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THE EVOLUTION OF BLOOD COAGULATION FACTOR VIII IN MAMMALS

Research Project

Project/Area Number 12670771
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNARA MEDICAL UNIVERSITY

Principal Investigator

TANAKA Ichiro  NARA MEDICAL UNIVERSITY, MEDICAL DEPARTMENT, ASSISTANT PROFESSOR, 医学部, 講師 (00201616)

Co-Investigator(Kenkyū-buntansha) NAKA Hiroyuki  NARA MEDICAL UNIVERSITY, MEDICAL DEPARTMENT, RESEARCH ASSOCIATE, 医学部, 助手 (40281761)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsFACTOR VIII / MAMMALS
Research Abstract

The coagulability in various mammals; monkeys, dogs, cats, pigs, cattle, mice and a killer whale were studied as compared to that in human. The levels of factor VIII (FVIII) coagulant activity in all mammals but monkeys were higher than that in human, resulting in their hypercoagulability in the intrinsic pathway of blood coagulation.Cross-reactivity of monoclonal antibodies against various mammalian FVIII was determined as compared to human FVIII. The cross-reactivity of C5 which recognized A1 domain of FVIII heavy chain were 7 % in monkeys, 2.7 % in dogs, 16.2 % in cats, and 0 % in the other mammals. The cross-reactivity of RFF/8, which recognized A2 domain of FVIII heavy chain were 1.3 % in monkeys, and 0 % in the others. No cross-reactivity of NMC-VIII/9, which recognized A3 domain of FVIII light chain, was observed in all mammals. The cross-reactivity of NMC-VIII/9, which recognized C2 domain of FVIII light chain were 54.5 % in monkeys, 130 % in dogs, 82.8 % in cats, 13.4 % in pigs, 0 % in the others. These data suggest that the stereoscopic structure of C2 epitope in the light chain of FVIII molecule is preserved among most of mammals and that C2 epitope is very important region to FVIII function.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Nogami K, Tanaka I, 他9名: "Rohe of factor VIIIC2 domain in factor VIII binding to factor Za"Journal of Biological Chemistry. 274. 31000-31007 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nogami K, Tanaka I, 他9名: "Idcntification of a factor VIII peptide, residues 2315-2330,wtich neutralises human VIII C2 inhibitor alloautibodies: reguiement of Cys2326 and Glu2327 for luayimu effect"British Journal of Haematology. 107. 196-203 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shibata M, Tanaka I, 他11名: "An alloantibody recoguizing the FVIII A1 Domain in a patiant with CRM redoced hemoplulcin A in cohom the coresponding DNA sequsnce is deleted"Thrombosis and Haemostasis. 84. 442-448 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nogami K, Tanaka I, 他7名: "Factor VIII C2 domain contains the thrombin-binding site restorsible for thcenbin-cataliyzed cleavage at Arg 1689"Journal of Biological Chemistry. 275. 25774-25780 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsumoto T, Tanaka I, 他6名: "Immunological Characteyotion of factor VIII autantibodies in patents with acqucied hemophilia A in the phesence or absebce of unchrlying disease"Thrombosis Research. 104. 381-388 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nogami K., Tanaka I. et al: "Roll of factor VIII C2 domain in factor VII ding to factor Xa"Journal of Biological Chemistry. 274. 31000-31007 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nogami K., Tanaka I. et al: "Identification of a factor VIII ide, residues 23 15-2330, which neutralizes human factor VIII inhibitor allo-antibodies : requirement of Cys 2336 and Glu 2327 for maximum effect"Journal of Biological Chemistry. 107. 196-203 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shibata M., Tanaka I. et al: "An all antibody recognizing the FVIII Al domain in a patient with CRM reduced hemophilia A in whom the corresponding DNA sequence is deleted ; Agreement of inhibitor epitope with gene mutation"Thrombosis and Haemostasis. 84. 442-448 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nogami K., Tanaka I. et al: "Factor VIII C2 domain contains the thrombin-binding site responsible for thrombin-catalyzed cleavage at Argl689"Journal of Biological Chemistry. 275. 25774-25780 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsumoto T., Tanaka I. et al: "Immunological characterization of factor VIII autoantibodies in patients with acquired hemophilia A in the presence or absence of underlying disease"Thrombosis Research. 104. 381-388 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsumoto T, Tanaka I, 他6名: "Immunological chanecterialuision of F VIII autoautibodres in patients with acquiesced hemophilia A with presence or absence of in delay clisome"Thronbosis Reseauch. 104. 381-388 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masouu Shibata, Ichiro Tanaka, 他6名: "Analloantibody recogujey the VIII A, Domain in a patient with CRH reduced howoplilia A in whom the corresponding DNA sequence is celled"Thronbosis and Haemostasis. 84. 442-448 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Nogami,I.Taraka 他7名: "Factor VIII C2 domain contains the thrombin-binding site responsible for thrombin-catalygecl cleavage at Arg^<1698>"Journal of Biological Chemistry. 275(33). 25774-25780 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Nogami,I.Taraka 他9名: "Roll of factor VIII C2 domain in factor VIII binding to factor Xa"Journal of Biological Chemistry. 274(43). 31000-31007 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Nogami,I.Taraka 他9名: "Identification of a factor VIII peptide, residues 2315-2330, which neutralizes human factor VIII C2 Inhibition alloantibodies"British Journal of Haematology. 107. 196-203 (1999)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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