1990 Fiscal Year Annual Research Report

VIIIーvon Willebrand因子,1X因子の分子生物学的研究

Research Project

Project/Area Number	02219103
Research Institution	Nagoya University
Principal Investigator	斎藤英彦名古屋大学, 医学部, 教授 (20153819)
Co-Investigator(Kenkyū-buntansha)	林正男お茶の水女子大学, 理学部, 助教授 (60110516) 高橋芳右新潟大学, 医学部, 助手 (70163285) 千谷晃一藤田学園保健衛生大学, 医学部, 教授 (60179942) 福井弘奈良県立医科大学, 教授 (20075104)
Keywords	第VIII因子 / 第1X因子 / von Willebrand因子 / 血友病 / ビトロネクチン
Research Abstract	第1X因子の遺伝子に関する研究では、3例のインヒビタ-陽性血友病B(第1X因子欠乏症)患者において、全エクソンとスプライスジァンクションをPCR法にて増幅後に塩基配列をしらべ、4種類の新しいDNA異常を発見した。プロモ-タ-領域,エクソンV1およびスプライスアクセプタ-サイトの点突然変異とエクソンIIIの2塩基欠損であった。これらの成績は、第1X因子の構造と機能との関係の解明に貴重な情報を与えるものである。vwfに対するモノクロナル抗体(NMCー4)は、リストセチンあるいはボトロセチン存在下におけるvwfの血小板膜糎蛋白GPIbへの結合を抑制するが、この性質を利用してvwf分子上の特定のアミノ酸残基(512〜673)がGPIbへの結合に重要な役割を果すことを示した。また蛇毒Bothrops jararacaから2種類の血小板凝集因子を分離してその構造を決定した。血中に存在するビトロネクチンには3型のあることが知られているが、ビトロネクチン遺伝子の解析により、Thr<381>___ーがビトロネクチンの多型性に重要であることを示した。血小板のトロンビン凝集に重要なGPVをヒト血小板より精製し部分構造を決定した。ロイジン残基のくり返し構造を持つ点でユニ-クであった。本研究は、臨在医学と分子生物学の分野の研究者の緊密な協力のもとに研究を進めたもので、その成果は血栓形成、止血機構の解明に重要であると思われる。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Matsushita,T.: "DNA sequence analysis of three inhibitorーpositive hemophilia B patients without gross gene deletion:Identification of four novel mutations in factor IX gene." J Lab Clin Med. 116. 492-497 (1990)
[Publications] Ito,T.: "Enhanced expression of thrombomodulin by cyclic AMP in two human megakaryoblastic leukemia cell lines." Thromb Res. 58. 615-624 (1990)
[Publications] Ogura,M.: "Localization and biosynthesis of functional thrombomudulin in human megakaryocytes and a human megakaryoblastic cell line (MECー01)." Thromb Haemost. 64. 297-301 (1990)
[Publications] Bajaj,M.S.: "Cultured normal human hepatocytes do not synthesize lipoproteinーassociated coagulation inhibitor: Evidence that endothelium is the principal site of its synthesis." Proc Natl Acad Sci U.S.A.87. 8869-8873 (1990)
[Publications] Hamaguchi,M.: "FDP Dーdimer induces the secretion of interleukinーl,urokinase type plasminogen activator and plasminogen activator inhibitorー2 in a human promonocytic leukemia cell line." Blood. 77. 94-100 (1991)
[Publications] Nishio,K.: "Enhanced botrocetinーinduced type IIB von Willebrand factor binding to platelet glycoprotein Ib initiates hyperagglutination of normal platelet." Am J Hematol. 33. 261-266 (1990)
[Publications] 嶋緑倫: "第VIII因子異常症" 血栓止血誌. 1. 285-296 (1990)
[Publications] 吉岡章: "遺伝子組換え型第VIII因子製剤(BAY w6240)中の第VIII因子の性状" 血栓止血誌. 1. 212-218 (1990)
[Publications] Shimomura,T.: "Rapid Purification and Characterization of Human Platelet Glycoprotein V: The Amino Acid Sequence Contains LeucineーRich Repetitive Modules as in Glycoprotein Ib." Blood. 75. 2349-2356 (1990)
[Publications] Fujimura,Y.: "Studies on Antiーvon Willebrand Factor (vWF) Monoclonal Antibody NMCー4 Which Inhibits Both Ristocetinー and Botrocetinー Induced vWF Binding to Platelet Glycoprotein Ib." Blood. 77. 113-120 (1990)
[Publications] Fujimura,Y.: "Isolation and Chemical Characterization of Two Structurally and Functionally Distinct Forms of Botrocetin,the Platelet Coaggulutinin Isolated from the Venom of <Bothrops Jararaca>___ー." Biochemistry. (1991)
[Publications] Takahashi,H.: "Thrombin vs plasmin generation in disseminated intravascular coagulation associated with various underlying disorders." Am J Hematol. 33. 90-95 (1990)
[Publications] Takahashi,H.: "Fibrinolysis and fibrinogenolysis in disseminated intravascular coagulation." Thromb and Haemost. 63. 340-344 (1990)
[Publications] Takahashi,H.: "Plasmin generation and fibrin(ogen)olysis following desmopressin infusion." Am J Hematol. (1991)
[Publications] KitagakiーOgawa,H.: "Diversities in animal vitronectins.Differences in molecular weight,immunoreactivity and carbohydrate chains." Biochim Biophys Acta. 1033. 49-56 (1990)
[Publications] Kubota,K.: "Polymorphism of the human vitronectin gene causes vitronectin blood type." Biochem Biophys Res Commun. 167. 1355-1360 (1990)
[Publications] 加畑隆通: "ウサギ角膜上皮創傷治癒過程に及ぼすビトロネクチンの影響" 日眼会誌. 94. 457-461 (1990)

1990 Fiscal Year Annual Research Report

VIIIーvon Willebrand因子,1X因子の分子生物学的研究

Principal Investigator

斎藤 英彦 名古屋大学, 医学部, 教授 (20153819)

Research Products

[Publications] Matsushita,T.: "DNA sequence analysis of three inhibitorーpositive hemophilia B patients without gross gene deletion:Identification of four novel mutations in factor IX gene." J Lab Clin Med. 116. 492-497 (1990)

[Publications] Ito,T.: "Enhanced expression of thrombomodulin by cyclic AMP in two human megakaryoblastic leukemia cell lines." Thromb Res. 58. 615-624 (1990)

[Publications] Ogura,M.: "Localization and biosynthesis of functional thrombomudulin in human megakaryocytes and a human megakaryoblastic cell line (MECー01)." Thromb Haemost. 64. 297-301 (1990)

[Publications] Bajaj,M.S.: "Cultured normal human hepatocytes do not synthesize lipoproteinーassociated coagulation inhibitor: Evidence that endothelium is the principal site of its synthesis." Proc Natl Acad Sci U.S.A.87. 8869-8873 (1990)

[Publications] Hamaguchi,M.: "FDP Dーdimer induces the secretion of interleukinーl,urokinase type plasminogen activator and plasminogen activator inhibitorー2 in a human promonocytic leukemia cell line." Blood. 77. 94-100 (1991)

[Publications] Nishio,K.: "Enhanced botrocetinーinduced type IIB von Willebrand factor binding to platelet glycoprotein Ib initiates hyperagglutination of normal platelet." Am J Hematol. 33. 261-266 (1990)

[Publications] 嶋 緑倫: "第VIII因子異常症" 血栓止血誌. 1. 285-296 (1990)

[Publications] 吉岡 章: "遺伝子組換え型第VIII因子製剤(BAY w6240)中の第VIII因子の性状" 血栓止血誌. 1. 212-218 (1990)

[Publications] Shimomura,T.: "Rapid Purification and Characterization of Human Platelet Glycoprotein V: The Amino Acid Sequence Contains LeucineーRich Repetitive Modules as in Glycoprotein Ib." Blood. 75. 2349-2356 (1990)

[Publications] Fujimura,Y.: "Studies on Antiーvon Willebrand Factor (vWF) Monoclonal Antibody NMCー4 Which Inhibits Both Ristocetinー and Botrocetinー Induced vWF Binding to Platelet Glycoprotein Ib." Blood. 77. 113-120 (1990)

[Publications] Fujimura,Y.: "Isolation and Chemical Characterization of Two Structurally and Functionally Distinct Forms of Botrocetin,the Platelet Coaggulutinin Isolated from the Venom of <Bothrops Jararaca>___ー." Biochemistry. (1991)

[Publications] Takahashi,H.: "Thrombin vs plasmin generation in disseminated intravascular coagulation associated with various underlying disorders." Am J Hematol. 33. 90-95 (1990)

[Publications] Takahashi,H.: "Fibrinolysis and fibrinogenolysis in disseminated intravascular coagulation." Thromb and Haemost. 63. 340-344 (1990)

[Publications] Takahashi,H.: "Plasmin generation and fibrin(ogen)olysis following desmopressin infusion." Am J Hematol. (1991)

[Publications] KitagakiーOgawa,H.: "Diversities in animal vitronectins.Differences in molecular weight,immunoreactivity and carbohydrate chains." Biochim Biophys Acta. 1033. 49-56 (1990)

[Publications] Kubota,K.: "Polymorphism of the human vitronectin gene causes vitronectin blood type." Biochem Biophys Res Commun. 167. 1355-1360 (1990)

[Publications] 加畑 隆通: "ウサギ角膜上皮創傷治癒過程に及ぼすビトロネクチンの影響" 日眼会誌. 94. 457-461 (1990)

斎藤英彦名古屋大学, 医学部, 教授 (20153819)

[Publications] 嶋緑倫: "第VIII因子異常症" 血栓止血誌. 1. 285-296 (1990)

[Publications] 吉岡章: "遺伝子組換え型第VIII因子製剤(BAY w6240)中の第VIII因子の性状" 血栓止血誌. 1. 212-218 (1990)

[Publications] 加畑隆通: "ウサギ角膜上皮創傷治癒過程に及ぼすビトロネクチンの影響" 日眼会誌. 94. 457-461 (1990)