1995 Fiscal Year Annual Research Report

血栓症の成因と病態,とくに血液凝固とその制御機構障害への分子生物学的アプローチ

Research Project

Project/Area Number	06404043
Research Institution	Jichi Medical School
Principal Investigator	松田道生自治医科大学, 医学部, 教授 (50048980)
Co-Investigator(Kenkyū-buntansha)	朝倉伸司自治医科大学, 医学部, 講師 (70245033) 三室淳自治医科大学, 医学部, 講師 (10221607) 諏合輝子自治医科大学, 医学部, 講師 (60183844) 坂田洋一自治医科大学, 医学部, 助教授 (40129028)
Keywords	フィブリノゲン / 遺伝性異常フィブリノゲン / フィブリン重合反応 / 架橋形成 / カルシウム依存性構造 / モノクローナル抗体 / 細胞接着 / 接着分子
Research Abstract	1.遺伝性異常フィブリノゲン(以下Gbg)の構造解析:これまでに報告のない新変異2型が同定され,Fbgの構造-機能関係に新知見が得られた.Fbg Kurashiki Iのγ268 Gly→Glu (Blood印刷中), Kamogawaのγ275 Arg→Ser(投稿準備中)で,共に最近提唱されているD : D self-association sitesの機能障害に結びつくことが判明した.この反応部位の障害は代表者が1983年に報告したFbg Tokyo IIで初めて見出され,海外の共同研究者により報告されたものである(J. Clin. Invest.に掲載).別の異常分子FbgKumamotoではAα19 Arg→Glyが同定された.本異常分子はフィブリン(以下Fbn)へのトロンビン吸着が障害されていることから血栓症に結びついており,血栓形成の自己制御機能に関する貴重な情報と思われる(投稿準備中).これらの他,国内外から依頼された8家系(旭川II,倉敷II,盛岡II,新潟II,名古屋II, Gerris, Guarenas,Marburg I)の解析を続けて来ている. 2.抗Fbgモノクローナル抗体(mAb)の作成と応用: Fbgの特異構造を認識する3種類のmAbの解析を終了し,その応用を検討した.(1)Dドメインのカルシウム依存性構造を認識するmAbが得られ,これを担体として親和性クロマトグラフィーによるFbg精製に応用してその有用性を確認した(Thromb. Haemostas.に掲載).(2)活性型XIII因子による架橋形成とFbn重合とを特異的に阻害するユニークなmAbが得られ,これらの反応の分子機作解明に利用している(日本血栓止血誌に投稿中).(3)Fbg→Fbn転換に伴なって生ずるEドメインの特異構造を認識するmAbが得られ,可溶性Fbnの形成機序の分析と血栓症の診断に応用し得ることが判明した(Bloodに印刷中)

Research Products
(9 results)

All Other

All Publications (9 results)

[Publications] Teruko Sugo: "Activation of prothrombin by factor Xa bound to the membrane surface of human umbilical vein endothlial cells : Its catalyic efficiency is similar to that of prothrombinase complex on platelets" J. Biochem.117. 244-250 (1995)
[Publications] Mikihiro Takebe: "Calsiumdepentent monoclonal antibody against human fibrinogen : preoaration, characterization, and application to fibrinogen purification." Thromb. Haemost.73(4). 662-667 (1995)
[Publications] Gilbu Soe: "A rapid latex immunoassay for the edtection of plasmin-α2-plasmin inhibitor complex : Utilization of two monoclonal antibodies differentially recognizing respective omponents of the complex." Blood Coagulation and Fibrinolysis. 6. 249-258 (1995)
[Publications] Michael W. Mosesson: "The role of fibrinogen D domain intermolecular association sites in the polymerization of fibrin and fibrinogen Tokyo II (γ275→Cys)." J. clin. Invest.96. 1053-1058 (1995)
[Publications] Sinnji Asakura: "New functions of kininogen." Jpn. J. Thromb. Hematol.6(3). 155-166 (1995)
[Publications] Teruko Sugo: "Calusium ion binding to vitamin K-dependent clotting factors." Jpn. J. Thromb. Hematol.6(4). 252-264 (1995)
[Publications] Matsuda Michio: "Hereditary dysfibrinogens with special reference to their structure-function relationship." Int. J. Hematol.(in press).
[Publications] Kazuki Niwa: "A γGly-268 to Glu substitution is responsible for impared fibrin assembly in a homozygous dysfibrinogen Kurashiki I." Blood. (in press).
[Publications] Gilbu Soe: "A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives. Its application to the measurement of soluble fibrin in plasma." Blood. (in press).

1995 Fiscal Year Annual Research Report

血栓症の成因と病態,とくに血液凝固とその制御機構障害への分子生物学的アプローチ

Principal Investigator

松田 道生 自治医科大学, 医学部, 教授 (50048980)

Research Products

[Publications] Teruko Sugo: "Activation of prothrombin by factor Xa bound to the membrane surface of human umbilical vein endothlial cells : Its catalyic efficiency is similar to that of prothrombinase complex on platelets" J. Biochem.117. 244-250 (1995)

[Publications] Mikihiro Takebe: "Calsiumdepentent monoclonal antibody against human fibrinogen : preoaration, characterization, and application to fibrinogen purification." Thromb. Haemost.73(4). 662-667 (1995)

[Publications] Gilbu Soe: "A rapid latex immunoassay for the edtection of plasmin-α2-plasmin inhibitor complex : Utilization of two monoclonal antibodies differentially recognizing respective omponents of the complex." Blood Coagulation and Fibrinolysis. 6. 249-258 (1995)

[Publications] Michael W. Mosesson: "The role of fibrinogen D domain intermolecular association sites in the polymerization of fibrin and fibrinogen Tokyo II (γ275→Cys)." J. clin. Invest.96. 1053-1058 (1995)

[Publications] Sinnji Asakura: "New functions of kininogen." Jpn. J. Thromb. Hematol.6(3). 155-166 (1995)

[Publications] Teruko Sugo: "Calusium ion binding to vitamin K-dependent clotting factors." Jpn. J. Thromb. Hematol.6(4). 252-264 (1995)

[Publications] Matsuda Michio: "Hereditary dysfibrinogens with special reference to their structure-function relationship." Int. J. Hematol.(in press).

[Publications] Kazuki Niwa: "A γGly-268 to Glu substitution is responsible for impared fibrin assembly in a homozygous dysfibrinogen Kurashiki I." Blood. (in press).

[Publications] Gilbu Soe: "A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives. Its application to the measurement of soluble fibrin in plasma." Blood. (in press).

松田道生自治医科大学, 医学部, 教授 (50048980)