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2001 Fiscal Year Final Research Report Summary

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
KeywordsVON WILLEBRAND FACTOR / SNAKE VENOM / PLACENTAL ECTO-ATPDase / VWF-Cpase / SHEAR-INDUCED PLATELET AGGREGATION / UPSHAW-SCHULMAN SYNDROME
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.

  • Research Products

    (28 results)

All Other

All Publications (28 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
  • [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
  • [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
  • [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
  • [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
  • [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)

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      「研究成果報告書概要(和文)」より
  • [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)

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      「研究成果報告書概要(和文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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)

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      「研究成果報告書概要(欧文)」より
  • [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
  • [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
  • [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)

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Published: 2003-09-17  

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