| Project/Area Number |
06454208
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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 |
Bacteriology (including Mycology)
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| Research Institution | Kumamoto University |
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Principal Investigator |
MAEDA Hiroshi Kumamoto University School of Medicine Professor, 医学部, 教授 (90004613)
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| Co-Investigator(Kenkyū-buntansha) |
NOGUCHI Youichiro Kumamoto University School of Medicine Instructor, 医学部, 助手 (10244112)
AKAIKE Takaaki Kumamoto University School of Medicine Associate Professor, 医学部, 助教授 (20231798)
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| Project Period (FY) |
1994 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1995: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | bacterial protease / bradykinin / matrix metalloprotease / sepsis / bacterial invasion / septic shock / 好中球プロコラゲナーゼ / 一酸化窒素 / 敗血症 / Vibrio vulnificus / S.pyogenes protease / NO / 血管透過性亢進 / 浮腫 / ブラジキニンアンタゴニスト |
|---|
| Research Abstract |
A hall-mark event as the involvement of host protease is the activation of Hageman factor-prekallikrein-kinin cascade which can be coupled with blood coagulation cascade and complement activation. In our previous study, it is revealed that kinin (bradykinin) is generated as a result of kinin-generating cascade which can be activated by all microbial proteases at one or more steps. This cascade is also activated by negatively charged surface of both gram positive (teichoic acid) and negative (lipopolysaccharide) bacteria. Bradykinin is responsible for pain, edema, extravasation, bacterial translocation/dissemination, thrombus formation or DIC and multiple organ failure, hypotension and shock. Our results obtained by the present research indicate that tissuedestruction by microbial proteases can take place either directly or indirectly by activating matrix metalloproteases of the hosts. Moreover, importance of development of kinin receptor antagonists and potent protease inhibitors with broad antiprotease spectrum is now realized.
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