A study for diagnosis and pathophysiology in neuromuscular disorders due to mitochondrial enzyme defects
| Project/Area Number |
61570397
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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 |
Neurology
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| Research Institution | National Institute of Neuroscience,NCNP |
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Principal Investigator |
NONAKA Ikuya Division of Ultrastructural Research,National Institute of Nauroscience,NCNP, 神経研究所・微細構造研究部, 部長 (80040210)
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| Co-Investigator(Kenkyū-buntansha) |
KIKUCHI Aiko Division of Ultrastructural Research,National Institute of Nauroscience,NCNP, 神経センター神経研究所・微細構造研究部, 研究員 (70159010)
AIKAWA Hisashi Division of Ultrastructural Research,National Institute of Nauroscience,NCNP, 神経センター神経研究所・微細構造研究部, 室長 (30184013)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1987: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1986: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Mitochondrial myopathy / Derect in electron transport system / Muscle biopsy / 筋病理 |
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| Research Abstract |
To confirm the presence of mitochondrial disorders,histochemical and biochemical examinations were performed on biopsied muscles from patients with increased serm lactate and pyruvate levels,and progressive neurological symptoms.From the present study,various enzyme defects were identified including 36 patients with cytochrome c oxidase (CCO) deficiency (2 patients; fatal infantile,2; bening infantile,12; encephalomyopathic,20; focal deficient form),and 13 complex I deficiency.In the encephalomyopathic CCO deficiency,the ragged-red fibers reflecting an abnormally proliterated mitochondria in the sarcoplasm were seen in 5 of 12 muscles mostly in patients more than 6 years of age.Muscle spindles and blood vessel walls in the biopsied muscles from 3 patients with rapid clinical aggravation had no CCO activity,suggesting that enzyme activity differed from tissue to tissue (tissue specificity). The tissue specificity was also confirmed an in vitro study using cultured muscle specimens and skin fibroblasts.In addition, four patients who had multiple muscle biopsies at several year intervals showed variability in the activity of respiratory chain enzymes.
The blooc vessels in the biopsied muscles from 7 patients with complex I deficiency with clinical character istics of MELAS (mitochondrial myopathy, encephalopathy,lactic acidosis and stroke-like episodes) showed striking abnormalities in blood vessels.Enlarged mitochondria with complicated cristae were increased in number in the pericytes of capillaries,endothelial cells and smooth muscle cells of the small arteries including terminal arterioles and precapillary shincters,predominantly in the smooth muscle cells.
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Report
(2 results)
Research Products
(16 results)
