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MOLECULAR DESIGN OF INHIBITORS ON THE FORMATION OF VON WILLEBRAND FACTOR-DEPENDENT PLATELET THROMBI

Research Project

Project/Area Number 11670704
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNARA MEDICAL UNIVERSITY

Principal Investigator

FUJIMURA Yoshihiro  NARA MEDICAL UNIVERSITY, DEPARTMENT OF BLOOD TRANSFUSION, PROFESSOR, 輸血部, 教授 (80118033)

Co-Investigator(Kenkyū-buntansha) YONG-DONG Park  NARA MEDICAL UNIVERSITY, DEPARTMENT OF BLOOD TRANSFUSION, RESEARCH ASSOCIATE, 輸血部, 助手 (10285364)
MATSUMOTO Masanori  NARA MEDICAL UNIVERSITY, DEPARTMENT OF BLOOD TRANSFUSION,RESEARCH ASSOCIATE, 輸血部, 助手 (60316081)
SAKAMOTO Yoshiharu  NARA MEDICAL UNIVERSITY, DEPARTMENT OF OBSTETRICS AND GYNECOLOGY, RESEARCH ASSOCIATETY, DEPARTMENT OF OBSTETRICS AND GYNECOLOGY, RESEARCH ASSOCIATE (40291611)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsVON WILLEBRAND FACTOR / SNAKE VENOM / PLACENTAL ECTO-ATPDase / VWF-Cpase / SHEAR-INDUCED PLATELET AGGREGATION / UPSHAW-SCHULMAN SYNDROME / 胎盤ecto-ATPDase / Upshaw-Cchulman症候群 / Stx-1 / 血小板膜等蛋白Ib結合蛋白 / マムシギン
Research Abstract

【○! 1】Snake venom : A metalloprotease, termed kaouthisgin, was purified from a crude snake venom of Naja naja kaouthia, and was found that the enzyme specifically cleaves von Willebrand factor, together with its inhibitory activity on shear induced platelet aggregation.
【○!2】 von Willebrand factor-cleaving protease (VWF-Cpage) : A complex bleeding diathesis, known as Upshaw-Schulman syndrome since 1960's, was demonstrated to be a congenital deficiency of VWF-Cpase activity. A unique transfusion effect of fresh frozen plasma to these patients was also elucidated.
【○!3】Placental ecto-ATPDase : Two isoforms of CD39 were cloned based on the N-terminal amino acid sequence, and their entire nucleotides were determined.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Ito M, et al.: "Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloprotease with two disintegrin-like sequences"Biochemistry USA. 40. 4503-4511 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kinoshita S, et al.: "Upshaw-Schulman syndrome revisited: A concept of congenital thrombotic throm bocytopenic purpura"International Journal of Hematology. 74. 101-108 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sakurai Y, et al.: "Inhibition of human platelet aggregation by L-amino acid oxidase purified from Najak kaouthia venom"Toxicon. 39. 1827-1833 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yagi H, et al.: "Plasma of patients with Upshaw-Schulman syndrome, a congenital deficiency of von Willebrand factor-cleaving protease, enhances the aggregation of normal platelets under high shear stress"British Journal of Haematology. 115. 991-997 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimura Y, et al.: "Von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome. In: Progress in Hematology"International Journal of Hematology. 75. 25-34 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Park Y-D, et al.: "Impaired activity of plasma von Willebrand factor-cleaving protease may predict the occurrence of hepatic veno-occlusive disease after stem cell transplantation"Bone Marrow Transplantation. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 藤村吉博 他: "血小板血栓形成の分子機構"アイプリコム出版社. 407 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shibata M, Shima M, Fujimuia Y, Takahashi Y, Nakai H, Sakurai Y, Asatani M, Nomura A, Take H, Giddings JC, Yoshioka A.: "identification of the binding site fpr an alloantibody to von Willebrand factor which inhibits binding to glycoprotein Ib within the amino-terminal region flanking the Al domain"Thromb. Haemost. 81. 793-798 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsumoto M, Sakurai Y, Kokubo T, Yagi H, Matsui T, Titani K, Fujimuia Y, Narita N.: "The cDNA cloning of human placenta! Ecto-ATP diphosphohydrolases I and II"FEBS Letters. 453. 335-340 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miura S, Sakurai Y, Takatsuka H, Yoshioka A, Matsumoto M, Yagi H, Kokubo T, Ikeda Y, Matsui T,Titani K, Fujimura Y.: "Total inhibition of high shear stress induced platelet aggregation by homodimeric von Willebrand factor Al-loop fragments"Brit. J. Haematol. 105. 1092-1100 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ueda S, Nishio K, Minamino N, Kubo A, Akai Y, Kangawa K, Matsuo H, Fujimura Y, Yoshioka A, Masui K,Doi N, Murao Y, Miyamoto S.: "Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome"Am. J. Resp. Crit. Care Med. 160. 132-136 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsui T, Shimoyama T, Matsumoto M, Fujimura Y, Takemoto Y, Sako M, Hamako J, Titani K.: "ABO blood group antigens on human von Willebrand factor after ABO-mismatched bone marrow transplanatation"Blood. 94. 2895-2900 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniuchi Y, Kawasaki T, Fujimura Y.: "The high molecular mass, glycoprotein Ib-binding protein flavocetin-A induces only small platelet aggregation in vivo"Thromb. Res. 97. 69-75 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto T, Moriwaki Y, Fujimura Y, Takahashi S, Tsutsumi Z, Tsutsui T, Higashino K, HadaT: "Effect of TEI-6720, a xanthine oxidase inhibitor, on the nucleoside transport in the lung cancer cell line A549"Pharmacology. 60. 34-40 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoh K, Asazuma N, Yatomi H, Fujimura Y, Miura S, Totani K, Ozaki Y: "Activation of protein-tyrosine kinase pathways in human platelets stimulated with the A1 domain of von Willebrand factor"Platelets. 11. 171-176 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nomura S, Imamura A, Okuno S, Komiyama N, Fujimura Y, Ikeda Y, Fukuhara S: "Platelet-derived microparticles in patients with arteriosclerosis obliterans: Enhancement of high shear-induced microparticle generation by cytokines"Thromb. Res. 98. 257-268 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] TakatsukaH, SakuraiY, YoshiokaA, KokupoT, UsamiY, Suzuki M, Titani K, YagiH, Matsumoto M, Fujimura Y: "Molecular characterization of L-amino acid oxidase from Agkistrodon halys blomhoffii with special reference to platelet aggregation"Biochem. Biophys: Acta. 1544. 267-277 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yagi H, Narita N, Matsumoto M, Sakurai Y, Ikari H, Yoshioka A, Kita E, Ikeda Y, Titani K, Fujimura Y.: "Enhanced low shear stress-induced platelet aggregation by Shiga-like toxin 1 purified from Escherichia coli O157"Am.J.Hematol. 66. 105-115 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito M, Bamako J, Sakurai Y, Matsumoto M, Fujimura Y, Suzuki M, Hashimoto K, Titani K: "Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloproteinase with two disintegrin-like sequences"Biochemistry USA. 40. 4503-4511 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kinoshita S, Yoshioka A, Park Y-D, Ishizashi H, Konno M, Funado M, Matsui T, Titani K, Yagi H, Matsumoto M, Fujimura Y.: "Upshaw-Schulman syndrome revisited : A concept of congenital thrombotic thrombocytopenic purpura"Int. J. Hematol. 74. 101-108 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugio Y, Okamura T, Shimoda K, Matsumoto M, Yagi H, Ishizashi H, Niho Y, Inaba S, Fujimura Y.: "Ticlopidine-associated thrombotic thrombocytopenic purpura with an IgG-type inhibitor to von Willebrand factor-cleaving protease activityTiclopidine-associated thrombotic thrombocytopenic purpura with an IgG-type inhibitor to von Willebrand factor-cleaving protease activity"Int. J. Hematol. 74. 347-351 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sakurai Y, Takatsuka H, Yoshioka A, Matsui T, Suzuki M, Titani K, Fujimura Y.: "Inhibition of human platelet aggregation by L-amino acid oxidase purified from Naja kaouthia venom"Toxicon. 39. 1827-1833 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yagi H, Konno M, Kinoshita S, Matsumoto M, Ishizashi H, Matsui T, Titani K, Fujimura Y: "Plasma of patients with Upshaw-Schulman syndrome, a congenital deficiency of von Willebrand factor-cleaving protease activity, enhances the aggregation of normal platelets under high shear stress"Brit. J. Hamatol. 115. 991-997 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hayashi T, Yagi H, Suzuki H, Nonaka Y, Nomura T, Sakurai Y, Shibata M, Matsumoto M, YamamotoY, Fujimura Y.: "LOW dosage intravenous imunoglobulin in the management of a patient with acquired von Willebrand syndrome associated with monoclonal gammopathy of undetermined significance"Haemostasis. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mori Y, Wada H, Gabazza EC, Minami N, Nobori T, Shiku H, Yagi H, Ishizashi H, Matsumoto M, Fujimura Y.: "von Willebrand factor-cleaving protease activity predicts response to plasma exchange in patients with TTR"Transfusion. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Park Y-D, Yoshioka A, Kawa K, Ishizashi H, YagiH, Yamamoto Y, Matsumoto M, Fujimura Y: "Impaired activity of plasma von Willebrand factor cleaving protease may predict the occurrence of hepatic veno-occulusive disease after stem cell transplantation"Bone Marrow Transplanation. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsui T, Fujimura Y, Titani K. Snake: "venom proteases affecting hemostasis and thrombosis"Biochem.Biophys. Acta. 1477. 146-156 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimura Y, Matsumoto M, Yagi H, Yoshioka A, Matsui T, Titani K: "von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome. In: Progress in Hematology"Int. J. Hematol. 75. 25-34 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito M, et al.: "Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloprotease with two disintegrin-like sequences"Biochemistry USA. 40. 4503-4511 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kinoshita S, et al.: "Upshaw-Schulman syndrome revisited : A concept of congenital thrombotic thrombocytopenic purpura"International Journal of Hematology. 74. 101-108 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakurai Y, et al.: "Inhibition of human platelet aggregation by L-amino acid oxidase purified from Najak kaouthia venom"Toxicon. 39. 1827-1833 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yagi H, et al.: "Plasma of patients with Upshaw-Schulman syndrome, a congenital deficiency of von Willebrand factor-cleaving protease, enhances the aggregation of normal platelets under high shear stress"British Journal of Haematology. 115. 991-997 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujimura Y, et al.: "Von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome. In : Progress in Hematology"International Journal of Hematology. 75. 25-34 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Park Y-D, et al.: "Impaired activity of plasma von Willebrand factor-cleaving protease may predict the occurrence of hepatic veno-occlusive disease after stem cell transplantation"Bone Marrow Transplantation. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 藤村吉博 他: "血小板血栓形成の分子機構"アイプリコム出版社. 407 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hideo Yagi, et al.: "Enhanced low shear stress induced platelet, aggregation by Shiga-like toxin 1 purified from Escherichia coli O157"American Journal of Hematology. 66. 105-115 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hideo Takatsuka, et al.: "Molecular characterization of L-amino acid oxidase from Agkistrodon halys blomhoffii with special reference to platelet aggregation"Biochimica et Biophysica Acta. 1544. 267-277 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Seiji Kinoshita, et al.: "Upshaw-Schulman syndrome revisited : A concept of congenital thrombotic thrombocytopenic purpura"International Journal of Hematology. (印刷中). *-* (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 松本雅則 他: "抗血小板剤とTTP"血液腫瘍科. 41. 238-244 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shuji Miura: "Total inhibition of high shear stress induced plateletaggregation by homodimeric von Willebrand factor Al-loop fragments"British Journal of Haematology. 105. 1092-1100 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Taei Matsui: "ABO blood group antigens on human plazma von Willebrand factor after ABO-Mismatched bone marrow transplantation"Blood. Vol94,No8. 2895-2900 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masanori Matsumoto: "The cDNA cloning of human placental acto-ATP diphosphohydrolases I and II"FEBS Letters. 453. 335-340 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Taei Matsui: "Snake venon proteases affecting hemostasis and thrombosis"Biochimica et Biophysica acta. 1477. 146-156 (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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