| Project/Area Number |
62570411
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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 |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
MIYABAYASHI Shigeaki Depertment of Pediatrics, Tohoku University School of Medicine, 医学部附属病院, 講師 (20174203)
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| Co-Investigator(Kenkyū-buntansha) |
HAGINOYA Kazuhiro Depertment of Pediatrics, Tohoku University School of Medicine, 医学部附属病院, 助手 (00208414)
黒羽根 郁夫 東北大学, 医学部・付属病院・小児科, 医員
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | mitochondrial myopathy / mitochondrial DNA / NADH-ubiquinone oxidoreductase deficiency / cytochrome c oxidase deficiency / immunoblotting / 細胞毎のモザイク / ミトコンドリアDNA / ミトコンドリア電子伝達系酸素欠損症 / ミトコンドリアサイトパチー / cytochrome C oxidase 欠損症 / NADH-coQ reductase欠損症 / 免疫組織化学 / 培養線維芽細胞 / Digitonin 処理 / 組織特異性 |
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| Research Abstract |
Biochemical studies revealed eleven cases of complex I (Hadh-ubiquinone oxidoreductase) deficiency, eleven cases of complex IV (cytochrome c oxidase, CCO) deficiency and five cases of deficiency of multiple oxidative phosphorylation enzymes. Immunochemical and immunohistochemical studies were performed on the skeletal muscle and fibroblasts of these patients in order to understand the molecular defect of this particular disorder.
All patients with complex I deficiency of muscular type were clinically diagnosed as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes). Western blotting using antiserum against complex I revealed generalized a decrease of all subunits, especially the decrease of higher molecular subunits (75, 42 and 39 kilodalton). In systemic complex I deficiency, the activity of complex I was decreased in fibroblasts. These patients showed early onset of clinical symptoms and high mortality.
In three cases of systemic complex IV deficiency i
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mmunoblot analysis revealed a mild decrease of all subunits in fibroblasts and brain as well as muscle and liver. In a case of muscular CCO deficiency immunological analysis revealed a generalized decrease of all sudunits and a complete defect of subunit II. In seven cases with partial CCO deficiency in muscle, histochemical and immunohistochemical analyses of their skeletal muscle showed mosaic pattern including positive and negative stained fibers.
Three cases had combined deficiency of complex I and Complex IV. Immunohistochemical and histochemical study on muscle showed mosaic pattern on CCO staininh. Two cases had multiple deficiencies of oxidative phosphorylation exzymes. They were clinically classified as the so-called fatal infantile type of CCO deficiency. In these two cases activities of other oxidative phosphorylation enzymes were markedly decreased as well as complex IV in muscle. Immunoblotting analysis in their muscle mitochondria showed reduction of CRM for antiserum against each complex enzyme in parallel with their activity.
Further study on mitochondrial DNA is necessary to understand the pathogenesis of mitochondrial myopathy. Less
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