| Project/Area Number |
63870032
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Kumamoto University |
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Principal Investigator |
MAEDA Hiroshi Kumamoto Univ. Med. School. Dept. Microbiol., Professor, 医学部, 教授 (90004613)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Yuichiro Kumamoto Univ. Med. School, Dept. Microbiol., Assist., 医学部, 助手 (50215258)
松村 保広 熊本大学, 医学部, 助手 (90209619)
井上 正康 熊本大学, 医学部, 助教授 (80040278)
佐々木 征治 天野製薬研究所, 主任研究員
小田 達也 熊本大学, 医学部, 講師 (60145307)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Bilirubin / Jaundice / Kernicterus / Bilirubin oxidase / Polyethylene glycol conjugate / Fluminant hepatitis / Hepatitis / Liver function / 黄疽 / 肝硬変 / ポリエチレングリコ-ル結合型酵素 / 肝不全 / 新生児核黄疸 / 減黄療法 / ポリエチレングリコール結合型酵素製剤 / PEG結合酵素 |
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| Research Abstract |
The clinical cause of jaundice is known to be due to elevated plasma level of bilirubin, and its removal is a critical factor. We have elucidated that bilirubin is toxic to even cells in culture in that it suppress DNA, RNA and protein syntheses and membrane transport. A microbial enzyme called bilirubin oxidase can detoxify all these toxic effects. The degradation products of bilirubin by this enzyme were found to be excreted from the kidney, thus, transhepatic elimination is not required for detoxification. Polymer conjugated bilirubin oxidase does the same job as expected in vitro. When rats were artificially made jaundice by ligating and cutting the bile duct and then, they were treated with polymer-conjugated bilirubin oxidase by intravenous (i. v.) injection. The result was that the polymer conjugate exhibited a pronounced reduction in the plasma bilirubin level to the normal upto 48hr after injection, whereas the native oxidase did so only a little at 30 min post injection only. Furthermore immunological problems associated with injection with native bilirubin oxidase was removed more than 95% in the polymer conjugated one. There was little toxicity observed upon i. v. injection of this polymer-enzyme conjugate at the therapeutic dose. Thus, its clinical application appears feasible.
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