| Project/Area Number |
13470108
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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 |
内科学一般
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
OZAKI Shoichi St. Marianna Univ Sch Med Professor, 医学部, 教授 (00231233)
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| Co-Investigator(Kenkyū-buntansha) |
KOIKE Kaoru Tohoku Univ Grad Sch Med Assoc Professor, 医学研究科, 助教授 (10267164)
YOSHIDA Michiteru Science Univ Tokyo Professor, 基礎工学部, 教授 (20005648)
YAMADA Hidehiro St. Marianna Univ Sch Med Assoc Professor, 医学部, 助教授 (00174730)
OHYA Kazuhiko St. Marianna Univ Med Biology Laboratory Chief Investigator, 伊那研究所応用技術部, 主任研究員
村上 雅朗 京都大学, 医学研究科, 助手 (90301738)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2001: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | HMG1 / receptor / anti-HMG antibody / Shock / autoimmune disease / ELISA / epitope / RAGE |
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| Research Abstract |
We isolated high mobility group (HMG) nonhisitone chromosomal proteins 1 and 2 (HMG1/HMG2) as target antigens of anti-neutrophil cytoplasmic antibody (ANCA), and have been analyzing the roles of those autoantibodies as well as the autoantigens. We found the existence of anti-HMG1/HMG2 antibodies in 89% of patients with autoimmune hepatitis. These antibodies seemed to be useful clinical markers in the disease based on the highest prevalence and the correlation with disease activity. We also observed that HMG1 selectively enhanced the proliferation of cholangial cell lines in a dose-dependent manner.
We established an ELISA system for soluble HMG1 protein by using both polyclonal and monoclonal anti-HMG1/HMG2 antibody, which enabled us to test a serum HMG1 level as high as 10 micrograms/ml. We found that serum HMG1 reached a detectable level in fatal shock patients as long as we tested. We also established a novel fatal mouse model, in which 90% of the hepatic blood flow was blocked by a surgical procedure. All mice died 60 hr after the ligation, prior to which their serum HMG1 levels significantly increased. The survival rate increased by a simultaneous ip injection of monoclonal anti-HMG1 antibody. Taken together, these data indicates that HMG1 protein may play an important role in a certain fatal condition, and that the intervention of serum HMG1 levels may serve as a new strategy for such a critical state.
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