| Project/Area Number |
07044232
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
HANDA Shizuo Department of Biochemistry, School of Medicine, Tokyo Medical and Dental University, Professor, 医学部, 教授 (00009987)
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| Co-Investigator(Kenkyū-buntansha) |
YU Robert K Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, 教授
TAKI Takao Department of Biochemistry, School of Medicine, Tokyo Medical and Dental Univers, 医学部, 助教授 (10046295)
ROBERT K.Yu Dept. of Biochemistry and Molecular Bioph, 教授
有賀 敏夫 Medical College of Virginia, Virginia Com, 助教授
YU Robert K. Medical College of Virginia, Virginia Com, 教授
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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 |
¥23,400,000 (Direct Cost: ¥23,400,000)
Fiscal Year 1996: ¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 1995: ¥11,700,000 (Direct Cost: ¥11,700,000)
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| Keywords | autoantibody / gangliosides / glycolipids / glycosphingolipds / lipopolysaccharides / motor neuron diseases / molecuular mimicry / nervous system / C.jejuni / フィッシャー症候群 / 先行感染 / 自己免疫疾患 |
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| Research Abstract |
Although the participation of the autoantibody is suspected, the etiology of the motor neuron diseases is not yet established.
In many cases high titer of antibodies, especially against to glycosphingolips, are detected. Glycosphingolipds are the membrane components of the nervous system, and their expression is different dependent on cells, differentiation, and cell growth. Frequently, autoantibodies against glycolipds reacted with the nervous cells and damaged the nervous functions.
In this research project we show the characteristic distribution of the glycolipids in the nervous system, and the expression of these glycolipids can be modulated by the introduction of the genes of the enzymes related to the metabolism of glycolipids.
Infections such as enteritis are frequently observed before the onset of the neural diseases, and we found that the microbes of the previous infection show the molecular mimicry with the sphingoglycolipids of the nervous system. These molecular mimicry between the lipopolysaccharides of several strains of C.jejuni and various kinds of gangliosides are proved immunologically and chemically.
Antibodies against sulfated glucuronyl glycolipids with or without M-proteinemia also reacted with nervous system. These reactions to the nervous system is confirmed morphologically, immunologically and electrophysiologically with the monoclonal antibody and also sera from the patients in vivo and also in vitro using the artificial model of blood-nerve barrier.
We can present the evidence that the anti-glycolipid antibody is produced by infection before the onset of disease, and this antibody damages the nerous system due to the molecular mimicry between the microbes and structural components of the nervou system.
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