| Project/Area Number |
05670977
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Institute for Developmental Research, Aichi prefectural colony |
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Principal Investigator |
KEINO Hiroomi Institute for Developmental Research, Aichi prefectural colony, Department of Perinatology, Section Chief, 周生期学部, 室長 (30090426)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAE Hidetoshi Aoyama Hospital Pediatrics, Section Chief, 小児科, 医長
OZEKI Junnko Institute for Developmental Research, Aichi prefectural colony, Department of Pe, 周生期学部, 助手
BANNO Toshikazu Institute for Developmental Research, Aichi prefectural colony, Department of Pe, 周生期学部, 助手
AONO Sachiko Institute for Developmental Research, Aichi prefectural colony, Department of Pe, 周生期学部, 研究員 (20231780)
長江 英利 青山病院, 小児科, 医長
鈴木 順子 愛知県心身障害者コロニー発達障害研究所, 助手
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Capping / Yeast / Guanylytransferase / Temperature-sensitive mutants / ガンラット / 遺伝子解析 / ポルフィリン / ラジカル / jaundice / bilirubin / Crigler Najjar type I / Crigler Najjar type II / Gilbert's syndrome / glucuronosylation / gene / EC 2.4.1.17 / クリグラーナジャー症候群 / ヘムオキシゲネース / 光増感性 / 遺伝子診断 / グルクロン酸転移酵素 |
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| Research Abstract |
We investigate new type of defect in the gene for bilirubin UGT in patient with Crigler-Najjar syndrome (CN) type I.This mutation is a single nucleotide substitution, and this mutation results in a stop codon. The patient is homozygous for the defect, and his nonconsanguineous parents, who are clinically normal, are heterozygous for the defective allele. We analyzed the CN sequeuce of the bilirubin UGT genes in patient with CN type II.Three point mutations were found on the genes. The abnormalities were single nucleotide substitutions. These three mutations result in changes of amino acid of the bilirubin UGT protein. Our patient was homozygous for this defects and his parents and elder brother were heterozygous for the defective alleles. The findings suggest that the CN type II is inherited as an autosomal recessive trait. We analyzed the genetic background of nine patients with Gilbert's syndrome (GS). Six kinds of point mutations were investigated in bilirubin UGT gene. Each patient was heterozygous for a point mutation.
The combination of injection of tin-protoporphyrin (SnPP) and photoirradiaiton produced an acute decrease in serum glucose levels and reacted with neurological signs, changes in blood pressure and eventual death. The release of arylsulfatase from lysosome was investigated in hepatocytes in vivo and in vitro. L-ascorbic acid was found to be most effective in protecting SnPP-treated rats against phototoxiocity. The survival period was markedly prolonged, and the frequency of abnormal behaviors was reduced with the treatment. Cobalt-mesoporphyrin inhibited the activity of rat splenic heme oxygenase but scarcely stimulated peroxidation of lipids. Cobalt-mesoporphyrin may be a promising candidate for a chemopreventive of neonatal hyperbilirubinemia.
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