families so that they can be advised to avoid drugs and other compounds that provoke the life-threatening acute neurovisceral crises that characterise the condition. We describe a prospective comparison of direct automated sequencing of cDNA (29 patients) or genomic DNA (28 patients) to identify HMBS mutations in 57 patients referred consecutively for mutational analysis; 39 different mutations were identified in 54 patients. The sensitivity of the cDNA and genomic DNA methods was 69% and 95%, respectively, indicating that analysis of genomic DNA provides a higher mutation detection rate. Thirty mutations were restricted to a single family; only one (R173W) occurred in more than three families. Of the mutations (6 missense, 8 splice defects, 10 frameshifts, 1 nonsense), 25 have not been reported previously. One novel mutation (344+33G-->T) was located in a putative intron splice enhancer in intron7. Our results define the extent of allelic heterogeneity and the types (41% missense; 59% truncating) and distribution (35% in exons 10, 12, 14) of HMBS mutations, for AIP in the United Kingdom.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S D",
      "lastName" : "Whatley",
      "authorRank" : 1,
      "name" : "Whatley SD",
      "referenceId" : "RGD:A479491"
    }, {
      "firstName" : "J R",
      "lastName" : "Woolf",
      "authorRank" : 2,
      "name" : "Woolf JR",
      "referenceId" : "RGD:A479492"
    }, {
      "firstName" : "G H",
      "lastName" : "Elder",
      "authorRank" : 3,
      "name" : "Elder GH",
      "referenceId" : "RGD:A444107"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:21079458"
    } ]
  }, {
    "primaryId" : "PMID:10453743",
    "title" : "Molecular analysis of hyperoxaluria type 1 in Italian patients reveals eight new  mutations in the alanine: glyoxylate aminotransferase gene.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Pirulli D, etal., Hum Genet. 1999 Jun;104(6):523-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:30:05.000-05:00",
    "volume" : "104",
    "pages" : "523-5",
    "abstract" : "Systematic screening using the SSCP technique followed by sequencing of bands with abnormal mobility derived from the AGXT exons of 15 unrelated Italian patients with primary hyperoxaluria type 1 (PH1) allowed us to characterize both  the mutant alleles in each individual. Eight new mutations were identified: C155del, C156ins, G244T, C252T, GAG408ins, G468A, G588A and G1098del. This study  demonstrates both the effectiveness of the screening strategy chosen to identify  all the mutant alleles and the high degree of allelic heterogeneity in PH1.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Pirulli",
      "authorRank" : 1,
      "name" : "Pirulli",
      "referenceId" : "RGD:A258032"
    }, {
      "firstName" : "D",
      "lastName" : "Puzzer",
      "authorRank" : 2,
      "name" : "Puzzer",
      "referenceId" : "RGD:A258033"
    }, {
      "firstName" : "L",
      "lastName" : "Ferri",
      "authorRank" : 3,
      "name" : "Ferri",
      "referenceId" : "RGD:A256383"
    }, {
      "firstName" : "S",
      "lastName" : "Crovella",
      "authorRank" : 4,
      "name" : "Crovella S",
      "referenceId" : "RGD:A134745"
    }, {
      "firstName" : "A",
      "lastName" : "Amoroso",
      "authorRank" : 5,
      "name" : "Amoroso A",
      "referenceId" : "RGD:A66898"
    }, {
      "firstName" : "C",
      "lastName" : "Ferrettini",
      "authorRank" : 6,
      "name" : "Ferrettini",
      "referenceId" : "RGD:A258034"
    }, {
      "firstName" : "M",
      "lastName" : "Marangella",
      "authorRank" : 7,
      "name" : "Marangella",
      "referenceId" : "RGD:A258035"
    }, {
      "firstName" : "G",
      "lastName" : "Mazzola",
      "authorRank" : 8,
      "name" : "Mazzola",
      "referenceId" : "RGD:A209683"
    }, {
      "firstName" : "F",
      "lastName" : "Florian",
      "authorRank" : 9,
      "name" : "Florian",
      "referenceId" : "RGD:A258036"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064284"
    } ]
  }, {
    "primaryId" : "PMID:10453785",
    "title" : "Immunohistochemical distribution of extracellular matrix components and keratin in experimentally induced otitis media.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Harada T, etal., Ann Otol Rhinol Laryngol. 1999 Aug;108(8):769-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-28T15:39:39.000-05:00",
    "volume" : "108",
    "pages" : "769-76",
    "abstract" : "The distribution of collagen types I, III, and IV and of laminin, fibronectin, and keratin was studied in otitis media experimentally induced by Streptococcus pneumoniae in the chinchilla. The expression of interstitial collagen types I and III and of fibronectin was increased in the subepithelial space that was thickened by inflammation in the acute period of infection. The expression of collagen type IV in the subepithelial space could be seen in the early period. The epithelial cells in the middle ear changed from flat cuboidal to pseudostratified columnar in pneumococcus-inoculated ears, and the number of keratin-positive epithelial cells in the middle ear increased remarkably after infection. These results indicate that changes in epithelial cell differentiation effected by the extracellular matrix correlate with changes in expression of keratin. It is proposed that the extracellular matrix may contribute to tissue repair in the middle ear after bacterial infection by interfering with cell proliferation of epithelial cells and fibroblasts.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Harada",
      "authorRank" : 1,
      "name" : "Harada",
      "referenceId" : "RGD:A403908"
    }, {
      "firstName" : "SK",
      "lastName" : "Juhn",
      "authorRank" : 2,
      "name" : "Juhn SK",
      "referenceId" : "RGD:A94714"
    }, {
      "firstName" : "Y",
      "lastName" : "Kim",
      "authorRank" : 3,
      "name" : "Kim Y",
      "referenceId" : "RGD:A6445"
    }, {
      "firstName" : "Y",
      "lastName" : "Sakakura",
      "authorRank" : 4,
      "name" : "Sakakura Y",
      "referenceId" : "RGD:A122552"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11556224"
    } ]
  }, {
    "primaryId" : "PMID:10454439",
    "title" : "Genetic isolation of a chromosome 1 region affecting susceptibility to hypertension-induced renal damage in the spontaneously hypertensive rat.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "St Lezin E, etal., Hypertension 1999 Aug;34(2):187-91.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-28T08:49:56.000-05:00",
    "volume" : "34",
    "pages" : "187-91",
    "abstract" : "Linkage studies in the fawn-hooded hypertensive rat have suggested that genes influencing susceptibility to hypertension-associated renal failure may exist on rat chromosome 1q. To investigate this possibility in a widely used model of hypertension, the spontaneously hypertensive rat (SHR), we compared susceptibility to hypertension-induced renal damage between an SHR progenitor strain and an SHR congenic strain that is genetically identical except for a defined region of chromosome 1q. Backcross breeding with selection for the markers D1Mit3 and Igf2 on chromosome 1 was used to create the congenic strain (designated SHR.BN-D1Mit3/Igf2) that carries a 22 cM segment of chromosome 1 transferred from the normotensive Brown Norway rat onto the SHR background. Systolic blood pressure (by radiotelemetry) and urine protein excretion were measured in the SHR progenitor and congenic strains before and after the induction of accelerated hypertension by administration of DOCA-salt. At the same level of DOCA-salt hypertension, the SHR.BN-D1Mit3/Igf2 congenic strain showed significantly greater proteinuria and histologically assessed renal vascular and glomerular injury than the SHR progenitor strain. These findings demonstrate that a gene or genes that influence susceptibility to hypertension-induced renal damage have been trapped in the differential chromosome segment of the SHR.BN-D1Mit3/Igf2 congenic strain. This congenic strain represents an important new model for the fine mapping of gene(s) on chromosome 1 that affect susceptibility to hypertension-induced renal injury in the rat.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "St Lezin",
      "authorRank" : 1,
      "name" : "St Lezin E",
      "referenceId" : "RGD:A77990"
    }, {
      "firstName" : "KA",
      "lastName" : "Griffin",
      "authorRank" : 2,
      "name" : "Griffin KA",
      "referenceId" : "RGD:A16738"
    }, {
      "firstName" : "M",
      "lastName" : "Picken",
      "authorRank" : 3,
      "name" : "Picken M",
      "referenceId" : "RGD:A16739"
    }, {
      "firstName" : "MC",
      "lastName" : "Churchill",
      "authorRank" : 4,
      "name" : "Churchill MC",
      "referenceId" : "RGD:A10947"
    }, {
      "firstName" : "PC",
      "lastName" : "Churchill",
      "authorRank" : 5,
      "name" : "Churchill PC",
      "referenceId" : "RGD:A10946"
    }, {
      "firstName" : "TW",
      "lastName" : "Kurtz",
      "authorRank" : 6,
      "name" : "Kurtz TW",
      "referenceId" : "RGD:A157907"
    }, {
      "firstName" : "W",
      "lastName" : "Liu",
      "authorRank" : 7,
      "name" : "Liu W",
      "referenceId" : "RGD:A161022"
    }, {
      "firstName" : "N",
      "lastName" : "Wang",
      "authorRank" : 8,
      "name" : "Wang N",
      "referenceId" : "RGD:A142478"
    }, {
      "firstName" : "V",
      "lastName" : "Kren",
      "authorRank" : 9,
      "name" : "Kren V",
      "referenceId" : "RGD:A138191"
    }, {
      "firstName" : "V",
      "lastName" : "Zidek",
      "authorRank" : 10,
      "name" : "Zidek V",
      "referenceId" : "RGD:A157902"
    }, {
      "firstName" : "M",
      "lastName" : "Pravenec",
      "authorRank" : 11,
      "name" : "Pravenec M",
      "referenceId" : "RGD:A157908"
    }, {
      "firstName" : "AK",
      "lastName" : "Bidani",
      "authorRank" : 12,
      "name" : "Bidani AK",
      "referenceId" : "RGD:A16746"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632218"
    } ]
  }, {
    "primaryId" : "PMID:10454496",
    "title" : "Comparative pharmacology of the nonpeptide neuromedin B receptor antagonist PD 168368.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Ryan RR, etal., J Pharmacol Exp Ther. 1999 Sep;290(3):1202-11.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-05-04T17:54:02.000-05:00",
    "volume" : "290",
    "pages" : "1202-11",
    "abstract" : "The mammalian peptide neuromedin B (NMB) and its receptor are expressed in a variety of tissues; however, little is definitively established about its physiological actions because of the lack of potent, specific antagonists. Recently, the peptoid PD 168368 was found to be a potent human NMB receptor antagonist. Because it had been shown previously that either synthetic analogs of bombesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist depends on animal species and receptor subtype studied, we  investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor subtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor subtype 3, and Bn receptor subtype 4) from human, mouse, rat, and frog. In binding studies, PD 168368 had similar high affinities (K(i) =  15-45 nM) for NMB receptors from each species examined, 30- to 60-fold lower affinity for gastrin-releasing peptide receptors, and >300-fold lower affinity for Bn receptor subtype 3 or 4. It inhibited NMB binding in a competitive manner. PD 168368 alone did not stimulate increases in either intracellular calcium concentration or [(3)H]inositol phosphates in any of the cells studied but inhibited NMB-induced responses with equivalent potencies in cells containing NMB receptors. PD 168368 was only minimally soluble in water. When hydroxypropyl-beta-cyclodextrin rather than dimethyl sulfoxide was used as the vehicle, both the affinity and the antagonist potency of PD 168368 were significantly greater. The results demonstrate that PD 168368 is a potent, competitive, and selective antagonist at NMB receptors, with a similar pharmacology across animal species. PD 168368 should prove useful for delineating the biological role of NMB and selectively blocking NMB signaling in bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RR",
      "lastName" : "Ryan",
      "authorRank" : 1,
      "name" : "Ryan",
      "referenceId" : "RGD:A288195"
    }, {
      "firstName" : "T",
      "lastName" : "Katsuno",
      "authorRank" : 2,
      "name" : "Katsuno T",
      "referenceId" : "RGD:A35500"
    }, {
      "firstName" : "SA",
      "lastName" : "Mantey",
      "authorRank" : 3,
      "name" : "Mantey SA",
      "referenceId" : "RGD:A121663"
    }, {
      "firstName" : "TK",
      "lastName" : "Pradhan",
      "authorRank" : 4,
      "name" : "Pradhan",
      "referenceId" : "RGD:A286576"
    }, {
      "firstName" : "HC",
      "lastName" : "Weber",
      "authorRank" : 5,
      "name" : "Weber",
      "referenceId" : "RGD:A288196"
    }, {
      "firstName" : "DH",
      "lastName" : "Coy",
      "authorRank" : 6,
      "name" : "Coy DH",
      "referenceId" : "RGD:A35502"
    }, {
      "firstName" : "JF",
      "lastName" : "Battey",
      "authorRank" : 7,
      "name" : "Battey",
      "referenceId" : "RGD:A368898"
    }, {
      "firstName" : "RT",
      "lastName" : "Jensen",
      "authorRank" : 8,
      "name" : "Jensen RT",
      "referenceId" : "RGD:A14881"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11074517"
    } ]
  }, {
    "primaryId" : "PMID:10454523",
    "title" : "Effect of calcium channel antagonists nifedipine and nicardipine on rat cytochrome P-450 2B and 3A forms.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Zangar RC, etal., J Pharmacol Exp Ther. 1999 Sep;290(3):1436-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-10-16T14:49:51.000-05:00",
    "volume" : "290",
    "pages" : "1436-41",
    "abstract" : "Calcium channel antagonists are widely prescribed for treatment of hypertension. In this study, we examined whether treatment with the calcium channel antagonists, nicardipine, nifedipine or diltiazem, alters cytochrome P-450 2B or 3A (CYP2B or CYP3A, respectively) expression in rat liver. Western blot analyses were undertaken using antibodies specific for one or several members of these cytochrome P-450 subfamilies. Nicardipine was found to be an effective inducer of CYP3A; in particular, CYP3A23 was increased approximately 36-fold following treatment with 100 mg of nicardipine/kg/day. Nicardipine induced CYP2B forms up to approximately 3.1-fold. Nifedipine did not alter CYP3A expression but did increase CYP2B expression such that total CYP2B, CYP2B1, and CYP2B2v (a splice variant of CYP2B2) were increased approximately 5- to 15-fold after treatment with 100 mg of nifedipine/kg/day, with increases in benzyloxyresorufin O-dealkylase and erythromycin N-demethylase activities, respectively. The distinct differences in cytochrome P-450 induction profile induced by nicardipine and nifedipine suggest that they may enhance cytochrome P-450 expression by different mechanisms unrelated to their effects on calcium channels.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RC",
      "lastName" : "Zangar",
      "authorRank" : 1,
      "name" : "Zangar RC",
      "referenceId" : "RGD:A101004"
    }, {
      "firstName" : "JR",
      "lastName" : "Okita",
      "authorRank" : 2,
      "name" : "Okita JR",
      "referenceId" : "RGD:A101005"
    }, {
      "firstName" : "H",
      "lastName" : "Kim",
      "authorRank" : 3,
      "name" : "Kim H",
      "referenceId" : "RGD:A10008"
    }, {
      "firstName" : "PE",
      "lastName" : "Thomas",
      "authorRank" : 4,
      "name" : "Thomas PE",
      "referenceId" : "RGD:A101006"
    }, {
      "firstName" : "A",
      "lastName" : "Anderson",
      "authorRank" : 5,
      "name" : "Anderson A",
      "referenceId" : "RGD:A17682"
    }, {
      "firstName" : "RJ",
      "lastName" : "Edwards",
      "authorRank" : 6,
      "name" : "Edwards RJ",
      "referenceId" : "RGD:A45063"
    }, {
      "firstName" : "DL",
      "lastName" : "Springer",
      "authorRank" : 7,
      "name" : "Springer DL",
      "referenceId" : "RGD:A101007"
    }, {
      "firstName" : "RT",
      "lastName" : "Okita",
      "authorRank" : 8,
      "name" : "Okita RT",
      "referenceId" : "RGD:A101008"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301464"
    } ]
  }, {
    "primaryId" : "PMID:10454528",
    "title" : "Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Wu X, etal., J Pharmacol Exp Ther 1999 Sep;290(3):1482-92.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-01-11T15:05:31.000-06:00",
    "volume" : "290",
    "pages" : "1482-92",
    "abstract" : "We have demonstrated in the present study that novel organic cation transporter (OCTN) 2 is a transporter for organic cations as well as carnitine. OCTN2 transports organic cations without involving Na(+), but it transports carnitine only in the presence of Na(+). The ability to transport organic cations and carnitine is demonstrable with human, rat, and mouse OCTN2s. Na(+) does not influence the affinity of OCTN2 for organic cations, but it increases the affinity severalfold for carnitine. The short-chain acyl esters of carnitine are also transported by OCTN2. Two mutations, M352R and P478L, in human OCTN2 are associated with loss of transport function, but the protein expression of these mutants is comparable to that of the wild-type human OCTN2. In situ hybridization in the rat shows that OCTN2 is expressed in the proximal and distal tubules and in the glomeruli in the kidney, in the myocardium, valves, and arterioles in the heart, in the labyrinthine layer of the placenta, and in the cortex, hippocampus, and cerebellum in the brain. This is the first report that OCTN2 is a Na(+)-independent organic cation transporter as well as a Na(+)-dependent carnitine transporter and that OCTN2 is expressed not only in the heart, kidney, and placenta but also in the brain.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "X",
      "lastName" : "Wu",
      "authorRank" : 1,
      "name" : "Wu X",
      "referenceId" : "RGD:A8038"
    }, {
      "firstName" : "W",
      "lastName" : "Huang",
      "authorRank" : 2,
      "name" : "Huang W",
      "referenceId" : "RGD:A5009"
    }, {
      "firstName" : "PD",
      "lastName" : "Prasad",
      "authorRank" : 3,
      "name" : "Prasad PD",
      "referenceId" : "RGD:A6423"
    }, {
      "firstName" : "P",
      "lastName" : "Seth",
      "authorRank" : 4,
      "name" : "Seth P",
      "referenceId" : "RGD:A5006"
    }, {
      "firstName" : "DP",
      "lastName" : "Rajan",
      "authorRank" : 5,
      "name" : "Rajan DP",
      "referenceId" : "RGD:A8039"
    }, {
      "firstName" : "FH",
      "lastName" : "Leibach",
      "authorRank" : 6,
      "name" : "Leibach FH",
      "referenceId" : "RGD:A5010"
    }, {
      "firstName" : "J",
      "lastName" : "Chen",
      "authorRank" : 7,
      "name" : "Chen J",
      "referenceId" : "RGD:A161502"
    }, {
      "firstName" : "SJ",
      "lastName" : "Conway",
      "authorRank" : 8,
      "name" : "Conway SJ",
      "referenceId" : "RGD:A8040"
    }, {
      "firstName" : "V",
      "lastName" : "Ganapathy",
      "authorRank" : 9,
      "name" : "Ganapathy V",
      "referenceId" : "RGD:A5011"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70011"
    } ]
  }, {
    "primaryId" : "PMID:10454575",
    "title" : "Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kitamura T, etal., Mol Cell Biol. 1999 Sep;19(9):6286-96.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:35:18.000-05:00",
    "volume" : "19",
    "pages" : "6286-96",
    "abstract" : "Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in adipocytes in a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation and activation of endogenous or recombinant PDE3B in 3T3-L1 adipocytes have now been shown to be inhibited by a dominant-negative mutant of the serine-threonine kinase Akt, suggesting that Akt is necessary for insulin-induced phosphorylation and activation of PDE3B. Serine-273 of mouse PDE3B is located within a motif (RXRXXS) that is preferentially phosphorylated by Akt. A mutant PDE3B in which serine-273  was replaced by alanine was not phosphorylated either in response to insulin in intact cells or by purified Akt in vitro. In contrast, PDE3B mutants in which alanine was substituted for either serine-296 or serine-421, each of which lies within a sequence (RRXS) preferentially phosphorylated by cAMP-dependent protein  kinase, were phosphorylated by Akt in vitro or in response to insulin in intact cells. Moreover, the serine-273 mutant of PDE3B was not activated by insulin when expressed in adipocytes. These results suggest that PDE3B is a physiological substrate of Akt and that Akt-mediated phosphorylation of PDE3B on serine-273 is  important for insulin-induced activation of PDE3B.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kitamura",
      "authorRank" : 1,
      "name" : "Kitamura",
      "referenceId" : "RGD:A392568"
    }, {
      "firstName" : "Y",
      "lastName" : "Kitamura",
      "authorRank" : 2,
      "name" : "Kitamura",
      "referenceId" : "RGD:A390790"
    }, {
      "firstName" : "S",
      "lastName" : "Kuroda",
      "authorRank" : 3,
      "name" : "Kuroda S",
      "referenceId" : "RGD:A4186"
    }, {
      "firstName" : "Y",
      "lastName" : "Hino",
      "authorRank" : 4,
      "name" : "Hino Y",
      "referenceId" : "RGD:A87191"
    }, {
      "firstName" : "M",
      "lastName" : "Ando",
      "authorRank" : 5,
      "name" : "Ando M",
      "referenceId" : "RGD:A51647"
    }, {
      "firstName" : "K",
      "lastName" : "Kotani",
      "authorRank" : 6,
      "name" : "Kotani K",
      "referenceId" : "RGD:A84922"
    }, {
      "firstName" : "H",
      "lastName" : "Konishi",
      "authorRank" : 7,
      "name" : "Konishi H",
      "referenceId" : "RGD:A4185"
    }, {
      "firstName" : "H",
      "lastName" : "Matsuzaki",
      "authorRank" : 8,
      "name" : "Matsuzaki H",
      "referenceId" : "RGD:A4188"
    }, {
      "firstName" : "U",
      "lastName" : "Kikkawa",
      "authorRank" : 9,
      "name" : "Kikkawa",
      "referenceId" : "RGD:A308107"
    }, {
      "firstName" : "W",
      "lastName" : "Ogawa",
      "authorRank" : 10,
      "name" : "Ogawa",
      "referenceId" : "RGD:A368568"
    }, {
      "firstName" : "M",
      "lastName" : "Kasuga",
      "authorRank" : 11,
      "name" : "Kasuga",
      "referenceId" : "RGD:A329486"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553650"
    } ]
  }, {
    "primaryId" : "PMID:10454827",
    "title" : "Differential effect of anti-TNF-alpha antibody on proinflammatory cytokine release by Kupffer cells following liver ischemia and reperfusion.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Wanner GA, etal., Shock. 1999 Jun;11(6):391-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2019-10-15T17:12:26.000-05:00",
    "volume" : "11",
    "pages" : "391-5",
    "abstract" : "To study the role of tumor necrosis factor-alpha (TNF-alpha) for induction of the proinflammatory cytokine cascade after liver ischemia and reperfusion (I/R), rats were injected intraperitoneally with anti-TNF-alpha monoclonal antibodies (mAb) or placebo (IgG1) 30 min prior to global hepatic ischemia. Blood levels of TNF-alpha, interleukin (IL)-1alpha and -6 were determined. In addition, Kupffer cells (KC) were harvested after 60 min of reperfusion and spontaneous cytokine release was measured. Sham-operated animals were used as controls. Levels of proinflammatory cytokines in serum and KC supernatants were detected using specific bioassays and ELISA. Liver I/R resulted in increased (p < .01) serum levels of TNF-alpha, IL-1alpha, and IL-6, which was associated with an enhanced (p < .05) release of these cytokines by KC. In vivo pretreatment with anti-TNF-alpha mAb led to complete neutralization of TNF-alpha serum levels and decreased (p < .01) IL-6 levels (-62%). Moreover, anti-TNF-alpha mAb markedly (p < .05) decreased the release of TNF-alpha (-69%) and IL-6 (-56%) by KC, while IL-1alpha was not affected. These data indicate that TNF-alpha produced early after liver I/R triggers both its own secretion as well as IL-6 release by KC during reperfusion while the release of IL-1alpha occurs independent from TNF-alpha.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G A",
      "lastName" : "Wanner",
      "authorRank" : 1,
      "name" : "Wanner GA",
      "referenceId" : "RGD:A475486"
    }, {
      "firstName" : "P E",
      "lastName" : "Müller",
      "authorRank" : 2,
      "name" : "Müller PE",
      "referenceId" : "RGD:A475487"
    }, {
      "firstName" : "W",
      "lastName" : "Ertel",
      "authorRank" : 3,
      "name" : "Ertel W",
      "referenceId" : "RGD:A475488"
    }, {
      "firstName" : "M",
      "lastName" : "Bauer",
      "authorRank" : 4,
      "name" : "Bauer M",
      "referenceId" : "RGD:A17037"
    }, {
      "firstName" : "M D",
      "lastName" : "Menger",
      "authorRank" : 5,
      "name" : "Menger MD",
      "referenceId" : "RGD:A475489"
    }, {
      "firstName" : "K",
      "lastName" : "Messmer",
      "authorRank" : 6,
      "name" : "Messmer K",
      "referenceId" : "RGD:A48896"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:14985258"
    } ]
  }, {
    "primaryId" : "PMID:10455019",
    "title" : "Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+,K+-ATPase.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Nakamura N, etal., Biochem J 1999 Sep 1;342 ( Pt 2):329-36.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-31T08:55:00.000-06:00",
    "volume" : "342 ( Pt 2)",
    "pages" : "329-36",
    "abstract" : "A novel inwardly rectifying K+ channel, Kir7.1, with unique pore properties, was cloned recently. Working in the field of osmoregulation, we have also identified the same human and rat channel and found that the channel is unique not only in its pore sequence but also in its dense localization in the follicular cells of the thyroid gland. Northern blot analysis revealed that the channel message was abundantly expressed in the thyroid gland and small intestine, and moderately in the kidney, stomach, spinal cord and brain. Immunohistochemistry of the rat thyroid, intestine and choroid plexus demonstrated the expression of the channel protein in the follicular cells and epithelial cells, suggesting a role in the regulation of the ion-transporting functions of these specialized cells. The unique pore properties of Kir7.1 make it a strong candidate for the hypothetical low-conductance K+ channel that is functionally coupled with Na+,K(+)-ATPase by recycling K+. We therefore further examined the co-localization of Kir7.1 and Na+,K(+)-ATPase and found that both are localized in the basolateral membrane of the thyroid follicular cell; in the choroid plexus, which is known to be unique in having Na+,K(+)-ATPase in the apical side of the epithelial cells, Kir7.1 was found in the apical membrane, implying a close functional coupling between the channel and Na+,K(+)-ATPase.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Nakamura",
      "authorRank" : 1,
      "name" : "Nakamura N",
      "referenceId" : "RGD:A5185"
    }, {
      "firstName" : "Y",
      "lastName" : "Suzuki",
      "authorRank" : 2,
      "name" : "Suzuki Y",
      "referenceId" : "RGD:A161488"
    }, {
      "firstName" : "H",
      "lastName" : "Sakuta",
      "authorRank" : 3,
      "name" : "Sakuta H",
      "referenceId" : "RGD:A27211"
    }, {
      "firstName" : "K",
      "lastName" : "Ookata",
      "authorRank" : 4,
      "name" : "Ookata K",
      "referenceId" : "RGD:A23541"
    }, {
      "firstName" : "K",
      "lastName" : "Kawahara",
      "authorRank" : 5,
      "name" : "Kawahara K",
      "referenceId" : "RGD:A22992"
    }, {
      "firstName" : "S",
      "lastName" : "Hirose",
      "authorRank" : 6,
      "name" : "Hirose S",
      "referenceId" : "RGD:A123061"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727278"
    } ]
  }, {
    "primaryId" : "PMID:10455105",
    "title" : "Association of neuronal calcium channels with modular adaptor proteins.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Maximov A, etal., J Biol Chem. 1999 Aug 27;274(35):24453-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:18:18.000-05:00",
    "volume" : "274",
    "pages" : "24453-6",
    "abstract" : "Presynaptic voltage-gated calcium (Ca(2+)) channels mediate Ca(2+) influx into the presynaptic terminal that triggers synaptic vesicle fusion and neurotransmitter release. The immediate proximity of Ca(2+) channels to the synaptic vesicle release apparatus is critical for rapid and efficient synaptic transmission. In a series of biochemical experiments, we demonstrate a specific association of the cytosolic carboxyl terminus of the N-type Ca(2+) channel pore-forming alpha(1B) subunit with the modular adaptor proteins Mint1 and CASK.  The carboxyl termini of alpha(1B) bind to the first PDZ domain of Mint1 (Mint1-1). The proline-rich region present in the carboxyl termini of alpha(1B) binds to the SH3 domain of CASK. Mint1-1 is specific for the E/D-X-W-C/S-COOH consensus, which defines a novel class of PDZ domains (class III). The Mint1-1 PDZ domain-binding motif is present only in the \"long\" carboxyl-terminal splice variants of N-type (alpha(1B)) and P/Q-type (alpha(1A)) Ca(2+) channels, but not  in R-type (alpha(1E)) or L-type (alpha(1C)) Ca(2+) channels. Our results directly link presynaptic Ca(2+) channels to a macromolecular complex formed by modular adaptor proteins at synaptic junction and advance our understanding of coupling between cell adhesion and synaptic vesicle exocytosis.",
    "issueName" : "35",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Maximov",
      "authorRank" : 1,
      "name" : "Maximov A",
      "referenceId" : "RGD:A13321"
    }, {
      "firstName" : "TC",
      "lastName" : "Sudhof",
      "authorRank" : 2,
      "name" : "Sudhof",
      "referenceId" : "RGD:A405617"
    }, {
      "firstName" : "I",
      "lastName" : "Bezprozvanny",
      "authorRank" : 3,
      "name" : "Bezprozvanny I",
      "referenceId" : "RGD:A13322"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041048"
    } ]
  }, {
    "primaryId" : "PMID:10455107",
    "title" : "MCD encodes peroxisomal and cytoplasmic forms of malonyl-CoA decarboxylase and is mutated in malonyl-CoA decarboxylase deficiency.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Sacksteder KA, etal., J Biol Chem. 1999 Aug 27;274(35):24461-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-27T15:28:39.000-05:00",
    "volume" : "274",
    "pages" : "24461-8",
    "abstract" : "Malonyl-CoA decarboxylase (MCD) catalyzes the proton-consuming conversion of malonyl-CoA to acetyl-CoA and CO(2). Although defects in MCD activity are associated with malonyl-CoA decarboxylase deficiency, a lethal disorder characterized by cardiomyopathy and developmental delay, the metabolic role of this enzyme in mammals is unknown. A computer-based search for novel peroxisomal proteins led to the identification of a candidate gene for human MCD, which encodes a protein with a canonical type-1 peroxisomal targeting signal of serine-lysine-leucine(COOH). We observed that recombinant MCD protein has high intrinsic malonyl-CoA decarboxylase activity and that a malonyl-CoA decarboxylase-deficient patient has a severe mutation in the MCD gene (c.947-948delTT), confirming that this gene encodes human MCD. Subcellular fractionation experiments revealed that MCD resides in both the cytoplasm and peroxisomes. Cytoplasmic MCD is positioned to play a role in the regulation of cytoplasmic malonyl-CoA abundance and, thus, of mitochondrial fatty acid uptake and oxidation. This hypothesis is supported by the fact that malonyl-CoA decarboxylase-deficient patients display a number of phenotypes that are reminiscent of mitochondrial fatty acid oxidation disorders. Additional support for this hypothesis comes from our observation that MCD mRNA is most abundant in cardiac and skeletal muscles, tissues in which cytoplasmic malonyl-CoA is a potent inhibitor of mitochondrial fatty acid oxidation and which derive significant amounts of energy from fatty acid oxidation. As for the role of peroxisomal MCD, we propose that this enzyme may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids.",
    "issueName" : "35",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "KA",
      "lastName" : "Sacksteder",
      "authorRank" : 1,
      "name" : "Sacksteder KA",
      "referenceId" : "RGD:A52345"
    }, {
      "firstName" : "JC",
      "lastName" : "Morrell",
      "authorRank" : 2,
      "name" : "Morrell JC",
      "referenceId" : "RGD:A52350"
    }, {
      "firstName" : "RJ",
      "lastName" : "Wanders",
      "authorRank" : 3,
      "name" : "Wanders RJ",
      "referenceId" : "RGD:A5204"
    }, {
      "firstName" : "R",
      "lastName" : "Matalon",
      "authorRank" : 4,
      "name" : "Matalon R",
      "referenceId" : "RGD:A36131"
    }, {
      "firstName" : "SJ",
      "lastName" : "Gould",
      "authorRank" : 5,
      "name" : "Gould SJ",
      "referenceId" : "RGD:A27102"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600798"
    } ]
  }, {
    "primaryId" : "PMID:10455179",
    "title" : "Molecular characterization of a novel basement membrane-associated proteoglycan, leprecan.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Wassenhove-McCarthy DJ and McCarthy KJ, J Biol Chem 1999 Aug 27;274(35):25004-17.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:03.000-05:00",
    "volume" : "274",
    "pages" : "25004-17",
    "abstract" : "A monoclonal antibody was used in early studies to identify a novel chondroitin sulfate proteoglycan, secreted by L-2 cells, the core protein of which was approximately 100 kDa. To characterize this proteoglycan core protein at the molecular level, an L-2 cell cDNA library was probed by expression screening and solution hybridization. Northern blot analysis assigned transcript size to approximately 3.1 kilobases and, after contig assembly, the coding region of the mRNA corresponded to 2.18 kilobases. Immunoassays were performed to confirm the identity of this sequence, using a polyclonal antibody raised against an expressed fusion protein encoded by sequence representing the carboxyl half of the molecule. The antibody recognized the core protein in Western blots after prior digestion of the intact proteoglycan with chondroitinase ABC. Immunostaining tissue sections with the same antibody localized the proteoglycan to basement membranes, and expression of the entire sequence in Chinese hamster ovary K-1 cells showed that the protein encoded by the sequence secreted as a chondroitin sulfate proteoglycan. The core protein not only has motifs permitting glycosylation as a proteoglycan, but also possesses the endoplasmic reticulum retrieval signal, KDEL, which suggests that, in addition to its role as a basement membrane component, it may also participate in the secretory pathway of cells.",
    "issueName" : "35",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Wassenhove-McCarthy",
      "authorRank" : 1,
      "name" : "Wassenhove-McCarthy DJ",
      "referenceId" : "RGD:A20235"
    }, {
      "firstName" : "KJ",
      "lastName" : "McCarthy",
      "authorRank" : 2,
      "name" : "McCarthy KJ",
      "referenceId" : "RGD:A20236"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633221"
    } ]
  }, {
    "primaryId" : "PMID:10455180",
    "title" : "New ether-a-go-go K(+) channel family members localized in human telencephalon.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Miyake A, etal., J Biol Chem 1999 Aug 27;274(35):25018-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-06-18T15:09:21.000-05:00",
    "volume" : "274",
    "pages" : "25018-25",
    "abstract" : "A cDNA encoding a novel voltage-gated K(+) channel protein was isolated from human brain. This protein, termed BEC1, is 46% identical to rat elk in the ether-a-go-go K(+) channel family. The BEC1 gene maps to the 12q13 region of the human genome. Northern blot analysis indicates that BEC1 is exclusively expressed in human brain, where the expression is concentrated in the telencephalic areas such as the cerebral cortex, amygdala, hippocampus, and striatum. By in situ hybridization, BEC1 is detected in the CA1-CA3 pyramidal cell layers and the dentate gyrus granule cell layers of the hippocampus. Specific signals are also found in neocortical neurons. Transfection of mammalian L929 and Chinese hamster ovary cells with BEC1 cDNA induces a voltage-gated outward current with a fast inactivation component. This current is insensitive to tetraethylammonium and quinidine. Additionally, a second related gene BEC2 was isolated from human brain. BEC2 is also brain-specific, located in the neocortex and the striatum, and functional as a channel gene. Phylogenetic analysis indicates that BEC1 and BEC2 constitute a subfamily, together with elk, in the ether-a-go-go family. The two genes may be involved in cellular excitability of restricted neurons in the human central nervous system.",
    "issueName" : "35",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Miyake",
      "authorRank" : 1,
      "name" : "Miyake A",
      "referenceId" : "RGD:A106596"
    }, {
      "firstName" : "S",
      "lastName" : "Mochizuki",
      "authorRank" : 2,
      "name" : "Mochizuki S",
      "referenceId" : "RGD:A64064"
    }, {
      "firstName" : "H",
      "lastName" : "Yokoi",
      "authorRank" : 3,
      "name" : "Yokoi H",
      "referenceId" : "RGD:A10195"
    }, {
      "firstName" : "M",
      "lastName" : "Kohda",
      "authorRank" : 4,
      "name" : "Kohda M",
      "referenceId" : "RGD:A10196"
    }, {
      "firstName" : "K",
      "lastName" : "Furuichi",
      "authorRank" : 5,
      "name" : "Furuichi K",
      "referenceId" : "RGD:A9610"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70783"
    } ]
  }, {
    "primaryId" : "PMID:10455199",
    "title" : "Elastase-mediated release of heparan sulfate proteoglycans from pulmonary fibroblast cultures. A mechanism for basic fibroblast growth factor (bFGF) release and attenuation of bfgf binding following elastase-induced injury.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Buczek-Thomas JA and Nugent MA, J Biol Chem. 1999 Aug 27;274(35):25167-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-20T14:03:03.000-05:00",
    "volume" : "274",
    "pages" : "25167-72",
    "abstract" : "We have investigated elastase-mediated alterations in the expression of basic fibroblast growth factor (bFGF) receptors and proteoglycan co-receptors and characterized the subsequent effects on bFGF receptor binding profiles. For these studies, pulmonary fibroblast cultures were treated with porcine pancreatic elastase, and elastase-mediated changes in bFGF receptor expression and binding profiles were assessed. Quantitation of [(35)S]sulfate-labeled proteoglycan and total glycosaminoglycan release from fibroblast matrices indicated that elastase  treatment released sulfated proteoglycan from the cell surface in a time- and dose-dependent fashion that correlated strongly with elastase-mediated bFGF release. Ligand binding studies indicated that elastase treatment decreased total binding of (125)I-bFGF to the cell surface and affected both fibroblast growth factor receptor and heparan sulfate proteoglycan (HSPG) binding sites. Western blot analyses indicated that elastase treatment did not release significant amounts of fibroblast growth factor receptor protein. These findings indicate that elastase-mediated HSPG release from fibroblast matrices reduces the effective affinity of bFGF for its receptor. Collectively, these studies suggest  that HSPG co-receptors are important mediators of the pulmonary fibroblast response to elastase treatment and that bFGF, HSPG, and other elastase-released entities play an important role in the response of the lung to chronic injury.",
    "issueName" : "35",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JA",
      "lastName" : "Buczek-Thomas",
      "authorRank" : 1,
      "name" : "Buczek-Thomas JA",
      "referenceId" : "RGD:A18675"
    }, {
      "firstName" : "MA",
      "lastName" : "Nugent",
      "authorRank" : 2,
      "name" : "Nugent MA",
      "referenceId" : "RGD:A41461"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8655641"
    } ]
  }, {
    "primaryId" : "PMID:10455887",
    "title" : "Evidence of a central role for p38 map kinase induction of tumor necrosis factor alpha in pancreatitis-associated pulmonary injury.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Yang J, etal., Surgery. 1999 Aug;126(2):216-22.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-23T11:07:43.000-05:00",
    "volume" : "126",
    "pages" : "216-22",
    "abstract" : "BACKGROUND: Tumor necrosis factor alpha (TNF alpha) has been implicated as an important mediator in acute pancreatitis-associated adult respiratory distress syndrome, but the precise pathogenesis remains unclear. The purpose of this work was to clarify the role of TNF alpha that is produced within the lung parenchyma in the inducement of pancreatitis-related pulmonary injury and to examine 1 of the potential pathways leading to the production of pulmonary TNF alpha. METHODS: Bile salt pancreatitis was induced in rats (n = 40) that were randomized to receive a p38 mitogen-activated protein (MAP) kinase inhibitor or vehicle. A separate group (n = 16) underwent sham operation. Pulmonary capillary permeability was determined with fluorescein isothiocyanate-labeled albumin and Evans blue dye, and lung histologic analysis was performed. TNF alpha protein was measured in bronchoalveolar lavage fluid, and p38 MAP kinase was activity determined by Western blot analysis. RESULTS: The induction of pancreatitis resulted in increased pulmonary capillary leakage and worsened histologic condition (P < .01 vs sham). Effective inhibition of p38 MAP kinase-induced TNF alpha production completely prevented pancreatitis-associated pulmonary injury (P < .01 vs vehicle). CONCLUSIONS: p38 MAP kinase-induced TNF alpha production plays a central role in the development of pulmonary dysfunction, which accompanies severe acute pancreatitis in this rodent model.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Yang",
      "authorRank" : 1,
      "name" : "Yang J",
      "referenceId" : "RGD:A161907"
    }, {
      "firstName" : "C",
      "lastName" : "Murphy",
      "authorRank" : 2,
      "name" : "Murphy C",
      "referenceId" : "RGD:A128111"
    }, {
      "firstName" : "W",
      "lastName" : "Denham",
      "authorRank" : 3,
      "name" : "Denham W",
      "referenceId" : "RGD:A98605"
    }, {
      "firstName" : "G",
      "lastName" : "Botchkina",
      "authorRank" : 4,
      "name" : "Botchkina G",
      "referenceId" : "RGD:A128112"
    }, {
      "firstName" : "KJ",
      "lastName" : "Tracey",
      "authorRank" : 5,
      "name" : "Tracey KJ",
      "referenceId" : "RGD:A30399"
    }, {
      "firstName" : "J",
      "lastName" : "Norman",
      "authorRank" : 6,
      "name" : "Norman J",
      "referenceId" : "RGD:A98607"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4143427"
    } ]
  }, {
    "primaryId" : "PMID:10456317",
    "title" : "Identification of a novel gene of the X,K-ATPase beta-subunit family that is predominantly expressed in skeletal and heart muscles.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Pestov NB, etal., FEBS Lett 1999 Aug 6;456(2):243-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:58.000-05:00",
    "volume" : "456",
    "pages" : "243-8",
    "abstract" : "We have identified the fifth member of the mammalian X,K-ATPase beta-subunit gene family. The human and rat genes are largely expressed in skeletal muscle and at a lower level in heart. The deduced human and rat proteins designated as beta(muscle) (beta(m)) consist of 357 and 356 amino acid residues, respectively, and exhibit 89% identity. The sequence homology of beta(m) proteins with known Na,K- and H,K-ATPase beta-subunits are 30.5-39.4%. Unlike other beta-subunits, putative beta(m) proteins have large N-terminal cytoplasmic domains containing long Glu-rich sequences. The data obtained indicate the existence of hitherto unknown X,K-ATPase (most probably Na,K-ATPase) isozymes in muscle cells.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NB",
      "lastName" : "Pestov",
      "authorRank" : 1,
      "name" : "Pestov NB",
      "referenceId" : "RGD:A15818"
    }, {
      "firstName" : "G",
      "lastName" : "Adams",
      "authorRank" : 2,
      "name" : "Adams G",
      "referenceId" : "RGD:A15819"
    }, {
      "firstName" : "MI",
      "lastName" : "Shakhparonov",
      "authorRank" : 3,
      "name" : "Shakhparonov MI",
      "referenceId" : "RGD:A15820"
    }, {
      "firstName" : "NN",
      "lastName" : "Modyanov",
      "authorRank" : 4,
      "name" : "Modyanov NN",
      "referenceId" : "RGD:A15821"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:631939"
    } ]
  }, {
    "primaryId" : "PMID:10456318",
    "title" : "Phosphorylation and activation of Ca2+/calmodulin-dependent protein kinase phosphatase by Ca2+/calmodulin-dependent protein kinase II.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kameshita I, etal., FEBS Lett. 1999 Aug 6;456(2):249-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-03-04T11:20:11.000-06:00",
    "volume" : "456",
    "pages" : "249-52",
    "abstract" : "Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKPase) is a protein phosphatase which dephosphorylates autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) and deactivates the enzyme (Ishida, A., Kameshita, I.  and Fujisawa, H. (1998) J. Biol. Chem. 273, 1904-1910). In this study, a phosphorylation-dephosphorylation relationship between CaMKII and CaMKPase was examined. CaMKPase was not significantly phosphorylated by CaMKII under the standard phosphorylation conditions but was phosphorylated in the presence of poly-L-lysine, which is a potent activator of CaMKPase. The maximal extent of the phosphorylation was about 1 mol of phosphate per mol of the enzyme and the phosphorylation resulted in an about 2-fold increase in the enzyme activity. Thus, the activity of CaMKPase appears to be regulated through phosphorylation by its target enzyme, CaMKII.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Kameshita",
      "authorRank" : 1,
      "name" : "Kameshita I",
      "referenceId" : "RGD:A17119"
    }, {
      "firstName" : "A",
      "lastName" : "Ishida",
      "authorRank" : 2,
      "name" : "Ishida A",
      "referenceId" : "RGD:A17117"
    }, {
      "firstName" : "H",
      "lastName" : "Fujisawa",
      "authorRank" : 3,
      "name" : "Fujisawa",
      "referenceId" : "RGD:A185168"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7241145"
    } ]
  }, {
    "primaryId" : "PMID:10456937",
    "title" : "Molecular cloning and characterization of rat genes encoding homologues of human beta-defensins.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Jia HP, etal., Infect Immun 1999 Sep;67(9):4827-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:35.000-05:00",
    "volume" : "67",
    "pages" : "4827-33",
    "abstract" : "beta-Defensins are cationic peptides with broad-spectrum antimicrobial activity that may play a role in mucosal defenses of several organs. They have been isolated in several species, and in humans, two beta-defensins have been identified. Here, we report the identification of two genes encoding beta-defensin homologues in the rat. Partial cDNAs were found by searching the expressed-sequence-tag database, and primers were designed to generate full-length mRNA coding sequences. One gene was highly similar to the human beta-defensin-1 (HBD-1) gene and mouse beta-defensin-1 gene at both the nucleic acid and amino acid levels and was termed rat beta-defensin-1 (RBD-1). The other gene, named RBD-2, was homologous to the HBD-2 and bovine tracheal antimicrobial peptide (TAP) genes. The predicted prepropeptides were strongly cationic, were 69 and 63 residues in length for RBD-1 and RBD-2, respectively, and contained the six-cysteine motif characteristic of beta-defensins. The beta-defensin genes mapped closely on rat chromosome 16 and were closely linked to the alpha-defensins genes, suggesting that they are part of a gene cluster, similar to the organization reported for humans. Northern blot analysis showed that both RBD-1 and RBD-2 mRNA transcripts were approximately 0.5 kb in length; RBD-1 mRNA was abundantly transcribed in the rat kidney, while RBD-2 was prevalent in the lung. Reverse transcription-PCR indicated that RBD-1 and RBD-2 mRNAs were distributed in a variety of other tissues. In the lung, RBD-1 mRNA expression localized to the tracheal epithelium while RBD-2 was expressed in alveolar type II cells. In conclusion, we characterized two novel beta-defensin homologues in the rat. The rat may be a useful model to investigate the function and contribution of beta-defensins to host defense in the lung, kidney, and other tissues.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HP",
      "lastName" : "Jia",
      "authorRank" : 1,
      "name" : "Jia HP",
      "referenceId" : "RGD:A18854"
    }, {
      "firstName" : "JN",
      "lastName" : "Mills",
      "authorRank" : 2,
      "name" : "Mills JN",
      "referenceId" : "RGD:A27213"
    }, {
      "firstName" : "F",
      "lastName" : "Barahmand-Pour",
      "authorRank" : 3,
      "name" : "Barahmand-Pour F",
      "referenceId" : "RGD:A27214"
    }, {
      "firstName" : "D",
      "lastName" : "Nishimura",
      "authorRank" : 4,
      "name" : "Nishimura D",
      "referenceId" : "RGD:A27215"
    }, {
      "firstName" : "RK",
      "lastName" : "Mallampali",
      "authorRank" : 5,
      "name" : "Mallampali RK",
      "referenceId" : "RGD:A27216"
    }, {
      "firstName" : "G",
      "lastName" : "Wang",
      "authorRank" : 6,
      "name" : "Wang G",
      "referenceId" : "RGD:A8960"
    }, {
      "firstName" : "K",
      "lastName" : "Wiles",
      "authorRank" : 7,
      "name" : "Wiles K",
      "referenceId" : "RGD:A27217"
    }, {
      "firstName" : "BF",
      "lastName" : "Tack",
      "authorRank" : 8,
      "name" : "Tack BF",
      "referenceId" : "RGD:A27218"
    }, {
      "firstName" : "CL",
      "lastName" : "Bevins",
      "authorRank" : 9,
      "name" : "Bevins CL",
      "referenceId" : "RGD:A27219"
    }, {
      "firstName" : "JR",
      "lastName" : "McCray PB",
      "authorRank" : 10,
      "name" : "McCray PB JR",
      "referenceId" : "RGD:A27220"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727279"
    } ]
  }, {
    "primaryId" : "PMID:10457052",
    "title" : "Cloning and functional expression of a novel degenerin-like Na+ channel gene in mammals.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Sakai H, etal., J Physiol 1999 Sep 1;519 Pt 2:323-33.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-10-10T17:14:55.000-05:00",
    "volume" : "519 Pt 2",
    "pages" : "323-33",
    "abstract" : "1. A degenerate polymerase chain reaction (PCR) homology screening procedure was applied to rat brain cDNA in order to identify novel genes belonging to the amiloride-sensitive Na+ channel and degenerin (NaC/DEG) family of ion channels. A single gene was identified that encodes a protein related to but clearly different from the already cloned members of the family (18-30 % amino acid sequence identity). Phylogenetic analysis linked this protein to the group of ligand-gated channels that includes the mammalian acid-sensing ion channels and the Phe-Met-Arg-Phe-amide (FMRFamide)-activated Na+ channel. 2. Expression of gain-of-function mutants after cRNA injection into Xenopus laevis oocytes or transient transfection of COS cells induced large constitutive currents. The activated channel was amiloride sensitive (IC50, 1.31 microM) and displayed a low conductance (9-10 pS) and a high selectivity for Na+ over K+ (ratio of the respective permeabilities, PNa+/PK+ >= 10), all of which are characteristic of NaC/DEG channel behaviour. 3. Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed a predominant expression of its mRNA in the small intestine, the liver (including hepatocytes) and the brain. This channel has been called the brain-liver-intestine amiloride-sensitive Na+ channel (BLINaC). 4. Corresponding gain-of-function mutations in Caenorhabditis elegans degenerins are responsible for inherited neurodegeneration in the nematode. Besides the BLINaC physiological function that remains to be established, mutations in this novel mammalian degenerin-like channel might be of pathophysiological importance in inherited neurodegeneration and liver or intestinal pathologies.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Sakai",
      "authorRank" : 1,
      "name" : "Sakai H",
      "referenceId" : "RGD:A160193"
    }, {
      "firstName" : "E",
      "lastName" : "Lingueglia",
      "authorRank" : 2,
      "name" : "Lingueglia E",
      "referenceId" : "RGD:A5929"
    }, {
      "firstName" : "G",
      "lastName" : "Champigny",
      "authorRank" : 3,
      "name" : "Champigny G",
      "referenceId" : "RGD:A5930"
    }, {
      "firstName" : "MG",
      "lastName" : "Mattei",
      "authorRank" : 4,
      "name" : "Mattei MG",
      "referenceId" : "RGD:A5931"
    }, {
      "firstName" : "M",
      "lastName" : "Lazdunski",
      "authorRank" : 5,
      "name" : "Lazdunski M",
      "referenceId" : "RGD:A119165"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68804"
    } ]
  }, {
    "primaryId" : "PMID:10457184",
    "title" : "Alternative splicing generates a novel isoform of the rat metabotropic GABA(B)R1 receptor.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Pfaff T, etal., Eur J Neurosci 1999 Aug;11(8):2874-82.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:36.000-05:00",
    "volume" : "11",
    "pages" : "2874-82",
    "abstract" : "Here we present a novel isoform of the metabotropic G-protein-coupled receptor for gamma-aminobutyric acid (GABA). The isoform, termed GABA(B)R1c (R1c), differs from the recently identified R1a and R1b receptors by an in-frame insertion of 31 amino acids between the second extracellular loop and the fifth transmembrane region. Analysis of the rat GABA(B)R1 gene demonstrates that the insertion is the result of an alternative splicing event within a 567-bp intron between exons 16 and 17. In situ hybridization in the rat brain shows a wide distribution of R1c transcripts and an overlap with the R1a and R1b transcripts. The highest mRNA levels are found in cerebellar Purkinje cells, cerebral cortex, thalamus and hippocampal CA1 and CA3 regions. Western blots and immunodetection of recombinant epitope-tagged receptors as well as [125I]CGP71872 photoaffinity labelling of cell membranes demonstrate that R1c is correctly expressed, although at a lower level than the previously identified isoforms. When coexpressed with the newly characterized GABA(B)R2, R1c functionally couples to G-protein-activated Kir3.1/3.2 channels in Xenopus oocytes and to PLC-activating chimeric G(alpha)qo subunits in HEK-293 cells with a similar EC50 for agonists. These data suggest that the R1c isoform represents a functional GABA(B)R in the rat brain.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Pfaff",
      "authorRank" : 1,
      "name" : "Pfaff T",
      "referenceId" : "RGD:A15139"
    }, {
      "firstName" : "B",
      "lastName" : "Malitschek",
      "authorRank" : 2,
      "name" : "Malitschek B",
      "referenceId" : "RGD:A18701"
    }, {
      "firstName" : "K",
      "lastName" : "Kaupmann",
      "authorRank" : 3,
      "name" : "Kaupmann K",
      "referenceId" : "RGD:A18702"
    }, {
      "firstName" : "L",
      "lastName" : "Prezeau",
      "authorRank" : 4,
      "name" : "Prezeau L",
      "referenceId" : "RGD:A18703"
    }, {
      "firstName" : "JP",
      "lastName" : "Pin",
      "authorRank" : 5,
      "name" : "Pin JP",
      "referenceId" : "RGD:A12446"
    }, {
      "firstName" : "B",
      "lastName" : "Bettler",
      "authorRank" : 6,
      "name" : "Bettler B",
      "referenceId" : "RGD:A30921"
    }, {
      "firstName" : "A",
      "lastName" : "Karschin",
      "authorRank" : 7,
      "name" : "Karschin A",
      "referenceId" : "RGD:A161576"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632816"
    } ]
  }, {
    "primaryId" : "PMID:10457335",
    "title" : "Cholecystokinin-A receptor messenger RNA expression in human pancreatic cancer.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Moonka R, etal., J Gastrointest Surg. 1999 Mar-Apr;3(2):134-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-08-18T10:47:11.000-05:00",
    "volume" : "3",
    "pages" : "134-40",
    "abstract" : "Cholecystokinin (CCK) is a gut peptide hormone known to stimulate postprandial gallbladder contraction and pancreatic enzyme secretion. It has also been shown to induce the growth of normal pancreas and of malignant and premalignant lesions in rodents. Although CCK has been shown to promote the growth of human adenocarcinoma cell lines, its role in the growth of human pancreatic adenocarcinomas in vivo is less clear. Localization of CCK receptors to neoplastic cells within resected human tissue specimens would be suggestive of its potential action as an in vivo promoter of human pancreatic cancer. Resected tissue specimens of pancreatic adenocarcinomas were therefore studied by both reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization for the presence of CCK-A receptors. Ninety percent of studied tumors demonstrated CCK-A expression by RT-PCR, and this expression was localized to neoplastic cells by in situ hybridization. An increase in the expression of CCK receptors is a mechanism by which pancreatic malignancies may gain a significant growth stimulus.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Moonka",
      "authorRank" : 1,
      "name" : "Moonka R",
      "referenceId" : "RGD:A126134"
    }, {
      "firstName" : "W",
      "lastName" : "Zhou",
      "authorRank" : 2,
      "name" : "Zhou W",
      "referenceId" : "RGD:A16135"
    }, {
      "firstName" : "JR",
      "lastName" : "Bell RH",
      "authorRank" : 3,
      "name" : "Bell RH JR",
      "referenceId" : "RGD:A126135"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4110817"
    } ]
  }, {
    "primaryId" : "PMID:10457370",
    "title" : "Rapid uptake and degradation of glycine by astroglial cells in culture: synthesis and release of serine and lactate.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Verleysdonk S, etal., Glia. 1999 Sep;27(3):239-48.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-09-16T13:56:01.000-05:00",
    "volume" : "27",
    "pages" : "239-48",
    "abstract" : "Free glycine is known to have vital functions in the mammalian brain, where it serves mainly as both neurotransmitter and neuromodulator. Despite its importance, little is known about the metabolic pathways of glycine synthesis and degradation in the central nervous system. In this study, the pathway of glycine metabolism in astroglia-rich primary cultures from rat brain was examined. The cells were allowed to degrade glycine in the presence of [U-(14)C]glycine, [U-(13)C]glycine or [(15)N]glycine. The resulting intra- and extracellular metabolites were analyzed both by high-performance liquid chromatography and by (13)C/(15)N nuclear magnetic resonance spectroscopy. Glycine was rapidly consumed in a process obeying first-order kinetics. The initial glycine consumption rate was 0.47 nmol per mg protein. The half-life of glycine radiolabel in the incubation medium was shorter than that of glycine mass. This suggests that glycine is produced from endogenous sources and released simultaneously with glycine uptake and metabolism. As the main metabolites of the glycine carbon skeleton in astroglia-rich primary cultures from rat brain, serine and lactate were released during glycine consumption. The main metabolite containing the glycine amino nitrogen was glutamine. To establish a metabolic pathway from glycine to serine in neural tissue, homogenates of rat brain and of neural primary cultures were assayed for their content of serine hydroxymethyltransferase (SHMT) and glycine cleavage system (GCS). SHMT activity was present in homogenates of rat brain as well as of astroglia-rich and neuron-rich primary cultures, whereas GCS activity was detectable only in homogenates of rat brain and astroglia-rich primary culture. Of the two known SHMT isoenzymes, only the mitochondrial form was found in rat brain homogenate. It is proposed that, in neural tissue, glycine is metabolized by the combined action of SHMT and the GCS. Owing to the absence of the GCS from neurons, astrocytes appear to be the only site of this part of glycine metabolism in brain. However, neurons are able to utilize as energy source the lactate formed by astroglial cells in this metabolic pathway.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Verleysdonk",
      "authorRank" : 1,
      "name" : "Verleysdonk S",
      "referenceId" : "RGD:A45084"
    }, {
      "firstName" : "H",
      "lastName" : "Martin",
      "authorRank" : 2,
      "name" : "Martin H",
      "referenceId" : "RGD:A100119"
    }, {
      "firstName" : "W",
      "lastName" : "Willker",
      "authorRank" : 3,
      "name" : "Willker W",
      "referenceId" : "RGD:A100120"
    }, {
      "firstName" : "D",
      "lastName" : "Leibfritz",
      "authorRank" : 4,
      "name" : "Leibfritz D",
      "referenceId" : "RGD:A100121"
    }, {
      "firstName" : "B",
      "lastName" : "Hamprecht",
      "authorRank" : 5,
      "name" : "Hamprecht B",
      "referenceId" : "RGD:A45085"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2300380"
    } ]
  }, {
    "primaryId" : "PMID:10457411",
    "title" : "Homozygous form of the Pelger-Huët anomaly.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Erice JG, etal., Haematologica. 1999 Aug;84(8):748.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T15:51:15.000-05:00",
    "volume" : "84",
    "pages" : "748",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J G",
      "lastName" : "Erice",
      "authorRank" : 1,
      "name" : "Erice JG",
      "referenceId" : "RGD:A585124"
    }, {
      "firstName" : "J M",
      "lastName" : "Pérez",
      "authorRank" : 2,
      "name" : "Pérez JM",
      "referenceId" : "RGD:A585125"
    }, {
      "firstName" : "F S",
      "lastName" : "Pericás",
      "authorRank" : 3,
      "name" : "Pericás FS",
      "referenceId" : "RGD:A585126"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598117075"
    } ]
  }, {
    "primaryId" : "PMID:10457895",
    "title" : "Nationwide collaborative study of HLA class II associations with distinct types of juvenile chronic arthritis (JCA) in Greece.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Pratsidou-Gertsi P, etal., Eur J Immunogenet. 1999 Aug;26(4):299-310.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-08-25T15:28:30.000-05:00",
    "volume" : "26",
    "pages" : "299-310",
    "abstract" : "The aim of this study was to investigate the association of different groups and subgroups of juvenile chronic arthritis (JCA) with HLA class II (DR, DP, DQ) alleles and/or haplotypes. Groups and subgroups were mainly distinguished on the basis of the type of onset, the course and complications of the disease, and some predefined disease markers according to the criteria proposed by the ILAR Standing Committee (Chile, 1994). On the basis of these criteria the following five JCA groups and their subgroups were included in the study: (1) define systemic onset (n = 25) and systemic progressing to persistent arthritis (n = 14); (2) JCA of oligoarthritis onset (O-JCA, n = 124) and of oligoarthritis onset and course (n = 98), O-JCA of early (< 6 years) or late (> 6 years) onset (EOO-JCA n = 71 and LOO-JCA n = 44), O-JCA with ANA positive (n = 69) or negative (n = 55) and O-JCA progressing to extended arthritis (n = 22); (3) JCA of polyarthritis onset (P-JCA) with rheumatic factor (RF) negative (n = 29), and P-JCA RF negative with antinuclear antibodies (ANA) positive (n = 13) or negative (n = 16); (4) JCA complicated with chronic anterior uveitis (CAU, n = 32); (5) juvenile psoriatic arthritis (n = 20). To assess the HLA allele frequencies in the above 223 Greek children with JCA, these frequencies were compared to those of 98 age-matched and 250 adult controls. The main findings were the following. A common HLA-DRB1* allele was not involved in the JCA groups and subgroups studied; on the other hand, the DQA1*0501 allele was found to be associated with different JCA groups/subgroups (O-JCA, P-JCA RF-negative ANA-positive, JCA with CAU), probably suggesting a closer relationship of this locus with the immunogenetic background of JCA. The DPB1*0201 allele was associated with the development of either EOO-JCA or CAU. Susceptibility to CAU was stronger when the DPB1*0201 was combined with the presence of DRB1*13. Another allele, DQB1*0301, was also associated with O-JCA and CAU. Finally, no specific HLA class II allele was found to be related to the presence of ANA or psoriatic lesions or to the severity of the arthritis. Our findings suggest that the wide clinical and laboratory spectrum of JCA is associated with an immunogenetic background that is linked with HLA alleles of more than one locus. Some of them, such as the DPB1*0201 allele, confer susceptibility to certain clinical onsets and courses or complications of the disease. The rapidly advancing techniques of typing of DNA profiles may lead to more definite conclusions.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Pratsidou-Gertsi",
      "authorRank" : 1,
      "name" : "Pratsidou-Gertsi P",
      "referenceId" : "RGD:A143835"
    }, {
      "firstName" : "F",
      "lastName" : "Kanakoudi-Tsakalidou",
      "authorRank" : 2,
      "name" : "Kanakoudi-Tsakalidou F",
      "referenceId" : "RGD:A143836"
    }, {
      "firstName" : "M",
      "lastName" : "Spyropoulou",
      "authorRank" : 3,
      "name" : "Spyropoulou M",
      "referenceId" : "RGD:A143837"
    }, {
      "firstName" : "A",
      "lastName" : "Germenis",
      "authorRank" : 4,
      "name" : "Germenis A",
      "referenceId" : "RGD:A62191"
    }, {
      "firstName" : "K",
      "lastName" : "Adam",
      "authorRank" : 5,
      "name" : "Adam K",
      "referenceId" : "RGD:A143838"
    }, {
      "firstName" : "A",
      "lastName" : "Taparkou",
      "authorRank" : 6,
      "name" : "Taparkou A",
      "referenceId" : "RGD:A143839"
    }, {
      "firstName" : "A",
      "lastName" : "Siamopoulou",
      "authorRank" : 7,
      "name" : "Siamopoulou A",
      "referenceId" : "RGD:A143840"
    }, {
      "firstName" : "C",
      "lastName" : "Drakou",
      "authorRank" : 8,
      "name" : "Drakou C",
      "referenceId" : "RGD:A143841"
    }, {
      "firstName" : "T",
      "lastName" : "Konstantinidis",
      "authorRank" : 9,
      "name" : "Konstantinidis T",
      "referenceId" : "RGD:A143842"
    }, {
      "firstName" : "AM",
      "lastName" : "Prieur",
      "authorRank" : 10,
      "name" : "Prieur AM",
      "referenceId" : "RGD:A143843"
    }, {
      "firstName" : "C",
      "lastName" : "Stavropoulos-Giokas",
      "authorRank" : 11,
      "name" : "Stavropoulos-Giokas C",
      "referenceId" : "RGD:A143844"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5147863"
    } ]
  }, {
    "primaryId" : "PMID:10458336",
    "title" : "Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Walther MM, etal., J Urol. 1999 Sep;162(3 Pt 1):659-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T23:59:55.000-05:00",
    "volume" : "162",
    "pages" : "659-64",
    "abstract" : "PURPOSE: Families with von Hippel-Lindau disease have variable risk of pheochromocytoma. Patients with von Hippel-Lindau disease and pheochromocytoma identified by screening can have no characteristic signs or symptoms. Families with von Hippel-Lindau disease were screened and followed to describe the natural history of von Hippel-Lindau pheochromocytoma, and to correlate these findings with von Hippel-Lindau germline mutation. MATERIALS AND METHODS: Between 1988 and 1997, 246 individuals with von Hippel-Lindau disease were identified (von Hippel-Lindau group). Between August 1990 and June 1997, 26 consecutive patients  with sporadic pheochromocytoma were evaluated (sporadic group). RESULTS: A total  of 64 patients with von Hippel-Lindau disease had manifestations of pheochromocytoma, including 33 newly diagnosed during screening at the National Institutes of Health and 31 previously treated (93 adrenal and 13 extra-adrenal pheochromocytomas). Germline von Hippel-Lindau gene missense mutation was associated with extra-adrenal pheochromocytoma, younger age at presentation and the only patient with metastases. Of the 33 newly diagnosed patients with von Hippel-Lindau disease 4 had pheochromocytoma 2 times (37 pheochromocytomas) during followup. Of these pheochromocytomas 35% (13 of 37) were associated with no symptoms, normal blood pressure and normal catecholamine testing. Comparison of urinary catecholamines in the von Hippel-Lindau and sporadic groups demonstrated increased epinephrine, metanephrines and vanillylmandelic acid in the sporadic group. Analysis of urinary catecholamine excretion in the von Hippel-Lindau and sporadic groups together demonstrated a correlation between tumor size, and urinary metanephrines, vanillylmandelic acid, norepinephrine, epinephrine and dopamine. In 12 patients without signs or symptoms of pheochromocytoma 17 newly diagnosed pheochromocytomas were followed for a median  of 34.5 months without morbidity. Median tumor doubling time was 17 months. CONCLUSIONS: Von Hippel-Lindau gene missense mutation correlated with the risk of pheochromocytoma in patients with von Hippel-Lindau disease. These findings support a von Hippel-Lindau disease clinical classification, wherein some families are at high risk for manifestations of pheochromocytoma. Von Hippel-Lindau disease pheochromocytomas identified by screening were smaller and  less functional than sporadic pheochromocytomas.",
    "issueName" : "3 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MM",
      "lastName" : "Walther",
      "authorRank" : 1,
      "name" : "Walther MM",
      "referenceId" : "RGD:A71861"
    }, {
      "firstName" : "R",
      "lastName" : "Reiter",
      "authorRank" : 2,
      "name" : "Reiter R",
      "referenceId" : "RGD:A149741"
    }, {
      "firstName" : "HR",
      "lastName" : "Keiser",
      "authorRank" : 3,
      "name" : "Keiser",
      "referenceId" : "RGD:A170986"
    }, {
      "firstName" : "PL",
      "lastName" : "Choyke",
      "authorRank" : 4,
      "name" : "Choyke",
      "referenceId" : "RGD:A190766"
    }, {
      "firstName" : "D",
      "lastName" : "Venzon",
      "authorRank" : 5,
      "name" : "Venzon",
      "referenceId" : "RGD:A182707"
    }, {
      "firstName" : "K",
      "lastName" : "Hurley",
      "authorRank" : 6,
      "name" : "Hurley",
      "referenceId" : "RGD:A259414"
    }, {
      "firstName" : "JR",
      "lastName" : "Gnarra",
      "authorRank" : 7,
      "name" : "Gnarra JR",
      "referenceId" : "RGD:A35013"
    }, {
      "firstName" : "JC",
      "lastName" : "Reynolds",
      "authorRank" : 8,
      "name" : "Reynolds",
      "referenceId" : "RGD:A254729"
    }, {
      "firstName" : "GM",
      "lastName" : "Glenn",
      "authorRank" : 9,
      "name" : "Glenn GM",
      "referenceId" : "RGD:A71853"
    }, {
      "firstName" : "B",
      "lastName" : "Zbar",
      "authorRank" : 10,
      "name" : "Zbar B",
      "referenceId" : "RGD:A47608"
    }, {
      "firstName" : "WM",
      "lastName" : "Linehan",
      "authorRank" : 11,
      "name" : "Linehan WM",
      "referenceId" : "RGD:A35014"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11071794"
    } ]
  }, {
    "primaryId" : "PMID:10458410",
    "title" : "Differential RNA expression of the pS2 gene in the human benign and malignant prostatic tissue.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Colombel M, etal., J Urol. 1999 Sep;162(3 Pt 1):927-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-07-11T12:33:33.000-05:00",
    "volume" : "162",
    "pages" : "927-30",
    "abstract" : "PURPOSE: The pS2 trefoil protein has been detected in close association with neuro-endocrine differentiation in prostate cancer and prostatic intraepithelial neoplasia. These preliminary results have suggested that pS2 is a candidate as a specific marker for prostate cancer tissue. To ascertain the specificity of pS2 in prostate cancer tissue, we have used an RT-PCR method from prostate biopsies provided from human malignant and benign prostatic hyperplasia (BPH) tissue. MATERIALS AND METHODS: Prostate biopsies were obtained from transrectal biopsies from 153 patients with an abnormal DRE or a PSA more than 4 ng./ml. or symptoms of BPH and a PSA more than 4 ng./ml. Total RNA was extracted from fresh frozen specimens of tissue samples. Detection of pS2 transcript compared with GADPH transcripts was done using RT-PCR. RESULTS: Biopsy results showed that 108 patients had prostate cancer (average Gleason score 6.39+/-0.74) and 45 patients had BPH. PS2 RT-PCR results showed that PS2 RNA expression was negative in 83% of the BPH cases. Conversely, 92% of prostate cancer specimens were positive (Chi-square: 86.09, p<0.001). There was no correlation with tumor stage or the Gleason score. Comparing the expression of pS2 in BPH and localized prostate cancer, we found a sensitivity of 92% and a specificity of 82%. CONCLUSIONS: On this large sample of prostate biopsies from patients at risk of having prostate cancer, pS2 was demonstrated as an interesting marker significantly associated with prostate cancer. Further work on the expression of pS2 according to differentiation and hormonal status is in progress.",
    "issueName" : "3 Pt 1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Colombel",
      "authorRank" : 1,
      "name" : "Colombel M",
      "referenceId" : "RGD:A97753"
    }, {
      "firstName" : "R",
      "lastName" : "Dante",
      "authorRank" : 2,
      "name" : "Dante R",
      "referenceId" : "RGD:A97888"
    }, {
      "firstName" : "R",
      "lastName" : "Bouvier",
      "authorRank" : 3,
      "name" : "Bouvier R",
      "referenceId" : "RGD:A71575"
    }, {
      "firstName" : "S",
      "lastName" : "Ribieras",
      "authorRank" : 4,
      "name" : "Ribieras S",
      "referenceId" : "RGD:A97889"
    }, {
      "firstName" : "C",
      "lastName" : "Pangaud",
      "authorRank" : 5,
      "name" : "Pangaud C",
      "referenceId" : "RGD:A97890"
    }, {
      "firstName" : "JM",
      "lastName" : "Marechal",
      "authorRank" : 6,
      "name" : "Marechal JM",
      "referenceId" : "RGD:A97891"
    }, {
      "firstName" : "Y",
      "lastName" : "Lasne",
      "authorRank" : 7,
      "name" : "Lasne Y",
      "referenceId" : "RGD:A97892"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2298571"
    } ]
  }, {
    "primaryId" : "PMID:10458478",
    "title" : "Better-surviving liver grafts by the injection of anti-CD2 antibody: the important roles of host CD8+ and CD2+CD28+ T cells in chronic graft rejection and beta type platelet-derived growth factor receptor (PDGFR-beta) expression on apoptotic liver grafts.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Nakatsuji T Tohoku J Exp Med. 1999 Mar;187(3):215-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-06-06T12:41:11.000-05:00",
    "volume" : "187",
    "pages" : "215-25",
    "abstract" : "Syngeneic liver grafts were implanted in the livers of 22 LEW/Sea strain rats. To prolong the graft survival, anti-CD2 monoclonal antibody (MAb) or anti beta type platelet-derived growth factor receptor (PDGFR-beta) antibody (Ab) was injected, or splenectomy was performed in the rats which were then followed until 10 to 11 weeks posttransplantation. The 22 rats with chronic graft rejection showed increased CD8a-like antigen (probably Fas ligand) on the peripheral blood T cells. All the liver grafts had both necrosis and apoptosis. The liver graft apoptosis was indicated by histopathological abnormalities, and by DNA strand breaks and hemosiderin depositions in the cytoplasm. PDGFR-beta expression in the apoptotic liver graft was demonstrated immunohistochemically. Among the 17 rats injected with anti-CD2 MAb, CD2 signaling on host T cells was effectively suppressed by the injection of anti-CD2 MAb in 4 rats with better-surviving liver grafts. In these 4 rats, CD28 antigen on thymic lymphocytes was down-modulated and high numbers (136-233-positive cells per lobe) of the epithelial reticular cells with apoptotic lymphocytes were counted. Anti-PDGFR-beta Ab caused high pulmonary secretions of growth factors and reticular fibrosis in the lungs of 5 rats injected with the Ab. Anti-PDGFR-beta Ab injection reduced the host cell apoptosis in the lung and thymus, but did not prolong the survival of liver grafts. In the 9 rats with both splenectomy and anti-CD2 MAb injection, pulmonary apoptosis was induced with the 6-16% reductions of CD4+ lymphocytes. Prolonged graft survival was observed in only one of the 9 rats. Anti-CD2 MAb was effective for prolonging the liver graft survival with suppressed CD28 antigen, but anti-PDGFR-beta Ab and splenectomy were not.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Nakatsuji",
      "authorRank" : 1,
      "name" : "Nakatsuji T",
      "referenceId" : "RGD:A83900"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1625382"
    } ]
  }, {
    "primaryId" : "PMID:10458767",
    "title" : "STAT-4 mediated IL-12 signaling pathway is critical for the development of protective immunity in cutaneous leishmaniasis.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Stamm LM, etal., Eur J Immunol. 1999 Aug;29(8):2524-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-06-12T14:55:21.000-05:00",
    "volume" : "29",
    "pages" : "2524-9",
    "abstract" : "Recent studies have demonstrated that two IL-12 signaling pathways, a STAT 4 - dependent and STAT4 - independent, are involved in the development of a Th1-like  response. To determine their roles in the development of protective immunity against Leishmania major, we monitored progression of cutaneous Leishmania major  infection in STAT4-deficient mice (STAT4-/-) compared to similarly infected wild-type (STAT4+/+) mice. Although the onset of lesion growth was delayed in STAT4-/- mice during the early phase of infection, these mice eventually developed large, non-healing lesions, whereas STAT4+/+ mice resolved their lesions. As infection progressed, both STAT4+/+ and STAT4-/- mice infected with L. major displayed similar titers of Leishmania-specific IgG1 and IgE but later produced lower IgG2a. On days 20 and 40 post-infection, Leishmania antigen-stimulated lymphnode cells from STAT4-/- mice produced significantly lower amounts of IFN-gamma than those from STAT4+/+ mice as measured by enzyme-linked immunosorbent assay. There was no significant difference, however,  in IL-4 and IL-12 production between the two groups. These results indicate that  STAT4-mediated IL-12 signaling is critical for the development of protective Th1  response following L. major infection in genetically resistant mice. Additionally, they demonstrate that, although genetically resistant mice lacking  STAT4 signaling pathway develop large, non-healing lesions, they do not default towards a Th2-like response.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LM",
      "lastName" : "Stamm",
      "authorRank" : 1,
      "name" : "Stamm",
      "referenceId" : "RGD:A189618"
    }, {
      "firstName" : "AA",
      "lastName" : "Satoskar",
      "authorRank" : 2,
      "name" : "Satoskar",
      "referenceId" : "RGD:A174669"
    }, {
      "firstName" : "SK",
      "lastName" : "Ghosh",
      "authorRank" : 3,
      "name" : "Ghosh SK",
      "referenceId" : "RGD:A11997"
    }, {
      "firstName" : "JR",
      "lastName" : "David",
      "authorRank" : 4,
      "name" : "David",
      "referenceId" : "RGD:A189619"
    }, {
      "firstName" : "AR",
      "lastName" : "Satoskar",
      "authorRank" : 5,
      "name" : "Satoskar",
      "referenceId" : "RGD:A189600"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8661703"
    } ]
  }, {
    "primaryId" : "PMID:10459012",
    "title" : "VAMP-7 mediates vesicular transport from endosomes to lysosomes.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Advani RJ, etal., J Cell Biol. 1999 Aug 23;146(4):765-76.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:43:49.000-05:00",
    "volume" : "146",
    "pages" : "765-76",
    "abstract" : "A more complete picture of the molecules that are critical for the organization of membrane compartments is beginning to emerge through the characterization of proteins in the vesicle-associated membrane protein (also called synaptobrevin) family of membrane trafficking proteins. To better understand the mechanisms of membrane trafficking within the endocytic pathway, we generated a series of monoclonal and polyclonal antibodies against the cytoplasmic domain of vesicle-associated membrane protein 7 (VAMP-7). The antibodies recognize a 25-kD  membrane-associated protein in multiple tissues and cell lines. Immunohistochemical analysis reveals colocalization with a marker of late endosomes and lysosomes, lysosome-associated membrane protein 1 (LAMP-1), but not with other membrane markers, including p115 and transferrin receptor. Treatment with nocodozole or brefeldin A does not disrupt the colocalization of VAMP-7 and  LAMP-1. Immunoelectron microscopy analysis shows that VAMP-7 is most concentrated in the trans-Golgi network region of the cell as well as late endosomes and transport vesicles that do not contain the mannose-6 phosphate receptor. In streptolysin- O-permeabilized cells, antibodies against VAMP-7 inhibit the breakdown of epidermal growth factor but not the recycling of transferrin. These  data are consistent with a role for VAMP-7 in the vesicular transport of proteins from the early endosome to the lysosome.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "RJ",
      "lastName" : "Advani",
      "authorRank" : 1,
      "name" : "Advani RJ",
      "referenceId" : "RGD:A23087"
    }, {
      "firstName" : "B",
      "lastName" : "Yang",
      "authorRank" : 2,
      "name" : "Yang B",
      "referenceId" : "RGD:A35618"
    }, {
      "firstName" : "R",
      "lastName" : "Prekeris",
      "authorRank" : 3,
      "name" : "Prekeris R",
      "referenceId" : "RGD:A23092"
    }, {
      "firstName" : "KC",
      "lastName" : "Lee",
      "authorRank" : 4,
      "name" : "Lee KC",
      "referenceId" : "RGD:A67703"
    }, {
      "firstName" : "J",
      "lastName" : "Klumperman",
      "authorRank" : 5,
      "name" : "Klumperman",
      "referenceId" : "RGD:A183839"
    }, {
      "firstName" : "RH",
      "lastName" : "Scheller",
      "authorRank" : 6,
      "name" : "Scheller",
      "referenceId" : "RGD:A408896"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554473"
    } ]
  }, {
    "primaryId" : "PMID:10459348",
    "title" : "Classification of IVS1-10T-->C as a polymorphism of BRCA1.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Fetzer S, etal., Cancer Genet Cytogenet. 1999 Aug;113(1):58-64.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:47:08.000-05:00",
    "volume" : "113",
    "pages" : "58-64",
    "abstract" : "Mutations inactivating the tumor suppressor gene BRCA1 may be responsible for disease for up to 80% of familial ovarian cancer cases. In this syndrome, tumorigenesis classically initiates from an inherited mutation in one allele followed by somatic deletion of the normal allele. Sequencing of BRCA1 amplified  from genomic DNA of lymphocytes and microdissected ovarian tumor cells of a familial ovarian cancer patient revealed three, rare heterozygous DNA variations  (2418delA, 233G-->A, and IVS1-10T-->C) in both tumor and constitutional (lymphocyte) DNA. Thus, both copies of BRCA1 were retained in tumor. Haplotype analysis of the patient and four siblings assigned 2418delA to one copy of BRCA1  and 233G-->A and IVS1-10T-->C to the other. The DNA change, 2418delA, is considered a mutation that inactivated one BRCA1 allele because it caused a frameshift and generation of a premature stop codon, resulting in synthesis of a  truncated peptide as evidenced by an in vitro protein truncation test. The DNA variation, 233G-->A, does not result in an amino acid change, and is considered a benign polymorphism. IVS1-10T-->C is a unique BRCA1 change that occurs in the last nucleotide of a consensus sequence for a branch site critical for RNA splicing. Therefore, we investigated whether IVS1-10T-->C deleteriously affected  BRCA1 splicing or expression, and thereby inactivated the other BRCA1 allele. Using the technique of reverse transcription-polymerase chain reaction (PCR) with RNA isolated from lymphoid cell lines of the patient and of controls, no evidence was found that IVS1-10TC abnormally disrupted mRNA splicing or caused the absence of BRCA1 mRNA. Thus, IVS1-10T-->C is not harmful to BRCA1 function, and is classified a benign polymorphism. Retention of the normal BRCA1 allele in the tumor with the heterozygous germline BRCA1 mutation, 2418delA, indicated that mutational inactivation of both BRCA1 alleles was not required for tumorigenesis. It is possible that the normal allele may be functionally inactivated by a nonmutational mechanism.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Fetzer",
      "authorRank" : 1,
      "name" : "Fetzer",
      "referenceId" : "RGD:A364827"
    }, {
      "firstName" : "HA",
      "lastName" : "Tworek",
      "authorRank" : 2,
      "name" : "Tworek",
      "referenceId" : "RGD:A364828"
    }, {
      "firstName" : "MS",
      "lastName" : "Piver",
      "authorRank" : 3,
      "name" : "Piver",
      "referenceId" : "RGD:A254860"
    }, {
      "firstName" : "RA",
      "lastName" : "Dicioccio",
      "authorRank" : 4,
      "name" : "Dicioccio RA",
      "referenceId" : "RGD:A97420"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11527875"
    } ]
  }, {
    "primaryId" : "PMID:10459747",
    "title" : "Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Fukutani Y, etal., Psychiatry Clin Neurosci. 1999 Jun;53(3):425-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:12:08.000-05:00",
    "volume" : "53",
    "pages" : "425-8",
    "abstract" : "A 26-year-old Japanese woman slowly developed a change of character such as hypospontaneity and blunted affect, followed by obvious mental deterioration. She was diagnosed as having a disorganized type of schizophrenia at the first examination. Brain magnetic resonance imaging demonstrated diffuse high intensity in the cerebral white matter, particularly in the frontal lobes. The single photon emission computed tomography images using 123I-IMP disclosed diffuse cerebral hypofusion, especially in the frontal lobes. Electroencephalogram showed a moderate amount of 5-6Hz theta waves on the background of alpha activity. Nerve conduction velocities in the extremities were delayed. The level of leucocyte arylsulphatase was low. In the arylsulphatase A gene analysis, a compound heterozygote having the 99Gly-->Asp and 409Thr-->Ile mutations was confirmed. The patient was diagnosed as having metachromatic leukodystrophy. She gradually showed obvious dementing symptoms such as memory disturbance and disorientation.  The characteristics of the psychiatric symptoms in the leukodystrophy are discussed.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Fukutani",
      "authorRank" : 1,
      "name" : "Fukutani",
      "referenceId" : "RGD:A275075"
    }, {
      "firstName" : "Y",
      "lastName" : "Noriki",
      "authorRank" : 2,
      "name" : "Noriki",
      "referenceId" : "RGD:A275076"
    }, {
      "firstName" : "K",
      "lastName" : "Sasaki",
      "authorRank" : 3,
      "name" : "Sasaki K",
      "referenceId" : "RGD:A10349"
    }, {
      "firstName" : "K",
      "lastName" : "Isaki",
      "authorRank" : 4,
      "name" : "Isaki",
      "referenceId" : "RGD:A275077"
    }, {
      "firstName" : "M",
      "lastName" : "Kuriyama",
      "authorRank" : 5,
      "name" : "Kuriyama M",
      "referenceId" : "RGD:A31338"
    }, {
      "firstName" : "K",
      "lastName" : "Kurosawa",
      "authorRank" : 6,
      "name" : "Kurosawa K",
      "referenceId" : "RGD:A77302"
    }, {
      "firstName" : "H",
      "lastName" : "Ida",
      "authorRank" : 7,
      "name" : "Ida H",
      "referenceId" : "RGD:A155646"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069855"
    } ]
  }, {
    "primaryId" : "PMID:104600",
    "title" : "Uterine anomalies associated with renal agenesis: role of gray scale ultrasonography.",
    "datePublished" : "1978-09-01T00:00:00.000-05:00",
    "citation" : "Fried AM, etal., AJR Am J Roentgenol 1978 Dec;131(6):973-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-26T11:04:46.000-05:00",
    "volume" : "131",
    "pages" : "973-5",
    "abstract" : "Anomalies of the female genital tract were successfully characterized by gray scale ultrasonography in three cases; all three were found in association with unilateral renal agenesis. Findings at intravenous urography prompted ultrasound studies. The high incidence of genital tract anomalies associated with unilateral renal agenesis, particularly in females, indicates ultrasonography be used to examine the pelvis (as well as the renal bed). Further diagnostic procedures can then be assessed on a more informed basis.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "AM",
      "lastName" : "Fried",
      "authorRank" : 1,
      "name" : "Fried AM",
      "referenceId" : "RGD:A25140"
    }, {
      "firstName" : "M",
      "lastName" : "Oliff",
      "authorRank" : 2,
      "name" : "Oliff M",
      "referenceId" : "RGD:A25141"
    }, {
      "firstName" : "EA",
      "lastName" : "Wilson",
      "authorRank" : 3,
      "name" : "Wilson EA",
      "referenceId" : "RGD:A25142"
    }, {
      "firstName" : "J",
      "lastName" : "Whisnant",
      "authorRank" : 4,
      "name" : "Whisnant J",
      "referenceId" : "RGD:A25143"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634811"
    } ]
  }, {
    "primaryId" : "PMID:10460069",
    "title" : "Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Danish University Antidepressant Group (DUAG).",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "NO_AUTHOR Clin Pharmacol Ther. 1999 Aug;66(2):152-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-06-08T20:25:15.000-05:00",
    "volume" : "66",
    "pages" : "152-65",
    "abstract" : "OBJECTIVE: To examine the problems of establishing dose-effect and concentration-effect relationships of antidepressant therapy with clomipramine. METHODS: This randomized double-blind study compared five fixed doses of clomipramine hydrochloride: 25, 50, 75, 125, and 200 mg/day in hospitalized or day patients at nine clinical centers in Denmark. A 1-week washout period was followed by 6 weeks of active treatment and weekly depression ratings. In total,  151 patients (100 women and 51 men) with major depression scoring > or =18 on the Hamilton Depression Scale (HDS) or > or =9 on the Hamilton Depression subscale (HDSS) before and after the washout period were randomized. The treatment groups  (n = 29 to 32) were well balanced with respect to sex, age, and depression rating. Serum concentrations of clomipramine plus metabolites were measured at weekly intervals. A sparteine test was performed before and during drug treatment. RESULTS: There was pronounced interpatient variability in response and kinetics at each dose. Drop-outs attributable to adverse events increased with rising doses, whereas drop-outs caused by worsening or lack of effect or nonresponse declined with increasing dose. Completer analyses showed a moderate and statistically significant relationship between depression rating and dose at  all ratings after 1 to 6 weeks of treatment (trend analysis). HDS items representing core symptoms of depression showed a particularly consistent dose-effect relationship. Early sustained response occurred more frequently with  the two highest doses. Serum levels of clomipramine and desmethylclomipramine showed weak correlation with depression ratings (Rs = -0.18 to -0.27; P < .05 to  P < .01). A few blood pressure measurements and a few typical side-effect ratings showed a statistically significant dose-effect and concentration-effect relationship. Serum concentration of clomipramine and desmethylclomipramine showed a pronounced disproportionate increase with increasing dose. Clomipramine  inhibited in a dose-dependent fashion CYP2D6 (sparteine oxidation). CONCLUSION: The dose-effect curves, indicating the probability of a certain outcome at a given dose, were flat and overlapping suggesting a narrow therapeutic range. This pattern is similar to that observed with newer antidepressants.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "authorRank" : 1,
      "name" : "",
      "referenceId" : "RGD:A417289"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11098854"
    } ]
  }, {
    "primaryId" : "PMID:10460242",
    "title" : "Ultrastructural localization of the serotonin transporter in limbic and motor compartments of the nucleus accumbens.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Pickel VM and Chan J, J Neurosci. 1999 Sep 1;19(17):7356-66.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-07-18T02:07:49.000-05:00",
    "volume" : "19",
    "pages" : "7356-66",
    "abstract" : "Extracellular levels of serotonin [5-hydroxytryptamine (5-HT)] in the nucleus accumbens (NAc) can influence both cognitive and motor functions involving extensive connections with the frontal cortex. The 5-HT levels reflect vesicular release and plasmalemmal reuptake through the serotonin transporter (SERT). We used electron microscopic immunocytochemistry to determine the sites for SERT activation in the limbic shell and motor-associated core of the rat NAc. Of the SERT-immunoreactive profiles in each region, >90% were serotonergic axons and axon terminals; the remainder were nonserotonergic dendrites and glia. Axonal SERT immunogold labeling was seen mainly at nonsynaptic sites on plasma membranes and often near 5-HT-containing large dense core vesicles (DCVs). SERT-labeled axonal profiles were larger and had a higher numerical density in the shell versus the core but showed no regional differences in their content of SERT immunogold particles. In contrast, immunoreactive dendrites had a lower numerical density in the shell than in the core. SERT labeling in dendrites was localized to segments of plasma membrane near synaptic contacts from unlabeled terminals and/or dendritic appositions. Our results suggest that in the NAc (1) reuptake into serotonergic axons is most efficient after exocytotic release from DCVs, and (2) increased 5-HT release without concomitant increase in SERT expression in individual axons may contribute to higher extracellular levels of serotonin in the shell versus the core. These findings also indicate that SERT may play a minor substrate-dependent role in serotonin uptake or channel activity in selective nonserotonergic neurons and glia in the NAc.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V M",
      "lastName" : "Pickel",
      "authorRank" : 1,
      "name" : "Pickel VM",
      "referenceId" : "RGD:A438016"
    }, {
      "firstName" : "J",
      "lastName" : "Chan",
      "authorRank" : 2,
      "name" : "Chan J",
      "referenceId" : "RGD:A43305"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13702349"
    } ]
  }, {
    "primaryId" : "PMID:10460248",
    "title" : "Regulated expression and subcellular localization of syndecan heparan sulfate proteoglycans and the syndecan-binding protein CASK/LIN-2 during rat brain development.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Hsueh YP and Sheng M, J Neurosci. 1999 Sep 1;19(17):7415-25.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-07-31T12:14:55.000-05:00",
    "volume" : "19",
    "pages" : "7415-25",
    "abstract" : "The syndecan family of cell surface heparan sulfate proteoglycans interacts via their cytoplasmic C-terminal tail with the PDZ domain of CASK/LIN-2, a membrane-associated guanylate kinase homolog. The syndecan-CASK interaction may be involved in intercellular signaling and/or cell adhesion. Here we show that syndecan-1 to syndecan-4 have distinctive mRNA distributions in adult rat brain by in situ hybridization, with syndecan-2 and -3 being the major syndecans expressed in neurons of the forebrain. At the protein level, syndecan-2 and -3 are differentially localized within neurons; syndecan-3 is concentrated in axons, whereas syndecan-2 is localized in synapses. The synaptic accumulation of syndecan-2 occurs late in synapse development. CASK is a cytoplasmic-binding partner for syndecans, and its subcellular distribution changes strikingly during development, shifting from a primarily axonal distribution in the first 2 postnatal weeks to a somatodendritic distribution in adult brain. This change in CASK distribution correlates temporally and spatially with the expression patterns of syndecan-3 and -2, consistent with the association of both of these syndecans with CASK in vivo. In support of this, we were able to coimmunoprecipitate a complex of CASK and syndecan-3 from brain extracts. Our results indicate that specific syndecans are differentially expressed in various cell types of the brain and are targeted to distinct subcellular compartments in neurons, where they may serve specialized functions. Moreover, CASK is appropriately expressed and localized to interact with both syndecan-2 and -3 in different compartments of the neuron throughout postnatal development.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YP",
      "lastName" : "Hsueh",
      "authorRank" : 1,
      "name" : "Hsueh YP",
      "referenceId" : "RGD:A30517"
    }, {
      "firstName" : "M",
      "lastName" : "Sheng",
      "authorRank" : 2,
      "name" : "Sheng M",
      "referenceId" : "RGD:A6139"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311711"
    } ]
  }, {
    "primaryId" : "PMID:10460255",
    "title" : "cAMP-dependent protein kinase phosphorylations on tau in Alzheimer's disease.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Jicha GA, etal., J Neurosci. 1999 Sep 1;19(17):7486-94.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-16T13:42:24.000-05:00",
    "volume" : "19",
    "pages" : "7486-94",
    "abstract" : "To elucidate the role cAMP-dependent protein kinase (PKA) phosphorylations on tau play in Alzheimer's disease, we have generated highly specific monoclonal antibodies, CP-3 and PG-5, which recognize the PKA-dependent phosphorylations of ser214 and ser409 in tau respectively. The present study demonstrates by immunohistochemical analysis, CP-3 and PG-5 immunoreactivity with neurofibrillary pathology in both early and advanced Alzheimer's disease, but not in normal brain tissue and demonstrates that cAMP-dependent protein kinase phosphorylations on tau precede or are coincident with the initial appearance of filamentous aggregates of tau. Studies using heat-stable preparations demonstrate that neither site appears to be phosphorylated to any appreciable extent in normal rodent or human brain. Further analysis demonstrates that the beta catalytic subunit of PKA (Cbeta), the beta II regulatory subunit of PKA (RIIbeta), and the 79 kDa A-kinase-anchoring-protein (AKAP79), are tightly associated with the neurofibrillary pathology, positioning cAMP-dependent protein kinase to participate directly in the pathological hyperphosphorylation of tau seen in Alzheimer's disease.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GA",
      "lastName" : "Jicha",
      "authorRank" : 1,
      "name" : "Jicha GA",
      "referenceId" : "RGD:A112214"
    }, {
      "firstName" : "C",
      "lastName" : "Weaver",
      "authorRank" : 2,
      "name" : "Weaver C",
      "referenceId" : "RGD:A112215"
    }, {
      "firstName" : "E",
      "lastName" : "Lane",
      "authorRank" : 3,
      "name" : "Lane E",
      "referenceId" : "RGD:A112216"
    }, {
      "firstName" : "C",
      "lastName" : "Vianna",
      "authorRank" : 4,
      "name" : "Vianna C",
      "referenceId" : "RGD:A112217"
    }, {
      "firstName" : "Y",
      "lastName" : "Kress",
      "authorRank" : 5,
      "name" : "Kress Y",
      "referenceId" : "RGD:A112218"
    }, {
      "firstName" : "J",
      "lastName" : "Rockwood",
      "authorRank" : 6,
      "name" : "Rockwood J",
      "referenceId" : "RGD:A46755"
    }, {
      "firstName" : "P",
      "lastName" : "Davies",
      "authorRank" : 7,
      "name" : "Davies P",
      "referenceId" : "RGD:A162052"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313287"
    } ]
  }, {
    "primaryId" : "PMID:10460412",
    "title" : "Identification and characterization of MmORC4 and MmORC5, two subunits of the mouse origin of replication recognition complex.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Springer J, etal., Chromosoma 1999 Aug;108(4):243-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:49:37.000-05:00",
    "volume" : "108",
    "pages" : "243-9",
    "abstract" : "Two new members of the mouse origin recognition complex (ORC) have been cloned that are closely related to Saccharomyces cerevisiae ORC4 and ORC5 as well as to their human homolog. Both MmORC4p and MmORC5p have a putative nucleotide triphosphate binding motif. Transcription of MmORC4 and MmORC5 is not suppressed in mouse NIH3T3 fibroblasts made quiescent by serum starvation. The transcription levels of both ORC genes are constantly high in all phases of the cell cycle. A screen based on the two-hybrid approach suggests that the product of the ORC4 gene interacts with the ORC2, but not with the ORC1 protein. The conservation of structure among members of the ORC4- and ORC5-related family of proteins suggests that these proteins play a key role in the initiation of DNA replication in all eukaryotes.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Springer",
      "authorRank" : 1,
      "name" : "Springer J",
      "referenceId" : "RGD:A47492"
    }, {
      "firstName" : "M",
      "lastName" : "Kneissl",
      "authorRank" : 2,
      "name" : "Kneissl M",
      "referenceId" : "RGD:A47493"
    }, {
      "firstName" : "V",
      "lastName" : "Putter",
      "authorRank" : 3,
      "name" : "Putter V",
      "referenceId" : "RGD:A47494"
    }, {
      "firstName" : "F",
      "lastName" : "Grummt",
      "authorRank" : 4,
      "name" : "Grummt F",
      "referenceId" : "RGD:A47495"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302845"
    } ]
  }, {
    "primaryId" : "PMID:10460751",
    "title" : "Selective expression of RT6 superfamily in human bronchial epithelial cells.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Balducci E, etal., Am J Respir Cell Mol Biol 1999 Sep;21(3):337-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-03T13:45:05.000-05:00",
    "volume" : "21",
    "pages" : "337-46",
    "abstract" : "RT6 proteins are glycosylphosphatidylinositol (GPI)-linked alloantigens that are localized to cytotoxic T lymphocytes and that have nicotinamide adenine dinucleotide glycohydrolase and adenosine diphosphate (ADP)-ribosyltransferase activities. In view of the importance of GPI-linked surface proteins in mediating interactions of cells with their milieu, and the varied functions of airway cells in inflammation, we undertook the present study to determine whether human homologues of the RT6 superfamily of ADP-ribosyltransferases (ART) are expressed in pulmonary epithelial cells. We hypothesized that these surface proteins or related family members may be present in cells that interact with inflammatory cells, and that they may thereby be involved in intercellular signaling. Using in situ analysis and Northern blot analysis, we identified ART1 messenger RNA (mRNA) in airway epithelial cells. As expected for GPI-anchored proteins, the localization of ART1 at the apical surface of ciliated epithelial cells was demonstrated by staining with polyclonal anti-ART1 antibody, and was confirmed by loss of this immunoreactivity after treatment with phosphatidylinositol-specific phospholipase C (PI-PLC), which selectively cleaves GPI anchors and releases proteins from the plasma membrane. Using in situ hybridization with specific ART3 and ART4 oligonucleotides, we also identified two additional members of the RT6 superfamily in epithelial cells. In accord with these findings, we identified ART3 and ART4 mRNAs through reverse transcription- polymerase chain reaction of polyadenine-positive RNA from human trachea. Interestingly, these proteins appeared to be preferentially localized to the airway epithelium. The localized expression of these members of the RT6 superfamily in human pulmonary epithelial cells may reflect a role for them in cell-cell signaling during immune responses within the airway.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Balducci",
      "authorRank" : 1,
      "name" : "Balducci E",
      "referenceId" : "RGD:A24385"
    }, {
      "firstName" : "K",
      "lastName" : "Horiba",
      "authorRank" : 2,
      "name" : "Horiba K",
      "referenceId" : "RGD:A24386"
    }, {
      "firstName" : "J",
      "lastName" : "Usuki",
      "authorRank" : 3,
      "name" : "Usuki J",
      "referenceId" : "RGD:A24387"
    }, {
      "firstName" : "M",
      "lastName" : "Park",
      "authorRank" : 4,
      "name" : "Park M",
      "referenceId" : "RGD:A8593"
    }, {
      "firstName" : "VJ",
      "lastName" : "Ferrans",
      "authorRank" : 5,
      "name" : "Ferrans VJ",
      "referenceId" : "RGD:A24388"
    }, {
      "firstName" : "J",
      "lastName" : "Moss",
      "authorRank" : 6,
      "name" : "Moss J",
      "referenceId" : "RGD:A5836"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634605"
    } ]
  }, {
    "primaryId" : "PMID:10460800",
    "title" : "Glucuronidation of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by rat UDP-glucuronosyltransferase 2B1.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Ren Q, etal., Drug Metab Dispos. 1999 Sep;27(9):1010-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2022-06-30T11:08:25.000-05:00",
    "volume" : "27",
    "pages" : "1010-6",
    "abstract" : "4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are potent lung carcinogens in animals. UDP-glucuronosyltransferase (UGT)-mediated glucuronidation of NNAL is a potentially important detoxification pathway for these carcinogens. To identify the UGT isozyme(s) involved in this pathway, we examined the glucuronidation of NNAL in rat liver microsomes and homogenates from cell lines overexpressing specific UGT isozymes. NNAL glucuronidation was induced in liver microsomes from rats treated with family 2 UGT inducers including phenobarbitol and 3, 5-di-tert-butyl-4-hydroxytoluene, which exhibited 1.7- and 2.6-fold higher rates of glucuronidation than microsomes from control rats. The rates of NNAL glucuronidation in liver microsomes from GUNN (deficient in family 1 UGTs) and RHA parental control rats were similar. All rat liver microsomes used in the present study catalyzed the glucuronidation of (S)-NNAL at a rate between 3.5 and 5.5 times that of the glucuronidation of (R)-NNAL. Liver microsomes from Wistar rats exhibiting the low-androsterone glucuronidation phenotype characteristic of the UGT2B2-deficient genotype glucuronidated NNAL at a rate similar to microsomes from Wistar rats exhibiting the high-androsterone glucuronidation phenotype/UGT2B2 [+] genotype. Homogenates from UGT2B1-overexpressing cells catalyzed the glucuronidation of NNAL at a K(m) of 745 microM. As with rat liver microsomes, NNAL-Gluc I was the major diastereomer formed by UGT2B1. Glucuronidation of NNAL was not detected with homogenates from UGT2B12-overexpressing cells. These results suggest that UGT2B1 plays an important role in the glucuronidation of NNAL in the rat.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Ren",
      "authorRank" : 1,
      "name" : "Ren Q",
      "referenceId" : "RGD:A110790"
    }, {
      "firstName" : "S E",
      "lastName" : "Murphy",
      "authorRank" : 2,
      "name" : "Murphy SE",
      "referenceId" : "RGD:A517846"
    }, {
      "firstName" : "A J",
      "lastName" : "Dannenberg",
      "authorRank" : 3,
      "name" : "Dannenberg AJ",
      "referenceId" : "RGD:A517847"
    }, {
      "firstName" : "J Y",
      "lastName" : "Park",
      "authorRank" : 4,
      "name" : "Park JY",
      "referenceId" : "RGD:A472494"
    }, {
      "firstName" : "T R",
      "lastName" : "Tephly",
      "authorRank" : 5,
      "name" : "Tephly TR",
      "referenceId" : "RGD:A436763"
    }, {
      "firstName" : "P",
      "lastName" : "Lazarus",
      "authorRank" : 6,
      "name" : "Lazarus P",
      "referenceId" : "RGD:A137515"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:152998887"
    } ]
  }, {
    "primaryId" : "PMID:10460895",
    "title" : "Expression of bone matrix proteins in urolithiasis model rats.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Yasui T, etal., Urol Res. 1999 Aug;27(4):255-61.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-11-11T12:51:41.000-06:00",
    "volume" : "27",
    "pages" : "255-61",
    "abstract" : "Urinary calcium stones are a pathological substance, and they show similarities to physiological mineralization and other pathological mineralizations. The expression of messenger (m) RNAs of osteopontin (OPN), matrix Gla protein (MGP), osteonectin (ON) and osteocalcin (OC) in bones and teeth has been described. We previously identified OPN as an important stone matrix protein. In addition, the spontaneous calcification of arteries and cartilage in mice lacking MGP was recently reported, a finding which indicates that MGP has a function as an inhibitor of mineralization. Here, we examined the mRNA expressions of OPN, MGP, ON, and OC in the kidneys of stone-forming model rats administered an oxalate precursor, ethylene glycol (EG) for up to 28 days. The Northern blotting showed that the mRNA expressions of OPN and MGP were markedly increased with the administration of EG, but their expression patterns differed. The OPN mRNA expression reached the maximal level at day 7 after the initiation of the EG treatment and showed no significant difference after 14 and 28 days, whereas the MGP mRNA expression rose gradually to day 28. The in situ hybridization demonstrated that the cell type expressing OPN mRNA was different from that expressing MGP. We suggest that OPN acts on calcification and MGP acts on suppression.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Yasui",
      "authorRank" : 1,
      "name" : "Yasui T",
      "referenceId" : "RGD:A66501"
    }, {
      "firstName" : "K",
      "lastName" : "Fujita",
      "authorRank" : 2,
      "name" : "Fujita K",
      "referenceId" : "RGD:A25057"
    }, {
      "firstName" : "S",
      "lastName" : "Sasaki",
      "authorRank" : 3,
      "name" : "Sasaki S",
      "referenceId" : "RGD:A158371"
    }, {
      "firstName" : "M",
      "lastName" : "Sato",
      "authorRank" : 4,
      "name" : "Sato M",
      "referenceId" : "RGD:A154914"
    }, {
      "firstName" : "M",
      "lastName" : "Sugimoto",
      "authorRank" : 5,
      "name" : "Sugimoto M",
      "referenceId" : "RGD:A18876"
    }, {
      "firstName" : "S",
      "lastName" : "Hirota",
      "authorRank" : 6,
      "name" : "Hirota S",
      "referenceId" : "RGD:A13881"
    }, {
      "firstName" : "Y",
      "lastName" : "Kitamura",
      "authorRank" : 7,
      "name" : "Kitamura Y",
      "referenceId" : "RGD:A142002"
    }, {
      "firstName" : "S",
      "lastName" : "Nomura",
      "authorRank" : 8,
      "name" : "Nomura S",
      "referenceId" : "RGD:A10331"
    }, {
      "firstName" : "K",
      "lastName" : "Kohri",
      "authorRank" : 9,
      "name" : "Kohri K",
      "referenceId" : "RGD:A66504"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1582511"
    } ]
  }, {
    "primaryId" : "PMID:10461474",
    "title" : "Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Johansen JS, etal., Rheumatology (Oxford). 1999 Jul;38(7):618-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-02-25T11:04:45.000-06:00",
    "volume" : "38",
    "pages" : "618-26",
    "abstract" : "OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JS",
      "lastName" : "Johansen",
      "authorRank" : 1,
      "name" : "Johansen JS",
      "referenceId" : "RGD:A135185"
    }, {
      "firstName" : "M",
      "lastName" : "Stoltenberg",
      "authorRank" : 2,
      "name" : "Stoltenberg M",
      "referenceId" : "RGD:A135193"
    }, {
      "firstName" : "M",
      "lastName" : "Hansen",
      "authorRank" : 3,
      "name" : "Hansen M",
      "referenceId" : "RGD:A118713"
    }, {
      "firstName" : "A",
      "lastName" : "Florescu",
      "authorRank" : 4,
      "name" : "Florescu A",
      "referenceId" : "RGD:A135194"
    }, {
      "firstName" : "K",
      "lastName" : "Horslev-Petersen",
      "authorRank" : 5,
      "name" : "Horslev-Petersen K",
      "referenceId" : "RGD:A135195"
    }, {
      "firstName" : "I",
      "lastName" : "Lorenzen",
      "authorRank" : 6,
      "name" : "Lorenzen I",
      "referenceId" : "RGD:A135196"
    }, {
      "firstName" : "PA",
      "lastName" : "Price",
      "authorRank" : 7,
      "name" : "Price PA",
      "referenceId" : "RGD:A31094"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892605"
    } ]
  }, {
    "primaryId" : "PMID:10461810",
    "title" : "Glucokinase is concentrated in insulin-secretory granules of pancreatic B-cells.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Toyoda Y, etal., Histochem Cell Biol. 1999 Jul;112(1):35-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-11-11T15:51:06.000-06:00",
    "volume" : "112",
    "pages" : "35-40",
    "abstract" : "We immunohistochemically examined the distribution of glucokinase (GK) in the B-cells of pancreatic islets of normal rats. GK was stained punctately in the cytoplasm of B-cells when examined under the light microscope. By use of a double-immunostaining technique, most of the GK immunoreactivity was observed to be colocalized with insulin immunoreactivity. Electron microscopic examination by the immunogold method revealed that GK immunoreactivity was predominantly located within insulin-secretory granules of pancreatic B-cells. Exploration of the intracellular distribution of GK in hepatocytes suggested that the shuttling of the enzyme between the nucleus and the cytoplasm is essential for the regulation of GK activity (Toyoda et al. 1994, 1995, 1996a,b, 1997a). As an approach to the elucidation of the mechanism of control of GK activity, we immunohistochemically investigated the intracellular distribution of the enzyme in pancreatic B-cells under both light microscopy and electron microscopy in this study. A preliminary report of the present study has been published.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Toyoda",
      "authorRank" : 1,
      "name" : "Toyoda Y",
      "referenceId" : "RGD:A55249"
    }, {
      "firstName" : "S",
      "lastName" : "Yoshie",
      "authorRank" : 2,
      "name" : "Yoshie S",
      "referenceId" : "RGD:A81594"
    }, {
      "firstName" : "H",
      "lastName" : "Shironoguchi",
      "authorRank" : 3,
      "name" : "Shironoguchi H",
      "referenceId" : "RGD:A101718"
    }, {
      "firstName" : "I",
      "lastName" : "Miwa",
      "authorRank" : 4,
      "name" : "Miwa I",
      "referenceId" : "RGD:A101719"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301947"
    } ]
  }, {
    "primaryId" : "PMID:10461879",
    "title" : "Characterization of the cDNA coding for rat brain cysteine sulfinate decarboxylase: brain and liver enzymes are identical proteins encoded by two distinct mRNAs.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Tappaz M, etal., J Neurochem 1999 Sep;73(3):903-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T14:36:12.000-05:00",
    "volume" : "73",
    "pages" : "903-12",
    "abstract" : "Cysteine sulfinate decarboxylase (CSD) is considered as the rate-limiting enzyme in the biosynthesis of taurine, a possible osmoregulator in brain. Through cloning and sequencing of RT-PCR and RACE-PCR products of rat brain mRNAs, a 2,396-bp cDNA sequence was obtained encoding a protein of 493 amino acids (calculated molecular mass, 55.2 kDa). The corresponding fusion protein showed a substrate specificity similar to that of the endogenous enzyme. The sequence of the encoded protein is identical to that encoded by liver CSD cDNA. Among other characterized amino acid decarboxylases, CSD shows the highest homology (54%) with either isoform of glutamic acid decarboxylase (GAD65 and GAD67). A single mRNA band, approximately 2.5 kb, was detected by northern blot in RNA extracts of brain, liver, and kidney. However, brain and liver CSD cDNA sequences differed in the 5' untranslated region. This indicates two forms of CSD mRNA. Analysis of PCR-amplified products of genomic DNA suggests that the brain form results from the use of a 3' alternative internal splicing site within an exon specifically found in liver CSD mRNA. Through selective RT-PCR the brain form was detected in brain only, whereas the liver form was found in liver and kidney. These results indicate a tissue-specific regulation of CSD genomic expression.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Tappaz",
      "authorRank" : 1,
      "name" : "Tappaz M",
      "referenceId" : "RGD:A17941"
    }, {
      "firstName" : "M",
      "lastName" : "Bitoun",
      "authorRank" : 2,
      "name" : "Bitoun M",
      "referenceId" : "RGD:A17942"
    }, {
      "firstName" : "I",
      "lastName" : "Reymond",
      "authorRank" : 3,
      "name" : "Reymond I",
      "referenceId" : "RGD:A17943"
    }, {
      "firstName" : "A",
      "lastName" : "Sergeant",
      "authorRank" : 4,
      "name" : "Sergeant A",
      "referenceId" : "RGD:A17944"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632597"
    } ]
  }, {
    "primaryId" : "PMID:10461883",
    "title" : "Calnexin and the immunoglobulin binding protein (BiP) coimmunoprecipitate with AMPA receptors.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Rubio ME and Wenthold RJ, J Neurochem. 1999 Sep;73(3):942-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-11T11:11:02.000-05:00",
    "volume" : "73",
    "pages" : "942-8",
    "abstract" : "To identify proteins that interact with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, we carried out coimmunoprecipitation analyses on detergent-solubilized rat forebrain membranes. Membranes were solubilized with Triton X-100, and immunoprecipitation was done using subunit-specific antibodies to GluR1, GluR2/3, and GluR4 attached to protein Aagarose. Proteins bound to the antibodies were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining and western blotting. With solubilization in low ionic strength buffer, several coimmunoprecipitating proteins, with Mr = 17,000-100,000, were identified in silver-stained gels. Western blots were then probed with antibodies to a series of candidate proteins that were chosen based on the molecular masses of the copurifying proteins. Two of these were identified as the molecular chaperones calnexin (90 kDa) and the immunoglobulin binding protein (BiP; 78 kDa). Immunoprecipitation with antibodies to calnexin and BiP demonstrated that glycosylated AMPA receptor subunits were associated. The relationship between AMPA receptors and calnexin and BiP was further studied with immunocytochemistry of the hippocampus. Both calnexin and BiP labeling was present not only in the cell body but also in dendrites of hippocampal pyramidal neurons, where double-label immunofluorescence also showed the presence of AMPA receptor subunits.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "ME",
      "lastName" : "Rubio",
      "authorRank" : 1,
      "name" : "Rubio ME",
      "referenceId" : "RGD:A88742"
    }, {
      "firstName" : "RJ",
      "lastName" : "Wenthold",
      "authorRank" : 2,
      "name" : "Wenthold RJ",
      "referenceId" : "RGD:A4782"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313156"
    } ]
  }, {
    "primaryId" : "PMID:10462376",
    "title" : "Abnormal regulation of aortic NOS2 and NOS3 activity and expression from portal vein-stenosed rats after lipopolysaccharide administration.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Heller J, etal., Hepatology. 1999 Sep;30(3):698-704.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-08T15:54:01.000-06:00",
    "volume" : "30",
    "pages" : "698-704",
    "abstract" : "Hyporeactivity to vasoconstrictors in aortae from portal vein-stenosed rats is associated with an increased activity of endothelial NO synthase (NOS3). In contrast, during sepsis, which is common in cirrhosis, vascular hyporeactivity is associated with an induction of inducible NOS2. The aim of this study was to investigate the in vitro reactivity to phenylephrine and the regulation of NOS2 and NOS3 in aortae from portal vein-stenosed rats after lipopolysaccharide (LPS)  administration. Aortic vascular reactivity for phenylephrine, aortic NOS activity, and NOS2 and NOS3 protein expression were determined 5 hours after intravenous LPS or saline administration. Moreover, aortic NOS activity was measured after 5-hour in vitro incubation in LPS. LPS induced a significantly smaller decrease in aortic tension in portal vein-stenosed than in sham-operated  rats. Under baseline conditions, aortic NOS activity and NOS3 protein expression  were higher in portal vein-stenosed than in sham-operated rats, and NOS2 protein  expression was not detected in aortae from either group. After LPS administration, NOS activity and NOS2 protein expression increased significantly  less in portal vein-stenosed than in sham-operated rat aortae. Similar results were obtained after in vitro incubation with LPS. Endothelium removal or NOS3 inhibition with the calmodulin inhibitor, W7, increased NOS activity in the aortae of portal vein-stenosed rats after LPS incubation. In conclusion, in aortae of portal vein-stenosed rats exposed to LPS, no further decrease in aortic reactivity to phenylephrine was observed, and the induction of NOS2 was down-regulated. Endothelium removal or calmodulin inhibition inhibits NOS3 overactivity and leads to normalized NOS2 activation after LPS in aortae from portal vein-stenosed rats.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Heller",
      "authorRank" : 1,
      "name" : "Heller J",
      "referenceId" : "RGD:A85074"
    }, {
      "firstName" : "P",
      "lastName" : "Sogni",
      "authorRank" : 2,
      "name" : "Sogni",
      "referenceId" : "RGD:A177654"
    }, {
      "firstName" : "KA",
      "lastName" : "Tazi",
      "authorRank" : 3,
      "name" : "Tazi KA",
      "referenceId" : "RGD:A94527"
    }, {
      "firstName" : "C",
      "lastName" : "Chagneau",
      "authorRank" : 4,
      "name" : "Chagneau C",
      "referenceId" : "RGD:A140116"
    }, {
      "firstName" : "O",
      "lastName" : "Poirel",
      "authorRank" : 5,
      "name" : "Poirel",
      "referenceId" : "RGD:A177655"
    }, {
      "firstName" : "R",
      "lastName" : "Moreau",
      "authorRank" : 6,
      "name" : "Moreau R",
      "referenceId" : "RGD:A94528"
    }, {
      "firstName" : "D",
      "lastName" : "Lebrec",
      "authorRank" : 7,
      "name" : "Lebrec D",
      "referenceId" : "RGD:A94529"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7794732"
    } ]
  }, {
    "primaryId" : "PMID:10462489",
    "title" : "Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Satoh M, etal., Biochem Biophys Res Commun. 1999 Aug 27;262(2):411-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-24T18:16:02.000-05:00",
    "volume" : "262",
    "pages" : "411-7",
    "abstract" : "Hypertrophic cardiomyopathy (HCM) is characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Molecular genetic analyses have revealed that mutations in 8 different genes cause HCM. Mutations in these disease genes, however, could be found in about half of HCM patients, suggesting that there are other unknown disease gene(s). Because the known disease genes encode sarcomeric proteins expressed in the cardiac muscle, we searched for a disease-associated mutation in the titin gene in 82 HCM patients who had no mutation in the known disease genes. A G to T transversion in codon 740, from CGC to CTC, replacing Arginine with Leucine was found in a patient. This mutation was not found in more than 500 normal chromosomes and increased the binding affinity of titin to alpha-actitin in the yeast two-hybrid assay. These observations suggest that the titin mutation may cause HCM in this patient via altered affinity to alpha-actinin.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Satoh",
      "authorRank" : 1,
      "name" : "Satoh M",
      "referenceId" : "RGD:A31606"
    }, {
      "firstName" : "M",
      "lastName" : "Takahashi",
      "authorRank" : 2,
      "name" : "Takahashi M",
      "referenceId" : "RGD:A4629"
    }, {
      "firstName" : "T",
      "lastName" : "Sakamoto",
      "authorRank" : 3,
      "name" : "Sakamoto T",
      "referenceId" : "RGD:A7932"
    }, {
      "firstName" : "M",
      "lastName" : "Hiroe",
      "authorRank" : 4,
      "name" : "Hiroe M",
      "referenceId" : "RGD:A10142"
    }, {
      "firstName" : "F",
      "lastName" : "Marumo",
      "authorRank" : 5,
      "name" : "Marumo F",
      "referenceId" : "RGD:A4690"
    }, {
      "firstName" : "A",
      "lastName" : "Kimura",
      "authorRank" : 6,
      "name" : "Kimura A",
      "referenceId" : "RGD:A18580"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580781"
    } ]
  }, {
    "primaryId" : "PMID:104625",
    "title" : "The fate of transplanted pancreatic islets in the rat.",
    "datePublished" : "1979-09-01T00:00:00.000-05:00",
    "citation" : "Franklin WA, etal., Am J Pathol 1979 Jan;94(1):85-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-26T11:04:46.000-05:00",
    "volume" : "94",
    "pages" : "85-95",
    "abstract" : "Syngeneic pancreatic islets transplanted into the liver or the spleen reverse streptozotocin-induced diabetes in the rat, but allogeneic islets function only briefly and are rejected. Shortly after transplantation, thrombi often form around transplanted tissue, particularly around nonislet tissue that contaminates islet preparations. These thrombi are a source of transient liver injury in recipients of intrahepatic grafts. A few days after transplantation, syngeneic islets injected into the portal vein are found at the periphery of portal tracts in direct contact with periportal hepatocytes, some of which become hypertrophied. Isografts remain situated in the portal tracts for prolonged periods without adverse effect on the surrounding liver. In contrast, allogeneic islets injected into the portal vein are infiltrated by small lymphocytes within 2 days of transplantation and are rapidly destroyed by the host. Syngeneic islets injected into the splenic pulp localize in the sinusoids and, 1 month or more after transplantation, are often surrounded by connective tissue or local collections of hemosiderin-laden macrophages. Allogeneic islets injected into the spleen are rejected with the same intensity and at approximately the same rate as allogeneic islets injected into the portal vein. Transplant rejection leaves no significant lasting morphologic effect on the host liver or spleen.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WA",
      "lastName" : "Franklin",
      "authorRank" : 1,
      "name" : "Franklin WA",
      "referenceId" : "RGD:A25054"
    }, {
      "firstName" : "JA",
      "lastName" : "Schulak",
      "authorRank" : 2,
      "name" : "Schulak JA",
      "referenceId" : "RGD:A25055"
    }, {
      "firstName" : "CR",
      "lastName" : "Reckard",
      "authorRank" : 3,
      "name" : "Reckard CR",
      "referenceId" : "RGD:A25056"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634777"
    } ]
  }, {
    "primaryId" : "PMID:10462548",
    "title" : "Incorporation of the pi subunit into functional gamma-aminobutyric Acid(A) receptors.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Neelands TR and Macdonald RL, Mol Pharmacol. 1999 Sep;56(3):598-610. doi: 10.1124/mol.56.3.598.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-04-20T06:10:01.000-05:00",
    "volume" : "56",
    "pages" : "598-610",
    "abstract" : "mRNA encoding the recently cloned gamma-aminobuytyric acid(A) receptor (GABAR) pi subunit is expressed in the hippocampus and in several non-neuronal tissues including the uterus and ovaries. Whereas native GABARs are pentamers composed primarily of alphabetagamma, alphabetadelta, or alphabetaepsilon subunits, it has not been demonstrated clearly that the pi subunit incorporates into functional GABARs to form alphabetapi receptors and, if so, with what properties. We provide electrophysiological evidence that the pi subunit can coassemble with either alpha5beta3 or alpha5beta3gamma3 subunits to produce recombinant GABARs with distinct pharmacological and biophysical properties. Compared with alpha5beta3 receptors, GABARs produced by coexpression of alpha5beta3pi subunits had a lower GABA EC(50) value, were enhanced to a lesser extent by loreclezole, had different IC(50) values for pregnenolone sulfate and lanthanum, and were insensitive to benzodiazepines. Incorporation of both pi and gamma3 subunits into an alpha5beta3gamma3pi isoform was suggested by reduced enhancement by diazepam and a high zinc IC(50) value. Current-voltage relations for the alpha5beta3pi subunit combination outwardly rectified more than currents from alpha5beta3gamma3 but less than alpha5beta3 combination GABARs. Single-channel alpha5beta3 GABAR currents had a main conductance state of 15.2 picoSeimens (pS). Coexpression of the pi subunit with alpha5beta3 subtypes increased the conductance level to 23.8 pS, similar to the conductance level of alpha5beta3gamma3 GABARs (26.9 pS). We conclude that the pi subunit coassembles with alpha, beta, and gamma subunits to form functional alphabetapi or alphabetagammapi GABARs and, thus, could have a significant impact on the function of native GABARs expressed in the brain or non-neuronal tissue.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T R",
      "lastName" : "Neelands",
      "authorRank" : 1,
      "name" : "Neelands TR",
      "referenceId" : "RGD:A540695"
    }, {
      "firstName" : "R L",
      "lastName" : "Macdonald",
      "authorRank" : 2,
      "name" : "Macdonald RL",
      "referenceId" : "RGD:A540697"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:405650343"
    } ]
  }, {
    "primaryId" : "PMID:10464145",
    "title" : "3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) induce hepatic expression of the phospholipid translocase mdr2 in rats.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Hooiveld GJ, etal., Gastroenterology. 1999 Sep;117(3):678-87.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-12-06T15:22:01.000-06:00",
    "volume" : "117",
    "pages" : "678-87",
    "abstract" : "BACKGROUND & AIMS: Biliary cholesterol secretion is coupled to that of phospholipids in a process controlled by mdr2 P-glycoprotein activity and bile salt secretion. Statins, the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, have been shown to affect hepatobiliary lipid secretion in rats. The aim of this study was to relate the effects of statins on bile formation to the expression of mdr2 and other hepatic adenosine triphosphate-dependent transport proteins involved in bile formation in rats. METHODS: Rats received simvastatin- or pravastatin-containing chow continuously for 5 days. In one group of rats, simvastatin treatment was withdrawn 9-12 hours before the end of the experiment to induce biliary cholesterol hypersecretion (rebound). Bile and liver tissue were collected for lipid analysis, and hepatic messenger RNA (mRNA) and protein levels were studied by reverse-transcription polymerase chain reaction, immunoblotting, and immunohistochemistry. RESULTS: Simvastatin feeding did not alter biliary bile salt secretion. Secretion of phospholipids and cholesterol was stimulated by 74% and 90%, respectively, in the simvastatin-continuous group and by 72% and 235%, respectively, in the rebound group compared with controls. mdr2 mRNA levels increased only in the continuous group. mdr2 protein levels increased in both simvastatin-fed groups. Induction was most pronounced in periportal hepatocytes. mdr1b mRNA levels were moderately increased in both simvastatin-fed groups. Levels of other hepatic transport proteins did not change. Similar results were obtained in pravastatin-fed rats. CONCLUSIONS: Statins increase expression of mdr2 and mdr1b in rats, revealing a novel effect of these commonly used drugs.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GJ",
      "lastName" : "Hooiveld",
      "authorRank" : 1,
      "name" : "Hooiveld GJ",
      "referenceId" : "RGD:A70856"
    }, {
      "firstName" : "TA",
      "lastName" : "Vos",
      "authorRank" : 2,
      "name" : "Vos TA",
      "referenceId" : "RGD:A70857"
    }, {
      "firstName" : "GL",
      "lastName" : "Scheffer",
      "authorRank" : 3,
      "name" : "Scheffer GL",
      "referenceId" : "RGD:A7248"
    }, {
      "firstName" : "H",
      "lastName" : "Van Goor",
      "authorRank" : 4,
      "name" : "Van Goor H",
      "referenceId" : "RGD:A14250"
    }, {
      "firstName" : "H",
      "lastName" : "Koning",
      "authorRank" : 5,
      "name" : "Koning H",
      "referenceId" : "RGD:A70858"
    }, {
      "firstName" : "V",
      "lastName" : "Bloks",
      "authorRank" : 6,
      "name" : "Bloks V",
      "referenceId" : "RGD:A70832"
    }, {
      "firstName" : "AE",
      "lastName" : "Loot",
      "authorRank" : 7,
      "name" : "Loot AE",
      "referenceId" : "RGD:A70859"
    }, {
      "firstName" : "DK",
      "lastName" : "Meijer",
      "authorRank" : 8,
      "name" : "Meijer DK",
      "referenceId" : "RGD:A43052"
    }, {
      "firstName" : "PL",
      "lastName" : "Jansen",
      "authorRank" : 9,
      "name" : "Jansen PL",
      "referenceId" : "RGD:A70860"
    }, {
      "firstName" : "F",
      "lastName" : "Kuipers",
      "authorRank" : 10,
      "name" : "Kuipers F",
      "referenceId" : "RGD:A57619"
    }, {
      "firstName" : "M",
      "lastName" : "Muller",
      "authorRank" : 11,
      "name" : "Muller M",
      "referenceId" : "RGD:A21301"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1598595"
    } ]
  }, {
    "primaryId" : "PMID:10464275",
    "title" : "Purification, redox sensitivity, and RNA binding properties of SECIS-binding protein 2, a protein involved in selenoprotein biosynthesis.",
    "datePublished" : "1999-09-03T00:00:00.000-05:00",
    "citation" : "Copeland PR and Driscoll DM, J Biol Chem. 1999 Sep 3;274(36):25447-54. doi: 10.1074/jbc.274.36.25447.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-02-14T01:55:57.000-06:00",
    "volume" : "274",
    "pages" : "25447-54",
    "abstract" : "In mammalian selenoprotein mRNAs, the highly structured 3' UTR contains selenocysteine insertion sequence (SECIS) elements that are required for the recognition of UGA as the selenocysteine codon. Our previous work demonstrated a tight correlation between codon-specific translational read-through and the activity of a 120-kDa RNA-binding protein that interacted specifically with the SECIS element in the phospholipid hydroperoxide glutathione peroxidase mRNA. This study reports the RNA binding and biochemical properties of this protein, SECIS-binding protein 2 (SBP2). We detected SBP2 binding activity in liver, hepatoma cell, and testis extracts from which SBP2 has been purified by anion exchange and RNA affinity chromatography. This scheme has allowed us to identify a 120-kDa polypeptide that co-elutes with SBP2 binding activity from wild-type but not mutant RNA affinity columns. A characterization of SBP2 biochemical properties reveals that SBP2 binding is sensitive to oxidation and the presence of heparin, rRNA, and poly(G). SBP2 activity elutes with a molecular mass of approximately 500 kDa during gel filtration chromatography, suggesting the existence of a large functional complex. Direct cross-linking and competition experiments demonstrate that the minimal phospholipid hydroperoxide glutathione peroxidase 3' UTR binding site is between 82 and 102 nucleotides, which correlates with the minimal sequence necessary for translational read-through. SBP2 also interacts specifically with the minimally functional 3' UTR of another selenoprotein mRNA, deiodinase 1.",
    "issueName" : "36",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P R",
      "lastName" : "Copeland",
      "authorRank" : 1,
      "name" : "Copeland PR",
      "referenceId" : "RGD:A538855"
    }, {
      "firstName" : "D M",
      "lastName" : "Driscoll",
      "authorRank" : 2,
      "name" : "Driscoll DM",
      "referenceId" : "RGD:A538856"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401966875"
    } ]
  }, {
    "primaryId" : "PMID:10464283",
    "title" : "Rab11BP/Rabphilin-11, a downstream target of rab11 small G protein implicated in vesicle recycling.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mammoto A, etal., J Biol Chem 1999 Sep 3;274(36):25517-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T17:28:55.000-05:00",
    "volume" : "274",
    "pages" : "25517-24",
    "abstract" : "Rab11 small G protein has been implicated in vesicle recycling, but its upstream regulators or downstream targets have not yet been identified. We isolated here a downstream target of Rab11, named rabphilin-11, from bovine brain. Moreover, we isolated from a rat brain cDNA library its cDNA, which encoded a protein with a M(r) of 100,946 and 908 amino acids (aa). Rabphilin-11 bound GTP-Rab11 more preferentially than GDP-Rab11 at the N-terminal region and was specific for Rab11 and inactive for other Rab and Rho small G proteins. Both GTP-Rab11 and rabphilin-11 were colocalized at perinuclear regions, presumably the Golgi complex and recycling endosomes, in Madin-Darby canine kidney cells. In HeLa cells cultured on fibronectin, both the proteins were localized not only at perinuclear regions but also along microtubules, which were oriented toward membrane lamellipodia. Treatment of HeLa cells with nocodazole caused disruption of microtubules and dispersion of GTP-Rab11 and rabphilin-11. Overexpression of the C-terminal fragment of rabphilin-11 (aa 607-730), lacking the GTP-Rab11 binding domain, in HeLa cells reduced accumulation of transferrin at perinuclear regions and cell migration. Rabphilin-11 turned out to be a rat counterpart of recently reported bovine Rab11BP. These results indicate that rabphilin-11 is a downstream target of Rab11 which is involved in vesicle recycling.",
    "issueName" : "36",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Mammoto",
      "authorRank" : 1,
      "name" : "Mammoto A",
      "referenceId" : "RGD:A43601"
    }, {
      "firstName" : "T",
      "lastName" : "Ohtsuka",
      "authorRank" : 2,
      "name" : "Ohtsuka T",
      "referenceId" : "RGD:A42922"
    }, {
      "firstName" : "I",
      "lastName" : "Hotta",
      "authorRank" : 3,
      "name" : "Hotta I",
      "referenceId" : "RGD:A43602"
    }, {
      "firstName" : "T",
      "lastName" : "Sasaki",
      "authorRank" : 4,
      "name" : "Sasaki T",
      "referenceId" : "RGD:A8065"
    }, {
      "firstName" : "Y",
      "lastName" : "Takai",
      "authorRank" : 5,
      "name" : "Takai Y",
      "referenceId" : "RGD:A151861"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299615"
    } ]
  }, {
    "primaryId" : "PMID:10464373",
    "title" : "Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "McFadden SL, etal., J Comp Neurol. 1999 Oct 11;413(1):101-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-20T15:58:27.000-05:00",
    "volume" : "413",
    "pages" : "101-12",
    "abstract" : "Copper/zinc superoxide dismutase (Cu/Zn SOD) is a first-line defense against free radical damage in the cochlea and other tissues. To determine whether deficiencies in Cu/Zn SOD increase age-related hearing loss and cochlear pathology, we collected auditory brainstem responses (ABRs) and determined cochlear hair cell loss in 13-month-old 129/CD-1 mice with (a) no measurable Cu/Zn SOD activity (homozygous knockout mice), (b) 50% reduction of Cu/Zn SOD (heterozygous knockout mice), and (c) normal levels of Cu/Zn SOD (wild-type mice). ABRs were obtained by using 4-, 8-, 16-, and 32-kHz tone bursts. Cochleas  were harvested immediately after testing, and separate counts were made of inner  and outer hair cells. Compared with wild-type mice, homozygous and heterozygous knockout mice exhibited significant threshold elevations and greater hair cell loss. Phenotypic variability was higher among heterozygous knockout mice than among wild-type or homozygous knockout mice. Separate groups of wild-type and homozygous knockout mice were examined for loss of spiral ganglion cells and eighth nerve fibers. At 13 months of age, both wild-type and knockout mice had significantly fewer nerve fibers than did 2-month-old wild-type mice, with significantly greater loss in aged knockout mice than in aged wild-type mice. Thirteen-month-old knockout mice also had a significant loss of spiral ganglion cells compared with 2-month-old wild-type mice. The results indicate that Cu/Zn SOD deficiencies increase the vulnerability of the cochlea to damage associated with normal aging, presumably through metabolic pathways involving the superoxide radical.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SL",
      "lastName" : "McFadden",
      "authorRank" : 1,
      "name" : "McFadden",
      "referenceId" : "RGD:A188139"
    }, {
      "firstName" : "D",
      "lastName" : "Ding",
      "authorRank" : 2,
      "name" : "Ding D",
      "referenceId" : "RGD:A127620"
    }, {
      "firstName" : "RF",
      "lastName" : "Burkard",
      "authorRank" : 3,
      "name" : "Burkard",
      "referenceId" : "RGD:A188140"
    }, {
      "firstName" : "H",
      "lastName" : "Jiang",
      "authorRank" : 4,
      "name" : "Jiang H",
      "referenceId" : "RGD:A4102"
    }, {
      "firstName" : "AG",
      "lastName" : "Reaume",
      "authorRank" : 5,
      "name" : "Reaume",
      "referenceId" : "RGD:A188141"
    }, {
      "firstName" : "DG",
      "lastName" : "Flood",
      "authorRank" : 6,
      "name" : "Flood DG",
      "referenceId" : "RGD:A96326"
    }, {
      "firstName" : "RJ",
      "lastName" : "Salvi",
      "authorRank" : 7,
      "name" : "Salvi",
      "referenceId" : "RGD:A188142"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8655665"
    } ]
  }, {
    "primaryId" : "PMID:10464394",
    "title" : "Antisense mRNA for NPY-Y1 receptor in the medial preoptic area increases prolactin secretion.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Silveira NA and Franci CR, Braz J Med Biol Res. 1999 Sep;32(9):1161-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-09-12T10:25:46.000-05:00",
    "volume" : "32",
    "pages" : "1161-5",
    "abstract" : "We investigated the participation of neuropeptide Y-Y1 receptors within the medial preoptic area in luteinizing hormone, follicle-stimulating hormone and prolactin release. Four bilateral microinjections of sense (control) or antisense 18-base oligonucleotides of messenger ribonucleic acid (mRNA) (250 ng) corresponding to the NH2-terminus of the neuropeptide Y1 receptor were performed at 12-h intervals for two days into the medial preoptic area of ovariectomized Wistar rats (N = 16), weighing 180 to 200 g, treated with estrogen (50 microg) and progesterone (25 mg) two days before the experiments between 8.00 and 10:00 a.m. Blockade of Y1 receptor synthesis in the medial preoptic area by the antisense mRNA did not change plasma luteinizing hormone or follicle-stimulating hormone but did increase prolactin from 19.6 +/- 5.9 ng/ml in the sense group to 52.9 +/- 9.6 ng/ml in the antisense group. The plasma hormones were measured by radioimmunoassay and the values are reported as mean +/- SEM. These data suggest that endogenous neuropeptide Y in the medial preoptic area has an inhibitory action on prolactin secretion through Y1 receptors.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NA",
      "lastName" : "Silveira",
      "authorRank" : 1,
      "name" : "Silveira NA",
      "referenceId" : "RGD:A87768"
    }, {
      "firstName" : "CR",
      "lastName" : "Franci",
      "authorRank" : 2,
      "name" : "Franci CR",
      "referenceId" : "RGD:A87769"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642321"
    } ]
  }, {
    "primaryId" : "PMID:10464559",
    "title" : "Expression of metalloproteinase-2 (gelatinase A) in labial salivary glands of patients with Sjogren's syndrome with HTLV-I infection.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Tominaga M, etal., Clin Exp Rheumatol. 1999 Jul-Aug;17(4):463-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-29T14:56:26.000-05:00",
    "volume" : "17",
    "pages" : "463-6",
    "abstract" : "OBJECTIVE: To determine whether gelatinase A (MMP-2) plays a significant role in  the pathogenesis of Sjogren's syndrome (SS) with or without HTLV-I infection. METHODS: We examined 24 patients with SS (14 HTLV-I-seropositive and 8 HTLV-I-seronegative). Labial salivary gland tissue samples were analysed immunohistochemically using anti-MMP-2 monoclonal antibodies. RESULTS: In normal  salivary glands, MMP-2 expression was not detected. All biopsy samples of 8 SS patients with HTLV-I-associated myelopathy (HAM) and 3 of 6 HTLV-I-seropositive SS patients without manifestation of HAM stained positively for MMP-2. However, the other samples were negative for MMP-2. CONCLUSION: Our study showed the MMP-2 expression in labial salivary glands of HTLV-I seropositive SS patients, especially in all SS patients with HAM. The presence of MMP-2 in the salivary glands of these patients suggests that it may play a role in cellular infiltration and destruction in salivary glands of SS.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Tominaga",
      "authorRank" : 1,
      "name" : "Tominaga M",
      "referenceId" : "RGD:A8187"
    }, {
      "firstName" : "K",
      "lastName" : "Migita",
      "authorRank" : 2,
      "name" : "Migita K",
      "referenceId" : "RGD:A59858"
    }, {
      "firstName" : "H",
      "lastName" : "Nakamura",
      "authorRank" : 3,
      "name" : "Nakamura",
      "referenceId" : "RGD:A401423"
    }, {
      "firstName" : "Y",
      "lastName" : "Ichinose",
      "authorRank" : 4,
      "name" : "Ichinose Y",
      "referenceId" : "RGD:A55366"
    }, {
      "firstName" : "T",
      "lastName" : "Furuya",
      "authorRank" : 5,
      "name" : "Furuya",
      "referenceId" : "RGD:A216058"
    }, {
      "firstName" : "T",
      "lastName" : "Origuchi",
      "authorRank" : 6,
      "name" : "Origuchi T",
      "referenceId" : "RGD:A155644"
    }, {
      "firstName" : "Y",
      "lastName" : "Kawabe",
      "authorRank" : 7,
      "name" : "Kawabe Y",
      "referenceId" : "RGD:A69857"
    }, {
      "firstName" : "A",
      "lastName" : "Hida",
      "authorRank" : 8,
      "name" : "Hida A",
      "referenceId" : "RGD:A26660"
    }, {
      "firstName" : "T",
      "lastName" : "Nakamura",
      "authorRank" : 9,
      "name" : "Nakamura",
      "referenceId" : "RGD:A416904"
    }, {
      "firstName" : "K",
      "lastName" : "Eguchi",
      "authorRank" : 10,
      "name" : "Eguchi K",
      "referenceId" : "RGD:A59865"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8657078"
    } ]
  }, {
    "primaryId" : "PMID:10464635",
    "title" : "Dystrophin point mutation screening using a multiplexed protein truncation test.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Whittock NV, etal., Genet Test. 1997;1(2):115-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:13:35.000-05:00",
    "volume" : "1",
    "pages" : "115-23",
    "abstract" : "We report here the first use of a multiplexed protein truncation test for the high throughput screening of dystrophin point mutations. We have developed a substantially more robust and efficient procedure incorporating large savings in  cost which uses muscle biopsy or lymphocyte total RNA as the template. The entire dystrophin open reading frame is screened in only five overlapping fragments using a long RT-PCR strategy to amplify dystrophin cDNA in excess of 3.7 kb. These five fragments are uniquely transcribed and translated in vitro in a single multiplexed reaction containing magnesium ions to reduce nonspecific internal initiation of translation. We have used this system to analyze mutations in 11 Duchenne muscular dystrophy patients (10 unrelated) with previously uncharacterized mutations. A single truncating mutation was identified in all patients, which was confirmed at the genomic level. Multiplex PTT provides the most efficient method for point mutation screening in this large gene and has potential applications to several disease genes with a significant proportion of  truncating mutations.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "NV",
      "lastName" : "Whittock",
      "authorRank" : 1,
      "name" : "Whittock NV",
      "referenceId" : "RGD:A38058"
    }, {
      "firstName" : "RG",
      "lastName" : "Roberts",
      "authorRank" : 2,
      "name" : "Roberts RG",
      "referenceId" : "RGD:A17956"
    }, {
      "firstName" : "CG",
      "lastName" : "Mathew",
      "authorRank" : 3,
      "name" : "Mathew CG",
      "referenceId" : "RGD:A71785"
    }, {
      "firstName" : "SJ",
      "lastName" : "Abbs",
      "authorRank" : 4,
      "name" : "Abbs",
      "referenceId" : "RGD:A272720"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069891"
    } ]
  }, {
    "primaryId" : "PMID:10464652",
    "title" : "Denaturing HPLC-identified novel FBN1 mutations, polymorphisms, and sequence variants in Marfan syndrome and related connective tissue disorders.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Liu WO, etal., Genet Test. 1997-1998;1(4):237-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:08:36.000-05:00",
    "volume" : "1",
    "pages" : "237-42",
    "abstract" : "Marfan syndrome (MFS), a common connective tissue disorder, is caused by fibrillin-1 (FBN1) mutations that are scattered throughout the gene and are largely unique to individual families. Mutation detection in this large gene of 65 exons is a considerable technical challenge. To develop an efficient method capable of identifying all possible mutations in this gene, we have explored the  use of a novel denaturing high-performance liquid chromatography (DHPLC) system.  This technique compares two or more chromosomes as a mixture of denatured and reannealed PCR amplicons. Under partially denaturing conditions, heteroduplexes can be separated from homoduplexes. A panel of 94 DNA samples from individuals with MFS or related connective tissue disorders was screened exon-by-exon by this method. A total of 66 unique heteroduplex profiles was identified. Sequencing of  the amplicons detected 37 novel and two previously reported mutations, as well as 15 novel and 10 known polymorphisms or unique sequence variants that are probably of no clinical significance. Of the 34 mutations found in definitive MFS cases, 16 were identified in the 21 samples that had not been screened before (76% detection rate) and 17/40 (43%) were in samples previously screened by other mutation detection methods. In 32 individuals with MFS-related phenotypes, five FBN1 mutations were identified (16%). Our results demonstrate the power of the DHPLC method to detect FBN1 mutations. It should be applicable for mutation screening in any gene in a large population.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "WO",
      "lastName" : "Liu",
      "authorRank" : 1,
      "name" : "Liu",
      "referenceId" : "RGD:A262323"
    }, {
      "firstName" : "PJ",
      "lastName" : "Oefner",
      "authorRank" : 2,
      "name" : "Oefner PJ",
      "referenceId" : "RGD:A55434"
    }, {
      "firstName" : "C",
      "lastName" : "Qian",
      "authorRank" : 3,
      "name" : "Qian C",
      "referenceId" : "RGD:A37095"
    }, {
      "firstName" : "RS",
      "lastName" : "Odom",
      "authorRank" : 4,
      "name" : "Odom",
      "referenceId" : "RGD:A262324"
    }, {
      "firstName" : "U",
      "lastName" : "Francke",
      "authorRank" : 5,
      "name" : "Francke U",
      "referenceId" : "RGD:A15635"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065569"
    } ]
  }, {
    "primaryId" : "PMID:10465122",
    "title" : "Identification of a frameshift mutation in the gene TWIST in a family affected with Robinow-Sorauf syndrome.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kunz J, etal., J Med Genet. 1999 Aug;36(8):650-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:58:12.000-05:00",
    "volume" : "36",
    "pages" : "650-2",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Kunz",
      "authorRank" : 1,
      "name" : "Kunz J",
      "referenceId" : "RGD:A35481"
    }, {
      "firstName" : "M",
      "lastName" : "Hudler",
      "authorRank" : 2,
      "name" : "Hudler M",
      "referenceId" : "RGD:A573333"
    }, {
      "firstName" : "B",
      "lastName" : "Fritz",
      "authorRank" : 3,
      "name" : "Fritz B",
      "referenceId" : "RGD:A573334"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598115517"
    } ]
  }, {
    "primaryId" : "PMID:10465288",
    "title" : "The rat growth hormone-releasing hormone receptor gene: structure, regulation, and generation of receptor isoforms with different signaling properties.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Miller TL, etal., Endocrinology. 1999 Sep;140(9):4152-65.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-05-14T11:47:19.000-05:00",
    "volume" : "140",
    "pages" : "4152-65",
    "abstract" : "The interaction of GHRH with membrane-bound receptors on somatotroph cells of the anterior pituitary is an important step in the regulation of GH synthesis and secretion. The identification of a G protein-coupled receptor for GHRH has made it possible to investigate the pathway by which GHRH regulates pituitary somatotroph cell function. To initiate an analysis of the mechanisms regulating expression and function of the GHRH receptor, the structure of the gene and its promoter region were analyzed. The coding sequence of the rat GHRH receptor gene is contained within 14 exons spanning approximately 15 kb of genomic DNA. Four transcription start sites are located within 286 bp upstream of the initiation codon. The 5' flanking region of the GHRH receptor gene acts as a functional promoter in rat pituitary tumor GH3 cells, and basal promoter activity is enhanced in GH3 and COS7 cells by cotransfection of an expression construct encoding the pituitary-specific transcription factor Pit-1. The rat GHRH receptor gene is subject to at least 1 alternative RNA processing event that generates 2 receptor isoforms differing by 41 amino acids within the third intracellular loop (IL) of the protein. The short isoform of the GHRH receptor is predominant in pituitary cells. The MtT/S pituitary tumor cell line was found to express the GHRH receptor, and different populations of these cells produce predominantly the long or short isoforms of the receptor messenger RNA, suggesting that the alternative splicing can be regulated. Functional analysis of the two GHRH receptor isoforms demonstrates that both bind GHRH, but only the short isoform signals through a cAMP-mediated pathway. Neither receptor isoform is able to stimulate calcium mobilization from internal stores after GHRH treatment. Our findings indicate that the pituitary-specific transcription factor Pit-1 is involved in the somatotroph-specific expression of the GHRH receptor gene and that functionally distinct receptor proteins are generated by an alternative RNA processing mechanism.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TL",
      "lastName" : "Miller",
      "authorRank" : 1,
      "name" : "Miller TL",
      "referenceId" : "RGD:A82700"
    }, {
      "firstName" : "PA",
      "lastName" : "Godfrey",
      "authorRank" : 2,
      "name" : "Godfrey PA",
      "referenceId" : "RGD:A82701"
    }, {
      "firstName" : "VI",
      "lastName" : "Dealmeida",
      "authorRank" : 3,
      "name" : "Dealmeida VI",
      "referenceId" : "RGD:A82702"
    }, {
      "firstName" : "KE",
      "lastName" : "Mayo",
      "authorRank" : 4,
      "name" : "Mayo KE",
      "referenceId" : "RGD:A137689"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1624951"
    } ]
  }, {
    "primaryId" : "PMID:10465294",
    "title" : "Tumor necrosis factor-alpha and interferon-gamma suppress both gene expression and deoxyribonucleic acid-binding of TTF-2 in FRTL-5 cells.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Miyazaki A, etal., Endocrinology. 1999 Sep;140(9):4214-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-11-15T15:54:17.000-06:00",
    "volume" : "140",
    "pages" : "4214-20",
    "abstract" : "Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are cytokines that can individually or additively suppress thyroid cell function and the expression of thyroid-specific genes, such as thyroglobulin (TG) and thyroperoxidase (TPO). Thyroid transcription factor-2 (TTF-2) is a DNA-binding protein that modulates the expression of TG and TPO genes. In the present study, we examine the effects of TNF-alpha and IFN-gamma on TTF-2 gene expression, as well as the DNA-binding activity of TTF-2. FRTL-5 cells were maintained in 5H medium containing 0.2% calf serum for 7 days, then incubated with TNF-alpha, IFN-gamma, or TNF-alpha plus IFN-gamma. Total RNA was isolated and Northern blotted. TNF-alpha (50 ng/ml) only slightly suppressed (61+/-2% compared with control), whereas IFN-gamma (100 U/ml) modestly decreased TTF-2 messenger RNA (mRNA) levels (34+/-4%). TNF-alpha and IFN-gamma simultaneously caused a marked decrease in TTF-2 mRNA levels (13+/-2%). The suppressive effects of TNF-alpha and IFN-gamma on TTF-2 mRNA levels were concentration dependent and maximal at 50 ng/ml TNF-alpha with 100 U/ml IFN-gamma. The suppressive effect was also time dependent, reaching a maximum 12 h after exposure. Moreover, the suppressive effects of TNF-alpha and IFN-gamma upon rat TG and TTF-2 mRNA levels were similar. To test whether TNF-alpha and IFN-gamma alter TTF-2-binding to DNA, we performed electrophoretic mobility shift assays using a TTF-2-binding element in the rat TG gene as a probe. Formation of the TTF-2/DNA complex was decreased by TNF-alpha and/or IFN-gamma. Our results demonstrate that TNF-alpha and IFN-gamma additively reduce the gene expression and DNA-binding of TTF-2. These data suggest that TTF-2 is involved in the TNF-alpha and IFN-gamma-induced suppression of thyroid-specific gene expression.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Miyazaki",
      "authorRank" : 1,
      "name" : "Miyazaki A",
      "referenceId" : "RGD:A162497"
    }, {
      "firstName" : "H",
      "lastName" : "Shimura",
      "authorRank" : 2,
      "name" : "Shimura H",
      "referenceId" : "RGD:A69690"
    }, {
      "firstName" : "T",
      "lastName" : "Endo",
      "authorRank" : 3,
      "name" : "Endo T",
      "referenceId" : "RGD:A8527"
    }, {
      "firstName" : "K",
      "lastName" : "Haraguchi",
      "authorRank" : 4,
      "name" : "Haraguchi K",
      "referenceId" : "RGD:A66724"
    }, {
      "firstName" : "T",
      "lastName" : "Onaya",
      "authorRank" : 5,
      "name" : "Onaya T",
      "referenceId" : "RGD:A8530"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1582629"
    } ]
  }, {
    "primaryId" : "PMID:10465442",
    "title" : "The topography and subcellular distribution of mitogen-activated protein kinase kinase1 (MEK1) in adult rat brain and differentiating PC12 cells.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Schipper HM, etal., Neuroscience. 1999;93(2):585-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-05-27T15:49:31.000-05:00",
    "volume" : "93",
    "pages" : "585-95",
    "abstract" : "Mitogen-activated protein kinase signal transduction pathway involved in the regulation of proliferation and differentiation of various mammalian cells consists of a sequential activation of three protein kinases, Raf, mitogen-activated protein kinase kinase, and mitogen-activated protein kinase. These kinases are highly expressed in brain and play an important role in neuronal signalling. In this study, to further characterize mitogen-activated protein kinase signalling pathway in brain, we have elucidated the topography and subcellular distribution of mitogen-activated protein kinase kinasel in adult rat brain and differentiating PC12 cells. Our immunohistochemical data indicate that mitogen-activated protein kinase kinase1 is widely distributed throughout the brain and expressed prominently in cortex, hippocampus, brainstem, hypothalamus and cerebellum. In these areas of brain mitogen-activated protein kinase kinasel is exclusively neuronal in origin and is localized within perikarya and dendrites. Confocal microscopy data has determined that a portion of mitogen-activated protein kinase kinase1 in rat brain is co-localized with microtubules. This co-localization was observed only within neuritic shaft and cilia of ventricular ependymal cells. In nerve growth factor-induced differentiating PC12 cells, mitogen-activated protein kinase kinase1 displays co-localization with microtubules within proximal regions of neuritic shafts and their junctions with the cell somas. From bovine brain extract, mitogen-activated protein kinase kinasel co-purifies with microtubules. In vitro kinase assay detected mitogen-activated protein kinase kinase1 activity within purified microtubules. These observations indicate that mitogen-activated protein kinase kinase1 is associated with microtubules within some specialized compartments of the brain and microtubule-associated mitogen-activated protein kinase kinase1 is catalytically active.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "HM",
      "lastName" : "Schipper",
      "authorRank" : 1,
      "name" : "Schipper HM",
      "referenceId" : "RGD:A53561"
    }, {
      "firstName" : "A",
      "lastName" : "Agarwal-Mawal",
      "authorRank" : 2,
      "name" : "Agarwal-Mawal A",
      "referenceId" : "RGD:A53493"
    }, {
      "firstName" : "HK",
      "lastName" : "Paudel",
      "authorRank" : 3,
      "name" : "Paudel HK",
      "referenceId" : "RGD:A53494"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2293321"
    } ]
  }, {
    "primaryId" : "PMID:10465462",
    "title" : "Expression of mt1 melatonin receptor in rat retina: evidence for multiple cell targets for melatonin.",
    "datePublished" : "1000-01-01T00:00:00.000-06:00",
    "citation" : "Fujieda H, etal., Neuroscience. 1999;93(2):793-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-28T12:50:31.000-06:00",
    "volume" : "93",
    "pages" : "793-9",
    "abstract" : "Melatonin is synthesized in the retina at night and acts as a local modulator within this tissue by mediating the effects of darkness. We investigated the expression and localization of the mt1 (Mel1a) melatonin receptor in rat retina in order to disclose the cellular and molecular bases of melatonin's action in the mammalian retina. Western blotting of the mt1 receptor in rat retina exhibited a single immunoreactive band of approximately 37,000 mol. wt, which corresponds to the predicted molecular size of the receptor. The mt1 receptor was immunocytochemically localized to both the inner and outer plexiform layers. During postnatal development, retina from two-week-old rats showed the highest mt1 immunoreactivity; the outer plexiform layer and horizontal cell bodies were strongly immunolabeled, with weaker labeling in the inner plexiform layer. Expression of mt1 receptor messenger RNA in the rat retina was demonstrated by reverse transcription-polymerase chain reaction and in situ hybridization. mt1 receptor transcripts were localized to ganglion cells, amacrine cells and horizontal cells. These results suggest that melatonin influences retinal physiology by acting on multiple retinal cell types, including ganglion, amacrine and horizontal cells, via the mt1 receptor expressed in their processes.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Fujieda",
      "authorRank" : 1,
      "name" : "Fujieda",
      "referenceId" : "RGD:A196141"
    }, {
      "firstName" : "SA",
      "lastName" : "Hamadanizadeh",
      "authorRank" : 2,
      "name" : "Hamadanizadeh",
      "referenceId" : "RGD:A198647"
    }, {
      "firstName" : "E",
      "lastName" : "Wankiewicz",
      "authorRank" : 3,
      "name" : "Wankiewicz",
      "referenceId" : "RGD:A198648"
    }, {
      "firstName" : "SF",
      "lastName" : "Pang",
      "authorRank" : 4,
      "name" : "Pang SF",
      "referenceId" : "RGD:A125749"
    }, {
      "firstName" : "GM",
      "lastName" : "Brown",
      "authorRank" : 5,
      "name" : "Brown",
      "referenceId" : "RGD:A196144"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9686054"
    } ]
  }, {
    "primaryId" : "PMID:10465581",
    "title" : "Intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) co-expression in cutaneous malignant melanoma lesions.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Ciotti P, etal., Melanoma Res. 1999 Jun;9(3):253-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-02-18T17:44:44.000-06:00",
    "volume" : "9",
    "pages" : "253-60",
    "abstract" : "The expression of intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) was investigated in 25  melanoma patients by evaluating 34 fresh biopsy specimens. ICAM-1 in situ hybridization and immunochemistry for ICAM-1 and GM-CSF were performed. Most of the metastatic melanoma samples (12 out of 18) and a few of the primary melanoma  lesions (three out of 16) showed ICAM-1 expression. The expression of ICAM-1 was  significantly (P < 0.01) higher in metastatic lesions than in primary tumours. GM-CSF mRNA and protein were detected in 10 of the 18 metastatic samples and in two of the 15 primary lesions. A significantly high degree (P < 0.0002) of concordance between ICAM-1 and GM-CSF expression was observed: the samples that were negative or positive for ICAM-1 expression were correspondingly negative or  positive for GM-CSF. Correlation with clinical and histological parameters was examined. The expression of both molecules in metastatic samples was found to be  significantly (P < 0.001) associated with a shorter recurrence-free period. These findings, if confirmed by a wider number of patients, could suggest the prognostic value of the simultaneous, and probably co-ordinated, expression of ICAM-1 and GM-CSF. They also highlight the importance of preventive molecular and biochemical characterization of neoplastic cell cytokine receptors, specifically  focusing on the particular cytokine to be used as anticancer therapy and/or as adjunct to chemotherapy.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Ciotti",
      "authorRank" : 1,
      "name" : "Ciotti",
      "referenceId" : "RGD:A179587"
    }, {
      "firstName" : "GP",
      "lastName" : "Pesce",
      "authorRank" : 2,
      "name" : "Pesce",
      "referenceId" : "RGD:A179588"
    }, {
      "firstName" : "F",
      "lastName" : "Cafiero",
      "authorRank" : 3,
      "name" : "Cafiero",
      "referenceId" : "RGD:A179589"
    }, {
      "firstName" : "ML",
      "lastName" : "Rainero",
      "authorRank" : 4,
      "name" : "Rainero",
      "referenceId" : "RGD:A179590"
    }, {
      "firstName" : "A",
      "lastName" : "Sementa",
      "authorRank" : 5,
      "name" : "Sementa",
      "referenceId" : "RGD:A179591"
    }, {
      "firstName" : "G",
      "lastName" : "Nicolo",
      "authorRank" : 6,
      "name" : "Nicolo",
      "referenceId" : "RGD:A179592"
    }, {
      "firstName" : "GS",
      "lastName" : "Mela",
      "authorRank" : 7,
      "name" : "Mela",
      "referenceId" : "RGD:A179593"
    }, {
      "firstName" : "M",
      "lastName" : "Bagnasco",
      "authorRank" : 8,
      "name" : "Bagnasco M",
      "referenceId" : "RGD:A12051"
    }, {
      "firstName" : "PL",
      "lastName" : "Santi",
      "authorRank" : 9,
      "name" : "Santi",
      "referenceId" : "RGD:A179594"
    }, {
      "firstName" : "G",
      "lastName" : "Bianchi-Scarra",
      "authorRank" : 10,
      "name" : "Bianchi-Scarra",
      "referenceId" : "RGD:A179595"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8547593"
    } ]
  }, {
    "primaryId" : "PMID:10465745",
    "title" : "The fractal structure of glycogen: A clever solution to optimize cell metabolism.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Melendez R, etal., Biophys J. 1999 Sep;77(3):1327-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-04-05T19:10:18.000-05:00",
    "volume" : "77",
    "pages" : "1327-32",
    "abstract" : "Fractal objects are complex structures built with a simple procedure involving very little information. This has an obvious interest for living beings, because they are splendid examples of optimization to achieve the most efficient structure for a number of goals by means of the most economic way. The lung alveolar structure, the capillary network, and the structure of several parts of higher plant organization, such as ears, spikes, umbels, etc., are supposed to be fractals, and, in fact, mathematical functions based on fractal geometry algorithms can be developed to simulate them. However, the statement that a given biological structure is fractal should imply that the iterative process of its construction has a real biological meaning, i.e., that its construction in nature is achieved by means of a single genetic, enzymatic, or biophysical mechanism successively repeated; thus, such an iterative process should not be just an abstract mathematical tool to reproduce that object. This property has not been proven at present for any biological structure, because the mechanisms that build the objects mentioned above are unknown in detail. In this work, we present results that show that the glycogen molecule could be the first known real biological fractal structure.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Melendez",
      "authorRank" : 1,
      "name" : "Melendez R",
      "referenceId" : "RGD:A137641"
    }, {
      "firstName" : "E",
      "lastName" : "Melendez-Hevia",
      "authorRank" : 2,
      "name" : "Melendez-Hevia E",
      "referenceId" : "RGD:A137642"
    }, {
      "firstName" : "EI",
      "lastName" : "Canela",
      "authorRank" : 3,
      "name" : "Canela EI",
      "referenceId" : "RGD:A49578"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5129716"
    } ]
  }, {
    "primaryId" : "PMID:10466419",
    "title" : "Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Lee-Chen GJ, etal., Clin Genet. 1999 Jul;56(1):66-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-10-12T20:16:51.000-05:00",
    "volume" : "56",
    "pages" : "66-70",
    "abstract" : "alpha-L-Iduronidase (IDUA) deficiency (mucopolysaccharidosis type I, MPS I) involves a broad spectrum of clinical severity ranging from a severe Hurler syndrome through an intermediate Hurler Scheie syndrome to a mild Scheie syndrome. To date, a number of mutations of the IDUA gene are known in Hurler syndrome, but only a few in Hurler Scheie or Scheie syndrome. The characterization of novel mutations in two patients with the Hurler-Scheie syndrome is reported on. The novel R619G mutation (C-G transversion in codon 619) was apparently homozygous. In transfected COS-7 cells, R619G caused significant reduction in enzyme activity (1.5% of normal activity), although it did not cause significant reduction in IDUA mRNA or protein level. Conversely, the previously described homozygous T364M mutation (C-T transition in codon 364) caused a decrease in the level of IDUA mRNA. Studies inhibiting RNA synthesis with actinomycin D or inhibiting protein synthesis with cycloheximide demonstrate that the decrease in the latter mutation is attributable to an increased rate of mRNA  decay. By examining the stability of IDUA mRNA and protein, studies provide better insight into the effect of mutation on IDUA activity.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GJ",
      "lastName" : "Lee-Chen",
      "authorRank" : 1,
      "name" : "Lee-Chen GJ",
      "referenceId" : "RGD:A67334"
    }, {
      "firstName" : "SP",
      "lastName" : "Lin",
      "authorRank" : 2,
      "name" : "Lin SP",
      "referenceId" : "RGD:A79396"
    }, {
      "firstName" : "YF",
      "lastName" : "Tang",
      "authorRank" : 3,
      "name" : "Tang",
      "referenceId" : "RGD:A396696"
    }, {
      "firstName" : "YW",
      "lastName" : "Chin",
      "authorRank" : 4,
      "name" : "Chin",
      "referenceId" : "RGD:A231069"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11553410"
    } ]
  }, {
    "primaryId" : "PMID:10466578",
    "title" : "Rat macrophage inflammatory protein-1alpha, a CC chemokine, acts as a neutrophil chemoattractant in vitro and in vivo.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Takano K, etal., Inflammation. 1999 Oct;23(5):411-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-02-02T15:54:27.000-06:00",
    "volume" : "23",
    "pages" : "411-24",
    "abstract" : "Recombinant rat macrophage inflammatory protein-1alpha (rMIP-1alpha) at a concentration of 3x10(-8) M had strong neutrophil chemotactic activity, though the potency of rMIP-1alpha was less than that of cytokine-induced neutrophil chemoattractant (CINC)-1 at lower concentrations. In addition, rMIP-1alpha induced neutrophil chemotaxis in vivo when rMIP-1alpha was injected into the preformed air-pouch on the back of rats. The adhesion of rMIP-1alpha-treated neutrophils to fibrinogen significantly increased, reaching a maximum adhesion at 10(-8) M. Stimulation of neutrophils with rMIP-1alpha induced a transient increase in intracellular free [Ca2+] dose-dependently. rMIP-1alpha still induced an increase in the intracellular [Ca2+] of rat neutrophils stimulated first with CINC-1, CINC-3 or C5a, suggesting that rat neutrophils have a specific receptor for rMIP-1alpha. Supporting these findings, an additive increase in chemotactic potency was found when both rMIP-1alpha and CINC-were added to the lower wells of Boyden chamber in vitro. In addition, high levels of rMIP-1alpha were detected in the inflammatory site of air-pouch/carrageenan-induced inflammation in rats. Our results suggest that rMIP-1alpha acts as a neutrophil chemoattractant and, together with CINCs, plays an important role in infiltration of neutrophils into inflammatory sites in rats.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Takano",
      "authorRank" : 1,
      "name" : "Takano K",
      "referenceId" : "RGD:A77262"
    }, {
      "firstName" : "M",
      "lastName" : "Al-Mokdad",
      "authorRank" : 2,
      "name" : "Al-Mokdad M",
      "referenceId" : "RGD:A103226"
    }, {
      "firstName" : "F",
      "lastName" : "Shibata",
      "authorRank" : 3,
      "name" : "Shibata F",
      "referenceId" : "RGD:A17240"
    }, {
      "firstName" : "H",
      "lastName" : "Tsuchiya",
      "authorRank" : 4,
      "name" : "Tsuchiya H",
      "referenceId" : "RGD:A29293"
    }, {
      "firstName" : "H",
      "lastName" : "Nakagawa",
      "authorRank" : 5,
      "name" : "Nakagawa H",
      "referenceId" : "RGD:A17242"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2303107"
    } ]
  }, {
    "primaryId" : "PMID:10466725",
    "title" : "Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Young LJ, etal., Nature 1999 Aug 19;400(6746):766-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T11:44:01.000-06:00",
    "volume" : "400",
    "pages" : "766-8",
    "abstract" : "Arginine vasopressin influences male reproductive and social behaviours in several vertebrate taxa through its actions at the V1a receptor in the brain. The neuroanatomical distribution of vasopressin V1a receptors varies greatly between species with different forms of social organization. Here we show that centrally administered arginine vasopressin increases affiliative behaviour in the highly social, monogamous prairie vole, but not in the relatively asocial, promiscuous montane vole. Molecular analyses indicate that gene duplication and/or changes in promoter structure of the prairie vole receptor gene may contribute to the species differences in vasopressin-receptor expression. We further show that mice that are transgenic for the prairie vole receptor gene have a neuroanatomical pattern of receptor binding that is similar to that of the prairie vole, and exhibit increased affiliative behaviour after injection with arginine vasopressin. These data indicate that the pattern of V1a-receptor gene expression in the brain may be functionally associated with species-typical social behaviours in male vertebrates.",
    "issueName" : "6746",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LJ",
      "lastName" : "Young",
      "authorRank" : 1,
      "name" : "Young LJ",
      "referenceId" : "RGD:A36252"
    }, {
      "firstName" : "R",
      "lastName" : "Nilsen",
      "authorRank" : 2,
      "name" : "Nilsen R",
      "referenceId" : "RGD:A36253"
    }, {
      "firstName" : "KG",
      "lastName" : "Waymire",
      "authorRank" : 3,
      "name" : "Waymire KG",
      "referenceId" : "RGD:A35871"
    }, {
      "firstName" : "GR",
      "lastName" : "MacGregor",
      "authorRank" : 4,
      "name" : "MacGregor GR",
      "referenceId" : "RGD:A35876"
    }, {
      "firstName" : "TR",
      "lastName" : "Insel",
      "authorRank" : 5,
      "name" : "Insel TR",
      "referenceId" : "RGD:A36254"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734625"
    } ]
  }, {
    "primaryId" : "PMID:10466890",
    "title" : "Age and species-dependent differences in the neurokinin B system in rat and human brain.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Mileusnic D, etal., Neurobiol Aging. 1999 Jan-Feb;20(1):19-35.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-03-16T14:59:00.000-05:00",
    "volume" : "20",
    "pages" : "19-35",
    "abstract" : "Neurokinin B and its cognate neurokinin-3 receptor are expressed more in the forebrain than in brain stem structures but little is known about the primary function of this peptide system in the central processing of information. In general, few studies have specifically addressed age-related changes of tachykinins, notably the changes in number and/or distribution of the neurokinin B-expressing and neurokinin-3 receptor-bearing neurons. Data on functions and changes of neurokinins in physiological aging are limited and apply mainly to the substance P/neurokinin-1 receptor system. In the present study, we analyzed neurokinin B/neurokinin-3 receptor system in young (5 months) versus middle aged (15 months) and old rats (23-25 months) and also in aging human brains. For the majority of the immunohistochemically examined regions of the rat brain, there was no statistically significant change in neuronal number and size of the neurokinin B and neurokinin-3 receptor staining. In the adult human brain, there was no age-associated change of the number or size of neurokinin-B-positive neurons. However, we found a major decline in number of neurokinin-3 receptor-expressing neurons between young/middle aged (30 years to 69 years) versus old (70 years and older) adults. Interestingly, numbers of neurokinin-3 receptor-positive microglia increased whereas the neurokinin-3 receptor-positive astrocytes remained unchanged in both aging rat and human brains. Finally, in addition to assessing the morphological and quantitative changes of the neurokinin B/neurokinin-3 receptor system in the rat and human brain, we discuss functional implications of the observed interspecies differences.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Mileusnic",
      "authorRank" : 1,
      "name" : "Mileusnic D",
      "referenceId" : "RGD:A104721"
    }, {
      "firstName" : "DJ",
      "lastName" : "Magnuson",
      "authorRank" : 2,
      "name" : "Magnuson DJ",
      "referenceId" : "RGD:A104722"
    }, {
      "firstName" : "MJ",
      "lastName" : "Hejna",
      "authorRank" : 3,
      "name" : "Hejna MJ",
      "referenceId" : "RGD:A104723"
    }, {
      "firstName" : "JB",
      "lastName" : "Lorens",
      "authorRank" : 4,
      "name" : "Lorens JB",
      "referenceId" : "RGD:A104724"
    }, {
      "firstName" : "SA",
      "lastName" : "Lorens",
      "authorRank" : 5,
      "name" : "Lorens SA",
      "referenceId" : "RGD:A104725"
    }, {
      "firstName" : "JM",
      "lastName" : "Lee",
      "authorRank" : 6,
      "name" : "Lee JM",
      "referenceId" : "RGD:A65078"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2305954"
    } ]
  }, {
    "primaryId" : "PMID:10467249",
    "title" : "Rhes: A striatal-specific Ras homolog related to Dexras1.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Falk JD, etal., J Neurosci Res 1999 Sep 15;57(6):782-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:42.000-05:00",
    "volume" : "57",
    "pages" : "782-8",
    "abstract" : "We have characterized an apparently full-length cDNA corresponding to a rat mRNA, SE6C, previously identified by subtractive hybridization as being expressed predominantly in the striatal region of the brain. The SE6C mRNA encodes a 266 amino acid protein with significant similarity to members of the Ras-like GTP-binding protein family; thus, we have chosen the name Rhes, for Ras homolog enriched in striatum. The human homolog was found in a genomic sequence from human chromosome 22q13.1 and shares 95% identity with rat Rhes. Among the family of small G-proteins, Rhes shares 62% identity with Dexras1, a mouse dexamethasone-inducible Ras-like protein. Both Rhes and Dexras1 have substantially longer C-termini than other members of the Ras-like small G-protein family. Divergence between the C-terminal sequences of Rhes and Dexras1 suggests that, although their functions are probably similar, they have unique properties. Bacterially expressed Rhes binds GTP, suggesting that the protein indeed has GTPase functionality. Although Rhes was not induced by dexamethasone, its full expression is dependent upon thyroid hormone availability. Its accumulation is postnatal, consistent with the dependence upon thyroid hormone. It is noteworthy that most striatum-\"specific\" mRNAs characterized to date encode components of signal transduction cascades.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JD",
      "lastName" : "Falk",
      "authorRank" : 1,
      "name" : "Falk JD",
      "referenceId" : "RGD:A25329"
    }, {
      "firstName" : "P",
      "lastName" : "Vargiu",
      "authorRank" : 2,
      "name" : "Vargiu P",
      "referenceId" : "RGD:A25330"
    }, {
      "firstName" : "PE",
      "lastName" : "Foye",
      "authorRank" : 3,
      "name" : "Foye PE",
      "referenceId" : "RGD:A4183"
    }, {
      "firstName" : "H",
      "lastName" : "Usui",
      "authorRank" : 4,
      "name" : "Usui H",
      "referenceId" : "RGD:A58279"
    }, {
      "firstName" : "J",
      "lastName" : "Perez",
      "authorRank" : 5,
      "name" : "Perez J",
      "referenceId" : "RGD:A25332"
    }, {
      "firstName" : "PE",
      "lastName" : "Danielson",
      "authorRank" : 6,
      "name" : "Danielson PE",
      "referenceId" : "RGD:A46154"
    }, {
      "firstName" : "DL",
      "lastName" : "Lerner",
      "authorRank" : 7,
      "name" : "Lerner DL",
      "referenceId" : "RGD:A25334"
    }, {
      "firstName" : "J",
      "lastName" : "Bernal",
      "authorRank" : 8,
      "name" : "Bernal J",
      "referenceId" : "RGD:A18020"
    }, {
      "firstName" : "JG",
      "lastName" : "Sutcliffe",
      "authorRank" : 9,
      "name" : "Sutcliffe JG",
      "referenceId" : "RGD:A153207"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:704350"
    } ]
  }, {
    "primaryId" : "PMID:10467273",
    "title" : "Molecular basis for Rh(null) syndrome: identification of three new missense mutations in the Rh50 glycoprotein gene.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Huang CH, etal., Am J Hematol. 1999 Sep;62(1):25-32.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-08T16:15:00.000-06:00",
    "volume" : "62",
    "pages" : "25-32",
    "abstract" : "Rh(null) is a rare autosomal recessive disorder characterized by an absence of Rh antigens and a varying degree of hemolytic anemia and spherostomatocytosis. We report studies of two Japanese Rh(null) cases and describe three new missense mutations of RHAG, the locus that encodes Rh50 glycoprotein and modulates Rh antigen expression. In Rh(null)(HT), RHAG harbored in exon 6 two G-->A transitions, GTT-->ATT and GGA-->AGA, which cause Val(270)-->Ile and Gly(280)-->Arg substitutions, respectively. These missense mutations were cotransmitted from the propositus to the children and were predicted to reside in endoloop 5 and transmembrane (TM) segment 9, respectively. In Rh(null)(WO), RHAG contained in exon 9 a single G-->T transversion, GGT-->GTT, which caused a Gly(380)-->Val missense change in TM12 segment. The G-->T transversion, which is located at the +1 position of exon 9, had also affected pre-mRNA splicing and caused partial exon skipping. Although both Rh(null) cases had a structurally normal RH antigen locus, hemagglutination and immunoblotting showed no expression of Rh antigens or proteins. These results correlate each mutation with a structural defect in the respective TM domain of Rh50 glycoprotein.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CH",
      "lastName" : "Huang",
      "authorRank" : 1,
      "name" : "Huang CH",
      "referenceId" : "RGD:A74557"
    }, {
      "firstName" : "G",
      "lastName" : "Cheng",
      "authorRank" : 2,
      "name" : "Cheng G",
      "referenceId" : "RGD:A20712"
    }, {
      "firstName" : "Z",
      "lastName" : "Liu",
      "authorRank" : 3,
      "name" : "Liu Z",
      "referenceId" : "RGD:A23590"
    }, {
      "firstName" : "Y",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen Y",
      "referenceId" : "RGD:A160056"
    }, {
      "firstName" : "ME",
      "lastName" : "Reid",
      "authorRank" : 5,
      "name" : "Reid ME",
      "referenceId" : "RGD:A74559"
    }, {
      "firstName" : "G",
      "lastName" : "Halverson",
      "authorRank" : 6,
      "name" : "Halverson G",
      "referenceId" : "RGD:A74560"
    }, {
      "firstName" : "Y",
      "lastName" : "Okubo",
      "authorRank" : 7,
      "name" : "Okubo Y",
      "referenceId" : "RGD:A52497"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599622"
    } ]
  }, {
    "primaryId" : "PMID:10467592",
    "title" : "Egr3/Pilot, a zinc finger transcription factor, is rapidly regulated by activity in brain neurons and colocalizes with Egr1/zif268.",
    "datePublished" : "1994-10-01T00:00:00.000-05:00",
    "citation" : "Yamagata K, etal., Learn Mem 1994 Jul-Aug;1(2):140-52.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:21.000-05:00",
    "volume" : "1",
    "pages" : "140-52",
    "abstract" : "Programs of gene activation may underlie long-term adaptive cellular responses to extracellular ligands. We have used a differential cDNA cloning strategy to identify genes that are strongly induced by excitatory stimuli in the adult rat hippocampus. Here, we report the rat cDNA sequence of a zinc-finger transcription factor, Egr3/Pilot, and characterize its regulated mRNA expression in brain. Egr3 mRNA is rapidly and transiently induced in neurons of the hippocampus and cortex by electroconvulsive seizure. mRNA levels peak 2 hr after the seizure and remain elevated for as long as 8 hr. Egr3 mRNA is also rapidly induced in granule cells of the dentate gyrus by synaptic NMDA receptor activation elicited by patterned stimulation of the perforant pathway and by drugs that alter dopamine neurotransmission in the striatum. Basal levels of Egr3 mRNA in the cortex appear to be driven by natural synaptic activity because monocular deprivation rapidly decreases Egr3 mRNA in the deafferented visual cortex. Aspects of the protein structure, sequence-specific DNA binding, transcriptional activity, and regulation of Egr3 are highly similar to another zinc-finger transcription factor, Egr1/zif268. Moreover, we demonstrate colocalization of Egr3 and zif268 mRNAs in neurons of normal and stimulated cortex. Our studies suggest that interactions between these coregulated transcription factors may be important in defining long-term, neuroplastic responses.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Yamagata",
      "authorRank" : 1,
      "name" : "Yamagata K",
      "referenceId" : "RGD:A125327"
    }, {
      "firstName" : "WE",
      "lastName" : "Kaufmann",
      "authorRank" : 2,
      "name" : "Kaufmann WE",
      "referenceId" : "RGD:A33478"
    }, {
      "firstName" : "A",
      "lastName" : "Lanahan",
      "authorRank" : 3,
      "name" : "Lanahan A",
      "referenceId" : "RGD:A4907"
    }, {
      "firstName" : "M",
      "lastName" : "Papapavlou",
      "authorRank" : 4,
      "name" : "Papapavlou M",
      "referenceId" : "RGD:A27223"
    }, {
      "firstName" : "CA",
      "lastName" : "Barnes",
      "authorRank" : 5,
      "name" : "Barnes CA",
      "referenceId" : "RGD:A48394"
    }, {
      "firstName" : "KI",
      "lastName" : "Andreasson",
      "authorRank" : 6,
      "name" : "Andreasson KI",
      "referenceId" : "RGD:A5725"
    }, {
      "firstName" : "PF",
      "lastName" : "Worley",
      "authorRank" : 7,
      "name" : "Worley PF",
      "referenceId" : "RGD:A49791"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:727280"
    } ]
  }, {
    "primaryId" : "PMID:10467595",
    "title" : "Temporal and spatial regulation of the expression of BAD2, a MAP kinase phosphatase, during seizure, kindling, and long-term potentiation.",
    "datePublished" : "1994-08-01T00:00:00.000-05:00",
    "citation" : "Qian Z, etal., Learn Mem 1994 Sep-Oct;1(3):180-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:11:19.000-05:00",
    "volume" : "1",
    "pages" : "180-8",
    "abstract" : "Recent studies indicate that stimulation of NMDA receptors in cultured hippocampal cells activates MAP kinase. Although the pathway whereby MAP kinase is activated has been been characterized, little is known about the mechanisms that shut off MAP kinase. In the course of analyzing several immediate-early genes identified previously by differential screen as inducible by seizure activity, we found that one of them, BAD2, encodes dual purpose, threonine/tyrosine phosphates with specific activity directed against MAP kinase (MKP-1). In situ hybridization of BAD2 demonstrates that stimuli that produce seizure, kindling, and long-term potentiation cause a rapid increase in BAD2 mRNA (within 0.5-1 hr after stimulation) that has, in each case, a distinctive pattern of expression in the brain. In these regions, the induction of a MAP kinase-specific phosphatase may provide a negative feedback control associated with long-term synaptic changes.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Z",
      "lastName" : "Qian",
      "authorRank" : 1,
      "name" : "Qian Z",
      "referenceId" : "RGD:A22100"
    }, {
      "firstName" : "M",
      "lastName" : "Gilbert",
      "authorRank" : 2,
      "name" : "Gilbert M",
      "referenceId" : "RGD:A22101"
    }, {
      "firstName" : "ER",
      "lastName" : "Kandel",
      "authorRank" : 3,
      "name" : "Kandel ER",
      "referenceId" : "RGD:A22102"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633770"
    } ]
  }, {
    "primaryId" : "PMID:10467734",
    "title" : "Aldehyde dehydrogenase from rat intestinal mucosa: purification and characterization of an isozyme with high affinity for gamma-aminobutyraldehyde.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Testore G, etal., Int J Biochem Cell Biol. 1999 Jul;31(7):777-86.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-09-23T14:00:04.000-05:00",
    "volume" : "31",
    "pages" : "777-86",
    "abstract" : "In rat adrenal gland and gastric mucosa putrescine is efficiently oxidized to GABA via gamma-aminobutyraldehyde (ABAL) by action of diamine oxidase and aldehyde dehydrogenase. Having turned our attention on the rat intestinal mucosa, where putrescine uptake and diamine oxidase are active, we have purified and characterized an aldehyde dehydrogenase optimally active on gamma-aminobutyraldehyde. A dimer with a subunit molecular weight of 52,000, the native enzyme binds ABAL and NAD+ with high affinity: at pH 7.4, Km values are equal to 18 and 14 microM, respectively. Affinity for betaine aldehyde is much lower (Km = 285 microM), but the efficiency is equally good, thanks to a high value of V. Unaffected by disulfiram and Mg2+, the enzyme is activated by high NAD+ concentrations (Vnn = 1.6 x Vn) and is competitively inhibited by NADH. According to the best fitting model, the dimeric enzyme only binds one NADH and the mixed complex enzyme-NAD(+)-NADH is inactive. The increase of activity promoted by NAD+ can therefore be ascribed to an allosteric effect, rather than to the activation of a second reaction center. Highly stable at pH 6.8 in the presence of dithiothreitol and high phosphate concentrations, ABALDH is inactivated by ion-exchange resins and by cationic buffers. Our results show that the enzyme can be effectively involved in the metabolism of biogenic amines and, with a K(m) for ABAL lower than 20 microM, in the synthesis of GABA.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G",
      "lastName" : "Testore",
      "authorRank" : 1,
      "name" : "Testore G",
      "referenceId" : "RGD:A112574"
    }, {
      "firstName" : "C",
      "lastName" : "Cravanzola",
      "authorRank" : 2,
      "name" : "Cravanzola C",
      "referenceId" : "RGD:A112575"
    }, {
      "firstName" : "S",
      "lastName" : "Bedino",
      "authorRank" : 3,
      "name" : "Bedino S",
      "referenceId" : "RGD:A112576"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2313412"
    } ]
  }, {
    "primaryId" : "PMID:10468085",
    "title" : "Circadian patterns of heart rate variability, fibrinolytic activity, and hemostatic factors in type I diabetes mellitus with cardiac autonomic neuropathy.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Aronson D, etal., Am J Cardiol. 1999 Aug 15;84(4):449-53.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-08-11T12:54:54.000-05:00",
    "volume" : "84",
    "pages" : "449-53",
    "abstract" : "Diabetes mellitus is associated with a marked increase in the risk of coronary events but with an altered circadian distribution that demonstrates an absent morning peak and higher infarction rate during the evening hours. To elucidate the mechanism of this phenomenon, the circadian pattern of heart rate variability was evaluated in 22 type I diabetic patients with diabetic autonomic neuropathy in conjunction with circadian changes of fibrinolytic and hemostatic factors. The circadian pattern (6 A.M. to 10 P.M. vs 10 P.M. to 6 A.M.) of 3 indexes of parasympathetic tone was evaluated using 24-hour heart rate variability analysis. The high-frequency power (3.0 +/- 0.2 vs 3.3 +/- 0.2 ms2, p = 0.08) and the percentage of RR intervals with >50 ms variation (0.47 +/- 0.18 vs 0.69 +/- 0.33 ms, p = 0.52) demonstrated no significant circadian variation. The square root of mean squared differences of successive RR intervals showed a small but significant increase during nighttime (8.5 +/- 0.7 vs 9.7 +/- 1.1 ms, p = 0.02). Fibrinolytic activity was significantly lower at 8 A.M. than at 4 P.M. (166.4 +/- 12.5 to 200.2 +/- 9.3 mm2, p = 0.0003), but with a low amplitude. Plasminogen activator inhibitor 1 showed no circadian variation. Factor VII and fibrinogen demonstrated a significant reduction from 8 A.M. to 4 P.M., but both peak and nadir values were elevated. The von Willebrand factor was markedly elevated with no circadian variation. Thus, diabetic autonomic neuropathy is associated with a loss of both the nocturnal predominance of parasympathetic activity and a prothrombotic state that persists throughout the day. These abnormalities may attenuate the relative protection from coronary events during the afternoon and nighttime.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Aronson",
      "authorRank" : 1,
      "name" : "Aronson D",
      "referenceId" : "RGD:A110641"
    }, {
      "firstName" : "LA",
      "lastName" : "Weinrauch",
      "authorRank" : 2,
      "name" : "Weinrauch LA",
      "referenceId" : "RGD:A110570"
    }, {
      "firstName" : "JA",
      "lastName" : "D'Elia",
      "authorRank" : 3,
      "name" : "D'Elia JA",
      "referenceId" : "RGD:A110569"
    }, {
      "firstName" : "GH",
      "lastName" : "Tofler",
      "authorRank" : 4,
      "name" : "Tofler GH",
      "referenceId" : "RGD:A57635"
    }, {
      "firstName" : "AJ",
      "lastName" : "Burger",
      "authorRank" : 5,
      "name" : "Burger AJ",
      "referenceId" : "RGD:A110642"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2312401"
    } ]
  }, {
    "primaryId" : "PMID:10468558",
    "title" : "Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Foulon V, etal., Proc Natl Acad Sci U S A 1999 Aug 31;96(18):10039-44.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-09-24T12:59:24.000-05:00",
    "volume" : "96",
    "pages" : "10039-44",
    "abstract" : "In the third step of the alpha-oxidation of 3-methyl-branched fatty acids such as phytanic acid, a 2-hydroxy-3-methylacyl-CoA is cleaved into formyl-CoA and a 2-methyl-branched fatty aldehyde. The cleavage enzyme was purified from the matrix protein fraction of rat liver peroxisomes and identified as a protein made up of four identical subunits of 63 kDa. Its activity proved to depend on Mg(2+) and thiamine pyrophosphate, a hitherto unrecognized cofactor of alpha-oxidation. Formyl-CoA and 2-methylpentadecanal were identified as reaction products when the purified enzyme was incubated with 2-hydroxy-3-methylhexadecanoyl-CoA as the substrate. Hence the enzyme catalyzes a carbon-carbon cleavage, and we propose calling it 2-hydroxyphytanoyl-CoA lyase. Sequences derived from tryptic peptides of the purified rat protein were used as queries to recover human expressed sequence tags from the databases. The composite cDNA sequence of the human lyase contained an ORF of 1,734 bases that encodes a polypeptide with a calculated molecular mass of 63,732 Da. Recombinant human protein, expressed in mammalian cells, exhibited lyase activity. The lyase displayed homology to a putative Caenorhabditis elegans protein that resembles bacterial oxalyl-CoA decarboxylases. Similarly to the decarboxylases, a thiamine pyrophosphate-binding consensus domain was present in the C-terminal part of the lyase. Although no peroxisome targeting signal, neither 1 nor 2, was apparent, transfection experiments with constructs encoding green fluorescent protein fused to the full-length lyase or its C-terminal pentapeptide indicated that the C terminus of the lyase represents a peroxisome targeting signal 1 variant.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Foulon",
      "authorRank" : 1,
      "name" : "Foulon V",
      "referenceId" : "RGD:A25896"
    }, {
      "firstName" : "VD",
      "lastName" : "Antonenkov",
      "authorRank" : 2,
      "name" : "Antonenkov VD",
      "referenceId" : "RGD:A25897"
    }, {
      "firstName" : "K",
      "lastName" : "Croes",
      "authorRank" : 3,
      "name" : "Croes K",
      "referenceId" : "RGD:A25898"
    }, {
      "firstName" : "E",
      "lastName" : "Waelkens",
      "authorRank" : 4,
      "name" : "Waelkens E",
      "referenceId" : "RGD:A25899"
    }, {
      "firstName" : "GP",
      "lastName" : "Mannaerts",
      "authorRank" : 5,
      "name" : "Mannaerts GP",
      "referenceId" : "RGD:A5616"
    }, {
      "firstName" : "PP",
      "lastName" : "Van Veldhoven",
      "authorRank" : 6,
      "name" : "Van Veldhoven PP",
      "referenceId" : "RGD:A5617"
    }, {
      "firstName" : "M",
      "lastName" : "Casteels",
      "authorRank" : 7,
      "name" : "Casteels M",
      "referenceId" : "RGD:A25900"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:708588"
    } ]
  }, {
    "primaryId" : "PMID:10468577",
    "title" : "A tubular endosomal fraction from rat liver: biochemical evidence of receptor sorting by default.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Verges M, etal., Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10146-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-02-22T17:14:21.000-06:00",
    "volume" : "96",
    "pages" : "10146-51",
    "abstract" : "We previously have isolated an endosomal fraction from rat liver, termed receptor-recycling compartment (RRC), which is highly enriched in recycling receptors and in the transcytotic polymeric Ig receptor (pIgR). We now have analyzed the RRC fraction by immunoisolation and found that no uniquely transcytotic elements were present, because recycling receptors and the pIgR were coisolated on the same elements. In addition, RRC was very rich in proteins previously shown to be associated with recycling endosomes, such as rab 11, cellubrevin, and endobrevin, but relatively poor in early endosome antigen 1. As RRC contains mainly tubules and small vesicles, our results indicate that it is enriched in elements of a tubular endosomal compartment involved in receptor sorting. Biochemical analysis showed that the density of recycling receptors and transcytotic pIgR in RRC membranes was similar to that in early endosome membranes. This observation supports the idea that increasing membrane surface area by endosome tubulation is the main mechanism to ensure efficient receptor sorting and, at the same time, locates RRC in a common step of the endocytotic system before final receptor segregation into distinct recycling and transcytotic pathways.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Verges",
      "authorRank" : 1,
      "name" : "Verges M",
      "referenceId" : "RGD:A82970"
    }, {
      "firstName" : "RJ",
      "lastName" : "Havel",
      "authorRank" : 2,
      "name" : "Havel RJ",
      "referenceId" : "RGD:A72792"
    }, {
      "firstName" : "KE",
      "lastName" : "Mostov",
      "authorRank" : 3,
      "name" : "Mostov KE",
      "referenceId" : "RGD:A139819"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892345"
    } ]
  }, {
    "primaryId" : "PMID:10468599",
    "title" : "Three new allelic mouse mutations that cause skeletal overgrowth involve the natriuretic peptide receptor C gene (Npr3).",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Jaubert J, etal., Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10278-83.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-08-24T15:51:02.000-05:00",
    "volume" : "96",
    "pages" : "10278-83",
    "abstract" : "In 1979, a BALB/cJ mouse was identified with an exceptionally long body. This phenotype was found to be caused by a recessive mutation, designated longjohn (lgj), that mapped to the proximal region of chromosome 15. Several years later, a mouse with a similarly elongated body was identified in an outbred stock after chemical mutagenesis with ethylnitrosourea. This phenotype also was caused by a recessive mutation, designated strigosus (stri). The two mutations were found to be allelic. A third allele was identified in a DBA/2J mouse and was designated longjohn-2J (lgj(2J)). Analysis of skeletal preparations of stri/stri mice indicated that the endochondral ossification process was slightly delayed, resulting in an extended proliferation zone. A recent study reported that mice overexpressing brain natriuretic peptide, one of the members of the natriuretic peptide family, exhibit a skeletal-overgrowth syndrome with endochondral ossification defects. The Npr3 gene coding for type C receptor for natriuretic peptides (NPR-C), which is mainly involved in the clearance of the natriuretic peptides, mapped in the vicinity of our mouse mutations and thus was a candidate gene. The present study reports that all three mutations involve the Npr3 gene and provides evidence in vivo that there is a natriuretic-related bone pathway, underscoring the importance of natriuretic peptide clearance by natriuretic peptide type C receptor.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Jaubert",
      "authorRank" : 1,
      "name" : "Jaubert J",
      "referenceId" : "RGD:A63989"
    }, {
      "firstName" : "F",
      "lastName" : "Jaubert",
      "authorRank" : 2,
      "name" : "Jaubert F",
      "referenceId" : "RGD:A63990"
    }, {
      "firstName" : "N",
      "lastName" : "Martin",
      "authorRank" : 3,
      "name" : "Martin N",
      "referenceId" : "RGD:A22487"
    }, {
      "firstName" : "LL",
      "lastName" : "Washburn",
      "authorRank" : 4,
      "name" : "Washburn LL",
      "referenceId" : "RGD:A55727"
    }, {
      "firstName" : "BK",
      "lastName" : "Lee",
      "authorRank" : 5,
      "name" : "Lee BK",
      "referenceId" : "RGD:A55728"
    }, {
      "firstName" : "EM",
      "lastName" : "Eicher",
      "authorRank" : 6,
      "name" : "Eicher EM",
      "referenceId" : "RGD:A18788"
    }, {
      "firstName" : "JL",
      "lastName" : "Guenet",
      "authorRank" : 7,
      "name" : "Guenet JL",
      "referenceId" : "RGD:A14765"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1580774"
    } ]
  }, {
    "primaryId" : "PMID:10468616",
    "title" : "Long-term expression of human coagulation factor VIII and correction of hemophilia A after in vivo retroviral gene transfer in factor VIII-deficient mice.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "VandenDriessche T, etal., Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10379-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-01-20T17:52:42.000-06:00",
    "volume" : "96",
    "pages" : "10379-84",
    "abstract" : "Hemophilia A is caused by a deficiency in coagulation factor VIII (FVIII) and predisposes to spontaneous bleeding that can be life-threatening or lead to chronic disabilities. It is well suited for gene therapy because a moderate increase in plasma FVIII concentration has therapeutic effects. Improved retroviral vectors expressing high levels of human FVIII were pseudotyped with the vesicular stomatitis virus G glycoprotein, were concentrated to high-titers (10(9)-10(10) colony-forming units/ml), and were injected intravenously into newborn, FVIII-deficient mice. High-levels (>/=200 milliunits/ml) of functional human FVIII production could be detected in 6 of the 13 animals, 4 of which expressed physiologic or higher levels (500-12,500 milliunits/ml). Five of the six expressers produced FVIII and survived an otherwise lethal tail-clipping, demonstrating phenotypic correction of the bleeding disorder. FVIII expression was sustained for >14 months. Gene transfer occurred into liver, spleen, and lungs with predominant FVIII mRNA expression in the liver. Six of the seven animals with transient or no detectable human FVIII developed FVIII inhibitors (7-350 Bethesda units/ml). These findings indicate that a genetic disease can be  corrected by in vivo gene therapy using retroviral vectors.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "VandenDriessche",
      "authorRank" : 1,
      "name" : "VandenDriessche",
      "referenceId" : "RGD:A210553"
    }, {
      "firstName" : "V",
      "lastName" : "Vanslembrouck",
      "authorRank" : 2,
      "name" : "Vanslembrouck",
      "referenceId" : "RGD:A210554"
    }, {
      "firstName" : "I",
      "lastName" : "Goovaerts",
      "authorRank" : 3,
      "name" : "Goovaerts",
      "referenceId" : "RGD:A210555"
    }, {
      "firstName" : "H",
      "lastName" : "Zwinnen",
      "authorRank" : 4,
      "name" : "Zwinnen",
      "referenceId" : "RGD:A210556"
    }, {
      "firstName" : "ML",
      "lastName" : "Vanderhaeghen",
      "authorRank" : 5,
      "name" : "Vanderhaeghen",
      "referenceId" : "RGD:A210557"
    }, {
      "firstName" : "D",
      "lastName" : "Collen",
      "authorRank" : 6,
      "name" : "Collen D",
      "referenceId" : "RGD:A54295"
    }, {
      "firstName" : "MK",
      "lastName" : "Chuah",
      "authorRank" : 7,
      "name" : "Chuah",
      "referenceId" : "RGD:A210558"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10450757"
    } ]
  }, {
    "primaryId" : "PMID:10468735",
    "title" : "MUC1 mucin as a tumour marker in bladder cancer.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Simms MS, etal., BJU Int. 1999 Aug;84(3):350-2.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-06-17T14:57:57.000-05:00",
    "volume" : "84",
    "pages" : "350-2",
    "abstract" : "OBJECTIVE: To evaluate serum MUC1 levels (a high molecular weight glycoprotein which is upregulated and abnormally glycosylated in bladder cancer and other carcinomas) in patients with a variety of stages and grades of transitional cell  carcinoma (TCC) of the bladder, to assess its potential as a tumour marker. PATIENTS AND METHODS: Blood samples were taken before treatment in 87 patients with TCC of the bladder and in 31 controls undergoing cystoscopy for benign conditions. Serum MUC1 levels were estimated with an enzyme-linked immunosorbent  assay using the C595 monoclonal antibody. RESULTS: Of patients with T4 tumours, 47% had MUC1 levels above the normal range (P<0.001); patients with T3 tumours also had significantly higher MUC1 levels than controls. The overall sensitivity  was only 24% for all tumours when the upper limit of normal was defined as 4.8 U/mL; the specificity was 97%. CONCLUSION: Serum MUC1 is not as useful tumour marker for screening, as it has a low sensitivity. However, MUC1 levels are high  in advanced disease and serum MUC1 levels may be useful for disease monitoring.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MS",
      "lastName" : "Simms",
      "authorRank" : 1,
      "name" : "Simms",
      "referenceId" : "RGD:A170778"
    }, {
      "firstName" : "OD",
      "lastName" : "Hughes",
      "authorRank" : 2,
      "name" : "Hughes",
      "referenceId" : "RGD:A170779"
    }, {
      "firstName" : "M",
      "lastName" : "Limb",
      "authorRank" : 3,
      "name" : "Limb",
      "referenceId" : "RGD:A170780"
    }, {
      "firstName" : "MR",
      "lastName" : "Price",
      "authorRank" : 4,
      "name" : "Price",
      "referenceId" : "RGD:A170781"
    }, {
      "firstName" : "MC",
      "lastName" : "Bishop",
      "authorRank" : 5,
      "name" : "Bishop",
      "referenceId" : "RGD:A170782"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7245967"
    } ]
  }, {
    "primaryId" : "PMID:10468909",
    "title" : "The HLA-DQ associations with Graves' disease in Chinese children.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Wong GW, etal., Clin Endocrinol (Oxf). 1999 Apr;50(4):493-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2013-11-21T14:06:14.000-06:00",
    "volume" : "50",
    "pages" : "493-5",
    "abstract" : "OBJECTIVE: Graves' disease has been documented to be associated with different HLA genes in Caucasians and Chinese adults. The incidence of childhood Graves' disease has been reported to be high in Hong Kong Chinese. The aims of this study were to examine the HLA-DQA1 and DQB1 associations with Graves' disease in Chinese children. PATIENTS AND DESIGN: Sixty-seven Chinese children with Graves'  disease (59 girls and 8 boys) and 51 racially matched healthy controls were recruited for the study. Genomic DNA was extracted from venous blood samples. HLA-DQ typings were determined by sequence-specific oligonucleotide probing of the respective enzymatically amplified gene. Frequencies of HLA-DQ alleles at each locus were compared between patients and controls using the chi 2-test. RESULTS: The frequency of HLA-DQB1.0303 was increased in the combined male and female patient group [53.7%; relative risk (RR) = 4.22; Pc = 0.005] and female patients (50.8%; RR = 3.76; Pc = 0.018) compared with that in the entire control  group (21.2%). HLA-DQB1*201 was protective for Graves' disease (10.4%; RR = 0.20; Pc = 0.006). In contrast to studies in Caucasians, DQA1*0501 was not associated with susceptibility for Graves' disease in Chinese children. CONCLUSIONS: This study confirms that DQB1*0303 is a race-specific susceptible allele for Graves' disease in Chinese. Both susceptible and protective HLA-DQ alleles for Graves' disease in Chinese children are different from those in Caucasians.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GW",
      "lastName" : "Wong",
      "authorRank" : 1,
      "name" : "Wong GW",
      "referenceId" : "RGD:A45942"
    }, {
      "firstName" : "SH",
      "lastName" : "Cheng",
      "authorRank" : 2,
      "name" : "Cheng",
      "referenceId" : "RGD:A174336"
    }, {
      "firstName" : "JS",
      "lastName" : "Dorman",
      "authorRank" : 3,
      "name" : "Dorman",
      "referenceId" : "RGD:A176008"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7421572"
    } ]
  }, {
    "primaryId" : "PMID:10469016",
    "title" : "Mutations in intron 3 of GH-1 gene associated with isolated GH deficiency type II in three Japanese families.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kamijo T, etal., Clin Endocrinol (Oxf). 1999 Sep;51(3):355-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T01:06:37.000-05:00",
    "volume" : "51",
    "pages" : "355-60",
    "abstract" : "OBJECTIVE: Isolated GH deficiency (IGHD) type II is a disorder inherited in an autosomal dominant manner. Three mutations at the donor splice site of intron 3 of the GH-I gene have been identified in five families. In this report, we describe a novel mutation also at the donor splice site of intron 3 in patients with IGHD type II. PATIENTS: Five individuals diagnosed as IGHD: two sporadic cases and one family with three affected individuals (two siblings and their father). MEASUREMENT: Genomic DNA was extracted from peripheral mononuclear cells. All the exons and introns of the GH-I gene were amplified by polymerase chain reaction (PCR) and subjected to sequence analysis. RESULTS: A guanine to adenine transition at the fifth base of intron 3 (mutE), which has not been reported, was identified in the familial case but not in unaffected members of the family including the paternal grandparents. In the other two families with sporadic cases, a guanine to adenine transition at the first base of intron 3 (mutA) was identified in the affected subjects but not in other members of the families. CONCLUSION: MutE has not been previously reported and is the fourth mutation associated with IGHD type II. The guanine residue mutated in mutA was the second nucleotide of a CpG dinucleotide, which is regarded as a hot spot for  mutations by a methylation-deamination mechanism. Since mutA has previously been  identified in three type II IGHD kindreds belonging to different ethnic backgrounds, this appears to be the most frequent GH-I gene mutation in IGHD with a dominant inheritance. Because de novo mutations appeared to have occurred in all three families analyzed in the present study and the presence or absence of these mutations can easily be tested by PCR and restriction enzyme digestion, not only the familial cases but also sporadic cases with IGHD should be examined for  a possible mutation at the donor splice site of intron 3 in the GH-1 gene.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kamijo",
      "authorRank" : 1,
      "name" : "Kamijo T",
      "referenceId" : "RGD:A15086"
    }, {
      "firstName" : "Y",
      "lastName" : "Hayashi",
      "authorRank" : 2,
      "name" : "Hayashi",
      "referenceId" : "RGD:A414320"
    }, {
      "firstName" : "A",
      "lastName" : "Shimatsu",
      "authorRank" : 3,
      "name" : "Shimatsu A",
      "referenceId" : "RGD:A32279"
    }, {
      "firstName" : "E",
      "lastName" : "Kinoshita",
      "authorRank" : 4,
      "name" : "Kinoshita",
      "referenceId" : "RGD:A272214"
    }, {
      "firstName" : "M",
      "lastName" : "Yoshimoto",
      "authorRank" : 5,
      "name" : "Yoshimoto M",
      "referenceId" : "RGD:A18198"
    }, {
      "firstName" : "M",
      "lastName" : "Ogawa",
      "authorRank" : 6,
      "name" : "Ogawa M",
      "referenceId" : "RGD:A6066"
    }, {
      "firstName" : "H",
      "lastName" : "Seo",
      "authorRank" : 7,
      "name" : "Seo",
      "referenceId" : "RGD:A413719"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11073020"
    } ]
  }, {
    "primaryId" : "PMID:10469027",
    "title" : "Polymorphisms in the beta2-adrenoreceptor gene are associated with decreased airway responsiveness.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ramsay CE, etal., Clin Exp Allergy. 1999 Sep;29(9):1195-203.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-03-07T10:58:35.000-06:00",
    "volume" : "29",
    "pages" : "1195-203",
    "abstract" : "BACKGROUND: There are a number of candidate genes thought to play a role in the development of asthma. Polymorphisms at amino acid positions 16 (arginine to glycine) and 27 (glutamine to glutamic acid) of the beta2-adrenoreceptor (B2AR) gene are known to be functionally relevant and have been associated with more severe forms of asthma, nocturnal asthma and decreased airway responsiveness in asthmatic subjects. OBJECTIVE: To determine if these polymorphisms contribute to  the development of asthma by investigating the associations between the polymorphisms at amino acid positions 16 and 27 of the B2AR gene and asthma-related parameters in a large, phenotypically well-characterized population which was unselected for asthma. METHODS: Subjects (n = 332) were characterized using physiological assessments, immuno-logical data and information obtained from questionnaire. PCR was used to generate a 229 base pair fragment spanning the mutations of interest. Genotype was determined using allele-specific oligonucleotide hybridization and confirmed in 10% of the samples by direct sequencing. Multivariate analysis of the association between genotype and phenotype was then undertaken. RESULTS: Homozygotes for Glu27 were significantly less responsive to histamine than Gln27 homozygotes. In addition, Arg16 homozygotes were more likely to 'wheeze during a cold', in comparison with  Gly16 homozygotes. However, there was no association between either polymorphism  and physician-diagnosed asthma, eczema, skin reactivity to common allergens or total and specific serum IgE levels. The two polymorphisms were found to be in significant linkage disequilibrium. CONCLUSION: The polymorphism at position 27 was associated with decreased airway responsiveness in the study population and the polymorphism at position 16 was associated with increased wheeze during respiratory infection, but neither was associated with physician-diagnosed asthma or any of the other variables considered.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CE",
      "lastName" : "Ramsay",
      "authorRank" : 1,
      "name" : "Ramsay",
      "referenceId" : "RGD:A180622"
    }, {
      "firstName" : "CM",
      "lastName" : "Hayden",
      "authorRank" : 2,
      "name" : "Hayden CM",
      "referenceId" : "RGD:A129070"
    }, {
      "firstName" : "KJ",
      "lastName" : "Tiller",
      "authorRank" : 3,
      "name" : "Tiller",
      "referenceId" : "RGD:A180623"
    }, {
      "firstName" : "PR",
      "lastName" : "Burton",
      "authorRank" : 4,
      "name" : "Burton PR",
      "referenceId" : "RGD:A64265"
    }, {
      "firstName" : "J",
      "lastName" : "Goldblatt",
      "authorRank" : 5,
      "name" : "Goldblatt J",
      "referenceId" : "RGD:A35913"
    }, {
      "firstName" : "PN",
      "lastName" : "LeSouef",
      "authorRank" : 6,
      "name" : "LeSouef PN",
      "referenceId" : "RGD:A129110"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8548496"
    } ]
  }, {
    "primaryId" : "PMID:10469141",
    "title" : "Purified apolipoprotein B gene regulatory factor-3 is DNA topoisomerase I.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Chuang SS, etal., Eur J Biochem. 1999 Aug;263(3):773-81.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-11T13:12:29.000-06:00",
    "volume" : "263",
    "pages" : "773-81",
    "abstract" : "Hepatic cell-specific expression of the human apolipoprotein B (apoB) gene is controlled by at least four cis-acting elements located between positions -128 and +122 [Chuang, S. S., & Das, H. K. (1996) Biochem. Biophys. Res. Commun. 220, 553-562]. A negative cis-acting element (+20 to +40) is located in the first nontranslated exon of the human apoB gene, and apoB regulatory factor-3 (BRF-3) interacts with this. In this paper, we report the purification and characterization of BRF-3 from rat liver nuclear extracts. BRF-3 has been purified to apparent homogeneity by DEAE-cellulose, heparin-agarose, and DNA-specific affinity chromatography. Purified BRF-3 produced two polypeptide bands with apparent molecular masses of 70 kDa and 67 kDa in SDS/PAGE as detected by silver staining. Both 70-kDa and 67-kDa proteins have been found to hybridize specifically with labeled double-stranded oligonucleotide containing BRF-3 binding site in a South-Western blot. Double-stranded oligonucleotide containing mutations in the BRF-3 binding site was found to abolish DNA binding by these two proteins. Amino acid sequences of tryptic peptides derived from affinity purified 70-kDa and 67-kDa rat BRF-3 proteins were found to have 100% sequence homologies with DNA topoisomerase I. These data suggest that the 70-kDa and 67-kDa forms of BRF-3 are derived by proteolytic cleavage of topoisomerase I, and therefore, topoisomerase I may play an important role in transcriptional regulation of apoB.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SS",
      "lastName" : "Chuang",
      "authorRank" : 1,
      "name" : "Chuang SS",
      "referenceId" : "RGD:A20590"
    }, {
      "firstName" : "D",
      "lastName" : "Banerjee",
      "authorRank" : 2,
      "name" : "Banerjee D",
      "referenceId" : "RGD:A56649"
    }, {
      "firstName" : "HK",
      "lastName" : "Das",
      "authorRank" : 3,
      "name" : "Das HK",
      "referenceId" : "RGD:A120252"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2317063"
    } ]
  }, {
    "primaryId" : "PMID:10469179",
    "title" : "Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or factor VII deficiency.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Scharrer I Haemophilia. 1999 Jul;5(4):253-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-25T15:33:24.000-05:00",
    "volume" : "5",
    "pages" : "253-9",
    "abstract" : "Inhibitors to factor VIII (FVIII) or IX (FIX) in patients with haemophilia A or B create a challenging problem for the treatment of these patients. Recombinant FVIIa (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) is a realistic treatment option, owing to its specific mode of action and lack of immunogenicity. This was a multicentre, open-label, compassionate-use trial in patients with severe haemophilia A (FVIII:C < 1%) or B (FIX:C < 1%) with inhibitors, acquired antibodies to FVIII or FIX, or FVII deficiency (FVII:C < 5%), for whom alternative therapies had failed or were contraindicated. Patients  received rFVIIa treatment for life- or limb-threatening bleeding episodes or for  coverage during essential surgery. The mean rFVIIa dose was approximately 90 microg kg-1 for haemophilia A/B and acquired inhibitor patients, and 25 microg kg-1 for FVII-deficient patients. Efficacy data for 67 treatment episodes (45 bleeding episodes, 22 surgical procedures) are presented; seven patients were treated for a concurrent serious bleeding episode and surgical procedure. At the  end of treatment, rFVIIa was effective or partially effective in 85% of serious bleeding episodes. During surgery, bleeding was assessed as none or less than or  equivalent to normal in 91% of surgical procedures; postoperatively, 91% of procedures were associated with no or minimal oozing. During 60 separate treatment episodes, 26 adverse events (22 nonserious, four serious) were reported in 15 patients, during 17 bleeding episodes or surgical procedures. Only 10 were  considered as having a possible, probable, or unknown relationship with rFVIIa; of these, fever (n=2) and thrombophlebitis (n=3) were the most common. There was  no evidence of disseminated intravascular coagulation. In conclusion, rFVIIa is an effective, well-tolerated treatment for serious bleeding episodes and bleeding associated with surgical procedures in patients with severe haemophilia A/B with  inhibitors, acquired inhibitors, or FVII deficiency.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Scharrer",
      "authorRank" : 1,
      "name" : "Scharrer I",
      "referenceId" : "RGD:A48317"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041654"
    } ]
  }, {
    "primaryId" : "PMID:10469244",
    "title" : "Molecular cloning, expression and characterization of the rat analogue of human membrane cofactor protein (MCP/CD46).",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mead R, etal., Immunology. 1999 Sep;98(1):137-43.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-06-05T11:25:23.000-05:00",
    "volume" : "98",
    "pages" : "137-43",
    "abstract" : "In humans, host cells are protected from homologous complement by membrane proteins encoded in the regulators of complement activation (RCA) gene cluster. These include complement receptor 1 (CR1), decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46). In mouse and rat a single membrane inhibitor, Crry, appeared to perform the functions of both DAF and MCP and was proposed to be the functional analogue of both. Recently, however, murine homologues of DAF and MCP have been identified, prompting a search for the rat counterparts. We have described the identification of rat DAF and here describe the cloning of rat MCP from cDNA and genomic libraries, using a probe based on the mouse MCP cDNA sequence. The domain structure for rat MCP was identical to that of mouse MCP with four short consensus repeats (SCRs) followed by a STP domain, transmembrane segment and cytoplasmic tail. Overall identity of rat and mouse MCP was 77% at the amino acid level and 88% at the nucleotide level. Northern blot analysis from a range of tissues indicated that high-level expression was limited to the testis, although expression in other tissues was detected using reverse transcription-polymerase chain reaction. Rat MCP mRNA localized to Sertoli cells and spermatogonia in seminiferous tubules by in situ hybridization, but was absent in mature sperm. In cofactor assays utilizing human factor I, a recombinant soluble form of rat MCP catalysed cleavage of human C3ma.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Mead",
      "authorRank" : 1,
      "name" : "Mead R",
      "referenceId" : "RGD:A96732"
    }, {
      "firstName" : "SJ",
      "lastName" : "Hinchliffe",
      "authorRank" : 2,
      "name" : "Hinchliffe SJ",
      "referenceId" : "RGD:A17613"
    }, {
      "firstName" : "BP",
      "lastName" : "Morgan",
      "authorRank" : 3,
      "name" : "Morgan BP",
      "referenceId" : "RGD:A17616"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2293568"
    } ]
  }, {
    "primaryId" : "PMID:10469263",
    "title" : "Up-regulation of cytokines in glomerulonephritis associated with murine malaria infection.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Sinniah R, etal., Int J Exp Pathol. 1999 Apr;80(2):87-95.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-10-29T13:14:34.000-05:00",
    "volume" : "80",
    "pages" : "87-95",
    "abstract" : "Malaria infections often cause glomerulonephritis (GN), and multiple factors have been implicated in the pathogenesis of glomerular injury. The role of cytokines in malaria associated glomerulonephritis has not been clearly defined. To study the importance of cytokines in malarial nephritis, we investigated the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-6, IL-10 and granulocyte macrophage-colony stimulating factor (GM-CSF) in kidneys acutely infected with murine malaria parasite Plasmodium berghei ANKA in  C57BL/6 J mice. Groups of six mice sacrificed on days 5, 8-10, 15, and 20 postinfection, and normal controls were used for cytokine analysis. Elevated levels of messenger RNA (mRNA) specific for these cytokines in infected kidneys after day 5 postinfection were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Kidney sections stained with specific antibodies against TNF-alpha, IL-1alpha, IL-6, IL-10 and GM-CSF by immunohistochemistry showed that the staining for these cytokines on the glomeruli was positive from day 10 postinfection, and increased progressively, mainly in the infiltrating macrophages and the glomerular mesangium. Strong correlation was found between the expression of TNF-alpha with IL-6, and IL-1alpha with IL-6. The expression of TNF-alpha, IL-1alpha, IL-6, and IL-10 also strongly correlated with the severity of proteinuria. Our findings show that there is up-regulation of cytokines in the pathogenesis of glomerulonephritis associated with murine malaria infection.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Sinniah",
      "authorRank" : 1,
      "name" : "Sinniah R",
      "referenceId" : "RGD:A159179"
    }, {
      "firstName" : "L",
      "lastName" : "Rui-Mei",
      "authorRank" : 2,
      "name" : "Rui-Mei L",
      "referenceId" : "RGD:A159180"
    }, {
      "firstName" : "A",
      "lastName" : "Kara",
      "authorRank" : 3,
      "name" : "Kara A",
      "referenceId" : "RGD:A159181"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:6907108"
    } ]
  }, {
    "primaryId" : "PMID:10469281",
    "title" : "Renal chloride channel, CLCN5, mutations in Dent's disease.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Cox JP, etal., J Bone Miner Res. 1999 Sep;14(9):1536-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:10:03.000-05:00",
    "volume" : "14",
    "pages" : "1536-42",
    "abstract" : "Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. Patients with Dent's disease may also suffer  from rickets and other features of the renal Fanconi Syndrome. Patients may have  mutations in the X-linked renal chloride channel gene, CLCN5, which encodes a 746-amino-acid protein with 12-13 transmembrane domains. We have investigated the 11 coding exons of CLCN5 for mutations in eight unrelated patients with Dent's disease. Leukocyte DNA was used for the polymerase chain reaction amplification of CLCN5 and the products analyzed for single-stranded conformational polymorphisms (SSCPs). Abnormal SSCPs were sequenced and revealed eight mutations. These consisted of three nonsense mutations (Arg34Stop, Arg648Stop, Arg704Stop), four deletions involving codons 40, 86, 157, and 241, and one acceptor splice consensus sequence mutation tgcag --> tgaag. The mutations were confirmed either by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis. In addition, an analysis of 110 alleles from 74 unrelated normal individuals demonstrated that the DNA sequence changes were not common polymorphisms. All of the mutations predict truncated chloride channels that are  likely to result in a functional loss. Thus, our findings expand the spectrum of  CLCN5 mutations associated with Dent's disease and the results will help to elucidate further the functional domains of this novel chloride channel.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JP",
      "lastName" : "Cox",
      "authorRank" : 1,
      "name" : "Cox",
      "referenceId" : "RGD:A255608"
    }, {
      "firstName" : "K",
      "lastName" : "Yamamoto",
      "authorRank" : 2,
      "name" : "Yamamoto K",
      "referenceId" : "RGD:A5107"
    }, {
      "firstName" : "PT",
      "lastName" : "Christie",
      "authorRank" : 3,
      "name" : "Christie PT",
      "referenceId" : "RGD:A160612"
    }, {
      "firstName" : "C",
      "lastName" : "Wooding",
      "authorRank" : 4,
      "name" : "Wooding",
      "referenceId" : "RGD:A255609"
    }, {
      "firstName" : "T",
      "lastName" : "Feest",
      "authorRank" : 5,
      "name" : "Feest",
      "referenceId" : "RGD:A255610"
    }, {
      "firstName" : "FA",
      "lastName" : "Flinter",
      "authorRank" : 6,
      "name" : "Flinter",
      "referenceId" : "RGD:A251347"
    }, {
      "firstName" : "PR",
      "lastName" : "Goodyer",
      "authorRank" : 7,
      "name" : "Goodyer",
      "referenceId" : "RGD:A255611"
    }, {
      "firstName" : "E",
      "lastName" : "Leumann",
      "authorRank" : 8,
      "name" : "Leumann",
      "referenceId" : "RGD:A255612"
    }, {
      "firstName" : "T",
      "lastName" : "Neuhaus",
      "authorRank" : 9,
      "name" : "Neuhaus T",
      "referenceId" : "RGD:A71565"
    }, {
      "firstName" : "C",
      "lastName" : "Reid",
      "authorRank" : 10,
      "name" : "Reid",
      "referenceId" : "RGD:A255613"
    }, {
      "firstName" : "PF",
      "lastName" : "Williams",
      "authorRank" : 11,
      "name" : "Williams",
      "referenceId" : "RGD:A255614"
    }, {
      "firstName" : "O",
      "lastName" : "Wrong",
      "authorRank" : 12,
      "name" : "Wrong O",
      "referenceId" : "RGD:A45499"
    }, {
      "firstName" : "RV",
      "lastName" : "Thakker",
      "authorRank" : 13,
      "name" : "Thakker RV",
      "referenceId" : "RGD:A15478"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063583"
    } ]
  }, {
    "primaryId" : "PMID:10469394",
    "title" : "Intracellular localization of HSP73 and HSP90 in rat kidneys with acute lysosomal thesaurismosis.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Komatsuda A, etal., Pathol Int. 1999 Jun;49(6):513-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-09-08T10:16:45.000-05:00",
    "volume" : "49",
    "pages" : "513-8",
    "abstract" : "We previously reported that HSP73 and HSP90, major chaperone proteins, accumulated within lysosomes of proximal tubular epithelial cells in rat kidneys with acute gentamicin nephropathy. In this study, we observed serial localization of HSP73 and HSP90 in rat kidneys with acute lysosomal thesaurismosis. Sprague-Dawley rats received poly-D-glutamic acid (PDGA) (250 mg/kg per day) for 3 days, and developed acute lysosomal thesaurismosis of proximal tubular epithelial cells. The intracellular localization of HSP73 and HSP90 was examined by electron microscopy. We also compared the results with those of a non-chaperone protein, a renal isoform of argininosuccinate synthetase, which is an abundant enzyme in proximal tubular epithelial cells. After the PDGA exposure, HSP73 and HSP90 accumulated within enlarged lysosomes of proximal tubular epithelial cells. These accumulations started to appear from day 4 after the first PDGA administration, enlarged in size until day 14, and continued until day 19. Argininosuccinate synthetase also accumulated within the lysosomes, but the magnitude of this lysosomal accumulation was less than those of HSP73 and HSP90. Our findings demonstrated that HSP73 and HSP90 chaperone proteins specifically accumulated within lysosomes of proximal tubular epithelial cells during the course of PDGA-induced acute lysosomal thesaurismosis.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Komatsuda",
      "authorRank" : 1,
      "name" : "Komatsuda A",
      "referenceId" : "RGD:A127047"
    }, {
      "firstName" : "H",
      "lastName" : "Wakui",
      "authorRank" : 2,
      "name" : "Wakui H",
      "referenceId" : "RGD:A114980"
    }, {
      "firstName" : "H",
      "lastName" : "Ohtani",
      "authorRank" : 3,
      "name" : "Ohtani H",
      "referenceId" : "RGD:A23145"
    }, {
      "firstName" : "H",
      "lastName" : "Imai",
      "authorRank" : 4,
      "name" : "Imai H",
      "referenceId" : "RGD:A5876"
    }, {
      "firstName" : "AB",
      "lastName" : "Miura",
      "authorRank" : 5,
      "name" : "Miura AB",
      "referenceId" : "RGD:A21466"
    }, {
      "firstName" : "H",
      "lastName" : "Itoh",
      "authorRank" : 6,
      "name" : "Itoh H",
      "referenceId" : "RGD:A7545"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4142786"
    } ]
  }, {
    "primaryId" : "PMID:10469456",
    "title" : "Homozygous deletion at the 9q32-33 candidate tumor suppressor locus in primary human bladder cancer.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Nishiyama H, etal., Genes Chromosomes Cancer 1999 Oct;26(2):171-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-07-20T14:20:41.000-05:00",
    "volume" : "26",
    "pages" : "171-5",
    "abstract" : "Loss of heterozygosity (LOH) on chromosome arm 9q is the most frequent genetic alteration found in superficial and invasive transitional cell carcinoma (TCC) in a previous microsatellite-based deletion mapping study of the bladder and upper urinary tract, indicating the presence of one or more important tumor suppressor genes (TSGs). One of the putative tumor suppressor loci on 9q (DBC1) was mapped to 9q32-33 and the candidate region was localized within a single YAC. We report here a case of superficial papillary TCC, which showed a homozygous deletion encompassing this candidate tumor suppressor region. The region of homozygous deletion spanned the interval between D9S275 and AFMA239XA9 at 9q32-33, and was estimated to be </=6 cM. Although homozygous deletion mapping did not narrow down the candidate tumor suppressor region, this case provides further support for the presence of a TSG for TCC in this chromosomal region. To our knowledge, this is the first report to show homozygous deletion at 9q32-33 in TCC or any other type of human tumor. Genes Chromosomes Cancer 26:171-175, 1999.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Nishiyama",
      "authorRank" : 1,
      "name" : "Nishiyama H",
      "referenceId" : "RGD:A26807"
    }, {
      "firstName" : "T",
      "lastName" : "Takahashi",
      "authorRank" : 2,
      "name" : "Takahashi T",
      "referenceId" : "RGD:A160762"
    }, {
      "firstName" : "Y",
      "lastName" : "Kakehi",
      "authorRank" : 3,
      "name" : "Kakehi Y",
      "referenceId" : "RGD:A27641"
    }, {
      "firstName" : "T",
      "lastName" : "Habuchi",
      "authorRank" : 4,
      "name" : "Habuchi T",
      "referenceId" : "RGD:A38157"
    }, {
      "firstName" : "MA",
      "lastName" : "Knowles",
      "authorRank" : 5,
      "name" : "Knowles MA",
      "referenceId" : "RGD:A45001"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1300390"
    } ]
  }, {
    "primaryId" : "PMID:10469592",
    "title" : "Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Barbulescu M, etal., Curr Biol. 1999 Aug 26;9(16):861-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-13T14:08:26.000-05:00",
    "volume" : "9",
    "pages" : "861-8",
    "abstract" : "BACKGROUND: Endogenous retroviruses contribute to the evolution of the host genome and can be associated with disease. Human endogenous retrovirus K (HERV-K) is related to the mouse mammary tumor virus and is present in the genomes of humans, apes and cercopithecoids (Old World monkeys). It is unknown how long ago  in primate evolution the full-length HERV-K proviruses that are in the human genome today were formed. RESULTS: Ten full-length HERV-K proviruses were cloned  from the human genome. Using provirus-specific probes, eight of the ten were found to be present in a genetically diverse set of humans but not in other extant hominoids. Intact preintegration sites for each of these eight proviruses  were present in the apes. A ninth provirus was detected in the human, chimpanzee, bonobo and gorilla genomes, but not in the orang-utan genome. The tenth was found only in humans, chimpanzees and bonobos. Complete sequencing of six of the human-specific proviruses showed that full-length open reading frames for the retroviral protein precursors Gag-Pro-Pol or Env were each present in multiple proviruses. CONCLUSIONS: At least eight full-length HERV-K genomes that are in the human germline today integrated after humans diverged from chimpanzees. All of the viral open reading frames and cis-acting sequences necessary for HERV-K replication must have been intact during the recent time when these proviruses formed. Multiple full-length open reading frames for all HERV-K proteins are present in the human genome today.",
    "issueName" : "16",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Barbulescu",
      "authorRank" : 1,
      "name" : "Barbulescu",
      "referenceId" : "RGD:A230725"
    }, {
      "firstName" : "G",
      "lastName" : "Turner",
      "authorRank" : 2,
      "name" : "Turner G",
      "referenceId" : "RGD:A45024"
    }, {
      "firstName" : "MI",
      "lastName" : "Seaman",
      "authorRank" : 3,
      "name" : "Seaman",
      "referenceId" : "RGD:A230726"
    }, {
      "firstName" : "AS",
      "lastName" : "Deinard",
      "authorRank" : 4,
      "name" : "Deinard",
      "referenceId" : "RGD:A230727"
    }, {
      "firstName" : "KK",
      "lastName" : "Kidd",
      "authorRank" : 5,
      "name" : "Kidd KK",
      "referenceId" : "RGD:A110517"
    }, {
      "firstName" : "J",
      "lastName" : "Lenz",
      "authorRank" : 6,
      "name" : "Lenz",
      "referenceId" : "RGD:A223170"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11055511"
    } ]
  }, {
    "primaryId" : "PMID:10469658",
    "title" : "Control of glycosylation of MHC class II-associated invariant chain by translocon-associated RAMP4.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Schroder K, etal., EMBO J 1999 Sep 1;18(17):4804-15.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:16.000-05:00",
    "volume" : "18",
    "pages" : "4804-15",
    "abstract" : "Protein translocation across the membrane of the endoplasmic reticulum (ER) proceeds through a proteinaceous translocation machinery, the translocon. To identify components that may regulate translocation by interacting with nascent polypeptides in the translocon, we used site-specific photo-crosslinking. We found that a region C-terminal of the two N-glycosylation sites of the MHC class II-associated invariant chain (Ii) interacts specifically with the ribosome-associated membrane protein 4 (RAMP4). RAMP4 is a small, tail-anchored protein of 66 amino acid residues that is homologous to the yeast YSY6 protein. YSY6 suppresses a secretion defect of a secY mutant in Escherichia coli. The interaction of RAMP4 with Ii occurred when nascent Ii chains reached a length of 170 amino acid residues and persisted until Ii chain completion, suggesting translocational pausing. Site-directed mutagenesis revealed that the region of Ii interacting with RAMP4 contains essential hydrophobic amino acid residues. Exchange of these residues for serines led to a reduced interaction with RAMP4 and inefficient N-glycosylation. We propose that RAMP4 controls modification of Ii and possibly also of other secretory and membrane proteins containing specific RAMP4-interacting sequences. Efficient or variable glycosylation of Ii may contribute to its capacity to modulate antigen presentation by MHC class II molecules.",
    "issueName" : "17",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Schroder",
      "authorRank" : 1,
      "name" : "Schroder K",
      "referenceId" : "RGD:A22429"
    }, {
      "firstName" : "B",
      "lastName" : "Martoglio",
      "authorRank" : 2,
      "name" : "Martoglio B",
      "referenceId" : "RGD:A22430"
    }, {
      "firstName" : "M",
      "lastName" : "Hofmann",
      "authorRank" : 3,
      "name" : "Hofmann M",
      "referenceId" : "RGD:A161641"
    }, {
      "firstName" : "C",
      "lastName" : "Holscher",
      "authorRank" : 4,
      "name" : "Holscher C",
      "referenceId" : "RGD:A22431"
    }, {
      "firstName" : "E",
      "lastName" : "Hartmann",
      "authorRank" : 5,
      "name" : "Hartmann E",
      "referenceId" : "RGD:A72123"
    }, {
      "firstName" : "S",
      "lastName" : "Prehn",
      "authorRank" : 6,
      "name" : "Prehn S",
      "referenceId" : "RGD:A56505"
    }, {
      "firstName" : "TA",
      "lastName" : "Rapoport",
      "authorRank" : 7,
      "name" : "Rapoport TA",
      "referenceId" : "RGD:A122893"
    }, {
      "firstName" : "B",
      "lastName" : "Dobberstein",
      "authorRank" : 8,
      "name" : "Dobberstein B",
      "referenceId" : "RGD:A22435"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633885"
    } ]
  }, {
    "primaryId" : "PMID:10469835",
    "title" : "Osteopetrosis and osteoporosis: two sides of the same coin.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Lazner F, etal., Hum Mol Genet 1999;8(10):1839-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-03T16:08:48.000-06:00",
    "volume" : "8",
    "pages" : "1839-46",
    "abstract" : "Together, osteoporosis and osteopetrosis comprise a substantial proportion of the bone diseases that severely affect humans. In order to understand and effectively treat these disorders, an understanding of the mechanisms controlling bone remodelling is essential. While numerous animal models of bone disease have been generated, the lack of correlation between these animal models and human disease has limited their utility in terms of defining therapeutic strategies. The generation and analysis of cathepsin K knockout mice has resulted in a model for pycnodysostosis, a rare human osteopetrotic disease, and is now providing considerable insights into both osteoclast function and potential therapeutic strategies for the treatment of bone disease. This review highlights the importance of genes such as cathepsin K in understanding bone remodelling and illustrates a new trend towards understanding bone disease as a complete entity rather than as a series of unrelated disorders.",
    "issueName" : "10",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Lazner",
      "authorRank" : 1,
      "name" : "Lazner F",
      "referenceId" : "RGD:A37699"
    }, {
      "firstName" : "M",
      "lastName" : "Gowen",
      "authorRank" : 2,
      "name" : "Gowen M",
      "referenceId" : "RGD:A37700"
    }, {
      "firstName" : "D",
      "lastName" : "Pavasovic",
      "authorRank" : 3,
      "name" : "Pavasovic D",
      "referenceId" : "RGD:A37701"
    }, {
      "firstName" : "I",
      "lastName" : "Kola",
      "authorRank" : 4,
      "name" : "Kola I",
      "referenceId" : "RGD:A36279"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:734856"
    } ]
  }, {
    "primaryId" : "PMID:10470077",
    "title" : "Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Enjyoji K, etal., Nat Med 1999 Sep;5(9):1010-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-04T13:19:34.000-06:00",
    "volume" : "5",
    "pages" : "1010-7",
    "abstract" : "CD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered an important inhibitor of platelet activation. Unexpectedly, cd39-deficient mice had prolonged bleeding times with minimally perturbed coagulation parameters. Platelet interactions with injured mesenteric vasculature were considerably reduced in vivo and purified mutant platelets failed to aggregate to standard agonists in vitro. This platelet hypofunction was reversible and associated with purinergic type P2Y1 receptor desensitization. In keeping with deficient vascular protective mechanisms, fibrin deposition was found at multiple organ sites in cd39-deficient mice and in transplanted cardiac grafts. Our data indicate a dual role for adenosine triphosphate diphosphohydrolase in modulating hemostasis and thrombotic reactions.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Enjyoji",
      "authorRank" : 1,
      "name" : "Enjyoji K",
      "referenceId" : "RGD:A77551"
    }, {
      "firstName" : "J",
      "lastName" : "Sevigny",
      "authorRank" : 2,
      "name" : "Sevigny J",
      "referenceId" : "RGD:A29750"
    }, {
      "firstName" : "Y",
      "lastName" : "Lin",
      "authorRank" : 3,
      "name" : "Lin Y",
      "referenceId" : "RGD:A27952"
    }, {
      "firstName" : "PS",
      "lastName" : "Frenette",
      "authorRank" : 4,
      "name" : "Frenette PS",
      "referenceId" : "RGD:A38570"
    }, {
      "firstName" : "PD",
      "lastName" : "Christie",
      "authorRank" : 5,
      "name" : "Christie PD",
      "referenceId" : "RGD:A38571"
    }, {
      "firstName" : "2ND",
      "lastName" : "Esch JS",
      "authorRank" : 6,
      "name" : "Esch JS 2ND",
      "referenceId" : "RGD:A38572"
    }, {
      "firstName" : "M",
      "lastName" : "Imai",
      "authorRank" : 7,
      "name" : "Imai M",
      "referenceId" : "RGD:A160808"
    }, {
      "firstName" : "JM",
      "lastName" : "Edelberg",
      "authorRank" : 8,
      "name" : "Edelberg JM",
      "referenceId" : "RGD:A38574"
    }, {
      "firstName" : "H",
      "lastName" : "Rayburn",
      "authorRank" : 9,
      "name" : "Rayburn H",
      "referenceId" : "RGD:A38575"
    }, {
      "firstName" : "M",
      "lastName" : "Lech",
      "authorRank" : 10,
      "name" : "Lech M",
      "referenceId" : "RGD:A38576"
    }, {
      "firstName" : "DL",
      "lastName" : "Beeler",
      "authorRank" : 11,
      "name" : "Beeler DL",
      "referenceId" : "RGD:A21819"
    }, {
      "firstName" : "E",
      "lastName" : "Csizmadia",
      "authorRank" : 12,
      "name" : "Csizmadia E",
      "referenceId" : "RGD:A38577"
    }, {
      "firstName" : "DD",
      "lastName" : "Wagner",
      "authorRank" : 13,
      "name" : "Wagner DD",
      "referenceId" : "RGD:A38578"
    }, {
      "firstName" : "SC",
      "lastName" : "Robson",
      "authorRank" : 14,
      "name" : "Robson SC",
      "referenceId" : "RGD:A29749"
    }, {
      "firstName" : "RD",
      "lastName" : "Rosenberg",
      "authorRank" : 15,
      "name" : "Rosenberg RD",
      "referenceId" : "RGD:A21821"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:735004"
    } ]
  }, {
    "primaryId" : "PMID:10470086",
    "title" : "Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Jones CR, etal., Nat Med. 1999 Sep;5(9):1062-5. doi: 10.1038/12502.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:41:17.000-05:00",
    "volume" : "5",
    "pages" : "1062-5",
    "abstract" : "Biological circadian clocks oscillate with an approximately 24-hour period, are ubiquitous, and presumably confer a selective advantage by anticipating the transitions between day and night. The circadian rhythms of sleep, melatonin secretion and body core temperature are thought to be generated by the suprachiasmatic nucleus of the hypothalamus, the anatomic locus of the mammalian circadian clock. Autosomal semi-dominant mutations in rodents with fast or slow biological clocks (that is, short or long endogenous period lengths; tau) are associated with phase-advanced or delayed sleep-wake rhythms, respectively. These models predict the existence of familial human circadian rhythm variants but none of the human circadian rhythm disorders are known to have a familial tendency. Although a slight 'morning lark' tendency is common, individuals with a large and disabling sleep phase-advance are rare. This disorder, advanced sleep-phase syndrome, is characterized by very early sleep onset and offset; only two cases are reported in young adults. Here we describe three kindreds with a profound phase advance of the sleep-wake, melatonin and temperature rhythms associated with a very short tau. The trait segregates as an autosomal dominant with high penetrance. These kindreds represent a well-characterized familial circadian rhythm variant in humans and provide a unique opportunity for genetic analysis of human circadian physiology.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C R",
      "lastName" : "Jones",
      "authorRank" : 1,
      "name" : "Jones CR",
      "referenceId" : "RGD:A569459"
    }, {
      "firstName" : "S S",
      "lastName" : "Campbell",
      "authorRank" : 2,
      "name" : "Campbell SS",
      "referenceId" : "RGD:A569460"
    }, {
      "firstName" : "S E",
      "lastName" : "Zone",
      "authorRank" : 3,
      "name" : "Zone SE",
      "referenceId" : "RGD:A569461"
    }, {
      "firstName" : "F",
      "lastName" : "Cooper",
      "authorRank" : 4,
      "name" : "Cooper F",
      "referenceId" : "RGD:A569462"
    }, {
      "firstName" : "A",
      "lastName" : "DeSano",
      "authorRank" : 5,
      "name" : "DeSano A",
      "referenceId" : "RGD:A569463"
    }, {
      "firstName" : "P J",
      "lastName" : "Murphy",
      "authorRank" : 6,
      "name" : "Murphy PJ",
      "referenceId" : "RGD:A569464"
    }, {
      "firstName" : "B",
      "lastName" : "Jones",
      "authorRank" : 7,
      "name" : "Jones B",
      "referenceId" : "RGD:A103270"
    }, {
      "firstName" : "L",
      "lastName" : "Czajkowski",
      "authorRank" : 8,
      "name" : "Czajkowski L",
      "referenceId" : "RGD:A569465"
    }, {
      "firstName" : "L J",
      "lastName" : "Ptácek",
      "authorRank" : 9,
      "name" : "Ptácek LJ",
      "referenceId" : "RGD:A569466"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598115026"
    } ]
  }, {
    "primaryId" : "PMID:10470286",
    "title" : "Mxi1 mutations in human neurofibrosarcomas.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Li XJ, etal., Jpn J Cancer Res. 1999 Jul;90(7):740-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-02T14:35:33.000-06:00",
    "volume" : "90",
    "pages" : "740-6",
    "abstract" : "Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.",
    "issueName" : "7",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "XJ",
      "lastName" : "Li",
      "authorRank" : 1,
      "name" : "Li XJ",
      "referenceId" : "RGD:A154516"
    }, {
      "firstName" : "DY",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang DY",
      "referenceId" : "RGD:A19857"
    }, {
      "firstName" : "Y",
      "lastName" : "Zhu",
      "authorRank" : 3,
      "name" : "Zhu Y",
      "referenceId" : "RGD:A162476"
    }, {
      "firstName" : "RJ",
      "lastName" : "Guo",
      "authorRank" : 4,
      "name" : "Guo RJ",
      "referenceId" : "RGD:A76526"
    }, {
      "firstName" : "XD",
      "lastName" : "Wang",
      "authorRank" : 5,
      "name" : "Wang XD",
      "referenceId" : "RGD:A34753"
    }, {
      "firstName" : "K",
      "lastName" : "Lubomir",
      "authorRank" : 6,
      "name" : "Lubomir K",
      "referenceId" : "RGD:A76527"
    }, {
      "firstName" : "K",
      "lastName" : "Mukai",
      "authorRank" : 7,
      "name" : "Mukai K",
      "referenceId" : "RGD:A29337"
    }, {
      "firstName" : "H",
      "lastName" : "Sasaki",
      "authorRank" : 8,
      "name" : "Sasaki H",
      "referenceId" : "RGD:A161655"
    }, {
      "firstName" : "H",
      "lastName" : "Yoshida",
      "authorRank" : 9,
      "name" : "Yoshida H",
      "referenceId" : "RGD:A24062"
    }, {
      "firstName" : "T",
      "lastName" : "Oka",
      "authorRank" : 10,
      "name" : "Oka T",
      "referenceId" : "RGD:A9885"
    }, {
      "firstName" : "R",
      "lastName" : "Machinami",
      "authorRank" : 11,
      "name" : "Machinami R",
      "referenceId" : "RGD:A76529"
    }, {
      "firstName" : "K",
      "lastName" : "Shinmura",
      "authorRank" : 12,
      "name" : "Shinmura K",
      "referenceId" : "RGD:A76530"
    }, {
      "firstName" : "M",
      "lastName" : "Tanaka",
      "authorRank" : 13,
      "name" : "Tanaka M",
      "referenceId" : "RGD:A159970"
    }, {
      "firstName" : "H",
      "lastName" : "Sugimura",
      "authorRank" : 14,
      "name" : "Sugimura H",
      "referenceId" : "RGD:A14389"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600205"
    } ]
  }, {
    "primaryId" : "PMID:10470376",
    "title" : "Study of the functional share of lysosomal cathepsins by the development of specific inhibitors.",
    "datePublished" : "1000-02-01T00:00:00.000-06:00",
    "citation" : "Katunuma N, etal., Adv Enzyme Regul. 1999;39:247-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-02-01T18:24:02.000-06:00",
    "volume" : "39",
    "pages" : "247-60",
    "abstract" : "To analyze the functional share of individual cathepsins, we developed powerful and specific inhibitors for individual cathepsins using computer graphics of substrate binding pockets based on X-ray crystallography. These new inhibitors were named CLIK group. Epoxy succinate peptide derivatives, CLIK-066, 088, 112, 121, 148, 181, 185 and 187, are typical specific inhibitors for cathepsin L. Aldehyde derivatives CLIK-060 and CLIK-164 showed specific inhibition against cathepsin S and cathepsin K, respectively. We found that pyridoxal phosphate (PLP), a coenzyme form of vitamin B6, inhibits all cathepsins and also new artificially synthesized pyridoxal derivatives, CLIK-071 and -072, in which the phosphate esters of PLP were replaced by propionic acid, exhibited strong inhibition for cathepsins. Furthermore, CLIK-071 was easy to incorporate into cells and showed powerful inhibition for intracellular cathepsins. Using these selective inhibitors, the allotment of individual cathepsin functions in cells has been studied as follows. Cathepsin L and/or K participate in bone resorption based on bone type-1 collagen degradation and the L-type protease inhibitors suppressed the bone resorption. Cathepsins B and S participate in antigen presentations based on antigen processing and invariant chain degradation, respectively. Also cathepsin L participates in cell apoptosis mediated by caspase III activation.",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Katunuma",
      "authorRank" : 1,
      "name" : "Katunuma N",
      "referenceId" : "RGD:A28514"
    }, {
      "firstName" : "A",
      "lastName" : "Matsui",
      "authorRank" : 2,
      "name" : "Matsui A",
      "referenceId" : "RGD:A27427"
    }, {
      "firstName" : "T",
      "lastName" : "Kakegawa",
      "authorRank" : 3,
      "name" : "Kakegawa T",
      "referenceId" : "RGD:A16842"
    }, {
      "firstName" : "E",
      "lastName" : "Murata",
      "authorRank" : 4,
      "name" : "Murata E",
      "referenceId" : "RGD:A92921"
    }, {
      "firstName" : "T",
      "lastName" : "Asao",
      "authorRank" : 5,
      "name" : "Asao T",
      "referenceId" : "RGD:A41431"
    }, {
      "firstName" : "Y",
      "lastName" : "Ohba",
      "authorRank" : 6,
      "name" : "Ohba Y",
      "referenceId" : "RGD:A23872"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5687153"
    } ]
  }, {
    "primaryId" : "PMID:10470852",
    "title" : "Structure of rat gamma-tubulin and its binding to HP33.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Nakadai T, etal., DNA Res 1999 Jun 30;6(3):207-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T17:34:32.000-05:00",
    "volume" : "6",
    "pages" : "207-9",
    "abstract" : "Gamma-tubulin is localized at the microtubule organizing center and is thought to participate in the organizing of the microtubule network. In this study, we isolated a cDNA of rat gamma-tubulin. The rat gamma-tubulin cDNA encoded 451 amino acids, the same number as that of its counterpart in other vertebrates, and its structure was found to be highly conserved in vertebrates. In a previous work, we identified HP33 (hepatocarcinogenesis- and hepatocellular proliferation-related 33-kDa protein) that was localized at the centrosome of hepatic cells and that exhibited MAP-like activity. In vitro GST pull-down assay using highly purified recombinant HP33 and bacterially expressed gamma-tubulin demonstrated that HP33 bound to gamma-tubulin directly. These results suggest that HP33 is localized at the centrosome via association with both the microtubule and its minus end-specific component, gamma-tubulin.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Nakadai",
      "authorRank" : 1,
      "name" : "Nakadai T",
      "referenceId" : "RGD:A23890"
    }, {
      "firstName" : "N",
      "lastName" : "Okada",
      "authorRank" : 2,
      "name" : "Okada N",
      "referenceId" : "RGD:A7541"
    }, {
      "firstName" : "Y",
      "lastName" : "Makino",
      "authorRank" : 3,
      "name" : "Makino Y",
      "referenceId" : "RGD:A5103"
    }, {
      "firstName" : "T",
      "lastName" : "Tamura",
      "authorRank" : 4,
      "name" : "Tamura T",
      "referenceId" : "RGD:A156706"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:634415"
    } ]
  }, {
    "primaryId" : "PMID:10470859",
    "title" : "Mannose 6-phosphate/insulin-like growth factor II receptor mediates the growth-inhibitory effects of retinoids.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Kang JX, etal., Cell Growth Differ. 1999 Aug;10(8):591-600.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-07-27T14:22:36.000-05:00",
    "volume" : "10",
    "pages" : "591-600",
    "abstract" : "Both retinoids and the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) have been shown to play an important role in controlling cell growth during embryonic development and oncogenesis. Our recent work (Kang et al., Proc. Natl. Acad. Sci. USA, 94: 13671-13676, 1997; Kang et al., Proc. Natl. Acad. Sci. USA, 95: 13687-13691, 1998) revealed a direct biochemical interaction between retinoic acid (RA) and the M6P/IGF2R, thereby leading us to hypothesize that the M6P/IGF2R may mediate a growth-inhibiting effect of RA. To test this hypothesis, cell growth and apoptosis in response to RA and various receptor-selective retinoids were examined in cells that lack or overexpress the M6P/IGF2R. RA and those retinoids capable of binding to the M6P/IGF2R induced a remarkable morphological change with characteristics of round shape and reduced spreading, apoptosis, and growth inhibition in stably transfected mouse P388D1 cells overexpressing the M6P/IGF2R but not in the M6P/IGF2R-deficient P388D1 cells. These effects of RA were neither blocked by a potent RA nuclear receptor (RAR) antagonist (AGN193109), nor mimicked by a selective RAR agonist (TTNPB), suggesting that the observed effects of RA are independent of RARs. Similar effects of the retinoids were observed in cultured neonatal rat cardiac myocytes that have high levels of the M6P/IGF2R. Furthermore, overexpression of the M6P/IGF2R in a RA-resistant cancer cell line (HL-60R) that lacked functional RARs gave the cells a susceptibility to RA-induced apoptosis. These data suggest that the M6P/ IGF2R may play an important role in mediating retinoid-induced apoptosis/growth-inhibition and provide insight into the similar biological effects of RA and the M6P/IGF2R on fetal development and carcinogenesis.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JX",
      "lastName" : "Kang",
      "authorRank" : 1,
      "name" : "Kang JX",
      "referenceId" : "RGD:A95631"
    }, {
      "firstName" : "J",
      "lastName" : "Bell",
      "authorRank" : 2,
      "name" : "Bell J",
      "referenceId" : "RGD:A109962"
    }, {
      "firstName" : "RL",
      "lastName" : "Beard",
      "authorRank" : 3,
      "name" : "Beard RL",
      "referenceId" : "RGD:A109963"
    }, {
      "firstName" : "RA",
      "lastName" : "Chandraratna",
      "authorRank" : 4,
      "name" : "Chandraratna RA",
      "referenceId" : "RGD:A109964"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2311628"
    } ]
  }, {
    "primaryId" : "PMID:10471063",
    "title" : "Proguanil disposition and toxicity in malaria patients from Vanuatu with high frequencies of CYP2C19 mutations.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Kaneko A, etal., Pharmacogenetics. 1999 Jun;9(3):317-26.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2021-03-18T10:25:06.000-05:00",
    "volume" : "9",
    "pages" : "317-26",
    "abstract" : "The increasing resistance of falciparum malaria to common antimalarial drugs has renewed interest in the compound proguanil normally metabolized to cycloguanil, a strong dihydrofolate reductase inhibitor, via the cytochrome P450 isozyme CYP2C19. The relationship between CYP2C19 genotypes and proguanil metabolism was therefore studied in 100 uncomplicated malaria patients on Malakula island in Vanuatu, where a CYP2C19-related poor metabolizer genotype status was known to be frequent. The patients (median age, 7 years) with Plasmodium falciparum or P. vivax infections, received proguanil treatment for 3 days in daily doses corresponding to adult doses of 300-500 mg. Capillary blood samples were collected on filter paper for determining both human CYP2C19 mutations by polymerase chain reaction and mutation-specific restriction enzyme digestion and blood concentrations of proguanil and its metabolites by high-performance liquid chromatography. The frequencies of the defective alleles, CYP2C19*2 and CYP2C19*3, were 0.57 and 0.25, respectively. The patients were genotyped as 68 CYP2C19-related poor metabolizers and 32 extensive metabolizers. Proguanil concentrations were higher and cycloguanil and 4-chlorophenylbiguanide concentrations were lower in poor compared to extensive metabolizers. Among the extensive metabolizers, 27 were heterozygous and five were homozygous for unmutated alleles. The tendency of an intermediate degree of proguanil metabolism in heterozygous extensive metabolizers as compared to homozygous extensive metabolizers and poor metabolizers suggests the trend towards the existence of a gene dose effect. Mild adverse events (mainly gastro-intestinal symptoms) were often reported and positively correlated with proguanil concentrations. The incidence was, however, similar in poor and extensive metabolizers. In conclusion, our data demonstrate an association between CYP2C19 mutations and poor metabolism of proguanil.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Kaneko",
      "authorRank" : 1,
      "name" : "Kaneko A",
      "referenceId" : "RGD:A31750"
    }, {
      "firstName" : "Y",
      "lastName" : "Bergqvist",
      "authorRank" : 2,
      "name" : "Bergqvist Y",
      "referenceId" : "RGD:A495719"
    }, {
      "firstName" : "G",
      "lastName" : "Taleo",
      "authorRank" : 3,
      "name" : "Taleo G",
      "referenceId" : "RGD:A495720"
    }, {
      "firstName" : "T",
      "lastName" : "Kobayakawa",
      "authorRank" : 4,
      "name" : "Kobayakawa T",
      "referenceId" : "RGD:A495721"
    }, {
      "firstName" : "T",
      "lastName" : "Ishizaki",
      "authorRank" : 5,
      "name" : "Ishizaki T",
      "referenceId" : "RGD:A8420"
    }, {
      "firstName" : "A",
      "lastName" : "Björkman",
      "authorRank" : 6,
      "name" : "Björkman A",
      "referenceId" : "RGD:A495722"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:124713538"
    } ]
  }, {
    "primaryId" : "PMID:10471199",
    "title" : "Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Namihira M, etal., Neurosci Lett. 1999 Aug 13;271(1):1-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-10-09T13:21:52.000-05:00",
    "volume" : "271",
    "pages" : "1-4",
    "abstract" : "Circadian expression and light-responsiveness of the mammalian clock genes, Clock and BMAL1, in the rat retina were examined by in situ hydbribization under constant darkness. A small but significant daily variation was detected in the Clock transcript level, but not in BMAL1. Light increased the Clock and BMAL1 expressions significantly when examined 60 min after exposure. The light-induced  gene expression was phase-dependent for Clock and peaked at ZT2, while rather constant throughout the day for BMAL1. These findings suggest that Clock and BMAL1 play different roles in the generation of circadian rhytm in the retina from those in the suprachiasmatic nucleus. Different roles are also suggested between the two genes in the photic signal transduction in the retina.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Namihira",
      "authorRank" : 1,
      "name" : "Namihira M",
      "referenceId" : "RGD:A4381"
    }, {
      "firstName" : "S",
      "lastName" : "Honma",
      "authorRank" : 2,
      "name" : "Honma S",
      "referenceId" : "RGD:A4377"
    }, {
      "firstName" : "H",
      "lastName" : "Abe",
      "authorRank" : 3,
      "name" : "Abe H",
      "referenceId" : "RGD:A4379"
    }, {
      "firstName" : "Y",
      "lastName" : "Tanahashi",
      "authorRank" : 4,
      "name" : "Tanahashi Y",
      "referenceId" : "RGD:A4380"
    }, {
      "firstName" : "M",
      "lastName" : "Ikeda",
      "authorRank" : 5,
      "name" : "Ikeda",
      "referenceId" : "RGD:A415575"
    }, {
      "firstName" : "K",
      "lastName" : "Honma",
      "authorRank" : 6,
      "name" : "Honma K",
      "referenceId" : "RGD:A4382"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10401879"
    } ]
  }, {
    "primaryId" : "PMID:10471355",
    "title" : "Developmental regulation of the translational repressor NAT1 during cardiac development.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Pak BJ and Pang SC, J Mol Cell Cardiol 1999 Sep;31(9):1717-24.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2002-02-19T13:22:33.000-06:00",
    "volume" : "31",
    "pages" : "1717-24",
    "abstract" : "The process of translation initiation has been postulated to play an important role in the regulation of cellular growth and proliferation. Here, we report the identification and differential expression of a fundamental translational repressor NAT1, during early postnatal cardiac development. Differential display analysis of RNA obtained from 3-day and 4-week-old rat hearts resulted in the cloning and identification of a 396 bp cDNA fragment (DRCF-6) which corresponded to the 3' terminal portion of NAT1. Northern blot analysis revealed that the mRNA expression of NAT1 was markedly elevated during the first 2 weeks of postnatal life, with an apparent peak level of expression occurring at 1 week. NAT1 mRNA levels then steadily decreased to 4 weeks of age. The NAT1 transcript has previously been shown to be extensively edited by the enzyme APOBEC-1, which deaminates specific cytidine bases to uridine; cytidine deamination at a glutamine codon (CAA) results in the formation of a stop codon (UAA) and consequently, premature termination of translation. Accordingly, Western blot analysis detected the presence of several smaller proteins in addition to the full length NAT1 protein (97 kDa), each exhibiting a distinct pattern of expression during cardiac development. APOBEC-1 editing of NAT1 during cardiac development was further supported by primer extension analysis of cytidine 1699, which was found to be predominantly edited to uridine. Immunohistochemical staining showed that NAT1 is expressed predominantly in atrial and ventricular myocytes, although staining was also detected in vascular smooth muscle cells and in the endocardium. These results suggest that NAT1 may play a role in the postnatal development of the heart and demonstrate that APOBEC-1 editing may possibly be a novel mechanism by which translation is regulated during cardiac development.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BJ",
      "lastName" : "Pak",
      "authorRank" : 1,
      "name" : "Pak BJ",
      "referenceId" : "RGD:A8443"
    }, {
      "firstName" : "SC",
      "lastName" : "Pang",
      "authorRank" : 2,
      "name" : "Pang SC",
      "referenceId" : "RGD:A8444"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:70273"
    } ]
  }, {
    "primaryId" : "PMID:10471365",
    "title" : "Identification of four new members of the rat prolactin/growth hormone gene family.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Ishibashi K and Imai M, Biochem Biophys Res Commun 1999 Sep 7;262(3):575-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:29.000-05:00",
    "volume" : "262",
    "pages" : "575-8",
    "abstract" : "The rodent prolactin (PRL)/growth hormone (GH) gene family currently consists of at least 14 distinct genes that are expressed mainly in pituitary, uterus, and/or placenta. We report here the identification of novel four members from rat with significant homology to PRL. The encoding proteins are not homologs of other known members of this hormone family. The four new cDNAs were assigned to PRL family based on sequence homology and were referred to as PRL-like protein-I (PLP-I), PLP-J, PLP-K, and PLP-L, following the current naming order of rodent PLP family, where PLP-H is the most recent gene. They encode amino acids with 211-228 amino acids, and 34-38% identity with PRL. All have one or two N-linked glycosylation sites. Among the examined rat tissues by Northern blot analysis, only PLP-I was expressed in testis. Our results indicate that the rodent PRL/GH gene family is large with at least 18 distinct genes.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Ishibashi",
      "authorRank" : 1,
      "name" : "Ishibashi K",
      "referenceId" : "RGD:A160807"
    }, {
      "firstName" : "M",
      "lastName" : "Imai",
      "authorRank" : 2,
      "name" : "Imai M",
      "referenceId" : "RGD:A160808"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633805"
    } ]
  }, {
    "primaryId" : "PMID:10471406",
    "title" : "Cloning and characterization of rat leukotriene B(4) receptor.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Toda A, etal., Biochem Biophys Res Commun 1999 Sep 7;262(3):806-12.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:09:47.000-05:00",
    "volume" : "262",
    "pages" : "806-12",
    "abstract" : "Leukotriene B(4) (LTB(4)) is a potent chemoattractant for neutrophils and eosinophils. cDNAs for LTB(4) receptor (BLT) have been cloned from human, mouse, and guinea pig. Here we report the isolation of BLT from rat genomic library. Rat BLT consists of 351 amino acids with homologies of 80.2, 93.2, and 71.6%, to human, mouse, and guinea pig BLT, respectively. When expressed in human embryonic kidney (HEK)-293 cells, rat BLT showed a specific and high-affinity binding to LTB(4) with a Kd value of 0.68 nM (mean, n = 3). Northern blot analysis showed that BLT is exclusively expressed in polymorphonuclear leukocytes. Furthermore, the expression of BLT was high in proteosepeptone-activated peritoneal macrophages, while the resident macrophages did not show significant expression. The present results suggest important roles of LTB(4) in macrophage recruitment and activation.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Toda",
      "authorRank" : 1,
      "name" : "Toda A",
      "referenceId" : "RGD:A20111"
    }, {
      "firstName" : "T",
      "lastName" : "Yokomizo",
      "authorRank" : 2,
      "name" : "Yokomizo T",
      "referenceId" : "RGD:A20112"
    }, {
      "firstName" : "K",
      "lastName" : "Masuda",
      "authorRank" : 3,
      "name" : "Masuda K",
      "referenceId" : "RGD:A6921"
    }, {
      "firstName" : "A",
      "lastName" : "Nakao",
      "authorRank" : 4,
      "name" : "Nakao A",
      "referenceId" : "RGD:A20113"
    }, {
      "firstName" : "T",
      "lastName" : "Izumi",
      "authorRank" : 5,
      "name" : "Izumi T",
      "referenceId" : "RGD:A20114"
    }, {
      "firstName" : "T",
      "lastName" : "Shimizu",
      "authorRank" : 6,
      "name" : "Shimizu T",
      "referenceId" : "RGD:A161715"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633182"
    } ]
  }, {
    "primaryId" : "PMID:10471491",
    "title" : "Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Cappellen D, etal., Nat Genet. 1999 Sep;23(1):18-20.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-02-15T15:14:49.000-06:00",
    "volume" : "23",
    "pages" : "18-20",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Cappellen",
      "authorRank" : 1,
      "name" : "Cappellen D",
      "referenceId" : "RGD:A91525"
    }, {
      "firstName" : "C",
      "lastName" : "De Oliveira",
      "authorRank" : 2,
      "name" : "De Oliveira C",
      "referenceId" : "RGD:A91933"
    }, {
      "firstName" : "D",
      "lastName" : "Ricol",
      "authorRank" : 3,
      "name" : "Ricol D",
      "referenceId" : "RGD:A91934"
    }, {
      "firstName" : "S",
      "lastName" : "De Medina",
      "authorRank" : 4,
      "name" : "De Medina S",
      "referenceId" : "RGD:A91935"
    }, {
      "firstName" : "J",
      "lastName" : "Bourdin",
      "authorRank" : 5,
      "name" : "Bourdin J",
      "referenceId" : "RGD:A91936"
    }, {
      "firstName" : "X",
      "lastName" : "Sastre-Garau",
      "authorRank" : 6,
      "name" : "Sastre-Garau X",
      "referenceId" : "RGD:A91937"
    }, {
      "firstName" : "D",
      "lastName" : "Chopin",
      "authorRank" : 7,
      "name" : "Chopin D",
      "referenceId" : "RGD:A91938"
    }, {
      "firstName" : "JP",
      "lastName" : "Thiery",
      "authorRank" : 8,
      "name" : "Thiery JP",
      "referenceId" : "RGD:A17457"
    }, {
      "firstName" : "F",
      "lastName" : "Radvanyi",
      "authorRank" : 9,
      "name" : "Radvanyi F",
      "referenceId" : "RGD:A91531"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289864"
    } ]
  }, {
    "primaryId" : "PMID:10471492",
    "title" : "Cardiac conduction defects associate with mutations in SCN5A.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Schott JJ, etal., Nat Genet. 1999 Sep;23(1):20-1.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T22:16:55.000-05:00",
    "volume" : "23",
    "pages" : "20-1",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JJ",
      "lastName" : "Schott",
      "authorRank" : 1,
      "name" : "Schott JJ",
      "referenceId" : "RGD:A385"
    }, {
      "firstName" : "C",
      "lastName" : "Alshinawi",
      "authorRank" : 2,
      "name" : "Alshinawi",
      "referenceId" : "RGD:A275450"
    }, {
      "firstName" : "F",
      "lastName" : "Kyndt",
      "authorRank" : 3,
      "name" : "Kyndt F",
      "referenceId" : "RGD:A35928"
    }, {
      "firstName" : "V",
      "lastName" : "Probst",
      "authorRank" : 4,
      "name" : "Probst V",
      "referenceId" : "RGD:A156348"
    }, {
      "firstName" : "TM",
      "lastName" : "Hoorntje",
      "authorRank" : 5,
      "name" : "Hoorntje",
      "referenceId" : "RGD:A262955"
    }, {
      "firstName" : "M",
      "lastName" : "Hulsbeek",
      "authorRank" : 6,
      "name" : "Hulsbeek",
      "referenceId" : "RGD:A275451"
    }, {
      "firstName" : "AA",
      "lastName" : "Wilde",
      "authorRank" : 7,
      "name" : "Wilde AA",
      "referenceId" : "RGD:A60672"
    }, {
      "firstName" : "D",
      "lastName" : "Escande",
      "authorRank" : 8,
      "name" : "Escande D",
      "referenceId" : "RGD:A35931"
    }, {
      "firstName" : "MM",
      "lastName" : "Mannens",
      "authorRank" : 9,
      "name" : "Mannens MM",
      "referenceId" : "RGD:A37889"
    }, {
      "firstName" : "H",
      "lastName" : "Le Marec",
      "authorRank" : 10,
      "name" : "Le Marec H",
      "referenceId" : "RGD:A35932"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11069967"
    } ]
  }, {
    "primaryId" : "PMID:10471494",
    "title" : "A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Carrie A, etal., Nat Genet 1999 Sep;23(1):25-31.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-04-25T09:49:38.000-05:00",
    "volume" : "23",
    "pages" : "25-31",
    "abstract" : "We demonstrate here the importance of interleukin signalling pathways in cognitive function and the normal physiology of the CNS. Thorough investigation of an MRX critical region in Xp22.1-21.3 enabled us to identify a new gene expressed in brain that is responsible for a non-specific form of X-linked mental retardation. This gene encodes a 696 amino acid protein that has homology to IL-1 receptor accessory proteins. Non-overlapping deletions and a nonsense mutation in this gene were identified in patients with cognitive impairment only. Its high level of expression in post-natal brain structures involved in the hippocampal memory system suggests a specialized role for this new gene in the physiological processes underlying memory and learning abilities.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Carrie",
      "authorRank" : 1,
      "name" : "Carrie A",
      "referenceId" : "RGD:A46281"
    }, {
      "firstName" : "L",
      "lastName" : "Jun",
      "authorRank" : 2,
      "name" : "Jun L",
      "referenceId" : "RGD:A46282"
    }, {
      "firstName" : "T",
      "lastName" : "Bienvenu",
      "authorRank" : 3,
      "name" : "Bienvenu T",
      "referenceId" : "RGD:A164938"
    }, {
      "firstName" : "MC",
      "lastName" : "Vinet",
      "authorRank" : 4,
      "name" : "Vinet MC",
      "referenceId" : "RGD:A46284"
    }, {
      "firstName" : "N",
      "lastName" : "McDonell",
      "authorRank" : 5,
      "name" : "McDonell N",
      "referenceId" : "RGD:A46285"
    }, {
      "firstName" : "P",
      "lastName" : "Couvert",
      "authorRank" : 6,
      "name" : "Couvert P",
      "referenceId" : "RGD:A46286"
    }, {
      "firstName" : "R",
      "lastName" : "Zemni",
      "authorRank" : 7,
      "name" : "Zemni R",
      "referenceId" : "RGD:A46287"
    }, {
      "firstName" : "A",
      "lastName" : "Cardona",
      "authorRank" : 8,
      "name" : "Cardona A",
      "referenceId" : "RGD:A46288"
    }, {
      "firstName" : "G",
      "lastName" : "Van Buggenhout",
      "authorRank" : 9,
      "name" : "Van Buggenhout G",
      "referenceId" : "RGD:A46289"
    }, {
      "firstName" : "S",
      "lastName" : "Frints",
      "authorRank" : 10,
      "name" : "Frints S",
      "referenceId" : "RGD:A46290"
    }, {
      "firstName" : "B",
      "lastName" : "Hamel",
      "authorRank" : 11,
      "name" : "Hamel B",
      "referenceId" : "RGD:A46291"
    }, {
      "firstName" : "C",
      "lastName" : "Moraine",
      "authorRank" : 12,
      "name" : "Moraine C",
      "referenceId" : "RGD:A46292"
    }, {
      "firstName" : "HH",
      "lastName" : "Ropers",
      "authorRank" : 13,
      "name" : "Ropers HH",
      "referenceId" : "RGD:A44094"
    }, {
      "firstName" : "T",
      "lastName" : "Strom",
      "authorRank" : 14,
      "name" : "Strom T",
      "referenceId" : "RGD:A46293"
    }, {
      "firstName" : "GR",
      "lastName" : "Howell",
      "authorRank" : 15,
      "name" : "Howell GR",
      "referenceId" : "RGD:A46294"
    }, {
      "firstName" : "A",
      "lastName" : "Whittaker",
      "authorRank" : 16,
      "name" : "Whittaker A",
      "referenceId" : "RGD:A46295"
    }, {
      "firstName" : "MT",
      "lastName" : "Ross",
      "authorRank" : 17,
      "name" : "Ross MT",
      "referenceId" : "RGD:A46296"
    }, {
      "firstName" : "A",
      "lastName" : "Kahn",
      "authorRank" : 18,
      "name" : "Kahn A",
      "referenceId" : "RGD:A16631"
    }, {
      "firstName" : "JP",
      "lastName" : "Fryns",
      "authorRank" : 19,
      "name" : "Fryns JP",
      "referenceId" : "RGD:A35229"
    }, {
      "firstName" : "C",
      "lastName" : "Beldjord",
      "authorRank" : 20,
      "name" : "Beldjord C",
      "referenceId" : "RGD:A46297"
    }, {
      "firstName" : "P",
      "lastName" : "Marynen",
      "authorRank" : 21,
      "name" : "Marynen P",
      "referenceId" : "RGD:A41839"
    }, {
      "firstName" : "J",
      "lastName" : "Chelly",
      "authorRank" : 22,
      "name" : "Chelly J",
      "referenceId" : "RGD:A44795"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302409"
    } ]
  }, {
    "primaryId" : "PMID:10471497",
    "title" : "Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Saigoh K, etal., Nat Genet 1999 Sep;23(1):47-51.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-10-14T15:53:16.000-05:00",
    "volume" : "23",
    "pages" : "47-51",
    "abstract" : "The gracile axonal dystrophy (gad) mouse is an autosomal recessive mutant that shows sensory ataxia at an early stage, followed by motor ataxia at a later stage. Pathologically, the mutant is characterized by 'dying-back' type axonal degeneration and formation of spheroid bodies in nerve terminals. Recent pathological observations have associated brain ageing and neurodegenerative diseases with progressive accumulation of ubiquitinated protein conjugates. In gad mice, accumulation of amyloid beta-protein and ubiquitin-positive deposits occur retrogradely along the sensory and motor nervous systems. We previously reported that the gad mutation was transmitted by a gene on chromosome 5 (refs 10,11). Here we find that the gad mutation is caused by an in-frame deletion including exons 7 and 8 of Uchl1, encoding the ubiquitin carboxy-terminal hydrolase (UCH) isozyme (Uch-l1) selectively expressed in the nervous system and testis. The gad allele encodes a truncated Uch-l1 lacking a segment of 42 amino acids containing a catalytic residue. As Uch-l1 is thought to stimulate protein degradation by generating free monomeric ubiquitin, the gad mutation appears to affect protein turnover. Our data suggest that altered function of the ubiquitin system directly causes neurodegeneration. The gad mouse provides a useful model for investigating human neurodegenerative disorders.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Saigoh",
      "authorRank" : 1,
      "name" : "Saigoh K",
      "referenceId" : "RGD:A46985"
    }, {
      "firstName" : "YL",
      "lastName" : "Wang",
      "authorRank" : 2,
      "name" : "Wang YL",
      "referenceId" : "RGD:A26995"
    }, {
      "firstName" : "JG",
      "lastName" : "Suh",
      "authorRank" : 3,
      "name" : "Suh JG",
      "referenceId" : "RGD:A20328"
    }, {
      "firstName" : "T",
      "lastName" : "Yamanishi",
      "authorRank" : 4,
      "name" : "Yamanishi T",
      "referenceId" : "RGD:A46986"
    }, {
      "firstName" : "Y",
      "lastName" : "Sakai",
      "authorRank" : 5,
      "name" : "Sakai Y",
      "referenceId" : "RGD:A6067"
    }, {
      "firstName" : "H",
      "lastName" : "Kiyosawa",
      "authorRank" : 6,
      "name" : "Kiyosawa H",
      "referenceId" : "RGD:A162383"
    }, {
      "firstName" : "T",
      "lastName" : "Harada",
      "authorRank" : 7,
      "name" : "Harada T",
      "referenceId" : "RGD:A314638"
    }, {
      "firstName" : "N",
      "lastName" : "Ichihara",
      "authorRank" : 8,
      "name" : "Ichihara N",
      "referenceId" : "RGD:A46988"
    }, {
      "firstName" : "S",
      "lastName" : "Wakana",
      "authorRank" : 9,
      "name" : "Wakana S",
      "referenceId" : "RGD:A7542"
    }, {
      "firstName" : "T",
      "lastName" : "Kikuchi",
      "authorRank" : 10,
      "name" : "Kikuchi T",
      "referenceId" : "RGD:A5371"
    }, {
      "firstName" : "K",
      "lastName" : "Wada",
      "authorRank" : 11,
      "name" : "Wada K",
      "referenceId" : "RGD:A149213"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1302562"
    } ]
  }, {
    "primaryId" : "PMID:10471498",
    "title" : "Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT. International Cystinuria Consortium.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Feliubadalo L, etal., Nat Genet 1999 Sep;23(1):52-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-02-26T11:00:00.000-06:00",
    "volume" : "23",
    "pages" : "52-7",
    "abstract" : "Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref. 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12-13.1 (Refs 3,4). We have identified a new transcript, encoding a protein (bo, +AT, for bo,+ amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co-transfection of bo,+AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes b o,+AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and G295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that bo,+AT is the light subunit of rBAT.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Feliubadalo",
      "authorRank" : 1,
      "name" : "Feliubadalo L",
      "referenceId" : "RGD:A39374"
    }, {
      "firstName" : "M",
      "lastName" : "Font",
      "authorRank" : 2,
      "name" : "Font M",
      "referenceId" : "RGD:A161834"
    }, {
      "firstName" : "J",
      "lastName" : "Purroy",
      "authorRank" : 3,
      "name" : "Purroy J",
      "referenceId" : "RGD:A161835"
    }, {
      "firstName" : "F",
      "lastName" : "Rousaud",
      "authorRank" : 4,
      "name" : "Rousaud F",
      "referenceId" : "RGD:A161836"
    }, {
      "firstName" : "X",
      "lastName" : "Estivill",
      "authorRank" : 5,
      "name" : "Estivill X",
      "referenceId" : "RGD:A295507"
    }, {
      "firstName" : "V",
      "lastName" : "Nunes",
      "authorRank" : 6,
      "name" : "Nunes V",
      "referenceId" : "RGD:A295508"
    }, {
      "firstName" : "E",
      "lastName" : "Golomb",
      "authorRank" : 7,
      "name" : "Golomb E",
      "referenceId" : "RGD:A295509"
    }, {
      "firstName" : "M",
      "lastName" : "Centola",
      "authorRank" : 8,
      "name" : "Centola M",
      "referenceId" : "RGD:A161840"
    }, {
      "firstName" : "I",
      "lastName" : "Aksentijevich",
      "authorRank" : 9,
      "name" : "Aksentijevich I",
      "referenceId" : "RGD:A161841"
    }, {
      "firstName" : "Y",
      "lastName" : "Kreiss",
      "authorRank" : 10,
      "name" : "Kreiss Y",
      "referenceId" : "RGD:A295510"
    }, {
      "firstName" : "B",
      "lastName" : "Goldman",
      "authorRank" : 11,
      "name" : "Goldman B",
      "referenceId" : "RGD:A161843"
    }, {
      "firstName" : "M",
      "lastName" : "Pras",
      "authorRank" : 12,
      "name" : "Pras M",
      "referenceId" : "RGD:A161844"
    }, {
      "firstName" : "DL",
      "lastName" : "Kastner",
      "authorRank" : 13,
      "name" : "Kastner DL",
      "referenceId" : "RGD:A155967"
    }, {
      "firstName" : "E",
      "lastName" : "Pras",
      "authorRank" : 14,
      "name" : "Pras E",
      "referenceId" : "RGD:A295511"
    }, {
      "firstName" : "P",
      "lastName" : "Gasparini",
      "authorRank" : 15,
      "name" : "Gasparini P",
      "referenceId" : "RGD:A295515"
    }, {
      "firstName" : "L",
      "lastName" : "Bisceglia",
      "authorRank" : 16,
      "name" : "Bisceglia L",
      "referenceId" : "RGD:A295512"
    }, {
      "firstName" : "E",
      "lastName" : "Beccia",
      "authorRank" : 17,
      "name" : "Beccia E",
      "referenceId" : "RGD:A161849"
    }, {
      "firstName" : "M",
      "lastName" : "Gallucci",
      "authorRank" : 18,
      "name" : "Gallucci M",
      "referenceId" : "RGD:A161850"
    }, {
      "firstName" : "L",
      "lastName" : "De Sanctis",
      "authorRank" : 19,
      "name" : "De Sanctis L",
      "referenceId" : "RGD:A39390"
    }, {
      "firstName" : "A",
      "lastName" : "Ponzone",
      "authorRank" : 20,
      "name" : "Ponzone A",
      "referenceId" : "RGD:A161852"
    }, {
      "firstName" : "GF",
      "lastName" : "Rizzoni",
      "authorRank" : 21,
      "name" : "Rizzoni GF",
      "referenceId" : "RGD:A39392"
    }, {
      "firstName" : "L",
      "lastName" : "Zelante",
      "authorRank" : 22,
      "name" : "Zelante L",
      "referenceId" : "RGD:A295514"
    }, {
      "firstName" : "MT",
      "lastName" : "Bassi",
      "authorRank" : 23,
      "name" : "Bassi MT",
      "referenceId" : "RGD:A28952"
    }, {
      "firstName" : "JR",
      "lastName" : "George AL",
      "authorRank" : 24,
      "name" : "George AL JR",
      "referenceId" : "RGD:A39394"
    }, {
      "firstName" : "M",
      "lastName" : "Palacin",
      "authorRank" : 25,
      "name" : "Palacin M",
      "referenceId" : "RGD:A39395"
    }, {
      "firstName" : "A",
      "lastName" : "De Grandi",
      "authorRank" : 26,
      "name" : "De Grandi A",
      "referenceId" : "RGD:A161858"
    }, {
      "firstName" : "M",
      "lastName" : "Riboni",
      "authorRank" : 27,
      "name" : "Riboni M",
      "referenceId" : "RGD:A161859"
    }, {
      "firstName" : "J K",
      "lastName" : "Endsley",
      "authorRank" : 28,
      "name" : "Endsley J K",
      "referenceId" : "RGD:A161860"
    }, {
      "firstName" : "A",
      "lastName" : "Ballabio",
      "authorRank" : 29,
      "name" : "Ballabio A",
      "referenceId" : "RGD:A161861"
    }, {
      "firstName" : "G",
      "lastName" : "Borsani",
      "authorRank" : 30,
      "name" : "Borsani G",
      "referenceId" : "RGD:A161862"
    }, {
      "firstName" : "N",
      "lastName" : "Reig",
      "authorRank" : 31,
      "name" : "Reig N",
      "referenceId" : "RGD:A161863"
    }, {
      "firstName" : "E",
      "lastName" : "Fernández",
      "authorRank" : 32,
      "name" : "Fernández E",
      "referenceId" : "RGD:A161864"
    }, {
      "firstName" : "R",
      "lastName" : "Estévez",
      "authorRank" : 33,
      "name" : "Estévez R",
      "referenceId" : "RGD:A161865"
    }, {
      "firstName" : "M",
      "lastName" : "Pineda",
      "authorRank" : 34,
      "name" : "Pineda M",
      "referenceId" : "RGD:A161866"
    }, {
      "firstName" : "D",
      "lastName" : "Torrents",
      "authorRank" : 35,
      "name" : "Torrents D",
      "referenceId" : "RGD:A161867"
    }, {
      "firstName" : "M",
      "lastName" : "Camps",
      "authorRank" : 36,
      "name" : "Camps M",
      "referenceId" : "RGD:A161868"
    }, {
      "firstName" : "J",
      "lastName" : "Lloberas",
      "authorRank" : 37,
      "name" : "Lloberas J",
      "referenceId" : "RGD:A161869"
    }, {
      "firstName" : "A",
      "lastName" : "Zorzano",
      "authorRank" : 38,
      "name" : "Zorzano A",
      "referenceId" : "RGD:A161870"
    }, {
      "firstName" : "M",
      "lastName" : "Palacín",
      "authorRank" : 39,
      "name" : "Palacín M",
      "referenceId" : "RGD:A161872"
    }, {
      "firstName" : "M",
      "lastName" : "Palacín",
      "authorRank" : 40,
      "name" : "Palacín M",
      "referenceId" : "RGD:A161872"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:737767"
    } ]
  }, {
    "primaryId" : "PMID:10471507",
    "title" : "Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hurvitz JR, etal., Nat Genet. 1999 Sep;23(1):94-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-19T13:14:54.000-06:00",
    "volume" : "23",
    "pages" : "94-8",
    "abstract" : "Members of the CCN (for CTGF, cyr61/cef10, nov) gene family encode cysteine-rich secreted proteins with roles in cell growth and differentiation. Cell-specific and tissue-specific differences in the expression and function of different CCN family members suggest they have non-redundant roles. Using a positional-candidate approach, we found that mutations in the CCN family member WISP3 are associated with the autosomal recessive skeletal disorder progressive pseudorheumatoid dysplasia (PPD; MIM 208230). PPD is an autosomal recessive disorder that may be initially misdiagnosed as juvenile rheumatoid arthritis. Its population incidence has been estimated at 1 per million in the United Kingdom, but it is likely to be higher in the Middle East and Gulf States. Affected individuals are asymptomatic in early childhood. Signs and symptoms of disease typically develop between three and eight years of age. Clinically and radiographically, patients experience continued cartilage loss and destructive bone changes as they age, in several instances necessitating joint replacement surgery by the third decade of life. Extraskeletal manifestations have not been reported in PPD. Cartilage appears to be the primary affected tissue, and in one patient, a biopsy of the iliac crest revealed abnormal nests of chondrocytes and loss of normal cell columnar organization in growth zones. We have identified nine different WISP3 mutations in unrelated, affected individuals, indicating that the gene is essential for normal post-natal skeletal growth and cartilage homeostasis.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JR",
      "lastName" : "Hurvitz",
      "authorRank" : 1,
      "name" : "Hurvitz JR",
      "referenceId" : "RGD:A75339"
    }, {
      "firstName" : "WM",
      "lastName" : "Suwairi",
      "authorRank" : 2,
      "name" : "Suwairi WM",
      "referenceId" : "RGD:A75340"
    }, {
      "firstName" : "W",
      "lastName" : "Van Hul",
      "authorRank" : 3,
      "name" : "Van Hul W",
      "referenceId" : "RGD:A13248"
    }, {
      "firstName" : "H",
      "lastName" : "El-Shanti",
      "authorRank" : 4,
      "name" : "El-Shanti H",
      "referenceId" : "RGD:A75341"
    }, {
      "firstName" : "A",
      "lastName" : "Superti-Furga",
      "authorRank" : 5,
      "name" : "Superti-Furga A",
      "referenceId" : "RGD:A35248"
    }, {
      "firstName" : "J",
      "lastName" : "Roudier",
      "authorRank" : 6,
      "name" : "Roudier J",
      "referenceId" : "RGD:A75342"
    }, {
      "firstName" : "D",
      "lastName" : "Holderbaum",
      "authorRank" : 7,
      "name" : "Holderbaum D",
      "referenceId" : "RGD:A75343"
    }, {
      "firstName" : "RM",
      "lastName" : "Pauli",
      "authorRank" : 8,
      "name" : "Pauli RM",
      "referenceId" : "RGD:A37627"
    }, {
      "firstName" : "JK",
      "lastName" : "Herd",
      "authorRank" : 9,
      "name" : "Herd JK",
      "referenceId" : "RGD:A75344"
    }, {
      "firstName" : "EV",
      "lastName" : "Van Hul",
      "authorRank" : 10,
      "name" : "Van Hul EV",
      "referenceId" : "RGD:A75345"
    }, {
      "firstName" : "H",
      "lastName" : "Rezai-Delui",
      "authorRank" : 11,
      "name" : "Rezai-Delui H",
      "referenceId" : "RGD:A75346"
    }, {
      "firstName" : "E",
      "lastName" : "Legius",
      "authorRank" : 12,
      "name" : "Legius E",
      "referenceId" : "RGD:A18791"
    }, {
      "firstName" : "M",
      "lastName" : "Le Merrer",
      "authorRank" : 13,
      "name" : "Le Merrer M",
      "referenceId" : "RGD:A57952"
    }, {
      "firstName" : "J",
      "lastName" : "Al-Alami",
      "authorRank" : 14,
      "name" : "Al-Alami J",
      "referenceId" : "RGD:A75347"
    }, {
      "firstName" : "SA",
      "lastName" : "Bahabri",
      "authorRank" : 15,
      "name" : "Bahabri SA",
      "referenceId" : "RGD:A75348"
    }, {
      "firstName" : "ML",
      "lastName" : "Warman",
      "authorRank" : 16,
      "name" : "Warman ML",
      "referenceId" : "RGD:A59365"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599850"
    } ]
  }, {
    "primaryId" : "PMID:10471508",
    "title" : "Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety.",
    "datePublished" : "1999-11-01T00:00:00.000-06:00",
    "citation" : "Tronche F, etal., Nat Genet. 1999 Sep;23(1):99-103.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2012-11-16T15:58:47.000-06:00",
    "volume" : "23",
    "pages" : "99-103",
    "abstract" : "The glucocorticoid receptor (Gr, encoded by the gene Grl1) controls transcription of target genes both directly by interaction with DNA regulatory elements and indirectly by cross-talk with other transcription factors. In response to various stimuli, including stress, glucocorticoids coordinate metabolic, endocrine, immune and nervous system responses and ensure an adequate profile of transcription. In the brain, Gr has been proposed to modulate emotional behaviour, cognitive functions and addictive states. Previously, these aspects were not studied in the absence of functional Gr because inactivation of Grl1 in  mice causes lethality at birth (F.T., C.K. and G.S., unpublished data). Therefore, we generated tissue-specific mutations of this gene using the Cre/loxP -recombination system. This allowed us to generate viable adult mice with loss of Gr function in selected tissues. Loss of Gr function in the nervous system impairs hypothalamus-pituitary-adrenal (HPA)-axis regulation, resulting in increased glucocorticoid (GC) levels that lead to symptoms reminiscent of those observed in Cushing syndrome. Conditional mutagenesis of Gr in the nervous system provides genetic evidence for the importance of Gr signalling in emotional behaviour because mutant animals show an impaired behavioural response to stress  and display reduced anxiety.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "F",
      "lastName" : "Tronche",
      "authorRank" : 1,
      "name" : "Tronche F",
      "referenceId" : "RGD:A37448"
    }, {
      "firstName" : "C",
      "lastName" : "Kellendonk",
      "authorRank" : 2,
      "name" : "Kellendonk C",
      "referenceId" : "RGD:A37449"
    }, {
      "firstName" : "O",
      "lastName" : "Kretz",
      "authorRank" : 3,
      "name" : "Kretz O",
      "referenceId" : "RGD:A37446"
    }, {
      "firstName" : "P",
      "lastName" : "Gass",
      "authorRank" : 4,
      "name" : "Gass P",
      "referenceId" : "RGD:A5174"
    }, {
      "firstName" : "K",
      "lastName" : "Anlag",
      "authorRank" : 5,
      "name" : "Anlag K",
      "referenceId" : "RGD:A159718"
    }, {
      "firstName" : "PC",
      "lastName" : "Orban",
      "authorRank" : 6,
      "name" : "Orban PC",
      "referenceId" : "RGD:A159719"
    }, {
      "firstName" : "R",
      "lastName" : "Bock",
      "authorRank" : 7,
      "name" : "Bock R",
      "referenceId" : "RGD:A159720"
    }, {
      "firstName" : "R",
      "lastName" : "Klein",
      "authorRank" : 8,
      "name" : "Klein R",
      "referenceId" : "RGD:A15463"
    }, {
      "firstName" : "G",
      "lastName" : "Schutz",
      "authorRank" : 9,
      "name" : "Schutz G",
      "referenceId" : "RGD:A37438"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7174722"
    } ]
  }, {
    "primaryId" : "PMID:10471622",
    "title" : "Anti-interleukin 5 but not anti-IgE prevents airway inflammation and airway hyperresponsiveness.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Hamelmann E, etal., Am J Respir Crit Care Med. 1999 Sep;160(3):934-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-07-29T15:56:34.000-05:00",
    "volume" : "160",
    "pages" : "934-41",
    "abstract" : "The role of IL-5 and allergen-specific IgE in the development of eosinophilic airway inflammation and airway hyperresponsiveness (AHR) was investigated in a murine model. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection on Days 1 and 14, followed by airway challenge with OVA on Days 28 and  29. Anti-IL-5 (TRFK-5) or anti-IgE (antibody 1-5) was administered before each airway challenge. Sensitized and challenged mice developed increased OVA-specific IgE serum levels, Th2 cytokine production by peribronchial lymph node (PBLN) cells, increased numbers of eosinophils (predominantly located in the peribronchial regions of the lungs), and increased airway responsiveness to methacholine (MCh). Anti-IgE treatment significantly decreased serum anti-OVA IgE levels and prevented the development of anaphylaxis but failed to affect T cell function, eosinophil airway infiltration, and AHR in sensitized and challenged mice. In contrast, treatment with anti-IL-5 antibody did not affect B cell (Ig serum levels), T cell (cytokine production), or mast cell function (immediate cutaneous reactivity) but completely inhibited development of eosinophilic lung inflammation and AHR. These data identify IL-5-mediated eosinophilia as a major target for development of AHR in this model, with little effect resulting from neutralization of IgE.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Hamelmann",
      "authorRank" : 1,
      "name" : "Hamelmann",
      "referenceId" : "RGD:A332664"
    }, {
      "firstName" : "G",
      "lastName" : "Cieslewicz",
      "authorRank" : 2,
      "name" : "Cieslewicz",
      "referenceId" : "RGD:A331563"
    }, {
      "firstName" : "J",
      "lastName" : "Schwarze",
      "authorRank" : 3,
      "name" : "Schwarze",
      "referenceId" : "RGD:A332665"
    }, {
      "firstName" : "T",
      "lastName" : "Ishizuka",
      "authorRank" : 4,
      "name" : "Ishizuka T",
      "referenceId" : "RGD:A9836"
    }, {
      "firstName" : "A",
      "lastName" : "Joetham",
      "authorRank" : 5,
      "name" : "Joetham A",
      "referenceId" : "RGD:A127641"
    }, {
      "firstName" : "C",
      "lastName" : "Heusser",
      "authorRank" : 6,
      "name" : "Heusser",
      "referenceId" : "RGD:A353333"
    }, {
      "firstName" : "EW",
      "lastName" : "Gelfand",
      "authorRank" : 7,
      "name" : "Gelfand EW",
      "referenceId" : "RGD:A127645"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11354935"
    } ]
  }, {
    "primaryId" : "PMID:10471785",
    "title" : "An ABC transporter homologous to TAP proteins.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Yamaguchi Y, etal., FEBS Lett 1999 Aug 27;457(2):231-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:42.000-05:00",
    "volume" : "457",
    "pages" : "231-6",
    "abstract" : "Polymerase chain reaction amplification of cDNA from rat intestine revealed the expression of a novel ABC transporter, TAPL (TAP-like). Subsequently, the protein sequence was deduced from the nucleotide sequence of cDNA carrying the entire coding region. TAPL is transcribed ubiquitously in various rat tissues. The protein, with 762 amino acid residues, has potential transmembrane domains, and an ATP-binding domain in its amino and carboxyl terminal regions, respectively, and is highly homologous to TAP1 and TAP2 (transporters associated with antigen presentation/processing): pairwise comparisons with TAPL demonstrated 39 and 41% of the residues are identical, respectively. These numerical values are essentially the same as that for TAP1 and TAP2 (39%), and the hydropathy profiles of TAPL, TAP1 and TAP2 are quite similar. The similarity among these three proteins suggests that they could be derived from a common ancestral gene. Furthermore, we found that there is a potential splicing isoform, sharing the amino terminal 720 amino acid residues of TAPL.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Y",
      "lastName" : "Yamaguchi",
      "authorRank" : 1,
      "name" : "Yamaguchi Y",
      "referenceId" : "RGD:A5502"
    }, {
      "firstName" : "M",
      "lastName" : "Kasano",
      "authorRank" : 2,
      "name" : "Kasano M",
      "referenceId" : "RGD:A16765"
    }, {
      "firstName" : "T",
      "lastName" : "Terada",
      "authorRank" : 3,
      "name" : "Terada T",
      "referenceId" : "RGD:A123211"
    }, {
      "firstName" : "R",
      "lastName" : "Sato",
      "authorRank" : 4,
      "name" : "Sato R",
      "referenceId" : "RGD:A16767"
    }, {
      "firstName" : "M",
      "lastName" : "Maeda",
      "authorRank" : 5,
      "name" : "Maeda M",
      "referenceId" : "RGD:A8064"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632226"
    } ]
  }, {
    "primaryId" : "PMID:10471789",
    "title" : "Association of the rat heterogeneous nuclear RNA-ribonucleoprotein F with TATA-binding protein.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Yoshida T, etal., FEBS Lett 1999 Aug 27;457(2):251-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:06:53.000-05:00",
    "volume" : "457",
    "pages" : "251-4",
    "abstract" : "Heterogeneous nuclear ribonucleoprotein F (hnRNP-F) has been shown to be a pre-mRNA splicing factor. Recent studies have uncovered the coordination of synthesis of pre-mRNA and its processing, including post-transcriptional modification and splicing. Here, we present evidence for an association between a splicing factor, hnRNP-F, and TATA-binding protein (TBP), which is an essential factor needed for transcription initiation. An affinity detection experiment revealed hnRNP-F in the preparation of TBP-interacting proteins. HnRNP-F was associated with TBP in nuclear extracts and was capable of direct binding to TBP in vitro. These results suggest that hnRNP-F is associated with TBP in the cell. HnRNP-F was observed in abundance in the thymus, spleen and testis, and its distribution pattern was similar to that of TBP, implying a functional coordination of transcription and splicing. We assume that the splicing machinery is associated with the transcription apparatus as a prerequisite prior to transcriptional elongation.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Yoshida",
      "authorRank" : 1,
      "name" : "Yoshida T",
      "referenceId" : "RGD:A160470"
    }, {
      "firstName" : "Y",
      "lastName" : "Makino",
      "authorRank" : 2,
      "name" : "Makino Y",
      "referenceId" : "RGD:A5103"
    }, {
      "firstName" : "T",
      "lastName" : "Tamura",
      "authorRank" : 3,
      "name" : "Tamura T",
      "referenceId" : "RGD:A156706"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632913"
    } ]
  }, {
    "primaryId" : "PMID:10471838",
    "title" : "Diverse PAH transcripts in lymphocytes of PKU patients with putative nonsense (G272X, Y356X) and missense (P281L, R408Q) mutations.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Ellingsen S, etal., FEBS Lett. 1999 Sep 3;457(3):505-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:17:53.000-05:00",
    "volume" : "457",
    "pages" : "505-8",
    "abstract" : "The majority of mutations in the human phenylalanine hydroxylase (PAH) gene that  lead to the recessive disease phenylketonuria (PKU) are believed to affect the activity or stability of the PAH enzyme. In this study we have performed in vivo  analyses of lymphocyte PAH mRNA from PKU patients homozygous for the PKU missense mutations P281L and R408Q as well as the nonsense mutations G272X and Y356X. The  mutations G272X, P281L and R408Q, which are located outside the consensus splice  site sequence, result in transcripts with one or more exons skipped in addition to full-length transcripts. The mutation Y356X results in transcripts with one or more exons skipped, but no full-length transcripts. Our findings question the value of functional and structural predictions of mutations at the protein level  without analyses of the corresponding transcript.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Ellingsen",
      "authorRank" : 1,
      "name" : "Ellingsen",
      "referenceId" : "RGD:A264431"
    }, {
      "firstName" : "PM",
      "lastName" : "Knappskog",
      "authorRank" : 2,
      "name" : "Knappskog PM",
      "referenceId" : "RGD:A79143"
    }, {
      "firstName" : "J",
      "lastName" : "Apold",
      "authorRank" : 3,
      "name" : "Apold",
      "referenceId" : "RGD:A364091"
    }, {
      "firstName" : "HG",
      "lastName" : "Eiken",
      "authorRank" : 4,
      "name" : "Eiken",
      "referenceId" : "RGD:A175808"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067163"
    } ]
  }, {
    "primaryId" : "PMID:10472540",
    "title" : "Novel donor splice site mutations of AGL gene in glycogen storage disease type IIIa.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Hadjigeorgiou GM, etal., J Inherit Metab Dis. 1999 Aug;22(6):762-3. doi: 10.1023/a:1005572906807.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:44:19.000-05:00",
    "volume" : "22",
    "pages" : "762-3",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "G M",
      "lastName" : "Hadjigeorgiou",
      "authorRank" : 1,
      "name" : "Hadjigeorgiou GM",
      "referenceId" : "RGD:A570404"
    }, {
      "firstName" : "G P",
      "lastName" : "Comi",
      "authorRank" : 2,
      "name" : "Comi GP",
      "referenceId" : "RGD:A565422"
    }, {
      "firstName" : "A",
      "lastName" : "Bordoni",
      "authorRank" : 3,
      "name" : "Bordoni A",
      "referenceId" : "RGD:A13446"
    }, {
      "firstName" : "J",
      "lastName" : "Shen",
      "authorRank" : 4,
      "name" : "Shen J",
      "referenceId" : "RGD:A11773"
    }, {
      "firstName" : "Y T",
      "lastName" : "Chen",
      "authorRank" : 5,
      "name" : "Chen YT",
      "referenceId" : "RGD:A595407"
    }, {
      "firstName" : "S",
      "lastName" : "Salani",
      "authorRank" : 6,
      "name" : "Salani S",
      "referenceId" : "RGD:A79753"
    }, {
      "firstName" : "A",
      "lastName" : "Toscano",
      "authorRank" : 7,
      "name" : "Toscano A",
      "referenceId" : "RGD:A77565"
    }, {
      "firstName" : "F",
      "lastName" : "Fortunato",
      "authorRank" : 8,
      "name" : "Fortunato F",
      "referenceId" : "RGD:A85780"
    }, {
      "firstName" : "S",
      "lastName" : "Lucchiari",
      "authorRank" : 9,
      "name" : "Lucchiari S",
      "referenceId" : "RGD:A79751"
    }, {
      "firstName" : "N",
      "lastName" : "Bresolin",
      "authorRank" : 10,
      "name" : "Bresolin N",
      "referenceId" : "RGD:A61825"
    }, {
      "firstName" : "C",
      "lastName" : "Rodolico",
      "authorRank" : 11,
      "name" : "Rodolico C",
      "referenceId" : "RGD:A79756"
    }, {
      "firstName" : "M G",
      "lastName" : "Piscaglia",
      "authorRank" : 12,
      "name" : "Piscaglia MG",
      "referenceId" : "RGD:A595408"
    }, {
      "firstName" : "L",
      "lastName" : "Franceschina",
      "authorRank" : 13,
      "name" : "Franceschina L",
      "referenceId" : "RGD:A595409"
    }, {
      "firstName" : "A",
      "lastName" : "Papadimitriou",
      "authorRank" : 14,
      "name" : "Papadimitriou A",
      "referenceId" : "RGD:A143362"
    }, {
      "firstName" : "G",
      "lastName" : "Scarlato",
      "authorRank" : 15,
      "name" : "Scarlato G",
      "referenceId" : "RGD:A64579"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598118634"
    } ]
  }, {
    "primaryId" : "PMID:10473120",
    "title" : "An octamer-binding site is crucial for the activity of an enhancer active at the embryonic met-/mesencephalic junction.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Mihailescu D, etal., Mech Dev 1999 Jun;84(1-2):55-67.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-29T15:03:03.000-05:00",
    "volume" : "84",
    "pages" : "55-67",
    "abstract" : "An enhancer sequence found in the Protease Nexin-1 (PN-1) gene was shown to drive lacZ expression specifically at the met-/mesencephalic junction in transgenic mouse embryos. A functional study of this enhancer has been performed to better understand the mechanisms regulating isthmic gene expression. An octamer-binding site for POU domain factors was found to be crucial for the activity of the enhancer in vivo. Comparative expression studies of POU domain factors, electrophoretic mobility shift assays and transient transfection experiments, strongly suggest that Brn-1/-2 regulate the enhancer activity in vivo. In addition, in vitro experiments indicated that FGF-8 was required for the maintenance of the enhancer activity, but not for the synthesis of Bn-1/-2. The data represents the first functional evidence for a role of POU factors in the regulation of met-/mesencephalic gene expression. It also implies that at least two regulatory pathways, namely the FGF-8 signaling and the octamer-binding site pathway, synergistically interact to control the PN-1 enhancer activity in vivo.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Mihailescu",
      "authorRank" : 1,
      "name" : "Mihailescu D",
      "referenceId" : "RGD:A18700"
    }, {
      "firstName" : "P",
      "lastName" : "Kury",
      "authorRank" : 2,
      "name" : "Kury P",
      "referenceId" : "RGD:A12447"
    }, {
      "firstName" : "D",
      "lastName" : "Monard",
      "authorRank" : 3,
      "name" : "Monard D",
      "referenceId" : "RGD:A8058"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632815"
    } ]
  }, {
    "primaryId" : "PMID:10473513",
    "title" : "Increased levels of alternatively spliced interleukin 4 (IL-4delta2) transcripts  in peripheral blood mononuclear cells from patients with systemic sclerosis.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Sakkas LI, etal., Clin Diagn Lab Immunol. 1999 Sep;6(5):660-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-01-28T12:55:19.000-06:00",
    "volume" : "6",
    "pages" : "660-4",
    "abstract" : "Recent in vitro studies have shown that interleukin 4 (IL-4) induces and gamma interferon (IFN-gamma) inhibits collagen production. To define the TH1(IFN-gamma) and TH2(IL-4) cytokine profiles in systemic sclerosis (Sscl), a disease characterized by widespread fibrosis, we investigated IL-4 and IFN-gamma transcripts in peripheral blood mononuclear cells and plasma protein levels in 13 patients with Sscl. Two previously identified IL-4 transcripts, a full-length transcript and an alternatively spliced (truncated) transcript (designated IL-4delta2), were identified in patients and normal controls. Significantly increased levels of total IL-4 transcripts (full-length plus IL-4delta2 transcripts) were found in patients with Sscl in comparison to those found in healthy controls (P = 0.003), and this increase was primarily due to an increase  in the level of the alternatively spliced IL-4delta2 form. The IL-4delta2/full-length-IL-4 transcript ratio was significantly increased in Sscl  patients (P < 0.0001, versus healthy controls). Sequencing analysis revealed that the frequency of IL-4 clones carrying the IL-4delta2 transcript was also substantially increased in patients with Sscl. Plasma IL-4 protein levels were increased in Sscl patients compared to those in healthy controls (P = 0.001) and  correlated with total IL-4 transcript levels. The up-regulation of the fibrogenic IL-4 (a TH2 cytokine) in Sscl suggests a pathogenic role for IL-4 in this disease.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LI",
      "lastName" : "Sakkas",
      "authorRank" : 1,
      "name" : "Sakkas",
      "referenceId" : "RGD:A178670"
    }, {
      "firstName" : "C",
      "lastName" : "Tourtellotte",
      "authorRank" : 2,
      "name" : "Tourtellotte",
      "referenceId" : "RGD:A178671"
    }, {
      "firstName" : "S",
      "lastName" : "Berney",
      "authorRank" : 3,
      "name" : "Berney",
      "referenceId" : "RGD:A178672"
    }, {
      "firstName" : "AR",
      "lastName" : "Myers",
      "authorRank" : 4,
      "name" : "Myers",
      "referenceId" : "RGD:A178673"
    }, {
      "firstName" : "CD",
      "lastName" : "Platsoucas",
      "authorRank" : 5,
      "name" : "Platsoucas",
      "referenceId" : "RGD:A178674"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:7829819"
    } ]
  }, {
    "primaryId" : "PMID:10473563",
    "title" : "Phospholipase C-delta1 is activated by capacitative calcium entry that follows phospholipase C-beta activation upon bradykinin stimulation.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Kim YH, etal., J Biol Chem. 1999 Sep 10;274(37):26127-34.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-09-22T10:10:43.000-05:00",
    "volume" : "274",
    "pages" : "26127-34",
    "abstract" : "To characterize the regulatory mechanism of phospholipase C-delta1 (PLC-delta1) in the bradykinin (BK) receptor-mediated signaling pathway, we used a clone of PC12 cells, which stably overexpress PLC-delta1 (PC12-D1). Stimulation with BK induced a significantly higher Ca(2+) elevation and inositol 1,4,5-trisphosphate (IP(3)) production with a much lower half-maximal effective concentration (EC(50)) of BK in PC12-D1 cells than in wild type (PC12-W) or vector-transfected (PC12-V) cells. However, BK-induced intracellular Ca(2+) release and IP(3) generation was similar between PC12-V and PC12-D1 cells in the absence of extracellular Ca(2+), suggesting that the availability of extracellular Ca(2+) is essential to the activation of PLC-delta1. When PC12-D1 cells were treated with agents that induce Ca(2+) influx, more IP(3) was produced, suggesting that the Ca(2+) entry induces IP(3) production in PC12-D1 cells. Furthermore, the additional IP(3) production after BK-induced capacitative calcium entry was detected in PC12-D1 cells, suggesting that PLC-delta1 is mainly activated by capacitative calcium entry. When cells were stimulated with BK in the presence of extracellular Ca(2+), [(3)H]norepinephrine secretion was much greater from PC12-D1 cells than from PC12-V cells. Our results suggest that PLC-delta1 is activated by capacitative calcium entry following the activation of PLC-beta, additively inducing IP(3) production and Ca(2+) rise in BK-stimulated PC12 cells.",
    "issueName" : "37",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "YH",
      "lastName" : "Kim",
      "authorRank" : 1,
      "name" : "Kim YH",
      "referenceId" : "RGD:A5695"
    }, {
      "firstName" : "TJ",
      "lastName" : "Park",
      "authorRank" : 2,
      "name" : "Park TJ",
      "referenceId" : "RGD:A31627"
    }, {
      "firstName" : "YH",
      "lastName" : "Lee",
      "authorRank" : 3,
      "name" : "Lee YH",
      "referenceId" : "RGD:A21811"
    }, {
      "firstName" : "KJ",
      "lastName" : "Baek",
      "authorRank" : 4,
      "name" : "Baek KJ",
      "referenceId" : "RGD:A23822"
    }, {
      "firstName" : "PG",
      "lastName" : "Suh",
      "authorRank" : 5,
      "name" : "Suh PG",
      "referenceId" : "RGD:A21418"
    }, {
      "firstName" : "SH",
      "lastName" : "Ryu",
      "authorRank" : 6,
      "name" : "Ryu SH",
      "referenceId" : "RGD:A21417"
    }, {
      "firstName" : "KT",
      "lastName" : "Kim",
      "authorRank" : 7,
      "name" : "Kim KT",
      "referenceId" : "RGD:A55085"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2301014"
    } ]
  }, {
    "primaryId" : "PMID:10473568",
    "title" : "Cloning and expression of a proteoglycan UDP-galactose:beta-xylose beta1,4-galactosyltransferase I. A seventh member of the human beta4-galactosyltransferase gene family.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Almeida R, etal., J Biol Chem. 1999 Sep 10;274(37):26165-71.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-02-02T16:30:12.000-06:00",
    "volume" : "274",
    "pages" : "26165-71",
    "abstract" : "A seventh member of the human beta4-galactosyltransferase family, beta4Gal-T7, was identified by BLAST analysis of expressed sequence tags. The coding region of beta4Gal-T7 depicts a type II transmembrane protein with sequence similarity to beta4-galactosyltransferases, but the sequence was distinct in known motifs and did not contain the cysteine residues conserved in the other six members of the beta4Gal-T family. The genomic organization of beta4Gal-T7 was different from previous beta4Gal-Ts. Expression of beta4Gal-T7 in insect cells showed that the gene product had beta1,4-galactosyltransferase activity with beta-xylosides, and the linkage formed was Galbeta1-4Xyl. Thus, beta4Gal-T7 represents galactosyltransferase I enzyme (xylosylprotein beta1, 4-galactosyltransferase; EC 2.4.1.133), which attaches the first galactose in the proteoglycan linkage region GlcAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser. Sequence analysis of beta4Gal-T7 from a fibroblast cell line of a patient with a progeroid syndrome and signs of the Ehlers-Danlos syndrome, previously shown to exhibit reduced galactosyltransferase I activity (Quentin, E., Gladen, A., Roden, L., and Kresse, H. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 1342-1346), revealed two inherited allelic variants, beta4Gal-T7(186D) and beta4Gal-T7(206P), each with a single missense substitution in the putative catalytic domain of the enzyme. beta4Gal-T7(186D) exhibited a 4-fold elevated K(m) for the donor substrate, whereas essentially no activity was demonstrated with beta4Gal-T7(206P). Molecular cloning of beta4Gal-T7 should facilitate general studies of its pathogenic role in progeroid syndromes and connective tissue disorders with affected proteoglycan biosynthesis.",
    "issueName" : "37",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Almeida",
      "authorRank" : 1,
      "name" : "Almeida R",
      "referenceId" : "RGD:A73817"
    }, {
      "firstName" : "SB",
      "lastName" : "Levery",
      "authorRank" : 2,
      "name" : "Levery SB",
      "referenceId" : "RGD:A29638"
    }, {
      "firstName" : "U",
      "lastName" : "Mandel",
      "authorRank" : 3,
      "name" : "Mandel U",
      "referenceId" : "RGD:A73818"
    }, {
      "firstName" : "H",
      "lastName" : "Kresse",
      "authorRank" : 4,
      "name" : "Kresse H",
      "referenceId" : "RGD:A43250"
    }, {
      "firstName" : "T",
      "lastName" : "Schwientek",
      "authorRank" : 5,
      "name" : "Schwientek T",
      "referenceId" : "RGD:A73819"
    }, {
      "firstName" : "EP",
      "lastName" : "Bennett",
      "authorRank" : 6,
      "name" : "Bennett EP",
      "referenceId" : "RGD:A73820"
    }, {
      "firstName" : "H",
      "lastName" : "Clausen",
      "authorRank" : 7,
      "name" : "Clausen H",
      "referenceId" : "RGD:A73821"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599433"
    } ]
  }, {
    "primaryId" : "PMID:10473900",
    "title" : "Expression of the genes of arginine-synthesizing enzymes in the rat kidney during development.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Goutal I, etal., Biol Neonate. 1999 Oct;76(4):253-60.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-25T12:44:29.000-06:00",
    "volume" : "76",
    "pages" : "253-60",
    "abstract" : "The expression of two genes, coding for argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL), enzymes which synthesize arginine, was studied by Northern analysis in various tissues of fetal rats. The highest expression of both genes was seen in the small intestine, liver and kidney of the fetus. The developmental expression was observed in the kidney where both mRNA levels remained low during the fetal period and they increased concomitantly in both kidney and liver throughout the perinatal life, suggesting that the aptitude to synthesize arginine appeared and developed within the same period in both organs. This developmental activation of the ASS and ASL genes expression corresponded, at least in part, to a transcriptional mechanism in both tissues, as measured by run-on assay. Bilateral adrenalectomy showed that glucocorticoids did not appear to control the developmental expression of both genes in the kidney, in contrast to the situation observed in the liver.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "I",
      "lastName" : "Goutal",
      "authorRank" : 1,
      "name" : "Goutal I",
      "referenceId" : "RGD:A73155"
    }, {
      "firstName" : "A",
      "lastName" : "Fairand",
      "authorRank" : 2,
      "name" : "Fairand A",
      "referenceId" : "RGD:A71501"
    }, {
      "firstName" : "A",
      "lastName" : "Husson",
      "authorRank" : 3,
      "name" : "Husson A",
      "referenceId" : "RGD:A5814"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599266"
    } ]
  }, {
    "primaryId" : "PMID:10474040",
    "title" : "Expression of tie1 and tie2 proteins during reendothelialization in balloon-injured rat carotid artery.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Fujikawa K, etal., J Vasc Res 1999 Jul-Aug;36(4):272-81.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-10-22T11:49:04.000-05:00",
    "volume" : "36",
    "pages" : "272-81",
    "abstract" : "The novel endothelial cell tyrosine kinase receptors, Tie1 and Tie2, are essential for vascular development and remodeling in the embryo but little is known regarding the regulation of their expression and their role in the maintenance and repair of the adult vascular system. We examined the expression of Tie1 and Tie2 in normal vessels and during reendothelialization following balloon injury of the adult rat carotid artery. Tie proteins were detected in quiescent endothelial cells of the adult rat carotid artery. Tie1 and Tie2 proteins were also detected in human and rat platelets. A weak expression of Tie1 and Tie2 proteins was detected in young endothelial cells which sparsely repopulated the denuded surface by day 14. Protein levels increased in the confluent layer of endothelial cells by day 28. Based on these observations, we tested whether Tie1 and Tie2 mRNA and protein levels are regulated by cell density. Tie1 and Tie2 expression significantly increased with higher density in cultured human endothelial cells, and this upregulation required cell-cell interaction. These data suggest that Tie1 and Tie2 may play a role in the maintenance and repair of the adult vascular system and that the expression of these proteins is regulated by cell density.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Fujikawa",
      "authorRank" : 1,
      "name" : "Fujikawa K",
      "referenceId" : "RGD:A26890"
    }, {
      "firstName" : "E",
      "lastName" : "Presman",
      "authorRank" : 2,
      "name" : "Presman E",
      "referenceId" : "RGD:A26891"
    }, {
      "firstName" : "JM",
      "lastName" : "Isner",
      "authorRank" : 3,
      "name" : "Isner JM",
      "referenceId" : "RGD:A26892"
    }, {
      "firstName" : "L",
      "lastName" : "Varticovski",
      "authorRank" : 4,
      "name" : "Varticovski L",
      "referenceId" : "RGD:A26893"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:724771"
    } ]
  }, {
    "primaryId" : "PMID:10474275",
    "title" : "Establishment of reference values for endocrine tests. II: Hyperprolactinemia.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Le Moli R, etal., Neth J Med. 1999 Aug;55(2):71-5. doi: 10.1016/s0300-2977(99)00040-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-02-26T07:47:37.000-06:00",
    "volume" : "55",
    "pages" : "71-5",
    "abstract" : "<br><b>BACKGROUND: </b>In patients with hyperprolactinemia, the thyrotropin-releasing hormone (TRH) stimulation test is widely applied to distinguish prolactinoma from other causes of hyperprolactinemia. In the present study, we established reference values for the plasma concentration of prolactin (PRL) and its response to TRH.<br><b>METHODS: </b>Basal PRL and the PRL response to 400 micrograms TRH i.v. was determined in 50 subjects recruited from the general population, equally distributed according to sex and age between 20 and 69 years. PRL was determined by a fluoroimmunometric assay. Reference values are given as the observed range.<br><b>RESULTS: </b>Plasma concentrations of PRL were 4.0-25 micrograms/l (median: 10.0 micrograms/l) in women and 0.5-19.0 micrograms/l (median: 8.5 micrograms/l) in men (p = 0.11). The peak PRL concentration after stimulation with TRH was slightly higher in women (median: 51 micrograms/l) than in men (median: 41 micrograms/l; p = 0.04) and was reached at t = 20 min in all subjects. The relative increase in plasma PRL (median: 440%) did not show a statistically significant effect of age or sex. In 12 subjects (24%), the relative increase in plasma PRL was lower than 250%, which has traditionally been considered the minimum cutoff for a normal response. There were no effects of smoking and alcohol, but regular ingestion of liquorice was associated with lower basal (p = 0.03) and lower stimulated (p = 0.05) plasma concentrations of PRL.<br><b>CONCLUSIONS: </b>The present study provides reference values for basal and TRH-stimulated plasma concentrations of PRL.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Le Moli",
      "authorRank" : 1,
      "name" : "Le Moli R",
      "referenceId" : "RGD:A539198"
    }, {
      "firstName" : "E",
      "lastName" : "Endert",
      "authorRank" : 2,
      "name" : "Endert E",
      "referenceId" : "RGD:A539199"
    }, {
      "firstName" : "E",
      "lastName" : "Fliers",
      "authorRank" : 3,
      "name" : "Fliers E",
      "referenceId" : "RGD:A13286"
    }, {
      "firstName" : "T",
      "lastName" : "Mulder",
      "authorRank" : 4,
      "name" : "Mulder T",
      "referenceId" : "RGD:A539200"
    }, {
      "firstName" : "M F",
      "lastName" : "Prummel",
      "authorRank" : 5,
      "name" : "Prummel MF",
      "referenceId" : "RGD:A539201"
    }, {
      "firstName" : "J A",
      "lastName" : "Romijn",
      "authorRank" : 6,
      "name" : "Romijn JA",
      "referenceId" : "RGD:A539202"
    }, {
      "firstName" : "W M",
      "lastName" : "Wiersinga",
      "authorRank" : 7,
      "name" : "Wiersinga WM",
      "referenceId" : "RGD:A539203"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401976448"
    } ]
  }, {
    "primaryId" : "PMID:10475345",
    "title" : "Immunolocalization of inducible and constitutive nitric oxide synthases in human bladder cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Klotz T, etal., Urology. 1999 Sep;54(3):416-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-10T13:07:28.000-05:00",
    "volume" : "54",
    "pages" : "416-9",
    "abstract" : "OBJECTIVES: Nitric oxide (NO) is synthesized by the enzyme family of NO synthases (NOS) and plays an important role in tumor growth and angiogenesis. NO generation by inducible NOS (iNOS) also influences the cytotoxicity of macrophages and tumor-induced immunosuppression. Before now, the expression of iNOS and constitutive NOS in bladder carcinoma tissue had not been determined. METHODS: Bladder carcinoma tissue specimens were procured from 18 patients (mean age 69.7 years) undergoing transurethral resection. In every patient, tumor biopsies were compared with biopsies of benign bladder regions. Histochemical NADPH-diaphorase staining and NOS immunohistochemistry were performed on all tissue specimens. RESULTS: Positive NADPH-diaphorase staining was detected in all sections from bladder carcinoma tissue. NOS immunohistochemistry showed a different pattern. The malignant epithelial cells were highly iNOS positive. Specimens of bladder mucosa outside of the malignant regions showed only a weak positive iNOS immunostaining. The endothelial cells of abundant precapillary vessels in the stroma of bladder tumors showed a highly positive endothelial NOS (eNOS) immunostaining compared with the stroma of nonmalignant bladder tissue. Neuronal NOS immunoreactivity was only found in nitrinergic fibers in the fibromuscular stroma. CONCLUSIONS: Bladder carcinoma tissue had a high iNOS content; benign tissue did not. NO generation from iNOS in the malignant epithelium and from eNOS in tumor stroma may play different roles in tumor angiogenesis and tumor-induced immunosuppression.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Klotz",
      "authorRank" : 1,
      "name" : "Klotz T",
      "referenceId" : "RGD:A94453"
    }, {
      "firstName" : "W",
      "lastName" : "Bloch",
      "authorRank" : 2,
      "name" : "Bloch W",
      "referenceId" : "RGD:A65869"
    }, {
      "firstName" : "G",
      "lastName" : "Jacobs",
      "authorRank" : 3,
      "name" : "Jacobs G",
      "referenceId" : "RGD:A94454"
    }, {
      "firstName" : "S",
      "lastName" : "Niggemann",
      "authorRank" : 4,
      "name" : "Niggemann S",
      "referenceId" : "RGD:A94455"
    }, {
      "firstName" : "U",
      "lastName" : "Engelmann",
      "authorRank" : 5,
      "name" : "Engelmann U",
      "referenceId" : "RGD:A94456"
    }, {
      "firstName" : "K",
      "lastName" : "Addicks",
      "authorRank" : 6,
      "name" : "Addicks K",
      "referenceId" : "RGD:A92863"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292089"
    } ]
  }, {
    "primaryId" : "PMID:10475375",
    "title" : "Expression of vascular endothelial growth factor receptors in human prostate cancer.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Ferrer FA, etal., Urology. 1999 Sep;54(3):567-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-02-19T17:54:53.000-06:00",
    "volume" : "54",
    "pages" : "567-72",
    "abstract" : "OBJECTIVES: We recently reported the expression and cytokine regulation of vascular endothelial growth factor (VEGF) in human prostate cancer (PCa). VEGF exerts its angiogenic and pro-tumorigenic properties by way of two high affinity receptors, fms-like tyrosine kinase 1 (FLT-1) and fetal liver kinase 1 (FLK-1). We hypothesized that these receptors are expressed and control VEGF functions in the PCa microenvironment. Herein, we evaluate the expression of these receptors in ex vivo PCa tissue, benign prostatic hypertrophy (BPH) tissue, and cultured PCa cell lines. METHODS: Ex vivo PCa specimens were obtained from patients undergoing radical retropubic prostatectomy. Specimens were selected to contain both PCa and BPH tissue (n = 15). Immunohistochemical analysis using antihuman FLT-1 and FLK-1 was performed and specimens were analyzed to characterize the expression and distribution of both receptors. Immunocytochemical analysis for FLT-1 and FLK-1 was also performed on cultured PCa cell lines (DU-145 and LNCaP). RESULTS: PCa cells expressed the VEGF receptor FLT-1 in 100% of specimens evaluated. Expression of FLK-1 was variable and related to tumor grade; high-grade tumors displayed little or no FLK-1 expression. Vascular endothelial cells (VECs) within areas of PCa consistently expressed both FLT-1 and FLK-1 receptors. FLT-1 and FLK-1 were both expressed in BPH tissue. FLT-1 was expressed in the glandular epithelial cells in BPH, but in most cases FLK-1 was localized specifically to the basal cell layer of hypertrophic glands. FLT-1, but not FLK-1, was expressed by the DU-145 and LNCaP cell lines. CONCLUSIONS: Although they are differentially expressed, both FLT-1 and FLK-1 are present in PCa and BPH. Expression of receptors on VECs of tumor vessels supports the well-established role of VEGF in paracrine stimulation of VECs in the tumor microenvironment. The expression of FLT-1 and FLK-1 on tumor cells themselves suggests a potential autocrine function for VEGF (such as regulating tumor cell proliferation). These findings imply that a novel dual role may exist for VEGF, such that it is involved in tumor cell activation (autocrine), in addition to paracrine actions whereby it regulates endothelial cell functions and subsequent neovascular development.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "FA",
      "lastName" : "Ferrer",
      "authorRank" : 1,
      "name" : "Ferrer FA",
      "referenceId" : "RGD:A92175"
    }, {
      "firstName" : "LJ",
      "lastName" : "Miller",
      "authorRank" : 2,
      "name" : "Miller LJ",
      "referenceId" : "RGD:A92176"
    }, {
      "firstName" : "R",
      "lastName" : "Lindquist",
      "authorRank" : 3,
      "name" : "Lindquist R",
      "referenceId" : "RGD:A92177"
    }, {
      "firstName" : "P",
      "lastName" : "Kowalczyk",
      "authorRank" : 4,
      "name" : "Kowalczyk P",
      "referenceId" : "RGD:A92178"
    }, {
      "firstName" : "VP",
      "lastName" : "Laudone",
      "authorRank" : 5,
      "name" : "Laudone VP",
      "referenceId" : "RGD:A92179"
    }, {
      "firstName" : "PC",
      "lastName" : "Albertsen",
      "authorRank" : 6,
      "name" : "Albertsen PC",
      "referenceId" : "RGD:A92180"
    }, {
      "firstName" : "DL",
      "lastName" : "Kreutzer",
      "authorRank" : 7,
      "name" : "Kreutzer DL",
      "referenceId" : "RGD:A92181"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2289936"
    } ]
  }, {
    "primaryId" : "PMID:10475757",
    "title" : "A novel mutation of the myelin P(o) gene segregating Charcot-Marie-Toothdisease type 1B manifesting as trigeminal nerve thickening.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Shizuka M, etal., J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):250-1.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T20:26:53.000-05:00",
    "volume" : "67",
    "pages" : "250-1",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Shizuka",
      "authorRank" : 1,
      "name" : "Shizuka",
      "referenceId" : "RGD:A267988"
    }, {
      "firstName" : "Y",
      "lastName" : "Ikeda",
      "authorRank" : 2,
      "name" : "Ikeda Y",
      "referenceId" : "RGD:A5269"
    }, {
      "firstName" : "M",
      "lastName" : "Watanabe",
      "authorRank" : 3,
      "name" : "Watanabe",
      "referenceId" : "RGD:A417010"
    }, {
      "firstName" : "K",
      "lastName" : "Okamoto",
      "authorRank" : 4,
      "name" : "Okamoto K",
      "referenceId" : "RGD:A9575"
    }, {
      "firstName" : "M",
      "lastName" : "Shoji",
      "authorRank" : 5,
      "name" : "Shoji M",
      "referenceId" : "RGD:A30760"
    }, {
      "firstName" : "T",
      "lastName" : "Ikegami",
      "authorRank" : 6,
      "name" : "Ikegami",
      "referenceId" : "RGD:A369301"
    }, {
      "firstName" : "K",
      "lastName" : "Hayasaka",
      "authorRank" : 7,
      "name" : "Hayasaka K",
      "referenceId" : "RGD:A52908"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11067399"
    } ]
  }, {
    "primaryId" : "PMID:10477120",
    "title" : "Genetic association between alpha-2 macroglobulin and Japanese sporadic Alzheimer's disease.",
    "datePublished" : "1999-07-01T00:00:00.000-05:00",
    "citation" : "Shibata N, etal., Neurosci Lett. 1999 Aug 20;271(2):132-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-07-01T13:51:14.000-05:00",
    "volume" : "271",
    "pages" : "132-4",
    "abstract" : "Alpha-2 macroglobulin (encoded by the gene A2M) is a serum pan-protease inhibitor that may be related with the pathogenesis of Alzheimer's disease (AD) because of  its ability to mediate amyloid beta degradation. Recently, several groups have reported that the five-nucleotides deletion in A2M gene at the 5' splice site of  exon 18 might increase risk for AD. In the present study, therefore, this mutation was studied in 69 healthy controls and 55 sporadic AD cases by polymerase chain reaction- restriction fragment length polymorphism method. The allelic frequencies with the deletion (A2M-2) are 9.4 and 6.4% in the control and AD groups, respectively. There is no significant difference in the A2M-2 frequencies between the controls and sporadic AD cases. This is the first report  to study the frequencies of A2M-2 in Japanese AD cases, suggesting its no genetic association with sporadic AD.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Shibata",
      "authorRank" : 1,
      "name" : "Shibata N",
      "referenceId" : "RGD:A14713"
    }, {
      "firstName" : "T",
      "lastName" : "Ohnuma",
      "authorRank" : 2,
      "name" : "Ohnuma T",
      "referenceId" : "RGD:A53205"
    }, {
      "firstName" : "T",
      "lastName" : "Takahashi",
      "authorRank" : 3,
      "name" : "Takahashi",
      "referenceId" : "RGD:A415985"
    }, {
      "firstName" : "E",
      "lastName" : "Ohtsuka",
      "authorRank" : 4,
      "name" : "Ohtsuka E",
      "referenceId" : "RGD:A18864"
    }, {
      "firstName" : "A",
      "lastName" : "Ueki",
      "authorRank" : 5,
      "name" : "Ueki",
      "referenceId" : "RGD:A366077"
    }, {
      "firstName" : "H",
      "lastName" : "Arai",
      "authorRank" : 6,
      "name" : "Arai H",
      "referenceId" : "RGD:A9492"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10046013"
    } ]
  }, {
    "primaryId" : "PMID:10477432",
    "title" : "Identification of 12 novel mutations and two new polymorphisms in the arylsulfatase A gene: haplotype and genotype-phenotype correlation studies in Spanish metachromatic leukodystrophy patients.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "Gort L, etal., Hum Mutat. 1999;14(3):240-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T17:57:28.000-05:00",
    "volume" : "14",
    "pages" : "240-8",
    "abstract" : "Arylsulfatase A (ARSA) deficiency is the main cause of metachromatic leukodystrophy (MLD), a lysosomal disorder with no specific treatment. In view of the importance of genetic counseling, analyses of mutations and polymorphisms, including the ARSA pseudodeficiency allele, were carried out in 18 unrelated Spanish MLD patients. A systematic search allowed us to identify 100% of the alleles involving 17 different mutations, 12 of which are novel: G32S, L68P, R84W, P94A, G99V, P136S, W193X, H227Y, R288H, G308D, T327I, and IVS6-12C-->G. Two new polymorphisms, 2033C>T and 2059C>T, were identified in intron 6 which, in combination with two polymorphisms previously described (2161C>G and 2213C>G), gave rise to four different haplotypes in the control population. In addition, we also studied polymorphism 842G>T. Linkage disequilibrium was detected between mutations IVS2+1G-->A, D255H, and T327I and specific haplotypes, suggesting a unique origin for these mutations. Moreover, mutation T327I was always associated with the T allele of the new rare variant A210A (893C>T). The distribution of mutation D255H (frequency 19.4%) among patients with different MLD clinical presentation revealed a clear genotype-phenotype correlation paralleling that reported for mutation IVS2+1G-->A (frequency 25%). Among the novel mutations, only P136S and R288H occurred on a background of the ARSA pseudodeficiency allele. Screening 182 normal chromosomes identified a frequency of 8.8% of this allele; moreover, we identified two unrelated subjects with the polyA- mutation in the absence of the N350S mutation, and this infrequent haplotype reinforced the heterogeneity of conditions with ARSA deficiency.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Gort",
      "authorRank" : 1,
      "name" : "Gort",
      "referenceId" : "RGD:A253722"
    }, {
      "firstName" : "MJ",
      "lastName" : "Coll",
      "authorRank" : 2,
      "name" : "Coll MJ",
      "referenceId" : "RGD:A44116"
    }, {
      "firstName" : "A",
      "lastName" : "Chabas",
      "authorRank" : 3,
      "name" : "Chabas A",
      "referenceId" : "RGD:A44117"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063084"
    } ]
  }, {
    "primaryId" : "PMID:10477434",
    "title" : "Molecular basis of late-life globoid cell leukodystrophy.",
    "datePublished" : "1000-04-01T00:00:00.000-06:00",
    "citation" : "De Gasperi R, etal., Hum Mutat. 1999;14(3):256-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:10:11.000-05:00",
    "volume" : "14",
    "pages" : "256-62",
    "abstract" : "Globoid cell leukodystrophy is an autosomal recessive inherited disease caused by deficiency of the lysosomal enzyme galactocerebrosidase (GALC). Although the severe, rapidly progressing infantile form is the most common, late-onset forms have been described. We investigated the molecular basis of GALC deficiency in a  patient with a late-life mild form of globoid cell leukodystrophy who survived into the eighth decade. Since material suitable for mutation analysis was no longer available from the proband, her GALC genotype was reconstructed by analyzing this gene in her six obligate carrier offspring. One allele contained the mutation 809G>A (G270D) in the 1637C background, while the other allele contained three sequence variants: 1609G>A (G537R), 1873G>A (A625T), and 1650T>A  (V550V) in the 1637T background. These mutations were confirmed in the proband's  genomic DNA isolated from a sural nerve biopsy. Expression studies indicated that the G537R is a disease-causing mutation, as it resulted in no GALC activity, either alone or together with the A625T. This A625T sequence variant did not affect the enzyme activity, at least when expressed in the 1637T background. The  mild clinical phenotype was likely to be associated with the 809G>A, since residual GALC activity, about 17% of the control activity, was detected in the expression studies of this mutation. This mutation has been found in several other patients with late-onset GLD.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "De Gasperi",
      "authorRank" : 1,
      "name" : "De Gasperi R",
      "referenceId" : "RGD:A63622"
    }, {
      "firstName" : "MA",
      "lastName" : "Gama Sosa",
      "authorRank" : 2,
      "name" : "Gama Sosa MA",
      "referenceId" : "RGD:A140887"
    }, {
      "firstName" : "E",
      "lastName" : "Sartorato",
      "authorRank" : 3,
      "name" : "Sartorato",
      "referenceId" : "RGD:A271337"
    }, {
      "firstName" : "S",
      "lastName" : "Battistini",
      "authorRank" : 4,
      "name" : "Battistini S",
      "referenceId" : "RGD:A157086"
    }, {
      "firstName" : "S",
      "lastName" : "Raghavan",
      "authorRank" : 5,
      "name" : "Raghavan S",
      "referenceId" : "RGD:A142078"
    }, {
      "firstName" : "EH",
      "lastName" : "Kolodny",
      "authorRank" : 6,
      "name" : "Kolodny EH",
      "referenceId" : "RGD:A140888"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068504"
    } ]
  }, {
    "primaryId" : "PMID:10477457",
    "title" : "C677T substitution in the methylenetetrahydrofolate reductase gene as a risk factor for venous thrombosis and arterial disease in selected patients.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Gemmati D, etal., Haematologica. 1999 Sep;84(9):824-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-12-29T10:18:18.000-06:00",
    "volume" : "84",
    "pages" : "824-8",
    "abstract" : "BACKGROUND AND OBJECTIVE: Hyperhomocysteinemia, due to a combination of genetic and environmental factors, is considered to be a risk factor for vascular disease. Individuals with the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR), due to homozygous C677T MTHFR gene mutation, have significantly raised plasma levels of homocysteine and may be at increased risk of vascular disease. However, it is still controversial a direct association between C677T homozygosity and the occurrence of vascular disease is still controversial. DESIGN AND METHODS: To clarify the contribution of C677T MTHFR mutation in arterial occlusive disease (AOD) or venous thromboembolism (VTE), we  performed a case-controlled study including 160 cases with AOD and 180 cases with VTE attending our referral center and compared them with 200 matched healthy controls. MTHFR gene mutation was evaluated by PCR and odds ratios (OR) and the 95% confidence intervals (CI) were used to estimate the risk for venous or arterial thrombosis. RESULTS: There was a high prevalence of homozygotes for the  mutated MTHFR allele among the whole group of cases with arterial disease (OR = 2.35, p = 0.001). Considering the AOD cases with and those without associated risk factors for arterial disease separately the difference remained significant  only in the latter group (p = 0.168 and P<0.001 respectively). In contrast, the prevalence of mutated homozygotes among the whole group of cases with VTE was not significantly different from that in the control group (OR = 1.67; p = 0.070). Excluding VTE cases with inherited thrombophilia or with circumstantial risk situations the value increased in both subgroups (OR = 2.26; p = 0.006 and OR = 2.03; p = 0.033 respectively). Considering only VTE cases with neither inherited  thrombophilia nor circumstantial risk situations the risk increased further (OR = 2.57; p = 0.017). INTERPRETATION AND CONCLUSIONS: These data suggest that in selected patients homozygosity for the MTHFR mutation increases the risk of both  arterial and venous thromboses and that differences in selection criteria for the patient group may be responsible in part for the controversial association of the MTHFR mutation and vascular disease.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Gemmati",
      "authorRank" : 1,
      "name" : "Gemmati D",
      "referenceId" : "RGD:A65190"
    }, {
      "firstName" : "ML",
      "lastName" : "Serino",
      "authorRank" : 2,
      "name" : "Serino ML",
      "referenceId" : "RGD:A65191"
    }, {
      "firstName" : "C",
      "lastName" : "Trivellato",
      "authorRank" : 3,
      "name" : "Trivellato",
      "referenceId" : "RGD:A209618"
    }, {
      "firstName" : "S",
      "lastName" : "Fiorini",
      "authorRank" : 4,
      "name" : "Fiorini",
      "referenceId" : "RGD:A209619"
    }, {
      "firstName" : "GL",
      "lastName" : "Scapoli",
      "authorRank" : 5,
      "name" : "Scapoli GL",
      "referenceId" : "RGD:A65197"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10449401"
    } ]
  }, {
    "primaryId" : "PMID:10477520",
    "title" : "Differential stimulation of PKC phosphorylation of potassium channels by ZIP1 and ZIP2.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Gong J, etal., Science. 1999 Sep 3;285(5433):1565-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-10-09T15:03:14.000-05:00",
    "volume" : "285",
    "pages" : "1565-9",
    "abstract" : "Targeting of protein modification enzymes is a key biochemical step to achieve specific and effective posttranslational modifications. Two alternatively spliced ZIP1 and ZIP2 proteins are described, which bind to both Kvbeta2 subunits of potassium channel and protein kinase C (PKC) zeta, thereby acting as a physical link in the assembly of PKCzeta-ZIP-potassium channel complexes. ZIP1 and ZIP2 differentially stimulate phosphorylation of Kvbeta2 by PKCzeta. They also interact to form heteromultimers, which allows for a hybrid stimulatory activity to PKCzeta. Finally, ZIP1 and ZIP2 coexist in the same cell type and are elevated differentially by neurotrophic factors. These results provide a mechanism for specificity and regulation of PKCzeta-targeted phosphorylation.",
    "issueName" : "5433",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Gong",
      "authorRank" : 1,
      "name" : "Gong J",
      "referenceId" : "RGD:A28486"
    }, {
      "firstName" : "J",
      "lastName" : "Xu",
      "authorRank" : 2,
      "name" : "Xu J",
      "referenceId" : "RGD:A162581"
    }, {
      "firstName" : "M",
      "lastName" : "Bezanilla",
      "authorRank" : 3,
      "name" : "Bezanilla M",
      "referenceId" : "RGD:A88787"
    }, {
      "firstName" : "R",
      "lastName" : "Van Huizen",
      "authorRank" : 4,
      "name" : "Van Huizen R",
      "referenceId" : "RGD:A42210"
    }, {
      "firstName" : "R",
      "lastName" : "Derin",
      "authorRank" : 5,
      "name" : "Derin R",
      "referenceId" : "RGD:A11935"
    }, {
      "firstName" : "M",
      "lastName" : "Li",
      "authorRank" : 6,
      "name" : "Li M",
      "referenceId" : "RGD:A5679"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1642693"
    } ]
  }, {
    "primaryId" : "PMID:10477557",
    "title" : "Studies in B7-deficient mice reveal a critical role for B7 costimulation in both induction and effector phases of experimental autoimmune encephalomyelitis.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Chang TT, etal., J Exp Med. 1999 Sep 6;190(5):733-40.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-02-15T09:15:38.000-06:00",
    "volume" : "190",
    "pages" : "733-40",
    "abstract" : "The importance of B7 costimulation in regulating T cell expansion and peripheral tolerance suggests that it may also play a significant regulatory role in the development of autoimmune disease. It is unclear whether B7 costimulation is involved only in the expansion of autoreactive T cells in the periphery, or if it is also required for effector activation of autoreactive T cells in the target organ for mediating tissue injury and propagating autoimmune disease. In this study, the role of B7-CD28 costimulation and the relative importance of B7 costimulators for the induction and effector phases of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) peptide were examined. Wild-type, B7-1/B7-2-deficient mice, or CD28-deficient C57BL/6 mice were immunized with MOG 35-55 peptide. Mice lacking both B7-1 and B7-2 or CD28 showed no or minimal clinical signs of EAE and markedly reduced inflammatory infiltrates in the brain and spinal cord. However, mice lacking either B7-1 or B7-2 alone developed clinical and pathologic EAE that was comparable to EAE in wild-type mice, indicating overlapping functions for B7-1 and B7-2. Resistance to EAE was not due to a lack of induction of T helper type 1 (Th1) cytokines, since T cells from B7-1/B7-2(-/-) mice show reduced proliferative responses, but greater interferon gamma production compared with T cells from wild-type mice. To study the role of B7 molecules in the effector phase of the disease, MOG 35-55-specific T lines were adoptively transferred into the B7-1/B7-2(-/-) and wild-type mice. Clinical and histologic EAE were markedly reduced in B7-1/B7-2(-/-) compared with wild-type recipient mice. These results demonstrate that B7 costimulation has critical roles not only in the initial activation and expansion of MOG-reactive T cells, but also in the effector phase of encephalitogenic T cell activation within the central nervous system.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "TT",
      "lastName" : "Chang",
      "authorRank" : 1,
      "name" : "Chang TT",
      "referenceId" : "RGD:A120956"
    }, {
      "firstName" : "C",
      "lastName" : "Jabs",
      "authorRank" : 2,
      "name" : "Jabs C",
      "referenceId" : "RGD:A134690"
    }, {
      "firstName" : "RA",
      "lastName" : "Sobel",
      "authorRank" : 3,
      "name" : "Sobel RA",
      "referenceId" : "RGD:A66340"
    }, {
      "firstName" : "VK",
      "lastName" : "Kuchroo",
      "authorRank" : 4,
      "name" : "Kuchroo VK",
      "referenceId" : "RGD:A136591"
    }, {
      "firstName" : "AH",
      "lastName" : "Sharpe",
      "authorRank" : 5,
      "name" : "Sharpe AH",
      "referenceId" : "RGD:A82236"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:4892227"
    } ]
  }, {
    "primaryId" : "PMID:10477596",
    "title" : "Selective diapedesis of Th1 cells induced by endothelial cell RANTES.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Kawai T, etal., J Immunol. 1999 Sep 15;163(6):3269-78.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:35:30.000-05:00",
    "volume" : "163",
    "pages" : "3269-78",
    "abstract" : "Differentiated CD4 T cells can be divided into Th1 and Th2 types based on the cytokines they produce. Differential expression of chemokine receptors on either  the Th1-type or the Th2-type cell suggests that Th1-type and Th2-type cells differ not only in cytokine production but also in their migratory capacity. Stimulation of endothelial cells with IFN-gamma selectively enhanced transmigration of Th1-type cells, but not Th2-type cells, in a transendothelial migration assay. Enhanced transmigration of Th1-type cells was dependent on the chemokine RANTES produced by endothelial cells, as indicated by the findings that Ab neutralizing RANTES, or Ab to its receptor CCR5, inhibited transmigration. Neutralizing Ab to chemokines macrophage-inflammatory protein-1alpha or monocyte  chemotactic protein-1 did not inhibit Th1 selective migration. Whereas anti-CD18  and anti-CD54 blocked basal levels of Th1-type cell adherence to endothelial cells and also inhibited transmigration, anti-RANTES blocked only transmigration, indicating that RANTES appeared to induce transmigration of adherent T cells. RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor. Thus, enhancement of Th1-type selective migration appeared to be responsible for the diapedesis induced by interaction between CCR5 on Th1-type cells and RANTES produced by endothelial cells. Further evidence that CCR5 and RANTES play a modulatory role in Th1-type selective migration derives from the abrogation of this migration by anti-RANTES and anti-CCR5 Abs.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Kawai",
      "authorRank" : 1,
      "name" : "Kawai T",
      "referenceId" : "RGD:A16409"
    }, {
      "firstName" : "M",
      "lastName" : "Seki",
      "authorRank" : 2,
      "name" : "Seki M",
      "referenceId" : "RGD:A15591"
    }, {
      "firstName" : "K",
      "lastName" : "Hiromatsu",
      "authorRank" : 3,
      "name" : "Hiromatsu",
      "referenceId" : "RGD:A184614"
    }, {
      "firstName" : "JW",
      "lastName" : "Eastcott",
      "authorRank" : 4,
      "name" : "Eastcott JW",
      "referenceId" : "RGD:A158245"
    }, {
      "firstName" : "GF",
      "lastName" : "Watts",
      "authorRank" : 5,
      "name" : "Watts GF",
      "referenceId" : "RGD:A79626"
    }, {
      "firstName" : "M",
      "lastName" : "Sugai",
      "authorRank" : 6,
      "name" : "Sugai M",
      "referenceId" : "RGD:A18461"
    }, {
      "firstName" : "DJ",
      "lastName" : "Smith",
      "authorRank" : 7,
      "name" : "Smith DJ",
      "referenceId" : "RGD:A113719"
    }, {
      "firstName" : "SA",
      "lastName" : "Porcelli",
      "authorRank" : 8,
      "name" : "Porcelli SA",
      "referenceId" : "RGD:A93226"
    }, {
      "firstName" : "MA",
      "lastName" : "Taubman",
      "authorRank" : 9,
      "name" : "Taubman MA",
      "referenceId" : "RGD:A158246"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8553666"
    } ]
  }, {
    "primaryId" : "PMID:10477710",
    "title" : "Identification of the molecular genetic defect of patients with methemoglobin M-Kankakee (M-Iwate), alpha87 (F8) His --> Tyr: evidence for an electrostatic model of alphaM hemoglobin assembly.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Ameri A, etal., Blood. 1999 Sep 1;94(5):1825-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-03-27T16:09:48.000-05:00",
    "volume" : "94",
    "pages" : "1825-6",
    "abstract" : "We determined that the molecular defect of 2 patients with hemoglobin (Hb) M-Kankakee [Hb M-Iwate, alpha87 (F8) His --> Tyr] resides in the alpha1-globin gene. The proportion of Hb M observed is higher than that predicted for an alpha1-globin variant. Our evidence suggests that the greater-than-expected proportion of Hb M-Kankakee results from preferential association of the electronegative beta-globin chains with the alpha(M)-globin chains that are more electropositive than normal alpha-globin chains.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Ameri",
      "authorRank" : 1,
      "name" : "Ameri A",
      "referenceId" : "RGD:A78525"
    }, {
      "firstName" : "VF",
      "lastName" : "Fairbanks",
      "authorRank" : 2,
      "name" : "Fairbanks VF",
      "referenceId" : "RGD:A78526"
    }, {
      "firstName" : "GA",
      "lastName" : "Yanik",
      "authorRank" : 3,
      "name" : "Yanik GA",
      "referenceId" : "RGD:A78527"
    }, {
      "firstName" : "F",
      "lastName" : "Mahdi",
      "authorRank" : 4,
      "name" : "Mahdi F",
      "referenceId" : "RGD:A78528"
    }, {
      "firstName" : "SN",
      "lastName" : "Thibodeau",
      "authorRank" : 5,
      "name" : "Thibodeau SN",
      "referenceId" : "RGD:A37105"
    }, {
      "firstName" : "DJ",
      "lastName" : "McCormick",
      "authorRank" : 6,
      "name" : "McCormick DJ",
      "referenceId" : "RGD:A78529"
    }, {
      "firstName" : "LA",
      "lastName" : "Boxer",
      "authorRank" : 7,
      "name" : "Boxer LA",
      "referenceId" : "RGD:A78530"
    }, {
      "firstName" : "KT",
      "lastName" : "McDonagh",
      "authorRank" : 8,
      "name" : "McDonagh KT",
      "referenceId" : "RGD:A78531"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1600805"
    } ]
  }, {
    "primaryId" : "PMID:10477717",
    "title" : "Macrophage-derived chemokine is localized to thymic medullary epithelial cells and is a chemoattractant for CD3(+), CD4(+), CD8(low) thymocytes.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Chantry D, etal., Blood 1999 Sep 15;94(6):1890-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:25.000-05:00",
    "volume" : "94",
    "pages" : "1890-8",
    "abstract" : "Macrophage-derived chemokine (MDC) is a recently identified CC chemokine that is a potent chemoattractant for dendritic cells, natural killer (NK) cells, and the Th2 subset of peripheral blood T cells. In normal tissues, MDC mRNA is expressed principally in the thymus. Immunohistochemical analysis performed on 5 human postnatal thymuses showed high MDC immunoreactivity, which was selectively localized to epithelial cells within the medulla. To examine the effects of MDC on immature T cells, we have identified cDNA clones for mouse and rat MDC. Expression of MDC in murine tissues is also highly restricted, with significant levels of mRNA found only in the thymus. Thymocytes express high-affinity binding sites for MDC (kd = 0.7 nmol/L), and, in vitro, MDC is a chemoattractant for these cells. MDC-responsive murine thymocytes express mRNA for CCR4, a recently identified receptor for MDC. Phenotypic analysis of MDC-responsive cells shows that they are enriched for a subset of double-positive cells that express high levels of CD3 and CD4 and that have reduced levels of CD8. This subset of MDC-responsive cells is consistent with the observed expression of MDC within the medulla, because more mature cells are found there. MDC may therefore play a role in the migration of T-cell subsets during development within the thymus.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "D",
      "lastName" : "Chantry",
      "authorRank" : 1,
      "name" : "Chantry D",
      "referenceId" : "RGD:A17290"
    }, {
      "firstName" : "P",
      "lastName" : "Romagnani",
      "authorRank" : 2,
      "name" : "Romagnani P",
      "referenceId" : "RGD:A17291"
    }, {
      "firstName" : "CJ",
      "lastName" : "Raport",
      "authorRank" : 3,
      "name" : "Raport CJ",
      "referenceId" : "RGD:A17292"
    }, {
      "firstName" : "CL",
      "lastName" : "Wood",
      "authorRank" : 4,
      "name" : "Wood CL",
      "referenceId" : "RGD:A17293"
    }, {
      "firstName" : "A",
      "lastName" : "Epp",
      "authorRank" : 5,
      "name" : "Epp A",
      "referenceId" : "RGD:A17294"
    }, {
      "firstName" : "S",
      "lastName" : "Romagnani",
      "authorRank" : 6,
      "name" : "Romagnani S",
      "referenceId" : "RGD:A17295"
    }, {
      "firstName" : "PW",
      "lastName" : "Gray",
      "authorRank" : 7,
      "name" : "Gray PW",
      "referenceId" : "RGD:A7166"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:632422"
    } ]
  }, {
    "primaryId" : "PMID:10477728",
    "title" : "Osteoclast-derived zinc finger (OCZF) protein with POZ domain, a possible transcriptional repressor, is involved in osteoclastogenesis.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Kukita A, etal., Blood 1999 Sep 15;94(6):1987-97.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-05-25T09:10:11.000-05:00",
    "volume" : "94",
    "pages" : "1987-97",
    "abstract" : "The differentiation of osteoclasts is regulated by transcription factors expressed in cells of osteoclast lineage. We isolated here a potential transcription factor from a cDNA library of an enriched population of preosteoclasts and osteoclasts. The cDNA encodes a protein with N-terminal POZ domain and C-terminal Kruppel-like zinc fingers. We designate this protein as osteoclast-derived zinc finger (OCZF). OCZF was found to be rat homologue of mouse leukemia/lymphoma-related factor (LRF). Northern blot and in situ hybridization analysis showed OCZF mRNA at a high level in osteoclasts and kidney cells. OCZF had a nuclear targeting sequence and was localized in the nucleus of transfected cells. In addition, OCZF specifically bound to the guanine-rich consensus sequences of Egr-1 and c-Krox. Transient transfection assays indicate that OCZF can repress transcription activity like other POZ domain proteins. Furthermore, antisense but not sense phosphorothioate oligodeoxynucleotides (ODNs) for OCZF cDNA suppressed the formation of osteoclast-like multinucleated cells (MNCs) in bone marrow culture, whereas the same ODNs did not significantly affect the formation of macrophage polykaryons and mononuclear preosteoclast-like cells (POCs). These results suggest that OCZF is a unique transcription factor that plays an important role in the late stage of osteoclastogenesis.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Kukita",
      "authorRank" : 1,
      "name" : "Kukita A",
      "referenceId" : "RGD:A20482"
    }, {
      "firstName" : "T",
      "lastName" : "Kukita",
      "authorRank" : 2,
      "name" : "Kukita T",
      "referenceId" : "RGD:A20483"
    }, {
      "firstName" : "M",
      "lastName" : "Ouchida",
      "authorRank" : 3,
      "name" : "Ouchida M",
      "referenceId" : "RGD:A20484"
    }, {
      "firstName" : "H",
      "lastName" : "Maeda",
      "authorRank" : 4,
      "name" : "Maeda H",
      "referenceId" : "RGD:A20485"
    }, {
      "firstName" : "H",
      "lastName" : "Yatsuki",
      "authorRank" : 5,
      "name" : "Yatsuki H",
      "referenceId" : "RGD:A16622"
    }, {
      "firstName" : "O",
      "lastName" : "Kohashi",
      "authorRank" : 6,
      "name" : "Kohashi O",
      "referenceId" : "RGD:A20486"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:633299"
    } ]
  }, {
    "primaryId" : "PMID:10477737",
    "title" : "The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Hussey DJ, etal., Blood. 1999 Sep 15;94(6):2072-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-02-11T16:02:11.000-06:00",
    "volume" : "94",
    "pages" : "2072-9",
    "abstract" : "We determined the breakpoint genes of the translocation t(4;11)(q21;p15) that occurred in a case of adult T-cell acute lymphocytic leukemia (T-ALL). The chromosome 11 breakpoint was mapped to the region between D11S470 and D11S860. The nucleoporin 98 gene (NUP98), which is rearranged in several acute myeloid leukemia translocations, is located within this region. Analysis of somatic cell  hybrids segregating the translocation chromosomes showed that the chromosome 11 breakpoint occurs within NUP98. The fusion partner of NUP98 was identified as the RAP1GDS1 gene using 3' RACE. RAP1GDS1 codes for smgGDS, a ubiquitously expressed  guanine nucleotide exchange factor that stimulates the conversion of the inactive GDP-bound form of several ras family small GTPases to the active GTP-bound form.  In the NUP98-RAP1GDS1 fusion transcript (abbreviated as NRG), the 5' end of the NUP98 gene is joined in frame to the coding region of the RAP1GDS1 gene. This joins the FG repeat-rich region of NUP98 to RAP1GDS1, which largely consists of tandem armadillo repeats. NRG fusion transcripts were detected in the leukemic cells of 2 other adult T-ALL patients. One of these patients had a variant translocation with a more 5' breakpoint in NUP98. This is the first report of an  NUP98 translocation in lymphocytic leukemia and the first time that RAP1GDS1 has  been implicated in any human malignancy.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Hussey",
      "authorRank" : 1,
      "name" : "Hussey",
      "referenceId" : "RGD:A199043"
    }, {
      "firstName" : "M",
      "lastName" : "Nicola",
      "authorRank" : 2,
      "name" : "Nicola",
      "referenceId" : "RGD:A199044"
    }, {
      "firstName" : "S",
      "lastName" : "Moore",
      "authorRank" : 3,
      "name" : "Moore",
      "referenceId" : "RGD:A199045"
    }, {
      "firstName" : "GB",
      "lastName" : "Peters",
      "authorRank" : 4,
      "name" : "Peters",
      "referenceId" : "RGD:A199046"
    }, {
      "firstName" : "A",
      "lastName" : "Dobrovic",
      "authorRank" : 5,
      "name" : "Dobrovic A",
      "referenceId" : "RGD:A96047"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9693698"
    } ]
  }, {
    "primaryId" : "PMID:10477754",
    "title" : "Gamma-synergin: an EH domain-containing protein that interacts with gamma-adaptin.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Page LJ, etal., J Cell Biol 1999 Sep 6;146(5):993-1004.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-21T16:22:56.000-05:00",
    "volume" : "146",
    "pages" : "993-1004",
    "abstract" : "The AP-1 adaptor complex is associated with the TGN, where it links selected membrane proteins to the clathrin lattice, enabling these proteins to be concentrated in clathrin-coated vesicles. To identify other proteins that participate in the clathrin-coated vesicle cycle at the TGN, we have carried out a yeast two- hybrid library screen using the gamma-adaptin subunit of the AP-1 complex as bait. Two novel, ubiquitously expressed proteins were found: p34, which interacts with both gamma-adaptin and alpha-adaptin, and gamma-synergin, an alternatively spliced protein with an apparent molecular mass of approximately 110-190 kD, which only interacts with gamma-adaptin. gamma-Synergin is associated with AP-1 both in the cytosol and on TGN membranes, and it is strongly enriched in clathrin-coated vesicles. It binds directly to the ear domain of gamma-adaptin and it contains an Eps15 homology (EH) domain, although the EH domain is not part of the gamma-adaptin binding site. In cells expressing alpha-adaptin with the gamma-adaptin ear, a construct that goes mainly to the plasma membrane, much of the gamma-synergin is also rerouted to the plasma membrane, indicating that it follows AP-1 onto membranes rather than leading it there. The presence of an EH domain suggests that gamma-synergin links the AP-1 complex to another protein or proteins.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LJ",
      "lastName" : "Page",
      "authorRank" : 1,
      "name" : "Page LJ",
      "referenceId" : "RGD:A15845"
    }, {
      "firstName" : "PJ",
      "lastName" : "Sowerby",
      "authorRank" : 2,
      "name" : "Sowerby PJ",
      "referenceId" : "RGD:A15846"
    }, {
      "firstName" : "WW",
      "lastName" : "Lui",
      "authorRank" : 3,
      "name" : "Lui WW",
      "referenceId" : "RGD:A15847"
    }, {
      "firstName" : "MS",
      "lastName" : "Robinson",
      "authorRank" : 4,
      "name" : "Robinson MS",
      "referenceId" : "RGD:A6985"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:631945"
    } ]
  }, {
    "primaryId" : "PMID:10477767",
    "title" : "CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Sun L, etal., J Cell Biol. 1999 Sep 6;146(5):1161-72.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2009-05-26T12:11:10.000-05:00",
    "volume" : "146",
    "pages" : "1161-72",
    "abstract" : "The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr). The latter gates Ca(2+) release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library. The predicted amino acid sequence displayed 59, 59, and 50% similarity, respectively, to the mouse, rat, and human CD38. In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts, confirming CD38 mRNA expression. Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CD38 protein. The ADP-ribosyl cyclase activity of osteoclastic CD38 was next demonstrated by its ability to cyclize the NAD(+) surrogate, NGD(+), to its fluorescent derivative cGDP-ribose. We then examined the effects of CD38 on osteoclast function. CD38 activation by an agonist antibody (A10) in the presence of substrate (NAD(+)) triggered a cytosolic Ca(2+) signal. Both ryanodine receptor modulators, ryanodine, and caffeine, markedly attenuated this cytosolic Ca(2+) change. Furthermore, the anti-CD38 agonist antibody expectedly inhibited bone resorption in the pit assay and elevated interleukin-6 (IL-6) secretion. IL-6, in turn, enhanced CD38 mRNA expression. Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr.",
    "issueName" : "5",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "L",
      "lastName" : "Sun",
      "authorRank" : 1,
      "name" : "Sun L",
      "referenceId" : "RGD:A11341"
    }, {
      "firstName" : "OA",
      "lastName" : "Adebanjo",
      "authorRank" : 2,
      "name" : "Adebanjo OA",
      "referenceId" : "RGD:A107413"
    }, {
      "firstName" : "BS",
      "lastName" : "Moonga",
      "authorRank" : 3,
      "name" : "Moonga BS",
      "referenceId" : "RGD:A107414"
    }, {
      "firstName" : "S",
      "lastName" : "Corisdeo",
      "authorRank" : 4,
      "name" : "Corisdeo S",
      "referenceId" : "RGD:A107415"
    }, {
      "firstName" : "HK",
      "lastName" : "Anandatheerthavarada",
      "authorRank" : 5,
      "name" : "Anandatheerthavarada HK",
      "referenceId" : "RGD:A43978"
    }, {
      "firstName" : "G",
      "lastName" : "Biswas",
      "authorRank" : 6,
      "name" : "Biswas G",
      "referenceId" : "RGD:A43981"
    }, {
      "firstName" : "T",
      "lastName" : "Arakawa",
      "authorRank" : 7,
      "name" : "Arakawa T",
      "referenceId" : "RGD:A299768"
    }, {
      "firstName" : "Y",
      "lastName" : "Hakeda",
      "authorRank" : 8,
      "name" : "Hakeda Y",
      "referenceId" : "RGD:A107416"
    }, {
      "firstName" : "A",
      "lastName" : "Koval",
      "authorRank" : 9,
      "name" : "Koval A",
      "referenceId" : "RGD:A107417"
    }, {
      "firstName" : "B",
      "lastName" : "Sodam",
      "authorRank" : 10,
      "name" : "Sodam B",
      "referenceId" : "RGD:A107418"
    }, {
      "firstName" : "PJ",
      "lastName" : "Bevis",
      "authorRank" : 11,
      "name" : "Bevis PJ",
      "referenceId" : "RGD:A107419"
    }, {
      "firstName" : "AJ",
      "lastName" : "Moser",
      "authorRank" : 12,
      "name" : "Moser AJ",
      "referenceId" : "RGD:A107420"
    }, {
      "firstName" : "FA",
      "lastName" : "Lai",
      "authorRank" : 13,
      "name" : "Lai FA",
      "referenceId" : "RGD:A57096"
    }, {
      "firstName" : "S",
      "lastName" : "Epstein",
      "authorRank" : 14,
      "name" : "Epstein S",
      "referenceId" : "RGD:A107421"
    }, {
      "firstName" : "BR",
      "lastName" : "Troen",
      "authorRank" : 15,
      "name" : "Troen BR",
      "referenceId" : "RGD:A107422"
    }, {
      "firstName" : "M",
      "lastName" : "Kumegawa",
      "authorRank" : 16,
      "name" : "Kumegawa M",
      "referenceId" : "RGD:A107423"
    }, {
      "firstName" : "M",
      "lastName" : "Zaidi",
      "authorRank" : 17,
      "name" : "Zaidi M",
      "referenceId" : "RGD:A107424"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2307268"
    } ]
  }, {
    "primaryId" : "PMID:10478824",
    "title" : "Activity of cathepsin G, elastase, and their inhibitors in plasma during methanol intoxication.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Skrzydlewska E, etal., J Toxicol Environ Health A. 1999 Jul 23;57(6):431-42.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2008-04-08T17:57:34.000-05:00",
    "volume" : "57",
    "pages" : "431-42",
    "abstract" : "Methanol oxidation in the liver is accompanied by formation of formaldehyde and free radicals. These compounds can react with biologically active proteins, including proteolytic enzymes and their inhibitors. The activity of cathepsin G and elastase and their inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in plasma of rats given methanol orally in doses of 1.5, 3, and 6 g/kg was investigated for 7 days. The activity of cathepsin G and elastase was increased from 12 h to 5 d, proportionally to methanol dose. At the same time, activity of their inhibitors was reduced. Methanol ingestion in humans caused changes in activities of proteases and their inhibitors with similar direction as in rats. These changes in activity of proteases and their inhibitors produce significant disturbances in proteolytic-antiproteolytic balance after methanol administration.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "E",
      "lastName" : "Skrzydlewska",
      "authorRank" : 1,
      "name" : "Skrzydlewska E",
      "referenceId" : "RGD:A94258"
    }, {
      "firstName" : "M",
      "lastName" : "Szmitkowski",
      "authorRank" : 2,
      "name" : "Szmitkowski M",
      "referenceId" : "RGD:A94259"
    }, {
      "firstName" : "R",
      "lastName" : "Farbiszewski",
      "authorRank" : 3,
      "name" : "Farbiszewski R",
      "referenceId" : "RGD:A94260"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2292013"
    } ]
  }, {
    "primaryId" : "PMID:10479455",
    "title" : "NT4/5 mutant mice have deficiency in gustatory papillae and taste bud formation.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Liebl DJ, etal., Dev Biol. 1999 Sep 15;213(2):378-89.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2014-05-08T16:39:12.000-05:00",
    "volume" : "213",
    "pages" : "378-89",
    "abstract" : "Neurotrophins are key determinants for controlling the survival of peripheral neurons during development. Brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4/5) exert their action through a common trkB receptor but independently support gustatory sensory neurons. To assess the role of NT4/5 during development, we examined the postnatal development and maintenance of fungiform taste buds in mice carrying a deletion of NT4/5. The absence of NT4/5 results in embryonic deficits in gustatory innervation and a reduced number of fungiform papillae at birth. No degenerative deficits of fungiform papillae were  observed for the first 3 weeks of postnatal development. However, these remaining fungiform papillae were smaller in appearance and many did not contain taste pores. By postnatal day 60, there was 63% decrease in the number of fungiform papillae, and remaining papillae were smaller in size or modified into filiform-like spines. These papillae had either no taste bud or a taste bud with  a reduced number of taste cells compared to controls. These findings demonstrate  that the NT4/5 gene functions in the maintenance of fungiform gustatory papillae  and raises the possibility for an earlier role in development.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DJ",
      "lastName" : "Liebl",
      "authorRank" : 1,
      "name" : "Liebl",
      "referenceId" : "RGD:A185467"
    }, {
      "firstName" : "JP",
      "lastName" : "Mbiene",
      "authorRank" : 2,
      "name" : "Mbiene",
      "referenceId" : "RGD:A185468"
    }, {
      "firstName" : "LF",
      "lastName" : "Parada",
      "authorRank" : 3,
      "name" : "Parada LF",
      "referenceId" : "RGD:A13864"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:8554019"
    } ]
  }, {
    "primaryId" : "PMID:10479481",
    "title" : "The mutant genotype is the main determinant of the metabolic phenotype in phenylalanine hydroxylase deficiency.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Benit P, etal., Mol Genet Metab. 1999 Sep;68(1):43-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:12:59.000-05:00",
    "volume" : "68",
    "pages" : "43-7",
    "abstract" : "Phenylketonuria and mild hyperphenylalaninemias are allelic disorders caused by mutations in the phenylalanine hydroxylase (PAH) gene. Following identification of the disease-causing mutation in 11 PAH-deficient patients, we tested the activity of the mutant gene products in an eukaryotic expression system. Two mutations markedly reduced PAH activity (A259V and L333F), one mutation mildly altered the enzyme activity (E390G), while the majority of mutant genotypes reduced the in vitro expression of PAH activity to 15-30% of controls. Comparing  the predicted residual activity derived from expression studies to the clinical phenotypes of our PAH-deficient patients, we found that homozygosity for the L333F and E390G mutations resulted in severe and mild PAH deficiencies, respectively, both in vivo and in vitro, while compound heterozygosity (L333F/E390G) resulted in an intermediate dietary tolerance. Similarly, in vitro  expression studies largely predicted dietary tolerance in compound heterozygotes  for the A259V/IVS12nt1 (typical PKU), A259V/A403V, G218V/I65T, and G218V/R158Q mutations (mild variants). Taken together, these results support the view that expression studies are useful in predicting residual enzyme activity and that the mutant genotype at the PAH locus is the major determinant of metabolic phenotype  in hyperphenylalaninemias.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "P",
      "lastName" : "Benit",
      "authorRank" : 1,
      "name" : "Benit P",
      "referenceId" : "RGD:A57106"
    }, {
      "firstName" : "F",
      "lastName" : "Rey",
      "authorRank" : 2,
      "name" : "Rey",
      "referenceId" : "RGD:A254837"
    }, {
      "firstName" : "F",
      "lastName" : "Blandin-Savoja",
      "authorRank" : 3,
      "name" : "Blandin-Savoja",
      "referenceId" : "RGD:A262751"
    }, {
      "firstName" : "A",
      "lastName" : "Munnich",
      "authorRank" : 4,
      "name" : "Munnich A",
      "referenceId" : "RGD:A26324"
    }, {
      "firstName" : "V",
      "lastName" : "Abadie",
      "authorRank" : 5,
      "name" : "Abadie V",
      "referenceId" : "RGD:A78995"
    }, {
      "firstName" : "J",
      "lastName" : "Rey",
      "authorRank" : 6,
      "name" : "Rey",
      "referenceId" : "RGD:A254843"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11065700"
    } ]
  }, {
    "primaryId" : "PMID:10479499",
    "title" : "Mutational analysis of the PMS2 gene in sporadic endometrial cancers with microsatellite instability.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Basil JB, etal., Gynecol Oncol. 1999 Sep;74(3):395-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:29:12.000-05:00",
    "volume" : "74",
    "pages" : "395-9",
    "abstract" : "OBJECTIVE: Approximately 20% of endometrial tumors have a defect in DNA mismatch  repair and exhibit microsatellite instability (MSI). We assessed the role of the  PMS2 DNA mismatch repair gene in MSI-positive sporadic endometrial tumors. METHODS: We examined 40 sporadic endometrial tumor specimens with MSI. All 15 exons of the PMS2 gene were investigated for sequence alterations by single-strand conformational variant analysis. RESULTS: Twelve polymorphisms were identified, 8 of which were in the coding sequence. Four specimens revealed mutations in intronic sequences that are not predicted to affect the PMS2 mRNA. No mutations were detected within the coding region of the PMS2 gene. CONCLUSION: We conclude that structural mutations in the PMS2 gene are not responsible for defective DNA mismatch repair in sporadic endometrial cancers with MSI. The identification of single nucleotide polymorphisms in the PMS2 locus may aid in the mapping and characterization of genetic diseases.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "JB",
      "lastName" : "Basil",
      "authorRank" : 1,
      "name" : "Basil",
      "referenceId" : "RGD:A272383"
    }, {
      "firstName" : "EM",
      "lastName" : "Swisher",
      "authorRank" : 2,
      "name" : "Swisher",
      "referenceId" : "RGD:A205015"
    }, {
      "firstName" : "TJ",
      "lastName" : "Herzog",
      "authorRank" : 3,
      "name" : "Herzog",
      "referenceId" : "RGD:A272384"
    }, {
      "firstName" : "JS",
      "lastName" : "Rader",
      "authorRank" : 4,
      "name" : "Rader JS",
      "referenceId" : "RGD:A90527"
    }, {
      "firstName" : "A",
      "lastName" : "Elbendary",
      "authorRank" : 5,
      "name" : "Elbendary",
      "referenceId" : "RGD:A272385"
    }, {
      "firstName" : "DG",
      "lastName" : "Mutch",
      "authorRank" : 6,
      "name" : "Mutch DG",
      "referenceId" : "RGD:A93160"
    }, {
      "firstName" : "PJ",
      "lastName" : "Goodfellow",
      "authorRank" : 7,
      "name" : "Goodfellow PJ",
      "referenceId" : "RGD:A90526"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068923"
    } ]
  }, {
    "primaryId" : "PMID:10479680",
    "title" : "Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Kurschner C and Yuzaki M, J Neurosci. 1999 Sep 15;19(18):7770-80.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-03-19T08:18:08.000-05:00",
    "volume" : "19",
    "pages" : "7770-80",
    "abstract" : "Interleukin (IL)-16 is a proinflammatory cytokine that has attracted widespread attention because of its ability to block HIV replication. We describe the identification and characterization of a large neuronal IL-16 precursor, NIL-16.  The N-terminal half of NIL-16 constitutes a novel PDZ domain protein sequence, whereas the C terminus is identical with splenocyte-derived mouse pro-IL-16. IL-16 has been characterized only in the immune system, and the identification of NIL-16 marks a previously unsuspected connection between the immune and the nervous systems. NIL-16 is a cytosolic protein that is detected only in neurons of the cerebellum and the hippocampus. The N-terminal portion of NIL-16 interacts selectively with a variety of neuronal ion channels, which is similar to the function of many other PDZ domain proteins that serve as intracellular scaffolding proteins. Among the NIL-16-interacting proteins is the class C alpha1 subunit of a mouse brain calcium channel (mbC alpha1). The C terminus of NIL-16 can be processed by caspase-3, resulting in the release of secreted IL-16. Furthermore, in cultured cerebellar granule neurons undergoing apoptosis, NIL-16  proteolysis parallels caspase-3 activation. Cerebellar granule neurons express the IL-16 receptor CD4. Exposure of these cells to IL-16 induces expression of the immediate-early gene, c-fos, via a signaling pathway that involves tyrosine phosphorylation. This suggests that IL-16 provides an autocrine function in the brain. Therefore, we hypothesize that NIL-16 is a dual function protein in the nervous system that serves as a secreted signaling molecule as well as a scaffolding protein.",
    "issueName" : "18",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Kurschner",
      "authorRank" : 1,
      "name" : "Kurschner",
      "referenceId" : "RGD:A184837"
    }, {
      "firstName" : "M",
      "lastName" : "Yuzaki",
      "authorRank" : 2,
      "name" : "Yuzaki M",
      "referenceId" : "RGD:A26582"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11041033"
    } ]
  }, {
    "primaryId" : "PMID:10479726",
    "title" : "A characterization of genetic variants in BRCA1 intron 8 identifies a mutation and a polymorphism.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Pyne MT, etal., Mutat Res. 1999 Aug;406(2-4):101-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:27:22.000-05:00",
    "volume" : "406",
    "pages" : "101-7",
    "abstract" : "The biochemical and genetic characterizations of two variants that occur in BRCA1 intron 8 are presented. The variant IVS8+2T-->C induces an aberrant transcript that deletes exon 8. This exon-skipping deletion disrupts the open reading frame  by juxtaposing exon 7 and exon 9 in the aberrant splice product. Theoretically, 50 abnormal residues from reading frame 2 are translated following exon 7 before  a stop codon is encountered. The chromosomal contribution to the relevant RNA species was tracked using a silent polymorphism at codon 694 (serine AGC or AGT). Nucleotide sequencing of this polymorphic codon demonstrated that the aberrant transcript was derived solely from the chromosome encoding AGT. The normally spliced productive transcript also displayed loss of heterozygosity and was derived solely from the chromosome encoding AGC at codon 694. Also, a haplotype analysis using a breast cancer patient database showed that the chromosome bearing serine 694-AGT carried IVS8+2T-->C. A second more common variant, IVS8-58delT, was characterized as a polymorphism. Analysis of RNA from patient samples used the same silent polymorphism at codon 694 and showed that the normal message was derived from both chromosomes.",
    "issueName" : "2-4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "MT",
      "lastName" : "Pyne",
      "authorRank" : 1,
      "name" : "Pyne",
      "referenceId" : "RGD:A362445"
    }, {
      "firstName" : "D",
      "lastName" : "Pruss",
      "authorRank" : 2,
      "name" : "Pruss D",
      "referenceId" : "RGD:A95337"
    }, {
      "firstName" : "BE",
      "lastName" : "Ward",
      "authorRank" : 3,
      "name" : "Ward",
      "referenceId" : "RGD:A250019"
    }, {
      "firstName" : "T",
      "lastName" : "Scholl",
      "authorRank" : 4,
      "name" : "Scholl",
      "referenceId" : "RGD:A176449"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11527024"
    } ]
  }, {
    "primaryId" : "PMID:10479997",
    "title" : "Cytogenetic localization of the growth and reproduction complex (Grc) in the rat and in the mouse and its position in relation to RT1.EC and other loci in the rat MHC.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Helou K, etal., Hereditas 1999;130(2):105-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2001-06-25T16:49:24.000-05:00",
    "volume" : "130",
    "pages" : "105-9",
    "abstract" : "The segment of rat chromosome 20 (RNO20p12) that contains the classical loci of the major histocompatibility complex (MHC; RT1.A-RT1.E) also contains genes affecting growth, reproduction and susceptibility to chemical carcinogens (the Grc) and multiple genes encoding class I MHC antigens (the EC region). The relative positions of the MHC, Grc, and EC region have not been demonstrated explicitly, although they have been postulated from genetic mapping studies. The present study was undertaken to map these regions cytogenetically by several different approaches using cosmids specific for the Rps 18, Hspa1 and Bat1 genes. The order was shown to be: centromere-Rps 18-Hspa1-Bat1-EC-Grc.",
    "issueName" : "2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "K",
      "lastName" : "Helou",
      "authorRank" : 1,
      "name" : "Helou K",
      "referenceId" : "RGD:A123303"
    }, {
      "firstName" : "Q",
      "lastName" : "Yan",
      "authorRank" : 2,
      "name" : "Yan Q",
      "referenceId" : "RGD:A4532"
    }, {
      "firstName" : "XJ",
      "lastName" : "Yuan",
      "authorRank" : 3,
      "name" : "Yuan XJ",
      "referenceId" : "RGD:A4533"
    }, {
      "firstName" : "HW",
      "lastName" : "Kunz",
      "authorRank" : 4,
      "name" : "Kunz HW",
      "referenceId" : "RGD:A112792"
    }, {
      "firstName" : "G",
      "lastName" : "Levan",
      "authorRank" : 5,
      "name" : "Levan G",
      "referenceId" : "RGD:A123304"
    }, {
      "firstName" : "3RD",
      "lastName" : "Gill TJ",
      "authorRank" : 6,
      "name" : "Gill TJ 3RD",
      "referenceId" : "RGD:A112793"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:68191"
    } ]
  }, {
    "primaryId" : "PMID:10480315",
    "title" : "Abundance of low molecular weight phosphotyrosine protein phosphatase in the nerve-ending fraction in the brain.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Tanino H, etal., Biol Pharm Bull 1999 Aug;22(8):794-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2003-08-19T11:13:28.000-05:00",
    "volume" : "22",
    "pages" : "794-8",
    "abstract" : "The distribution of low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) in subcellular fractions of rat brain tissue was investigated by immunoblotting analysis using anti-LMW-PTP antibody. The enzyme was detected in the 105000 g precipitate in addition to the supernatant of brain homogenate, even after the precipitate was extensively washed, and was abundant in the particulate fraction of nerve endings. Nerve ending LMW-PTP was effectively solubilized by 1% Triton X-100 or 1% deoxycholate, though the enzyme was solubilized by thorough sonication. Two forms of LMW-PTP, designated as LMW-PTP-I and -II, were separated from the nerve ending-rich fraction by chromatofocusing. Nerve endings PTP-I and -II were different in molecular weight, isoelectric point and susceptibility to activators and inhibitors. The properties of nerve endings LMW-PTP-I and -II were similar to those of cytosolic LMW-PTP-I and -II. The abundance of LMW-PTP in nerve endings as well as in the cytosol suggests that this enzyme plays an important role in synaptic function.",
    "issueName" : "8",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Tanino",
      "authorRank" : 1,
      "name" : "Tanino H",
      "referenceId" : "RGD:A15143"
    }, {
      "firstName" : "J",
      "lastName" : "Yoshida",
      "authorRank" : 2,
      "name" : "Yoshida J",
      "referenceId" : "RGD:A15144"
    }, {
      "firstName" : "R",
      "lastName" : "Yamamoto",
      "authorRank" : 3,
      "name" : "Yamamoto R",
      "referenceId" : "RGD:A161692"
    }, {
      "firstName" : "Y",
      "lastName" : "Kobayashi",
      "authorRank" : 4,
      "name" : "Kobayashi Y",
      "referenceId" : "RGD:A8337"
    }, {
      "firstName" : "S",
      "lastName" : "Shimohama",
      "authorRank" : 5,
      "name" : "Shimohama S",
      "referenceId" : "RGD:A15146"
    }, {
      "firstName" : "S",
      "lastName" : "Fujimoto",
      "authorRank" : 6,
      "name" : "Fujimoto S",
      "referenceId" : "RGD:A15147"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:631746"
    } ]
  }, {
    "primaryId" : "PMID:10480349",
    "title" : "NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Yamamoto T, etal., Hum Genet. 1999 Jul-Aug;105(1-2):10-6.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:03:01.000-05:00",
    "volume" : "105",
    "pages" : "10-6",
    "abstract" : "Complementary and genomic DNAs isolated from the fibroblasts of 10 Japanese (7 late infantile, 2 juvenile, and 1 adult form of the disease) and one Caucasian patient with Niemann-Pick disease type C were analyzed for mutations in the NPC1  gene. Fourteen novel mutations were found including small deletions and point mutations. A one-base deletion and a point mutation caused splicing errors. The mutations were not clustered in any particular region of the gene and were found  both in and out of the transmembrane domains. Three patients were homozygous, five were compound heterozygous, and the remaining three were suspected of being  compound hetrozygous with an unknown error in one of their NPC1 alleles. Of the 14 mutations, the G1553A substitution that caused a splicing error of exon 9 appeared to be relatively common in Japanese patients, because two patients were  homozygous and one patient was compound heterozygous for this mutation.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Yamamoto",
      "authorRank" : 1,
      "name" : "Yamamoto",
      "referenceId" : "RGD:A414894"
    }, {
      "firstName" : "E",
      "lastName" : "Nanba",
      "authorRank" : 2,
      "name" : "Nanba E",
      "referenceId" : "RGD:A53044"
    }, {
      "firstName" : "H",
      "lastName" : "Ninomiya",
      "authorRank" : 3,
      "name" : "Ninomiya H",
      "referenceId" : "RGD:A4661"
    }, {
      "firstName" : "K",
      "lastName" : "Higaki",
      "authorRank" : 4,
      "name" : "Higaki K",
      "referenceId" : "RGD:A9426"
    }, {
      "firstName" : "M",
      "lastName" : "Taniguchi",
      "authorRank" : 5,
      "name" : "Taniguchi M",
      "referenceId" : "RGD:A8611"
    }, {
      "firstName" : "H",
      "lastName" : "Zhang",
      "authorRank" : 6,
      "name" : "Zhang H",
      "referenceId" : "RGD:A6284"
    }, {
      "firstName" : "S",
      "lastName" : "Akaboshi",
      "authorRank" : 7,
      "name" : "Akaboshi",
      "referenceId" : "RGD:A254639"
    }, {
      "firstName" : "Y",
      "lastName" : "Watanabe",
      "authorRank" : 8,
      "name" : "Watanabe",
      "referenceId" : "RGD:A391143"
    }, {
      "firstName" : "T",
      "lastName" : "Takeshima",
      "authorRank" : 9,
      "name" : "Takeshima",
      "referenceId" : "RGD:A189447"
    }, {
      "firstName" : "K",
      "lastName" : "Inui",
      "authorRank" : 10,
      "name" : "Inui",
      "referenceId" : "RGD:A387003"
    }, {
      "firstName" : "S",
      "lastName" : "Okada",
      "authorRank" : 11,
      "name" : "Okada",
      "referenceId" : "RGD:A413891"
    }, {
      "firstName" : "A",
      "lastName" : "Tanaka",
      "authorRank" : 12,
      "name" : "Tanaka A",
      "referenceId" : "RGD:A9438"
    }, {
      "firstName" : "N",
      "lastName" : "Sakuragawa",
      "authorRank" : 13,
      "name" : "Sakuragawa",
      "referenceId" : "RGD:A254643"
    }, {
      "firstName" : "G",
      "lastName" : "Millat",
      "authorRank" : 14,
      "name" : "Millat G",
      "referenceId" : "RGD:A81143"
    }, {
      "firstName" : "MT",
      "lastName" : "Vanier",
      "authorRank" : 15,
      "name" : "Vanier MT",
      "referenceId" : "RGD:A81146"
    }, {
      "firstName" : "JA",
      "lastName" : "Morris",
      "authorRank" : 16,
      "name" : "Morris",
      "referenceId" : "RGD:A202255"
    }, {
      "firstName" : "PG",
      "lastName" : "Pentchev",
      "authorRank" : 17,
      "name" : "Pentchev",
      "referenceId" : "RGD:A254644"
    }, {
      "firstName" : "K",
      "lastName" : "Ohno",
      "authorRank" : 18,
      "name" : "Ohno K",
      "referenceId" : "RGD:A18083"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11063307"
    } ]
  }, {
    "primaryId" : "PMID:10480359",
    "title" : "Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Wang Q, etal., Hum Genet. 1999 Jul-Aug;105(1-2):79-85.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:41:11.000-05:00",
    "volume" : "105",
    "pages" : "79-85",
    "abstract" : "Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome characterized by  familial predisposition to colorectal carcinoma and extracolonic cancers of the gastrointestinal, urological, and female reproductive tracts. This dominant disorder is caused by germline defects in one of at least five DNA mismatch repair (MMR) genes: hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 (GTBP). Germline mutations of hMSH2 and hMLH1 are also frequently identified in families not fulfilling all the Amsterdam criteria, thereby demonstrating that the involvement of these genes is not confined to typical HNPCC. To evaluate the respective involvement of the various MMR genes in typical and incomplete HNPCC syndromes, we have performed an analysis of the hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes  in a large series of French kindreds (n=75) with colorectal tumors and/or aggregation of extracolonic cancers belonging to the HNPCC spectrum. Mutational analysis has been performed in all families, without preselection for the tumor phenotype. We have detected 26 pathogenic germline mutations of the hMLH1 and hMSH2 genes and several novel variants of the hPMS1, hPMS2, and hMSH6 genes. Our  data confirm that, regardless of the type of families and the tumor phenotype, hPMS1, hPMS2, and hMSH6 germline mutations are rare in familial aggregation of colorectal cancers. Furthermore, they suggest that the presence of multiple primary malignancies in a single individual and the observation of extracolonic tumors in relatives of a colorectal cancer patient should be included among the guidelines for referring patients for genetic testing.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "Q",
      "lastName" : "Wang",
      "authorRank" : 1,
      "name" : "Wang",
      "referenceId" : "RGD:A415158"
    }, {
      "firstName" : "C",
      "lastName" : "Lasset",
      "authorRank" : 2,
      "name" : "Lasset C",
      "referenceId" : "RGD:A95517"
    }, {
      "firstName" : "F",
      "lastName" : "Desseigne",
      "authorRank" : 3,
      "name" : "Desseigne",
      "referenceId" : "RGD:A264937"
    }, {
      "firstName" : "JC",
      "lastName" : "Saurin",
      "authorRank" : 4,
      "name" : "Saurin",
      "referenceId" : "RGD:A264938"
    }, {
      "firstName" : "C",
      "lastName" : "Maugard",
      "authorRank" : 5,
      "name" : "Maugard",
      "referenceId" : "RGD:A189147"
    }, {
      "firstName" : "C",
      "lastName" : "Navarro",
      "authorRank" : 6,
      "name" : "Navarro C",
      "referenceId" : "RGD:A28048"
    }, {
      "firstName" : "E",
      "lastName" : "Ruano",
      "authorRank" : 7,
      "name" : "Ruano",
      "referenceId" : "RGD:A266865"
    }, {
      "firstName" : "L",
      "lastName" : "Descos",
      "authorRank" : 8,
      "name" : "Descos",
      "referenceId" : "RGD:A282339"
    }, {
      "firstName" : "V",
      "lastName" : "Trillet-Lenoir",
      "authorRank" : 9,
      "name" : "Trillet-Lenoir",
      "referenceId" : "RGD:A282340"
    }, {
      "firstName" : "JF",
      "lastName" : "Bosset",
      "authorRank" : 10,
      "name" : "Bosset",
      "referenceId" : "RGD:A282341"
    }, {
      "firstName" : "A",
      "lastName" : "Puisieux",
      "authorRank" : 11,
      "name" : "Puisieux A",
      "referenceId" : "RGD:A90478"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072575"
    } ]
  }, {
    "primaryId" : "PMID:10480374",
    "title" : "Connexin 50 mutation in a family with congenital \"zonular nuclear\" pulverulent cataract of Pakistani origin.",
    "datePublished" : "1999-12-01T00:00:00.000-06:00",
    "citation" : "Berry V, etal., Hum Genet. 1999 Jul-Aug;105(1-2):168-70. doi: 10.1007/s004399900094.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:32:24.000-05:00",
    "volume" : "105",
    "pages" : "168-70",
    "abstract" : "Inherited cataract is a clinically and genetically heterogeneous disease that most often presents as a congenital autosomal dominant trait. Here we report linkage of a three-generation family of Pakistani origin with autosomal dominant cataract \"zonular nuclear\" pulverulent type (CZNP) on chromosome 1q21.1. Genome wide-linkage analysis excluded all the known cataract loci except on chromosome 1q. Significantly positive 2-point lod score values (Z=3.01 at theta=0) were obtained for markers D1S305 and D1S2721, which are known to flank the gene for connexin 50 (Cx50) or gap junction protein alpha-8 (Gja8). Previously a mutation in this gene has been reported in a British family with zonular pulverulent cataract (CZP). Here we describe a second mutation (E48K) in connexin 50 that confirms the involvement of this gene in cataractogenesis.",
    "issueName" : "1-2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "V",
      "lastName" : "Berry",
      "authorRank" : 1,
      "name" : "Berry V",
      "referenceId" : "RGD:A37514"
    }, {
      "firstName" : "D",
      "lastName" : "Mackay",
      "authorRank" : 2,
      "name" : "Mackay D",
      "referenceId" : "RGD:A71988"
    }, {
      "firstName" : "S",
      "lastName" : "Khaliq",
      "authorRank" : 3,
      "name" : "Khaliq S",
      "referenceId" : "RGD:A10311"
    }, {
      "firstName" : "P J",
      "lastName" : "Francis",
      "authorRank" : 4,
      "name" : "Francis PJ",
      "referenceId" : "RGD:A567149"
    }, {
      "firstName" : "A",
      "lastName" : "Hameed",
      "authorRank" : 5,
      "name" : "Hameed A",
      "referenceId" : "RGD:A74384"
    }, {
      "firstName" : "K",
      "lastName" : "Anwar",
      "authorRank" : 6,
      "name" : "Anwar K",
      "referenceId" : "RGD:A567150"
    }, {
      "firstName" : "S Q",
      "lastName" : "Mehdi",
      "authorRank" : 7,
      "name" : "Mehdi SQ",
      "referenceId" : "RGD:A567151"
    }, {
      "firstName" : "R J",
      "lastName" : "Newbold",
      "authorRank" : 8,
      "name" : "Newbold RJ",
      "referenceId" : "RGD:A567152"
    }, {
      "firstName" : "A",
      "lastName" : "Ionides",
      "authorRank" : 9,
      "name" : "Ionides A",
      "referenceId" : "RGD:A71989"
    }, {
      "firstName" : "A",
      "lastName" : "Shiels",
      "authorRank" : 10,
      "name" : "Shiels A",
      "referenceId" : "RGD:A29160"
    }, {
      "firstName" : "T",
      "lastName" : "Moore",
      "authorRank" : 11,
      "name" : "Moore T",
      "referenceId" : "RGD:A38692"
    }, {
      "firstName" : "S S",
      "lastName" : "Bhattacharya",
      "authorRank" : 12,
      "name" : "Bhattacharya SS",
      "referenceId" : "RGD:A567153"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598114762"
    } ]
  }, {
    "primaryId" : "PMID:10480620",
    "title" : "A quantitative trait locus influencing BMI maps to the region of the beta-3 adrenergic receptor.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Mitchell BD, etal., Diabetes 1999 Sep;48(9):1863-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-03-17T09:59:06.000-06:00",
    "volume" : "48",
    "pages" : "1863-7",
    "abstract" : "The beta-3 adrenergic receptor (ADRB3) has been implicated as a regulator of energy expenditure, and a polymorphism in codon 64 of this gene (Trp64Arg) has been associated in some studies with obesity and insulin resistance. However, many studies have failed to detect an effect of this variant, and the importance of the Trp64Arg variant in human obesity remains controversial. We performed a quantitative linkage analysis of the ADRB3 and obesity, using 12 markers (including the intragenic Trp64Arg polymorphism) spanning a 57-cM region of chromosome 8. The study population consisted of 470 individuals from 10 large multigenerational families of Mexican-American ancestry residing in San Antonio, TX. In two-point analysis, logarithm of odds (LOD) scores >1.0 were observed for six markers surrounding ADRB3 in a 33-cM region spanned by markers D8S1477 and D8S1136. The multipoint LOD score was 3.21, occurring between markers D8S1121 and ADRB3, approximately 2-3 cM from ADRB3. Adjusting for the presence of the Arg64 allele or excluding from the analysis the 11 individuals homozygous for the Arg64 allele did not reduce the evidence for linkage. A genome scan was conducted at 10 cM map density to detect other loci influencing variation in BMI. Multipoint LOD scores >1.0 were observed in four other regions, including two on chromosome 17, one on chromosome 6q, and one on chromosome 2p. These data suggest that the ADRB3 should continue to be regarded as a strong candidate gene for obesity even though evidence for an effect of the Trp64Arg polymorphism could not be established. It is also possible that a gene closely linked to ADRB3 may influence susceptibility to obesity.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "BD",
      "lastName" : "Mitchell",
      "authorRank" : 1,
      "name" : "Mitchell BD",
      "referenceId" : "RGD:A40101"
    }, {
      "firstName" : "SA",
      "lastName" : "Cole",
      "authorRank" : 2,
      "name" : "Cole SA",
      "referenceId" : "RGD:A51245"
    }, {
      "firstName" : "AG",
      "lastName" : "Comuzzie",
      "authorRank" : 3,
      "name" : "Comuzzie AG",
      "referenceId" : "RGD:A40006"
    }, {
      "firstName" : "L",
      "lastName" : "Almasy",
      "authorRank" : 4,
      "name" : "Almasy L",
      "referenceId" : "RGD:A39872"
    }, {
      "firstName" : "J",
      "lastName" : "Blangero",
      "authorRank" : 5,
      "name" : "Blangero J",
      "referenceId" : "RGD:A162628"
    }, {
      "firstName" : "JW",
      "lastName" : "MacCluer",
      "authorRank" : 6,
      "name" : "MacCluer JW",
      "referenceId" : "RGD:A40012"
    }, {
      "firstName" : "JE",
      "lastName" : "Hixson",
      "authorRank" : 7,
      "name" : "Hixson JE",
      "referenceId" : "RGD:A40011"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1354698"
    } ]
  }, {
    "primaryId" : "PMID:10480624",
    "title" : "A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Pizzuti A, etal., Diabetes. 1999 Sep;48(9):1881-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-04-04T13:15:13.000-05:00",
    "volume" : "48",
    "pages" : "1881-4",
    "abstract" : "The genes responsible for insulin resistance are poorly defined. Plasma cell differentiation antigen (PC-1) glycoprotein inhibits insulin receptor signaling and is associated with insulin resistance. We describe here a novel polymorphism in exon 4 of the PC-1 gene (K121Q) and demonstrate that it is strongly associated with insulin resistance in 121 healthy nonobese (BMI <30 kg/m2) nondiabetic (by oral glucose tolerance test [OGTT]) Caucasians from Sicily. Compared with 80 KK subjects, Q allele carriers (n = 41, 39 KQ and 2 QQ) showed higher glucose and insulin levels during OGTT (P < 0.001 by two-way analysis of variance) and insulin resistance by euglycemic clamp (M value = 5.25 +/- 1.38 [n = 24] vs. 6.30 +/- 1.39 mg x kg(-1) x min(-1) [n = 49], P = 0.005). Q carriers had higher risk of being hyperinsulinemic and insulin resistant (odds ratio [CI]: 2.99 [1.28-7.0], P < 0.001). Insulin receptor autophosphorylation was reduced (P < 0.01) in cultured skin fibroblasts from KQ versus KK subjects. Skeletal muscle PC-1 content was not different in 11 KQ versus 32 KK subjects (33 +/- 16.1 vs. 17.5 +/- 15 ng/mg protein, P = 0.3). These results suggest a cause-effect relationship between the Q carrying genotype and the insulin resistance phenotype, and raise the possibility that PC-1 genotyping could identify individuals who are at risk of developing insulin resistance, a condition that predisposes to type 2 diabetes and coronary artery disease.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Pizzuti",
      "authorRank" : 1,
      "name" : "Pizzuti A",
      "referenceId" : "RGD:A63424"
    }, {
      "firstName" : "L",
      "lastName" : "Frittitta",
      "authorRank" : 2,
      "name" : "Frittitta L",
      "referenceId" : "RGD:A79387"
    }, {
      "firstName" : "A",
      "lastName" : "Argiolas",
      "authorRank" : 3,
      "name" : "Argiolas A",
      "referenceId" : "RGD:A79388"
    }, {
      "firstName" : "R",
      "lastName" : "Baratta",
      "authorRank" : 4,
      "name" : "Baratta R",
      "referenceId" : "RGD:A79389"
    }, {
      "firstName" : "ID",
      "lastName" : "Goldfine",
      "authorRank" : 5,
      "name" : "Goldfine ID",
      "referenceId" : "RGD:A31944"
    }, {
      "firstName" : "M",
      "lastName" : "Bozzali",
      "authorRank" : 6,
      "name" : "Bozzali M",
      "referenceId" : "RGD:A79390"
    }, {
      "firstName" : "T",
      "lastName" : "Ercolino",
      "authorRank" : 7,
      "name" : "Ercolino T",
      "referenceId" : "RGD:A79391"
    }, {
      "firstName" : "G",
      "lastName" : "Scarlato",
      "authorRank" : 8,
      "name" : "Scarlato G",
      "referenceId" : "RGD:A64579"
    }, {
      "firstName" : "L",
      "lastName" : "Iacoviello",
      "authorRank" : 9,
      "name" : "Iacoviello L",
      "referenceId" : "RGD:A62299"
    }, {
      "firstName" : "R",
      "lastName" : "Vigneri",
      "authorRank" : 10,
      "name" : "Vigneri R",
      "referenceId" : "RGD:A79392"
    }, {
      "firstName" : "V",
      "lastName" : "Tassi",
      "authorRank" : 11,
      "name" : "Tassi V",
      "referenceId" : "RGD:A76863"
    }, {
      "firstName" : "V",
      "lastName" : "Trischitta",
      "authorRank" : 12,
      "name" : "Trischitta V",
      "referenceId" : "RGD:A79393"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1601043"
    } ]
  }, {
    "primaryId" : "PMID:10480919",
    "title" : "Sertolin is a novel gene marker of cell-cell interactions in the rat testis.",
    "datePublished" : "1999-06-01T00:00:00.000-05:00",
    "citation" : "Mruk DD and Cheng CY, J Biol Chem 1999 Sep 17;274(38):27056-68.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2004-06-01T17:21:45.000-05:00",
    "volume" : "274",
    "pages" : "27056-68",
    "abstract" : "A novel testicular protein designated sertolin was cloned. The full-length sertolin cDNA consists of 853 base pairs with an open reading frame of 381 base pairs coding for a 127-amino acid polypeptide that shares limited identities with antaxin/josephin and thrombospondin proteins. Sertolin (calculated molecular mass, 13,759 daltons) has two mRNA transcripts of 2.3 and 1 kilobase. A 22-amino acid peptide based on the deduced amino acid sequence of sertolin (NH(2)-KKEHFNLFKAASVSHLVQVVPQ) was synthesized and used for polyclonal antibody production. Immunoblot analysis detected a 17-kDa immunoreactive band in the Sertoli cell cytosol. Using Sertoli-germ cell cocultures, sertolin expression was found to be reduced by as much as 5-fold at the time when germ cells attach onto Sertoli cells but preceding the establishment of specialized inter-Sertoli-germ cell junctions. Neither FSH nor 17beta-hydroxy-5alpha-androstan-3-one was able to affect sertolin expression, whereas estradiol-17beta and progesterone induced a significant increase in Sertoli cell sertolin expression in vitro. In addition, interleukin-1alpha, a germ cell-derived cytokine, was also able to elicit a transient but significant increase in Sertoli cell sertolin expression. Sertolin expression was also shown to increase with testicular development and is likely to be associated with the onset of spermatogenesis. In addition, sertolin expression increased in the testis when generalized inflammation was induced in adult rats by injection of fermented yeast. These results show that sertolin will be useful in characterizing cell-cell interactions in the testis.",
    "issueName" : "38",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "DD",
      "lastName" : "Mruk",
      "authorRank" : 1,
      "name" : "Mruk DD",
      "referenceId" : "RGD:A43109"
    }, {
      "firstName" : "CY",
      "lastName" : "Cheng",
      "authorRank" : 2,
      "name" : "Cheng CY",
      "referenceId" : "RGD:A5746"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1299454"
    } ]
  }, {
    "primaryId" : "PMID:10481911",
    "title" : "Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy.",
    "datePublished" : "1999-08-20T00:00:00.000-05:00",
    "citation" : "Coral-Vazquez R, etal., Cell. 1999 Aug 20;98(4):465-74.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2018-06-11T13:03:19.000-05:00",
    "volume" : "98",
    "pages" : "465-74",
    "abstract" : "To investigate mechanisms in the pathogenesis of cardiomyopathy associated with mutations of the dystrophin-glycoprotein complex, we analyzed genetically engineered mice deficient for either alpha-sarcoglycan (Sgca) or delta-sarcoglycan (Sgcd). We found that only Sgcd null mice developed cardiomyopathy with focal areas of necrosis as the histological hallmark in cardiac and skeletal muscle. Absence of the sarcoglycan-sarcospan (SG-SSPN) complex in skeletal and cardiac membranes was observed in both animal models. Loss of vascular smooth muscle SG-SSPN complex was only detected in Sgcd null mice and associated with irregularities of the coronary vasculature. Administration of a vascular smooth muscle relaxant prevented onset of myocardial necrosis. Our data indicate that disruption of the SG-SSPN complex in vascular smooth muscle perturbs vascular function, which initiates cardiomyopathy and exacerbates muscular dystrophy.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Coral-Vazquez",
      "authorRank" : 1,
      "name" : "Coral-Vazquez R",
      "referenceId" : "RGD:A79609"
    }, {
      "firstName" : "R D",
      "lastName" : "Cohn",
      "authorRank" : 2,
      "name" : "Cohn RD",
      "referenceId" : "RGD:A458414"
    }, {
      "firstName" : "S A",
      "lastName" : "Moore",
      "authorRank" : 3,
      "name" : "Moore SA",
      "referenceId" : "RGD:A458390"
    }, {
      "firstName" : "J A",
      "lastName" : "Hill",
      "authorRank" : 4,
      "name" : "Hill JA",
      "referenceId" : "RGD:A458420"
    }, {
      "firstName" : "R M",
      "lastName" : "Weiss",
      "authorRank" : 5,
      "name" : "Weiss RM",
      "referenceId" : "RGD:A458421"
    }, {
      "firstName" : "R L",
      "lastName" : "Davisson",
      "authorRank" : 6,
      "name" : "Davisson RL",
      "referenceId" : "RGD:A458422"
    }, {
      "firstName" : "V",
      "lastName" : "Straub",
      "authorRank" : 7,
      "name" : "Straub V",
      "referenceId" : "RGD:A56102"
    }, {
      "firstName" : "R",
      "lastName" : "Barresi",
      "authorRank" : 8,
      "name" : "Barresi R",
      "referenceId" : "RGD:A37810"
    }, {
      "firstName" : "D",
      "lastName" : "Bansal",
      "authorRank" : 9,
      "name" : "Bansal D",
      "referenceId" : "RGD:A458423"
    }, {
      "firstName" : "R F",
      "lastName" : "Hrstka",
      "authorRank" : 10,
      "name" : "Hrstka RF",
      "referenceId" : "RGD:A458392"
    }, {
      "firstName" : "R",
      "lastName" : "Williamson",
      "authorRank" : 11,
      "name" : "Williamson R",
      "referenceId" : "RGD:A8895"
    }, {
      "firstName" : "K P",
      "lastName" : "Campbell",
      "authorRank" : 12,
      "name" : "Campbell KP",
      "referenceId" : "RGD:A458403"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13605616"
    } ]
  }, {
    "primaryId" : "PMID:10482285",
    "title" : "Effects of PAF on histamine H1 receptor mRNA expression in rat trigeminal ganglia.",
    "datePublished" : "1999-05-01T00:00:00.000-05:00",
    "citation" : "Nakasaki T, etal., Prostaglandins Other Lipid Mediat. 1999 Aug;58(1):29-41.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-05-11T13:41:10.000-05:00",
    "volume" : "58",
    "pages" : "29-41",
    "abstract" : "The application of platelet-activating factor (PAF) to the nasal mucosa of humans has been shown to increase histamine-induced hyper-reactivity. To test the hypothesis that PAF acts by increasing the reactivity of sensory nerve endings in the nasal mucosa to histamine, we examined PAF-stimulated rat trigeminal nerve ganglion cells. We found that relatively low concentrations of PAF (10(-12)-10(-9) M) induced increased histamine H1 receptor mRNA expression. This  increase appeared as early as 1 h after PAF stimulation, peaked at 4 h, and disappeared after 24 h. The PAF receptor antagonist WEB2086 inhibited the increased expression of histamine H1 receptor mRNA induced by PAF, suggesting that the effects of PAF are mediated by specific receptors. This PAF effect was abolished by actinomycin D, suggesting that PAF induces de novo transcription of  histamine H1 and/or PAF receptor mRNA. PAF may be important in the hyper-responsiveness of nasal mucosa exposed to histamine.",
    "issueName" : "1",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "T",
      "lastName" : "Nakasaki",
      "authorRank" : 1,
      "name" : "Nakasaki",
      "referenceId" : "RGD:A201779"
    }, {
      "firstName" : "K",
      "lastName" : "Masuyama",
      "authorRank" : 2,
      "name" : "Masuyama",
      "referenceId" : "RGD:A190751"
    }, {
      "firstName" : "H",
      "lastName" : "Fukui",
      "authorRank" : 3,
      "name" : "Fukui",
      "referenceId" : "RGD:A391554"
    }, {
      "firstName" : "S",
      "lastName" : "Ogino",
      "authorRank" : 4,
      "name" : "Ogino",
      "referenceId" : "RGD:A201781"
    }, {
      "firstName" : "M",
      "lastName" : "Eura",
      "authorRank" : 5,
      "name" : "Eura",
      "referenceId" : "RGD:A190749"
    }, {
      "firstName" : "Y",
      "lastName" : "Samejima",
      "authorRank" : 6,
      "name" : "Samejima",
      "referenceId" : "RGD:A201782"
    }, {
      "firstName" : "T",
      "lastName" : "Ishikawa",
      "authorRank" : 7,
      "name" : "Ishikawa",
      "referenceId" : "RGD:A396544"
    }, {
      "firstName" : "E",
      "lastName" : "Yumoto",
      "authorRank" : 8,
      "name" : "Yumoto",
      "referenceId" : "RGD:A201784"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:10041056"
    } ]
  }, {
    "primaryId" : "PMID:10482474",
    "title" : "Expression of transforming growth factor-beta superfamily receptors in developing rat eyes.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Yamada H, etal., Jpn J Ophthalmol. 1999 Jul-Aug;43(4):290-4.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2011-03-30T16:48:55.000-05:00",
    "volume" : "43",
    "pages" : "290-4",
    "abstract" : "PURPOSE: To ascertain the role played by the transforming growth factor (TGF)-beta superfamily in retinal development by determining the changes in the expression patterns of their receptors during development of the normal rat retina. METHODS: The expression of type I and type II receptors of the TGF-beta superfamily was observed at the protein level in rat eyes at embryonic age 17 days (E17), at birth (P0), at postnatal days 3, 6, 9, and at 11 weeks (P3, P6, P9, and adult, respectively). RESULTS: Activin type I receptor and BMP type IB receptor were first detected in P6 and P3 retinas, respectively, at the protein level, and activin type II receptor was first detected in the P0 retina. The other receptors (TGF-beta type I and II receptors, activin type IB receptor, BMP types IA and II receptors) were detected at E17. The period from P0 to P9 corresponded to the period of dynamic changes in the rat retinal development. CONCLUSION: The results suggest that the expression of TGF-beta superfamily is regulated along with retinal development and may be related to retinal development.",
    "issueName" : "4",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Yamada",
      "authorRank" : 1,
      "name" : "Yamada H",
      "referenceId" : "RGD:A13790"
    }, {
      "firstName" : "H",
      "lastName" : "Obata",
      "authorRank" : 2,
      "name" : "Obata H",
      "referenceId" : "RGD:A82660"
    }, {
      "firstName" : "Y",
      "lastName" : "Kaji",
      "authorRank" : 3,
      "name" : "Kaji Y",
      "referenceId" : "RGD:A63049"
    }, {
      "firstName" : "H",
      "lastName" : "Yamashita",
      "authorRank" : 4,
      "name" : "Yamashita H",
      "referenceId" : "RGD:A23379"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:5129487"
    } ]
  }, {
    "primaryId" : "PMID:10482766",
    "title" : "Kv3.1-Kv3.2 channels underlie a high-voltage-activating component of the delayed  rectifier K+ current in projecting neurons from the globus pallidus.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Hernandez-Pineda R, etal., J Neurophysiol. 1999 Sep;82(3):1512-28.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2015-01-27T12:19:06.000-06:00",
    "volume" : "82",
    "pages" : "1512-28",
    "abstract" : "The globus pallidus plays central roles in the basal ganglia circuitry involved in movement control as well as in cognitive and emotional functions. There is therefore great interest in the anatomic and electrophysiological characterization of this nucleus. Most pallidal neurons are GABAergic projecting  cells, a large fraction of which express the calcium binding protein parvalbumin  (PV). Here we show that PV-containing pallidal neurons coexpress Kv3. 1 and Kv3.2 K+ channel proteins and that both Kv3.1 and Kv3.2 antibodies coprecipitate both channel proteins from pallidal membrane extracts solubilized with nondenaturing detergents, suggesting that the two channel subunits are forming heteromeric channels. Kv3.1 and Kv3.2 channels have several unusual electrophysiological properties when expressed in heterologous expression systems and are thought to play special roles in neuronal excitability including facilitating sustained high-frequency firing in fast-spiking neurons such as interneurons in the cortex  and the hippocampus. Electrophysiological analysis of freshly dissociated pallidal neurons demonstrates that these cells have a current that is nearly identical to the currents expressed by Kv3.1 and Kv3.2 proteins in heterologous expression systems, including activation at very depolarized membrane potentials  (more positive than -10 mV) and very fast deactivation rates. These results suggest that the electrophysiological properties of native channels containing Kv3.1 and Kv3.2 proteins in pallidal neurons are not significantly affected by factors such as associated subunits or postranslational modifications that result in channels having different properties in heterologous expression systems and native neurons. Most neurons in the globus pallidus have been reported to fire sustained trains of action potentials at high-frequency. Kv3.1-Kv3.2 voltage-gated K+ channels may play a role in helping maintain sustained high-frequency repetitive firing as they probably do in other neurons.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "R",
      "lastName" : "Hernandez-Pineda",
      "authorRank" : 1,
      "name" : "Hernandez-Pineda R",
      "referenceId" : "RGD:A43291"
    }, {
      "firstName" : "A",
      "lastName" : "Chow",
      "authorRank" : 2,
      "name" : "Chow A",
      "referenceId" : "RGD:A88677"
    }, {
      "firstName" : "Y",
      "lastName" : "Amarillo",
      "authorRank" : 3,
      "name" : "Amarillo Y",
      "referenceId" : "RGD:A150754"
    }, {
      "firstName" : "H",
      "lastName" : "Moreno",
      "authorRank" : 4,
      "name" : "Moreno H",
      "referenceId" : "RGD:A28209"
    }, {
      "firstName" : "M",
      "lastName" : "Saganich",
      "authorRank" : 5,
      "name" : "Saganich",
      "referenceId" : "RGD:A198601"
    }, {
      "firstName" : "EC",
      "lastName" : "Vega-Saenz de Miera",
      "authorRank" : 6,
      "name" : "Vega-Saenz de Miera EC",
      "referenceId" : "RGD:A32248"
    }, {
      "firstName" : "A",
      "lastName" : "Hernandez-Cruz",
      "authorRank" : 7,
      "name" : "Hernandez-Cruz A",
      "referenceId" : "RGD:A88457"
    }, {
      "firstName" : "B",
      "lastName" : "Rudy",
      "authorRank" : 8,
      "name" : "Rudy B",
      "referenceId" : "RGD:A20011"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:9685780"
    } ]
  }, {
    "primaryId" : "PMID:10482877",
    "title" : "Characterization of a complex chromosomal rearrangement in a patient with a typical catlike cry and no other clinical findings of cri-du-chat syndrome.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Sreekantaiah C, etal., Am J Med Genet. 1999 Sep 17;86(3):264-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:34:18.000-05:00",
    "volume" : "86",
    "pages" : "264-8",
    "abstract" : "We report on the clinical, cytogenetic, and molecular cytogenetic findings in a 4-year-old girl who was evaluated for developmental delay and a catlike cry from  birth. No other findings of cri-du-chat syndrome were present. Karyotype analysis demonstrated a de novo deletion and inverted duplication of the 5p region. The abnormality was confirmed and further defined by detailed FISH analysis using cosmid and lambda phage clones previously mapped to distinct regions of 5p. The analyses documented deletion of 5p15.3-->pter and an inverted duplication of 5p14-->5p15.3. The deleted segment on 5p contains the region implicated in the isolated catlike cry feature of the cri-du-chat syndrome, confirming that the genes involved in the catlike cry map to the distal end of 5p. Except for the catlike cry and possibly the developmental delay that may be due to the deletion  of 5p, the duplication of 5p14-->5p15.3 in this patient did not present with additional anomalies. This study further demonstrates the usefulness of the molecular cytogenetic approach for characterizing complex chromosome rearrangements. Such analyses of patients with an isolated catlike cry can avoid  an incorrect diagnosis of the cri-du-chat syndrome, which is associated with a more severe prognosis.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "C",
      "lastName" : "Sreekantaiah",
      "authorRank" : 1,
      "name" : "Sreekantaiah",
      "referenceId" : "RGD:A363333"
    }, {
      "firstName" : "D",
      "lastName" : "Kronn",
      "authorRank" : 2,
      "name" : "Kronn",
      "referenceId" : "RGD:A252193"
    }, {
      "firstName" : "RC",
      "lastName" : "Marinescu",
      "authorRank" : 3,
      "name" : "Marinescu",
      "referenceId" : "RGD:A363334"
    }, {
      "firstName" : "B",
      "lastName" : "Goldin",
      "authorRank" : 4,
      "name" : "Goldin",
      "referenceId" : "RGD:A363335"
    }, {
      "firstName" : "J",
      "lastName" : "Overhauser",
      "authorRank" : 5,
      "name" : "Overhauser J",
      "referenceId" : "RGD:A28931"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11527335"
    } ]
  }, {
    "primaryId" : "PMID:10482955",
    "title" : "Identification of the Finnish founder mutation for diastrophic dysplasia (DTD).",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Hästbacka J, etal., Eur J Hum Genet. 1999 Sep;7(6):664-70.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2017-08-23T14:02:33.000-05:00",
    "volume" : "7",
    "pages" : "664-70",
    "abstract" : "Diastrophic dysplasia (DTD) is especially prevalent in Finland and the existence of a founder mutation has been previously inferred from the fact that 95% of Finnish DTD chromosomes have a rare ancestral haplotype found in only 4% of Finnish control chromosomes. Here we report the identification of the Finnish founder mutation as a GT-> GC transition (c.-26 + 2T > C) in the splice donor site of a previously undescribed 5'-untranslated exon of the diastrophic dysplasia sulfate transporter gene (DTDST); the mutation acts by severely reducing mRNA levels. Among 84 DTD families in Finland, patients carried two copies of the mutation in 69 families, one copy in 14 families, and no copies in one family. Roughly 90% of Finnish DTD chromosomes thus carry the splice-site mutation, which we have designated DTDST(Fin). Unexpectedly, we found that nine of the DTD chromosomes having the apparently ancestral haplotype did not carry DTDST(Fin), but rather two other mutations. Eight such chromosomes had an R279W mutation and one had a V340del deletion. We consider the possible implications of presence of multiple DTD mutations on this rare haplotype.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "J",
      "lastName" : "Hästbacka",
      "authorRank" : 1,
      "name" : "Hästbacka J",
      "referenceId" : "RGD:A449292"
    }, {
      "firstName" : "A",
      "lastName" : "Kerrebrock",
      "authorRank" : 2,
      "name" : "Kerrebrock A",
      "referenceId" : "RGD:A449293"
    }, {
      "firstName" : "K",
      "lastName" : "Mokkala",
      "authorRank" : 3,
      "name" : "Mokkala K",
      "referenceId" : "RGD:A449294"
    }, {
      "firstName" : "G",
      "lastName" : "Clines",
      "authorRank" : 4,
      "name" : "Clines G",
      "referenceId" : "RGD:A449295"
    }, {
      "firstName" : "M",
      "lastName" : "Lovett",
      "authorRank" : 5,
      "name" : "Lovett M",
      "referenceId" : "RGD:A61083"
    }, {
      "firstName" : "I",
      "lastName" : "Kaitila",
      "authorRank" : 6,
      "name" : "Kaitila I",
      "referenceId" : "RGD:A44826"
    }, {
      "firstName" : "A",
      "lastName" : "de la Chapelle",
      "authorRank" : 7,
      "name" : "de la Chapelle A",
      "referenceId" : "RGD:A449296"
    }, {
      "firstName" : "E S",
      "lastName" : "Lander",
      "authorRank" : 8,
      "name" : "Lander ES",
      "referenceId" : "RGD:A298659"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:13208932"
    } ]
  }, {
    "primaryId" : "PMID:10482962",
    "title" : "The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Veiga-da-Cunha M, etal., Eur J Hum Genet. 1999 Sep;7(6):717-23.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:49:48.000-05:00",
    "volume" : "7",
    "pages" : "717-23",
    "abstract" : "The purpose of this work was to test the hypothesis that mutations in the putative glucose 6-phosphate translocase gene would account for most of the cases of GSD I that are not explained by mutations in the phosphohydrolase gene, ie that are not type Ia. Twenty-three additional families diagnosed as having GSD I  non-a (GSDIb, Ic or Id) have now been analysed. The 9exons of the gene were amplified by PCR and mutations searched both by SSCP and heteroduplex analysis. Except for one family in which only one mutation was found, all patients had two  allelic mutations in the gene encoding the putative glucose 6-phosphate translocase. Sixteen of the mutations are new and they are all predicted to lead  to non-functional proteins. All investigated patients had some degree of neutropenia or neutrophil dysfunction and the clinical phenotype of the four new  patients who had been diagnosed as GSD Ic and the one diagnosed as GSD Id was no  different from the GSD Ib patients. Since these patients, and the four type Ic patients from two families previously studied, shared several mutations with GSD  Ib patients, we conclude that their basic defect is in the putative glucose 6-phosphate translocase and that they should be reclassified as GSD Ib. Isolated  defects in microsomal Pi transporter or in microsomal glucose transporter must be very rare or have phenotypes that are not recognised as GSD I, so that in practice there are only two subtypes of GSD I (GSD Ia and GSD Ib).",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "M",
      "lastName" : "Veiga-da-Cunha",
      "authorRank" : 1,
      "name" : "Veiga-da-Cunha M",
      "referenceId" : "RGD:A44086"
    }, {
      "firstName" : "I",
      "lastName" : "Gerin",
      "authorRank" : 2,
      "name" : "Gerin I",
      "referenceId" : "RGD:A72107"
    }, {
      "firstName" : "YT",
      "lastName" : "Chen",
      "authorRank" : 3,
      "name" : "Chen YT",
      "referenceId" : "RGD:A35620"
    }, {
      "firstName" : "PJ",
      "lastName" : "Lee",
      "authorRank" : 4,
      "name" : "Lee PJ",
      "referenceId" : "RGD:A12999"
    }, {
      "firstName" : "JV",
      "lastName" : "Leonard",
      "authorRank" : 5,
      "name" : "Leonard JV",
      "referenceId" : "RGD:A58240"
    }, {
      "firstName" : "I",
      "lastName" : "Maire",
      "authorRank" : 6,
      "name" : "Maire I",
      "referenceId" : "RGD:A39078"
    }, {
      "firstName" : "U",
      "lastName" : "Wendel",
      "authorRank" : 7,
      "name" : "Wendel",
      "referenceId" : "RGD:A251848"
    }, {
      "firstName" : "M",
      "lastName" : "Vikkula",
      "authorRank" : 8,
      "name" : "Vikkula M",
      "referenceId" : "RGD:A35539"
    }, {
      "firstName" : "E",
      "lastName" : "Van Schaftingen",
      "authorRank" : 9,
      "name" : "Van Schaftingen E",
      "referenceId" : "RGD:A17332"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11064963"
    } ]
  }, {
    "primaryId" : "PMID:10482963",
    "title" : "Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Larsen LA, etal., Eur J Hum Genet. 1999 Sep;7(6):724-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-28T00:55:12.000-05:00",
    "volume" : "7",
    "pages" : "724-8",
    "abstract" : "We describe a Swedish family with the proband and his brother suffering from severe Romano-Ward syndome (RWS) associated with compound heterozygosity for two  mutations in the KVLQT1 (also known as KCNQ1 and KCNA9) gene (R518X and A525T). The mutations were found to segregate as heterozygotes in the maternal and the paternal lineage, respectively. None of the heterozygotes exhibited clinical long QT syndrome (LQTS). No hearing defects were found in the proband. The data strongly indicates that the compound heterozygosity for R518X and A525T is the cause of an autosomal recessive form of RWS in this family. Our findings support  the implication of a higher frequency of gene carriers than previously expected.  We suggest that relatives of 'sporadic RWS' patients should be considered potential carriers, at risk of dying suddenly from drug-induced LQTS.",
    "issueName" : "6",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LA",
      "lastName" : "Larsen",
      "authorRank" : 1,
      "name" : "Larsen LA",
      "referenceId" : "RGD:A61734"
    }, {
      "firstName" : "I",
      "lastName" : "Fosdal",
      "authorRank" : 2,
      "name" : "Fosdal",
      "referenceId" : "RGD:A253833"
    }, {
      "firstName" : "PS",
      "lastName" : "Andersen",
      "authorRank" : 3,
      "name" : "Andersen PS",
      "referenceId" : "RGD:A61730"
    }, {
      "firstName" : "JK",
      "lastName" : "Kanters",
      "authorRank" : 4,
      "name" : "Kanters",
      "referenceId" : "RGD:A253786"
    }, {
      "firstName" : "J",
      "lastName" : "Vuust",
      "authorRank" : 5,
      "name" : "Vuust J",
      "referenceId" : "RGD:A61738"
    }, {
      "firstName" : "G",
      "lastName" : "Wettrell",
      "authorRank" : 6,
      "name" : "Wettrell",
      "referenceId" : "RGD:A252635"
    }, {
      "firstName" : "M",
      "lastName" : "Christiansen",
      "authorRank" : 7,
      "name" : "Christiansen M",
      "referenceId" : "RGD:A61739"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11072817"
    } ]
  }, {
    "primaryId" : "PMID:10483362",
    "title" : "UVB and gamma-radiation induce the expression of mRNAs encoding the ribosomal subunit L13A in rat keratinocytes.",
    "datePublished" : "1999-02-01T00:00:00.000-06:00",
    "citation" : "Shahmolky N, etal., Photochem Photobiol. 1999 Sep;70(3):341-7.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-02-17T15:16:28.000-06:00",
    "volume" : "70",
    "pages" : "341-7",
    "abstract" : "Ultraviolet B radiation produces an array of cellular perturbations in the skin.  We isolated a keratinocyte cDNA encoding the rat 60S ribosomal subunit protein L13a following differential cDNA library screening with UVB-enriched probes. In contrast to the reported structure of liver L13a, the keratinocyte L13a cDNA contains a longer 3'-untranslated region. Northern blot analysis detected two L13a mRNA transcripts, approximately 800 bp and approximately 1.2 kb, in keratinocytes and a variety of rat tissues. Both L13a mRNA transcripts were induced by UVB irradiation, forskolin and gamma-irradiation. In contrast, no induction of L13a mRNA transcript levels was observed following exposure of keratinocytes to 12-O-tetradecanoylphorbol-13-acetate, serum and the DNA damage-inducing agents methyl methanesulfonate or 4-nitroquinoline-N-oxide. These observations suggest that increased expression of ribosomal subunit genes may be  a molecular component of the keratinocyte response to UVB in particular and not part of a nonspecific response to DNA damage.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Shahmolky",
      "authorRank" : 1,
      "name" : "Shahmolky N",
      "referenceId" : "RGD:A5525"
    }, {
      "firstName" : "DL",
      "lastName" : "Lefebvre",
      "authorRank" : 2,
      "name" : "Lefebvre DL",
      "referenceId" : "RGD:A5523"
    }, {
      "firstName" : "R",
      "lastName" : "Poon",
      "authorRank" : 3,
      "name" : "Poon R",
      "referenceId" : "RGD:A5527"
    }, {
      "firstName" : "Y",
      "lastName" : "Bai",
      "authorRank" : 4,
      "name" : "Bai Y",
      "referenceId" : "RGD:A5524"
    }, {
      "firstName" : "M",
      "lastName" : "Sharma",
      "authorRank" : 5,
      "name" : "Sharma M",
      "referenceId" : "RGD:A5526"
    }, {
      "firstName" : "CF",
      "lastName" : "Rosen",
      "authorRank" : 6,
      "name" : "Rosen CF",
      "referenceId" : "RGD:A5529"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11036101"
    } ]
  }, {
    "primaryId" : "PMID:10483966",
    "title" : "Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Swan H, etal., J Am Coll Cardiol. 1999 Sep;34(3):823-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:31:51.000-05:00",
    "volume" : "34",
    "pages" : "823-9",
    "abstract" : "OBJECTIVES: This study was performed to evaluate the QT interval and heart rate responses to exercise and recovery in gene and mutation type-specific subgroups of long QT syndrome (LQTS) patients. BACKGROUND: Reduced heart rate and repolarization abnormalities are encountered among long QT syndrome (LQTS) patients. The most common types of LQTS are LQT1 and LQT2. METHODS: An exercise stress test was performed in 23 patients with a pore region mutation and in 22 patients with a C-terminal end mutation of the cardiac potassium channel gene causing LQT1 type of long QT syndrome (KVLQT1 gene), as well as in 20 patients with mutations of the cardiac potassium channel gene causing LQT2 type of long QT syndrome (HERG gene) and in 33 healthy relatives. The QT intervals were measured  on electrocardiograms at rest and during and after exercise. QT intervals were compared at similar heart rates, and rate adaptation of QT was studied as QT/heart rate slopes. RESULTS: In contrast to the LQT2 patients, achieved maximum heart rate was decreased in both LQT1 patient groups, being only 76 +/- 5% of predicted in patients with pore region mutation of KvLQT1. The QT/heart rate slopes were significantly steeper in LQT2 patients than in controls during exercise. During recovery, the QT/heart rate slopes were steeper in all LQTS groups than in controls, signifying that QT intervals lengthened excessively when heart rate decreased. At heart rates of 110 or 100 beats/min during recovery, all LQT1 patients and 89% of LQT2 patients had QT intervals longer than any of the controls. CONCLUSIONS: LQT1 is associated with diminished chronotropic response and exaggerated prolongation of QT interval after exercise. LQT2 patients differ  from LQT1 patients by having marked QT interval shortening and normal heart rate  response to exercise. Observing QT duration during recovery enhances the clinical diagnosis of these LQTS types.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "H",
      "lastName" : "Swan",
      "authorRank" : 1,
      "name" : "Swan",
      "referenceId" : "RGD:A253155"
    }, {
      "firstName" : "M",
      "lastName" : "Viitasalo",
      "authorRank" : 2,
      "name" : "Viitasalo",
      "referenceId" : "RGD:A253156"
    }, {
      "firstName" : "K",
      "lastName" : "Piippo",
      "authorRank" : 3,
      "name" : "Piippo",
      "referenceId" : "RGD:A253154"
    }, {
      "firstName" : "P",
      "lastName" : "Laitinen",
      "authorRank" : 4,
      "name" : "Laitinen",
      "referenceId" : "RGD:A253222"
    }, {
      "firstName" : "K",
      "lastName" : "Kontula",
      "authorRank" : 5,
      "name" : "Kontula K",
      "referenceId" : "RGD:A40137"
    }, {
      "firstName" : "L",
      "lastName" : "Toivonen",
      "authorRank" : 6,
      "name" : "Toivonen L",
      "referenceId" : "RGD:A62577"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066145"
    } ]
  }, {
    "primaryId" : "PMID:10484424",
    "title" : "NO alters cell shape and motility in aortic smooth muscle cells via protein tyrosine phosphatase 1B activation.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Hassid A, etal., Am J Physiol. 1999 Sep;277(3):H1014-26. doi: 10.1152/ajpheart.1999.277.3.H1014.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2024-02-08T14:33:40.000-06:00",
    "volume" : "277",
    "pages" : "H1014-26",
    "abstract" : "Cell motility is an important determinant of vascular disease. We examined mechanisms underlying the effect of nitric oxide (NO) on motility in cultured primary aortic smooth muscle cells from newborn rats. The NO donor S-nitroso-N-acetyl-penicillamine (SNAP) increased the activity of protein tyrosine phosphatase 1B (PTP-1B). This effect was mimicked by a cGMP analog and blocked by the guanyl cyclase antagonist 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, indicating the involvement of cGMP. Treatment of cells with antisense, but not control oligodeoxynucleotide (ODN), against PTP-1B attenuated the inhibitory effect of NO on cell motility. Cell shape and adhesion are important determinants of cell motility. We report that SNAP induced cell rounding and reduced adhesion and caused dissociation of actin stress fibers. Moreover, SNAP reduced phosphotyrosine levels in focal adhesion proteins, paxillin, and focal adhesion kinase. The PTP inhibitor phenylarsine oxide or decrease of PTP-1B protein levels via the use of antisense ODN prevented NO-induced cell-shape change, altered adhesion, and migration. These results indicate that NO regulates cell shape, adhesion, and migration by dephosphorylation of focal adhesion proteins via a mechanism that requires PTP-1B activity.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Hassid",
      "authorRank" : 1,
      "name" : "Hassid A",
      "referenceId" : "RGD:A41195"
    }, {
      "firstName" : "J",
      "lastName" : "Yao",
      "authorRank" : 2,
      "name" : "Yao J",
      "referenceId" : "RGD:A23266"
    }, {
      "firstName" : "S",
      "lastName" : "Huang",
      "authorRank" : 3,
      "name" : "Huang S",
      "referenceId" : "RGD:A19334"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:401965470"
    } ]
  }, {
    "primaryId" : "PMID:10484477",
    "title" : "Salt-sensitive hypertension in ANP knockout mice is prevented by AT1 receptor antagonist losartan.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Melo LG, etal., Am J Physiol. 1999 Sep;277(3 Pt 2):R624-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2006-03-06T16:11:25.000-06:00",
    "volume" : "277",
    "pages" : "R624-30",
    "abstract" : "Mice harboring a functional deletion of the pro-atrial natriuretic peptide (ANP) gene (-/-) develop salt-sensitive hypertension relative to their wild-type (+/+) counterparts after prolonged (>1 wk) maintenance on high-salt (HS, 8% NaCl) diet. We reported recently that the sensitization of arterial blood pressure (ABP) to dietary salt in the -/- mice is associated with failure to downregulate plasma renin activity. To further characterize the role and mechanism of ANG II in the sensitization of ABP to salt in the ANP \"knockout\" mice, we measured ABP, heart rate (HR), and plasma catecholamine and aldosterone concentrations in -/- and +/+ mice maintained on HS for 4 wk and treated with daily injections of AT1 receptor antagonist DuP-753 (losartan) or distilled water (control). Daily food and water intake and fluid and electrolyte excretion were also measured during the first and last weeks of the dietary regimen. Cumulative urinary excretion of fluid and electrolytes did not differ significantly between genotypes and was not altered by chronic treatment with losartan. Basal ABP and HR were significantly elevated in control -/- mice compared with control +/+ mice. Losartan did not affect ABP or HR in +/+ mice, but reduced ABP and HR in the -/- mice to the levels in the +/+ mice. Total plasma catecholamine was elevated by approximately ten-fold in control -/- mice compared with control +/+ mice. Losartan reduced plasma catecholamine concentration significantly in -/- mice and abrogated the difference in plasma catecholamine between -/- and +/+ mice on HS diet. Plasma aldosterone did not differ significantly between genotypes and was not altered by losartan. We conclude that salt sensitivity of ABP in ANP knockout mice is mediated, at least in part, by a synergistic interaction between ANG II and sympathetic nerve activity.",
    "issueName" : "3 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "LG",
      "lastName" : "Melo",
      "authorRank" : 1,
      "name" : "Melo LG",
      "referenceId" : "RGD:A58585"
    }, {
      "firstName" : "AT",
      "lastName" : "Veress",
      "authorRank" : 2,
      "name" : "Veress AT",
      "referenceId" : "RGD:A58586"
    }, {
      "firstName" : "CK",
      "lastName" : "Chong",
      "authorRank" : 3,
      "name" : "Chong CK",
      "referenceId" : "RGD:A58589"
    }, {
      "firstName" : "U",
      "lastName" : "Ackermann",
      "authorRank" : 4,
      "name" : "Ackermann U",
      "referenceId" : "RGD:A58587"
    }, {
      "firstName" : "H",
      "lastName" : "Sonnenberg",
      "authorRank" : 5,
      "name" : "Sonnenberg H",
      "referenceId" : "RGD:A58588"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1578333"
    } ]
  }, {
    "primaryId" : "PMID:10484527",
    "title" : "Distribution of angiotensin AT1 and AT2 receptor subtypes in the rat kidney.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Miyata N, etal., Am J Physiol 1999 Sep;277(3 Pt 2):F437-46.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2005-04-12T11:00:27.000-05:00",
    "volume" : "277",
    "pages" : "F437-46",
    "abstract" : "ANG II contributes importantly to the regulation of renal vascular resistance, glomerular filtration, and tubular epithelial transport, yet there remains a paucity of information regarding the localization of the ANG II type 1 and 2 (AT1 and AT2) receptors within the rat kidney particularly within the vasculature. The present study was designed to localize the transcriptional and translational site(s) of AT1 and AT2 receptor (AT1R and AT2R, respectively) expression within the rat kidney. Using immunohistochemistry, we detected the AT(1)R translational sites throughout the kidney, with the strongest labeling found in the vasculature of the renal cortex and the proximal tubules of the outer medulla. The AT2R protein expression was found throughout the rat kidney, although there was little to no expression found in the glomerulus and medullary thick ascending limbs of Henle (TAL). Gene-specific primers were then designed to distinguish between the receptor subtypes within microdissected renal tubular and vascular segments using RT-PCR. AT1AR, AT1BR, and AT2R mRNA were found within the renal vasculature (afferent arterioles, arcuate artery, and outer medullary descending vasa recta). The mRNA for both the AT1R isoforms was also detected in the glomeruli and the renal tubules (proximal tubules, TAL, and collecting ducts); however, no AT2R mRNA was detected within the glomerulus and was inconsistently found within the medullary TAL (MTAL). Taken together, these data show that mRNA for the AT1R subtypes was located in all of the renal tubular and vascular segments. Evidence for AT2R mRNA was also found in all but two of the vascular and tubular segments, the MTAL, and the glomeruli. These results are consistent with the whole tissue immunohistochemically localized receptors.",
    "issueName" : "3 Pt 2",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "N",
      "lastName" : "Miyata",
      "authorRank" : 1,
      "name" : "Miyata N",
      "referenceId" : "RGD:A14219"
    }, {
      "firstName" : "F",
      "lastName" : "Park",
      "authorRank" : 2,
      "name" : "Park F",
      "referenceId" : "RGD:A14220"
    }, {
      "firstName" : "XF",
      "lastName" : "Li",
      "authorRank" : 3,
      "name" : "Li XF",
      "referenceId" : "RGD:A6156"
    }, {
      "firstName" : "JR",
      "lastName" : "Cowley AW",
      "authorRank" : 4,
      "name" : "Cowley AW JR",
      "referenceId" : "RGD:A6483"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1357917"
    } ]
  }, {
    "primaryId" : "PMID:10484604",
    "title" : "Differential binding of proteins to peroxisomes in rat hepatoma cells: unique association of enzymes involved in isoprenoid metabolism.",
    "datePublished" : "1999-03-01T00:00:00.000-06:00",
    "citation" : "Gupta SD, etal., J Lipid Res. 1999 Sep;40(9):1572-84.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2010-03-02T14:55:07.000-06:00",
    "volume" : "40",
    "pages" : "1572-84",
    "abstract" : "Farnesyl diphosphate synthase (FPPS: EC2.5.1.10), a key enzyme in isoprenoid metabolic pathways, catalyzes the synthesis of farnesyl diphosphate (FPP) an intermediate in the biosynthesis of both sterol and non-sterol isoprenoid end products. The localization of FPPS to peroxisomes has been reported (Krisans, S. K., J. Ericsson, P. A. Edwards, and G. A. Keller. 1994. J. Biol. Chem. 269: 14165;-14169). Using indirect immunofluorescence and immunoelectron microscopic techniques we show here that FPPS is localized predominantly in the peroxisomes of rat hepatoma H35 cells. However, the partial release of 60;-70% of cellular FPPS activity is observed by selective permeabilization of these cells with digitonin. Under these conditions, lactate dehydrogenase, a cytosolic enzyme, is completely released whereas catalase, a known peroxisomal enzyme, is fully retained. Digitonin treatment of H35 cells differentially affects the release of other peroxisomal enzymes involved in isoprenoid metabolism. For instance, mevalonate kinase and phosphomevalonate kinase are almost totally released (95% and 91%, respectively), whereas 3-hydroxy-3-methylglutaryl-CoA reductase is fully retained. Indirect immunoflourescence studies indicate that FPPS is localized in peroxisomes of Chinese hamster ovary (CHO)-K1 cells but is dispersed in the cytosol of ZR-82 cells, a mutant that lacks peroxisomes. Unlike in H35 cells, FPPS is completely released upon digitonin permeabilization of CHO-K1 and ZR-82 cells. In contrast, under the same permeabilization conditions, catalase is fully retained in CHO-K1 cells but completely released from ZR-82 cells. These studies indicate that FPPS and other enzymes in the isoprenoid biosynthetic pathways, involved in the formation of FPP, are differentially associated with peroxisomes and may easily diffuse to the cytosol. Based on these observations, the significance and a possible regulatory model in the formation of isoprenoid end-products are discussed.",
    "issueName" : "9",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SD",
      "lastName" : "Gupta",
      "authorRank" : 1,
      "name" : "Gupta SD",
      "referenceId" : "RGD:A91444"
    }, {
      "firstName" : "RS",
      "lastName" : "Mehan",
      "authorRank" : 2,
      "name" : "Mehan RS",
      "referenceId" : "RGD:A119987"
    }, {
      "firstName" : "TR",
      "lastName" : "Tansey",
      "authorRank" : 3,
      "name" : "Tansey TR",
      "referenceId" : "RGD:A119988"
    }, {
      "firstName" : "HT",
      "lastName" : "Chen",
      "authorRank" : 4,
      "name" : "Chen HT",
      "referenceId" : "RGD:A119989"
    }, {
      "firstName" : "G",
      "lastName" : "Goping",
      "authorRank" : 5,
      "name" : "Goping G",
      "referenceId" : "RGD:A38367"
    }, {
      "firstName" : "I",
      "lastName" : "Goldberg",
      "authorRank" : 6,
      "name" : "Goldberg I",
      "referenceId" : "RGD:A84325"
    }, {
      "firstName" : "I",
      "lastName" : "Shechter",
      "authorRank" : 7,
      "name" : "Shechter I",
      "referenceId" : "RGD:A119990"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:2316922"
    } ]
  }, {
    "primaryId" : "PMID:10484766",
    "title" : "Instability of the EPM1 minisatellite.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Larson GP, etal., Hum Mol Genet. 1999 Oct;8(11):1985-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T19:40:22.000-05:00",
    "volume" : "8",
    "pages" : "1985-8",
    "abstract" : "Inherited mutations in the cystatin B gene ( CSTB ) are responsible for progressive myoclonus epilepsy type 1 (EPM1; MIM 254800). This autosomal recessive disease is characterized by variable progression to mental retardation, dementia and ataxia. The majority of EPM1 alleles identified to date contain expansions of a dodecamer repeat located upstream of the transcription start site of the CSTB gene. Normal alleles contain two or three copies of the repeat, whereas pathogenic alleles contain >40 repeats. We examined the meiotic stability of pathogenic, expanded EPM1 alleles from 17 EPM1 families by employing a fluorescence-based PCR-based genotyping assay capable of detecting single dodecamer repeat unit differences on an automated DNA sequencer. We followed 74 expanded allele transmissions to 30 affected individuals and 22 carriers. Thirty-five of 74 expanded allele transmissions demonstrated either contraction or expansion of the minisatellite, typically by a single repeat unit. Thus expanded alleles of the EPM1 minisatellite demonstrate a mutation rate of 47%, the highest yet observed for pathogenetic alleles of a human minisatellite.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "GP",
      "lastName" : "Larson",
      "authorRank" : 1,
      "name" : "Larson GP",
      "referenceId" : "RGD:A91973"
    }, {
      "firstName" : "S",
      "lastName" : "Ding",
      "authorRank" : 2,
      "name" : "Ding",
      "referenceId" : "RGD:A173880"
    }, {
      "firstName" : "RG",
      "lastName" : "Lafreniere",
      "authorRank" : 3,
      "name" : "Lafreniere RG",
      "referenceId" : "RGD:A48362"
    }, {
      "firstName" : "GA",
      "lastName" : "Rouleau",
      "authorRank" : 4,
      "name" : "Rouleau GA",
      "referenceId" : "RGD:A43672"
    }, {
      "firstName" : "TG",
      "lastName" : "Krontiris",
      "authorRank" : 5,
      "name" : "Krontiris TG",
      "referenceId" : "RGD:A91991"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11066379"
    } ]
  }, {
    "primaryId" : "PMID:10484771",
    "title" : "Mutation -59c-->t in repeat 2 of the LDL receptor promoter: reduction in transcriptional activity and possible allelic interaction in a South African family with familial hypercholesterolaemia.",
    "datePublished" : "1999-08-01T00:00:00.000-05:00",
    "citation" : "Scholtz CL, etal., Hum Mol Genet. 1999 Oct;8(11):2025-30.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-08-10T20:14:13.000-05:00",
    "volume" : "8",
    "pages" : "2025-30",
    "abstract" : "The low-density lipoprotein receptor (LDLR) plays a major role in cholesterol homeostasis. Mutations in the regulatory region of the LDLR gene, although rare,  have been shown to alter transcriptional activity of the gene and can cause familial hypercholesterolaemia (FH). In this study, a transition (c-->t) was identified at nucleotide position -59 within repeat 2 of the LDLR promoter in a South African FH patient of mixed ancestry. By screening 17 family members of the index case for this promoter mutation, two additional single base changes (-124c-->t and-175g-->t) were identified, located at recently described cis- acting regulatory sequences of the LDLR promoter. Both the-59c-->t and the-124c-->t transitions were identified in the normocholesterolaemic son of the  index patient. Reporter plasmids containing the normal and mutant promoter fragments were constructed by directional cloning. Transcription studies using a  luciferase reporter system demonstrated that the-59c-->t mutation significantly reduces promoter activity in both the presence and absence of sterols ( approximately 40% of normal activity), while the-124c-->t variant increases transcription ( approximately 160%) of the LDLR gene. The intra-familial phenotypic variability observed amongst individuals with the-59c-->t mutation can probably be ascribed to allelic interaction, suggesting that variation in the LDLR promoter region may contribute significantly to the phenotypic expression of FH-related mutations in populations where these mutations prevail.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "CL",
      "lastName" : "Scholtz",
      "authorRank" : 1,
      "name" : "Scholtz",
      "referenceId" : "RGD:A282255"
    }, {
      "firstName" : "AV",
      "lastName" : "Peeters",
      "authorRank" : 2,
      "name" : "Peeters",
      "referenceId" : "RGD:A320462"
    }, {
      "firstName" : "CF",
      "lastName" : "Hoogendijk",
      "authorRank" : 3,
      "name" : "Hoogendijk",
      "referenceId" : "RGD:A282257"
    }, {
      "firstName" : "R",
      "lastName" : "Thiart",
      "authorRank" : 4,
      "name" : "Thiart",
      "referenceId" : "RGD:A282254"
    }, {
      "firstName" : "JN",
      "lastName" : "De Villiers",
      "authorRank" : 5,
      "name" : "De Villiers",
      "referenceId" : "RGD:A282258"
    }, {
      "firstName" : "R",
      "lastName" : "Hillermann",
      "authorRank" : 6,
      "name" : "Hillermann",
      "referenceId" : "RGD:A360540"
    }, {
      "firstName" : "J",
      "lastName" : "Liu",
      "authorRank" : 7,
      "name" : "Liu",
      "referenceId" : "RGD:A416319"
    }, {
      "firstName" : "AD",
      "lastName" : "Marais",
      "authorRank" : 8,
      "name" : "Marais",
      "referenceId" : "RGD:A360280"
    }, {
      "firstName" : "MJ",
      "lastName" : "Kotze",
      "authorRank" : 9,
      "name" : "Kotze MJ",
      "referenceId" : "RGD:A148949"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11526370"
    } ]
  }, {
    "primaryId" : "PMID:10484775",
    "title" : "Screening of the ryanodine receptor gene in 105 malignant hyperthermia families:  novel mutations and concordance with the in vitro contracture test.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Brandt A, etal., Hum Mol Genet. 1999 Oct;8(11):2055-62.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T21:11:36.000-05:00",
    "volume" : "8",
    "pages" : "2055-62",
    "abstract" : "Malignant hyperthermia (MH) in man is an autosomal dominant disorder of skeletal  muscle Ca(2+)-regulation. During anesthesia in predisposed individuals, it is triggered by volatile anesthetics and depolarizing muscle relaxants. In >50% of the families, MH susceptibility is linked to the gene encoding the skeletal muscle ryanodine receptor (RYR1), the calcium release channel of the sarcoplasmic reticulum, on chromosome 19q12-13.2. To date, 21 RYR1 mutations have been identified in a number of pedigrees. Four of them are also associated with central core disease (CCD), a congenital myopathy. Screening for these 21 mutations in 105 MH families including 10 CCD families phenotyped by the in vitro contracture test (IVCT) according to the European protocol revealed the following approximate distribution: 9% Arg-614-Cys, 1% Arg-614-Leu, 1% Arg-2163-Cys, 1% Val-2168-Met, 3% Thr-2206-Met and 7% Gly-2434-Arg. In one CCD family, the disease was caused by a recently reported MH mutation, Arg-2454-His. Two novel mutations, Thr-2206-Arg and Arg-2454-Cys were detected, each in a single pedigree. In the 109 individuals of the 25 families with RYR1 mutations cosegregation between genetic result and IVCT was almost perfect, only three genotypes were discordant  with the IVCT phenotypes, suggesting a true sensitivity of 98.5% and a specificity of minimally 81.8% for this test. Screening of the transmembraneous region of RYR1 did not yield a new mutation confirming the cytosolic portion of the protein to be of main functional importance for disease pathogenesis.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A",
      "lastName" : "Brandt",
      "authorRank" : 1,
      "name" : "Brandt A",
      "referenceId" : "RGD:A72935"
    }, {
      "firstName" : "L",
      "lastName" : "Schleithoff",
      "authorRank" : 2,
      "name" : "Schleithoff",
      "referenceId" : "RGD:A271413"
    }, {
      "firstName" : "K",
      "lastName" : "Jurkat-Rott",
      "authorRank" : 3,
      "name" : "Jurkat-Rott K",
      "referenceId" : "RGD:A44874"
    }, {
      "firstName" : "W",
      "lastName" : "Klingler",
      "authorRank" : 4,
      "name" : "Klingler",
      "referenceId" : "RGD:A269954"
    }, {
      "firstName" : "C",
      "lastName" : "Baur",
      "authorRank" : 5,
      "name" : "Baur",
      "referenceId" : "RGD:A271414"
    }, {
      "firstName" : "F",
      "lastName" : "Lehmann-Horn",
      "authorRank" : 6,
      "name" : "Lehmann-Horn F",
      "referenceId" : "RGD:A82229"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:11068538"
    } ]
  }, {
    "primaryId" : "PMID:10484776",
    "title" : "The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II.",
    "datePublished" : "1999-01-01T00:00:00.000-06:00",
    "citation" : "Cramer SD, etal., Hum Mol Genet. 1999 Oct;8(11):2063-9.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2007-01-30T11:12:16.000-06:00",
    "volume" : "8",
    "pages" : "2063-9",
    "abstract" : "Primary hyperoxaluria type II (PH2) is a rare monogenic disorder that is characterized by a lack of the enzyme that catalyzes the reduction of hydroxypyruvate to D-glycerate, the reduction of glyoxylate to glycolate and the oxidation of D-glycerate to hydroxypyruvate. The disease is characterized by an elevated urinary excretion of oxalate and L-glycerate. The increased oxalate excretion can cause nephrolithiasis and nephrocalci-nosis and can, in some cases, result in renal failure and systemic oxalate deposition. We identified a glyoxylate reductase/hydroxypyruvate reductase (GRHPR) cDNA clone from a human liver expressed sequence tag (EST) library. Nucleotide sequence analysis identified a 1198 nucleotide clone that encoded a 984 nucleotide open reading frame. The open reading frame encodes a predicted 328 amino acid protein with a mass of 35 563 Da. Transient transfection of the cDNA clone into COS cells verified that it encoded an enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Database analysis of human ESTs reveals widespread tissue expression, indicating that the enzyme may have a previously unrecognized role in metabolism. The genomic structure of the human GRHPR gene was determined and contains nine exons and eight introns and spans approximately 9 kb pericentromeric on chromosome 9. Four PH2 patients representing two pairs of siblings from two unrelated families were analyzed for mutations in GRHPR by single strand conformation polymorphism analysis. All four patients were homozygous for a single nucleotide deletion at codon 35 in exon 2, resulting in a premature stop codon at codon 45. The cDNA that we have identified represents the first characterization of an animal GRHPR sequence. The data we present will facilitate future genetic testing to confirm the clinical diagnosis of PH2. These data will also facilitate heterozygote testing and prenatal testing in families affected with PH2 to aid in genetic counseling.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "SD",
      "lastName" : "Cramer",
      "authorRank" : 1,
      "name" : "Cramer SD",
      "referenceId" : "RGD:A73328"
    }, {
      "firstName" : "PM",
      "lastName" : "Ferree",
      "authorRank" : 2,
      "name" : "Ferree PM",
      "referenceId" : "RGD:A73329"
    }, {
      "firstName" : "K",
      "lastName" : "Lin",
      "authorRank" : 3,
      "name" : "Lin K",
      "referenceId" : "RGD:A66460"
    }, {
      "firstName" : "DS",
      "lastName" : "Milliner",
      "authorRank" : 4,
      "name" : "Milliner DS",
      "referenceId" : "RGD:A8974"
    }, {
      "firstName" : "RP",
      "lastName" : "Holmes",
      "authorRank" : 5,
      "name" : "Holmes RP",
      "referenceId" : "RGD:A73330"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:1599318"
    } ]
  }, {
    "primaryId" : "PMID:10484780",
    "title" : "Splicing modulation of integrin beta4 pre-mRNA carrying a branch point mutation underlies epidermolysis bullosa with pyloric atresia undergoing spontaneous amelioration with ageing.",
    "datePublished" : "1999-10-01T00:00:00.000-05:00",
    "citation" : "Chavanas S, etal., Hum Mol Genet. 1999 Oct;8(11):2097-105. doi: 10.1093/hmg/8.11.2097.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T16:16:47.000-05:00",
    "volume" : "8",
    "pages" : "2097-105",
    "abstract" : "A general improvement with ageing has been reported in a few cases of epidermolysis bullosa with pyloric atresia (PA-JEB), an autosomal recessive skin disease characterized by extensive disadhesion of epithelia. In a patient who improved from severe to mild PA-JEB, a search for mutations in the integrin beta4 gene (IGTB4) detected heterozygosity for a novel base substitution 3986-19T-->A in the putative branchpoint sequence of intron 31, and a point mutation 3802+1G-->A in the donor splice site of intron 30 previously associated with severe PA-JEB. Analysis of mRNA showed that the intronic mutation prevents legitimate splicing of the beta4 pre-mRNA. Functional splicing can be restored in vitro by seeding the proband's keratinocytes on feeders of irradiated fibroblasts. Study of mRNA in wild-type keratinocytes transfected with IGTB4 minigenes containing intron 31 with or without mutation 3986-19T-->A, confirmed the causative role of the intronic mutation in PA-JEB, and highlighted the influence of feeders on the maturation process of the mutated beta4 pre-mRNA. Our results show that in a context of overall reduction of the beta4 mRNA levels, activation of the legitimate splice site in the aberrant beta4 pre-mRNA underlies the transient severity of the condition. The results also point to the relevance which the interaction between epithelial and stromal cells may have in modulating expression of integrin receptors.",
    "issueName" : "11",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Chavanas",
      "authorRank" : 1,
      "name" : "Chavanas S",
      "referenceId" : "RGD:A72486"
    }, {
      "firstName" : "Y",
      "lastName" : "Gache",
      "authorRank" : 2,
      "name" : "Gache Y",
      "referenceId" : "RGD:A590412"
    }, {
      "firstName" : "J",
      "lastName" : "Vailly",
      "authorRank" : 3,
      "name" : "Vailly J",
      "referenceId" : "RGD:A590413"
    }, {
      "firstName" : "J",
      "lastName" : "Kanitakis",
      "authorRank" : 4,
      "name" : "Kanitakis J",
      "referenceId" : "RGD:A590414"
    }, {
      "firstName" : "L",
      "lastName" : "Pulkkinen",
      "authorRank" : 5,
      "name" : "Pulkkinen L",
      "referenceId" : "RGD:A55940"
    }, {
      "firstName" : "J",
      "lastName" : "Uitto",
      "authorRank" : 6,
      "name" : "Uitto J",
      "referenceId" : "RGD:A50586"
    }, {
      "firstName" : "J",
      "lastName" : "Ortonne",
      "authorRank" : 7,
      "name" : "Ortonne J",
      "referenceId" : "RGD:A590415"
    }, {
      "firstName" : "G",
      "lastName" : "Meneguzzi",
      "authorRank" : 8,
      "name" : "Meneguzzi G",
      "referenceId" : "RGD:A75897"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598117812"
    } ]
  }, {
    "primaryId" : "PMID:10484795",
    "title" : "Genetic analysis of the G4.5 gene in families with suspected Barth syndrome.",
    "datePublished" : "1999-09-01T00:00:00.000-05:00",
    "citation" : "Cantlay AM, etal., J Pediatr. 1999 Sep;135(3):311-5. doi: 10.1016/s0022-3476(99)70126-5.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2025-04-07T14:31:05.000-05:00",
    "volume" : "135",
    "pages" : "311-5",
    "abstract" : "Mutations have recently been identified in the G4.5 gene (Xq28), encoding the tafazzin protein, in patients with Barth syndrome. We performed mutational analysis in 5 families with suspected Barth syndrome. In 4 families a male child had all the cardinal features of this syndrome, and mutations of G4.5 were found in each case. A mutation was also found in a fifth family with an extensive history of early infant death from heart disease. The recognition of 5 unrelated families in 1 hospital during a 7-year period suggests that this disease may be underdiagnosed.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "A M",
      "lastName" : "Cantlay",
      "authorRank" : 1,
      "name" : "Cantlay AM",
      "referenceId" : "RGD:A566808"
    }, {
      "firstName" : "K",
      "lastName" : "Shokrollahi",
      "authorRank" : 2,
      "name" : "Shokrollahi K",
      "referenceId" : "RGD:A566809"
    }, {
      "firstName" : "J T",
      "lastName" : "Allen",
      "authorRank" : 3,
      "name" : "Allen JT",
      "referenceId" : "RGD:A566810"
    }, {
      "firstName" : "P W",
      "lastName" : "Lunt",
      "authorRank" : 4,
      "name" : "Lunt PW",
      "referenceId" : "RGD:A566811"
    }, {
      "firstName" : "R A",
      "lastName" : "Newbury-Ecob",
      "authorRank" : 5,
      "name" : "Newbury-Ecob RA",
      "referenceId" : "RGD:A566812"
    }, {
      "firstName" : "C G",
      "lastName" : "Steward",
      "authorRank" : 6,
      "name" : "Steward CG",
      "referenceId" : "RGD:A566813"
    } ],
    "crossReferences" : [ {
      "pages" : [ "reference" ],
      "id" : "RGD:598114723"
    } ]
  }, {
    "primaryId" : "PMID:10484807",
    "title" : "Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.",
    "datePublished" : "1999-04-01T00:00:00.000-06:00",
    "citation" : "Kure S, etal., J Pediatr. 1999 Sep;135(3):375-8.",
    "allianceCategory" : "Research Article",
    "dateLastModified" : "2016-04-27T18:37:29.000-05:00",
    "volume" : "135",
    "pages" : "375-8",
    "abstract" : "Serum phenylalanine concentrations decreased in 4 patients with hyperphenylalaninemia after loading with tetrahydrobiopterin. There were no abnormalities in urinary pteridine excretion or in dihydropteridine reductase activity. However, mutations were detected in the phenylalanine hydroxylase gene, suggesting a novel subtype of phenylalanine hydroxylase deficiency that may respond to treatment with cofactor supplementation.",
    "issueName" : "3",
    "MODReferenceTypes" : [ {
      "referenceType" : "JOURNAL ARTICLE",
      "source" : "RGD"
    } ],
    "authors" : [ {
      "firstName" : "S",
      "lastName" : "Kure",
      "authorRank" : 1,
      "name" : "Kure S",
      "referenceId" : "RGD:A16148"
    }, {
      "firstName" : "DC",
      "lastName" : "Hou",
      "authorRank" : 2,
      "name" : "Hou",
      "referenceId" : "RGD:A258962"
    }, {
      "firstName" : "T",
      "lastName" : "Ohura",
      "authorRank" : 3,
      "name" : "Ohura T",
      "referenceId" : "RGD:A21436"
    }, {
      "firstName" : "H",
      "lastName" : "Iwamoto",
      "authorRank" : 4,
      "name" : "Iwamoto H",
      "referenceId" : "RGD:A29614"
    }, {
      "firstName" : "S",
      "lastName" : "Suzuki",
      "authorRank" : 5,
      "name" : "Suzuki S",
      "referenceId" : "RGD:A9090"
    }, {
      "firstName" : "N",
      "lastName" : "Sugiyama",
      "authorRank" : 6,
      "name" : "Sugiyama N",