1998 Fiscal Year Final Research Report Summary
INTIMAL HYPERPLASIA and GENE MAPPING IN MOYAMOYA DISEASE
| Project/Area Number |
09671412
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | TOKYO MEDICAL & DENTAL UNIVERSITY,SCHOOL OF MEDICINE |
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Principal Investigator |
MATSUSHIMA Yoshiharu TOKYO MEDICAL & DENTAL UNIVERSITY,SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (20134679)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Masashi TOKYO MEDICAL & DENTAL UNIVERSITY,SCHOOL OF MEDICINE,INSTRUCTOR, 医学部, 助手 (30301154)
YAMAMOTO Kiyotaka TOKYO METROPORITAN INSTITUTE OF GERONTOLOGY,DEPARTMENT OF CELL BIOLOGY,CHIEF RES, 細胞生物部門, 主任研究員 (90073022)
AOYAGI Masaru TOKYO MEDICAL & DENTAL UNIVERSITY,SCHOOL OF MEDICINE,LECTURER, 医学部, 講師 (40134704)
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| Project Period (FY) |
1997 – 1998
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| Keywords | moyamoya disease / familial occurence / gene analysis / muscle, smooth / arterial wall / elastin / IL-1 |
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| Research Abstract |
(1) We investigated the elastin synthesis and elastin mRNA levels both in sections from superficial temporal arteries (STA) and cultured SMCs derived from moyamoya patients. The intimal lesions of STA of moyamoya patients contained strongly stained multilayered elastic fibers while no difference in collagen staining was seen between moyamoya and control STA.In situ hybridyzation for tropoelastin transcripts showed strong positive signals in neontimal SMCs of moyamoya patients. Elastin mRNA and protein synthesis levels were significantly greater in cultured moyamoya SMCs than control SMCs. The data indicate that the increased elastin synthesis and mRNA is a stable maker of moyamoya SMCs and that genetic changes which can regulate the elastin transcripts may be responsible for the pathogenesis of moyamoya disease. (2) We examined the chemotactic and proliferative activities of growth factors and inflammmatroy cytokines on arterial smooth muscle cells (SMC) derived from moyamoya patients. Interleukin-1beta (IL-1beta) significantly stimulated the migation and DNA syntehsis of control SMC, while it inhibited moyamoya SMC migration. The differences in responses to PDGF and IL-1 in moyamoya SMC are involved in the mechanism by which intimal thickening develops in moyamoya disease. (3) We investigated the familial occurence of moyamoya disease using magnetic resonance angiography (MRA). We colleted three familial moyamoya pedigrees. We collected blood samples from moyamoya patients and normal subjects in these families, and are now performing linkage analysis using the genomic DNA.The final results have not been obtained. However, much larger pedigrees may be necessary for the sucessful gene mapping of this disease.
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