| Project/Area Number |
03304049
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
AOKI Nobuo Tokyo Medical & Dental University, Department of Medicine, Professor, 医学部, 教授 (20048937)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Hidehiko Nagoya University, Department of Medicine, Professor, 医学部, 教授 (20153819)
OHKUMA Minoru Kyoto University, Department of Medicine, Professor, 医学部, 教授 (50026986)
IWANAGA Sadaaki Kyushu University, Department of Science, Professor, 理学部, 教授 (90029942)
KURAMOTO Atsushi Hiroshima University, Research Institute for Nuclear Medicine and Biology, Profe, 原爆放射能医学研究所・臨床部門, 教授 (50034070)
TITANI Koichi Fujita Health University, Institute for Medical Sciences, Professor, 総合医科学研究所, 教授 (60179942)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥23,900,000 (Direct Cost: ¥23,900,000)
Fiscal Year 1992: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 1991: ¥12,900,000 (Direct Cost: ¥12,900,000)
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| Keywords | thrombosis / blood coagulation / platelet / fibrinolysis / blood group / blood vessels / プロテインC / 組織因子 / プラスミノゲンアクチベ-タ-インヒビタ- / 血小板膜糖蛋白 / フオンウイルブランド因子 |
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| Research Abstract |
The study was focused mainly on the four subjects : Regulatory components of thrombus formation, initiation steps of extrinsic coagulation system, sugar chains of coagulation-related components, and platelet membrane. 1. Reguratory components of thrombus formation : Thrombomodulin, anticoagulant protein on surface membrane of endothelial cells, is increased by many stimulants. Its increase was found to be caused mainly by the increase of a high molecular weight type (a sugar-rich type). Four genetic abnormalities causing protein-C deficiency in 3 independent families were elucidated.The deficiency was found to be caused by failure of intracellular transport and secretion of the abnormal proteins produced. Structurally and functionally abnormal protein S, a cofactor of activated protein C, was newly discovered and characterized. 2. Initiation steps of extrinsic coagulation system : Cloning of cDNA for tissue factor in coagulation and its expression were successfully carried out. Monoclonal antibodies to recombinant tissue factor were produced, and the antibodies were used for the study on tissue factor antigen levels in circulation under various disease states. 3. Sugar chains of coagulation-related proteins : Sugar chains of coagulation factors VII, IX, XII and von Willebrand factor were characterized. ABO(H) blood type sugar chains were found to be present in von Willebrand factor and alpha 2 macroglobulin. 4. Cloning and structural characterization of cDNA for platelet membrane GPV were carried out. GPV was found to contain leucin-rich repeated structure and be released into plasma as a soluble form by thrombin. Interaction reaction of platelet and collagen was analyzed, and platelet membrane glycoprotein p62 (GP VI) was suggested to be involved in the reaction leading to the platelet activation. Platelet membrane receptor for thromboxane A2, a powerful agonist for platelet aggregation, was cloned and purified.
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