Project/Area Number |
63304045
|
Research Category |
Grant-in-Aid for Co-operative Research (A)
|
Allocation Type | Single-year Grants |
Research Field |
Hematology
|
Research Institution | Kyushu University |
Principal Investigator |
SUEISHI Katsuo Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (70108710)
|
Co-Investigator(Kenkyū-buntansha) |
SUZUKI Koji Tokushima University, Faculty of Medicine, Professor, 医学部, 教授 (70077808)
TAKADA Akikazu Hamamatsu University, Faculty of Medicine, Professor, 教授 (80092980)
AOKI Nobuo Tokyo Medical and Dental University, Faculty of Medicine Professor, 医学部, 教授 (20048937)
IWANAGA Sadaaki Kyushu University, Faculty of Science, Professor, 理学部, 教授 (90029942)
SUMIYOSHI Akinobu Miyazaki Medical College, Faculty of Medicine, Professor, 教授 (80038695)
|
Project Period (FY) |
1988 – 1990
|
Project Status |
Completed (Fiscal Year 1990)
|
Budget Amount *help |
¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 1990: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1989: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1988: ¥11,200,000 (Direct Cost: ¥11,200,000)
|
Keywords | Thrombosis / Fibrinolysis / Coagulation factors / Vascular endothelial cells / Platelets / Pathogenesis / Diagnosis / Treatment / 血栓 / 凝固 / 線維素溶解 / アラキドン酸 |
Research Abstract |
This project was co-operatively performed to elucidate the recent topics as the important factors participating in the thrombosis, namely molecular characteristics of coagulation and fibrinolysis factors, genetical expression and regulation of these factors, physiological and pathological properties of endothelial cells, risk factors of endothelial injuries, the interaction between endothelial cells, blood cells and smooth muscle cells, the molecular mechanism of platelet adherence and aggregation, biochemical and immunohistochemical studies of initiating and regulating factors of coagulation-fibrinolysis system. In addition, on these basic researches clinical or preclinical alterations of coagulatory and fibrinolytic functions were enzymologically and immunochemically analyzed for platelets and several factors of coagulation-fibrinolysis system. We established the immunoenzymatic and specific enzymatic assay methods for several serine-proteases and inhibitors. 1. Studies on the mechani
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sm of thrombus-formation and thrombolysis : The clearance mechanism of endotoxin in vivo, in the relation to the thrombogenesis, was immunohistochemically and ultrastructurally investigated by the novel histochemical method using crab-shoe horse Factor C as a specific ligand to endotoxin. Angiogenesis was regulated by the endothelial expression of protease activities in an autocrine manner, and also modulated by cytokines such as TGF beta released from smooth muscle cells and macrophages. The several factors of coagulation-fibrinolysis system were analyzed for immunochemical properties using monoclonal antibodies, and for cDNA sequences. The functional domains of thrombomodulin (TM), Factors VII and IX and others were clarified at the molecular bases partly using recombinant peptides. 2. Studies on the pathogenesis, diagnosis and treatment of clinical thrombosis : The several parameters in plasma such as TAT, TM and others were clinically estimated for the diagnosis of thrombotic and prethrombotic states. The antiplatelet therapy was clinically standardized to establish the therapeutical plans for thrombotic diseases. Congenital coagulopathies and their heterogeneity were genetically and enzymologically clarified. Less
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