| Project/Area Number |
07457155
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Shinshu University |
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Principal Investigator |
KOH Shosei Shinshu University Hispital, Department of Medicine (Neurology), Assistant Professor, 医学部・附属病院, 講師 (80143981)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Atsushi Shinshu University School of Medicine, Department of Medicine (Neurology), Assoc, 医学部, 助手 (50213145)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | multiple sclerosis / demyelination / Theiler's virus / antibody / adhesion molecules / 実験的自己免疫性脳脊髄炎 / タイラー脳脊髄炎ウイルス / 免疫寛容 |
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| Research Abstract |
We examined the role of leukocyte function-asociated antigen-1 (LFA-1) and its counter-receptor intercellular adhesion molecule-1 (ICAM-1), one of the most important pairs among adhesion molecules, in the development of Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD). Immunohistochemical study showed hyperexpression of ICAM-1 on vascular endothelial cells and LFA-1 on mononuclear infiltrating cells in spinal cord from TMEV infected mice. Treatment with anti ICAM-1 or anti LFA-1 monoclonal antibody showed suppressive effect on developement of demyelinating disease both clinically and histologically. There was downregulation in the CNS of the respective adhesion molecule after treatment. In mice treated with monoclonal antobodies to these adhesion molecules, TMEV specific delayd type hypersensitrvity and the proliferative response of T cells were decreased, and the production of TNFa and IFNg in the spleen cells was decreased and that of IL4 remained unchanged. These data suggest that ICAM-1-LFA-1 pathway is critically involved in the pathogenesis of TMEV-IDD and that antibodies to these adhesion molecules could be a novel therapeutic approach to demyelinating disease such as human multiple sclerosis.
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