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Clinical and Biomolecular Studies on Thrombophilia in Children.

Research Project

Project/Area Number 10470212
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNara Medical University

Principal Investigator

YOSHIOKA Akira  Nara Medical Univ, Professor, 医学部, 教授 (40106498)

Co-Investigator(Kenkyū-buntansha) TANAKA Ichiro  Nara Medical Univ, Assistant Professor, 医学部, 講師 (00201616)
SUGIMOTO Mitsuhiko  Nara Medical Univ, Assistant Professor, 医学部, 講師 (80192128)
TAKAHASHI Yukihiro  Nara Medical Univ, Associate Professor, 医学部, 助教授 (60142379)
TAKAMIYA Osamu  Shinshu University, Professor, 医療短期大学部, 教授 (50216785)
NAKA Hiroyuki  Nara Medical Univ, Assistant, 医学部, 助手 (40281761)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥9,100,000 (Direct Cost: ¥9,100,000)
Keywordsthrombophilia / antithrombin / protein C / protein S / Heparin cofactor-II / Upshaw-Schulman Syndome / VWF-cleaving protease / children / Upshaw-Schulman症侯群 / von Willebrand factor (vWF) / VWF-cleaving protease / 溶血性尿毒症症候群 / アンチトロンビンIII / APCレジスタンス
Research Abstract

In order to know the patients' number and its clinical conditions, we conducted a nation-wide survey of thrombophilia in children using questionnaire. We sent the first questionnaire to 1, 319 medical doctors and got 806 answers (61.1 %). They are as follows; congenital antithrombin(AT) deficiency 137 families/190 cases (15 children), protein C (PC) deficiency 146/182(27), protein S (PS) deficiency 62/84(16), heparin cofactor-Iiciency (HC-II2/3(0), abnormal plasminogenemia 65/65+α (7), abnormal fibrinogenemia 47/57 (13), others 16/20 (4), and totally 475/601 (82). We got answers of 36 cases (43.9 %) from 82 cases by the 2nd questionnaire. It was divided into 2 groups, positive history of thromboembolic events in childhood, 21 cases (AT 4, PC10, PS7) and negative history of those in childhood, 15 cases (AT3, PC4, PS8). Sex ratio of theformergroup was M11: F10. Age at onset of the events was ranged between newborn period and adlescence. Main initial events of thromboembolism were deep vein thrombosis in lower extremity (DVT), pulmonary thromboembolism (PTE), brain embolism and etc. Laboratory examinations showed medium low levels of activity and antigen of AT, PC and PS (Type I, heterozygote) in the majority of the cases and extremely low levels of those of PC and PS in only 3 cases, gene analysis was performed in 8 cases. Several kinds of antithrombotic agents were used at the in itial events of thromboembolism in these cases and warfarin was mostly applied for prophylaxis treatment after establishment of each diagnosis. Prothrombin time-INR and/or Thrombotest were used as a monitor to evalute good hemostatic control. It is suggested that careful and continuous observation is most important in children with thrombophilia. Other clinical and biomolecular studies on thrombophilia in children were also performed.

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (69 results)

All Other

All Publications (69 results)

  • [Publications] 池田祐貴子, 高橋幸博, 他計9名: "洞不全症候群の経過中に腎梗塞と脳梗塞を発生した先天性プロテインS欠損症の1例"奈良医学雑誌. 48. 45-52 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Sugimoto, A.Yoshioka et al.(total 5): "Activated protein C concentrate: A new tool for the treatment of acute thromboembolism in patients with congenital protein C deficiency"Thrombosis & Haemostasis. 77. 1215-1224 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 齊藤英彦, 杉本充彦, 吉岡章, 他計6名: "プロテインC欠乏症患者の血栓症に対する乾燥濃縮ヒト活性化プロテインC製剤(CTC-111)の臨床試験"新薬と臨床. 45・5. 718-732 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 川口千晴, 吉岡章, 高橋幸博: "新生児の出血・血栓とその対策.新生児の血栓症"Neonatal Care. 11・12. 1026-1031 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 高宮脩: "血栓形成に関する遺伝的検討と人種差,アジアにおけるAPCレジスタンス(Factor V Leiden)"Vascular Science. 5. 11-13 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Kodera, O.Takamiya et al.: "Resistance to activated Protein C, and Arg 506 Gln factor V mutation are uncommon in eastern Asian population"Acta Haematologica. 98. 22-25 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 高宮脩: "血栓症傾向の検査"小児臨床. 50・4. 699-706 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 嶋緑倫, 吉岡章: "凝固因子およびその制御因子のgene targetingによる新しい機能の解析"Annual Review 血液1998. 203-209 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] R.Celikel, A.Yoshioka et al.: "Crystal structure of the vWF AI domain in complex with the function blocking NMC-4 Fab"Nature Structural Biology. 5・3. 189-194 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Keiji Nogami,Midori Shima,and Akira Yoshioka et al.: "Factor VIII C2 domain contains the thrombin-binding siteresponsible for thrombin-catalyzed cleavage at Arg1689"Journal of Biological Chemistry. 275・33. 25774-25780 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S Miyagawa,Y Uchida,K Taira,A Yoshioka and T Shirai et al.: "Autoantibody responses to cardiolipin and DNA in infancy : associated with lymphocytic panniculitis"Lupus. 9. 637-640 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Shibata,M.Shima,S.Morichika,D.Scandella,Akira.Yoshioka et al.: "An Alloantibody Recognizing the FVIII A1 Domain in a Patient with CRM Reduced Haemophilia A due to Deletion of a Large Portion of the A1 Domain DNA Sequence"Thromb Haemost. 84. 442-448 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akira Shirahata,Akira Yoshioka, et al.: "Pharmacokinetics, Prophylactic effects, and safety of a new recombinant FVIII formulated with sucrose (BAY 14-2222) in Japanese patients with hemophilia A."International Journal of Hematology. 72. 101-107 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Kinoshita,A.Yoshioka,Y-D Park, K.Titani,H.Yagi,M.Matsumoto and Y.Fujimura: "Upshaw-Schulman Syndrome revisited ; A concept of congenital thrombotic thrombocy topenic purpura."Int J Hematol. (in press). (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉岡章: "血友病治療薬 エプタコグアルファ"カレントテラヒー. 18・9. 165-167 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉岡章: "血友病の新しい治療戦略"臨床血液 別刷. 第41巻 第5号. 365-369 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉岡章: "病原性大腸菌O-157患者の臨床医学的解析"病原性大腸菌O-157による疾患の重症化の予防及び治療を目的とした医薬品の開発研究研究報告書第4分野課題番号42282;2000. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 箕輪秀樹,高橋幸博,中宏之,吉岡章: "先天性PAI-1欠乏症"日本血栓止血学会誌. 11. 289-295 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋幸博: "「新生児の生理と異常」血液(1)"Neonatal Careメディカ出版. vol.13 No.5. 540-545 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 杉本充彦,吉岡章: "血栓性素因(プロテインC、プロテインS、アンチトロンビン欠乏症)"抗凝固薬の適正な使い方 医歯薬出版株式会社. 204-209 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 田中一郎,吉岡章: "内科治療のグローバルスタンダード-血友病-"臨床医 増刊号. 26. 542-545 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 田中一郎、嶋緑倫: "血友病A"日本血栓止血学会誌. 11. 397-405 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 田中一郎,中宏之,嶋緑倫: "血友病インヒビター"日本血栓止血学会誌. 11. 559-571 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 森近省吾,嶋緑倫,柴田優,中宏之,神末政樹,田中一郎,吉岡章: "重症血友病Aにおける第VIII因子遺伝子逆位の解析"臨床細胞分子遺伝 第4巻 CYTOMOLECULAR GENETICS VOL.4 1999.4月 臨床細胞分子遺伝研究会. 40. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高宮脩: "ルーチン検査(1)検査の実際 (b)APTT"検査と技術 (増刊号). VOL.28 no.7. 839-840 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 嶋緑倫,吉岡章: "血友病インヒビター症例の治療-最近の考え方 Annual Review 血液"中外医学社. 259-265 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Mazzucato,A.Yoshioka et.al: "Identification of Domains Responsible for von Willebrand Factor Type VI Collagen Interaction Mediating Platelet Adhesion under High Flow"The Journal of Biological Chemistry. 274・(5). 3033-3041 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Nogami,A.Yoshioka et.al: "Role of Factor VIII C2 Domain in Factor VIII Binding to Factor Xa"The Journal of Biological Chemistry. 274・(43). 31000-31007 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Sugimoto,A.Yoshioka et al.: "Shear-dependent functions of the interaction between soluble von Willebrand factor and platelet glycoprotein Ib in mural thrombus formation on a collagen surface"International Journal of Hematology. 69. 48-53 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] I.Kuwabara,A.Yoshioka et.al: "Mapping of the minimal domain encoding a conformational epitope byλ phage surface display: factor VIII inhibitor antibodies from haemophilia A patients"Journal of Immunological Methods. 224. 89-99 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Miura,A.Yoshioka et al: "Total inhibition of high shear stress induced platelet aggregation by homodimeric von Willebrand factor AI-loop fragments"British Journal of Haematology. 105. 1092-1100 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Nogami,I.Tanaka,A.Yoshioka et al: "Identification of a factor VIII peptide,residuse 2315-2330,which neutralizes human factor VIII C2 inhibitor alloantibodies: requirement of Cys^<2326> and Glu^<2327> for maximum effec"British Journal of Haematology. 107. 196-203 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Tsuji,M.Sugimoto,A.Yoshioka et al: "Real-Time Analysis of Mural Thrombus Formation in Various Platelet Aggregation Disorders: Distinct Shear-Dependent Roles of Platelet Receptors and Adhesive Proteins Unde Flow"Blood. 94・(3). 968-975 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Kuwahara,M.Sugimoto,A.Yoshioka et al: "Cytosolic Calcium Changes in a Process Platelet Adhesion and Cohesion on a von Willebrand Factor-Coated Surface Under Flow Conditions"Blood. 94・(4). 1149-1155 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 高橋幸博: "新生児の血栓症"日本産婦人科・新生児血液学会誌. 8・(4). 111-121 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中宏之,吉岡章: "血友病-最近の進歩、遺伝子診断"血液・腫瘍科. 38・(4). 251-258 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 箕輪秀樹,中宏之,高橋幸博,吉岡章 他: "プラスミノゲンアクチベーターインヒビター1(PAI-1)シグナルペプチド遺伝子上の新しいpolymorphism;1340G/A(-7Val/Ile)"日本血栓止血学会誌. 10・(4). 267-277 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 松井英人、杉本充彦,高橋幸博,吉岡章 他: ""vWF assay ELISAキット"(Shield社)によるvon Willebrand因子(vWf)抗原量の測定"医薬と薬学. 42・(2). 317-322 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 西野正人,吉岡章: "先天性凝固因子異常症"小児科診療. 62. 296-300 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉岡章,高橋幸博(分担): "血友病の告知とインフォームドコンセント"医薬ジャーナル社. 19/158 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 杉本充彦,吉岡章(分担): "エッセンシャル血液病学(第5版)"医歯薬出版. 7/276 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉岡章,田中一郎,高宮脩,中宏之,高橋幸博,杉本充彦(分担): "小児慢性特定疾患治療マニュアル"診断と治療社. 36/511 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉岡章(分担): "内科学"朝倉書店. 4/2110 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉岡章(分担): "内科学(II)"文光堂. 3/2233 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉岡章(分担): "今日の治療指針 1999"医学書院. 2/1494 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] R.C.Madhusudan,A.Yoshioka et al.: "Crystal structure of NMC-4 Fab anti-vWGA1 domain" Blood Cells,Molemles,and Diseases. 23・7. 123-134 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.Gianelli,A.Yoshioka et al.: "Haemophilia B: database of point mutations and short additions and deletions,7th edition" Nucleic Acids Research. 25・1. 133-135 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 嶋 緑倫,吉岡 章: "凝固因子およびその制御因子のgene targetingによる新しい機能の解析" Annual Review 血液 1998(中外医学社). 203-209 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 斎藤英孝,吉岡 章 他: "プロテインC欠乏症患者の血栓症に対する乾燥濃縮ヒト活性化プロテインC製剤(CTC-III)の臨床試験" 新薬と臨床. 47・5. 718-732 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] R.Celikel,A.Yoshiok et al.: "Crystal Structure of the vWF A1 dowain in complex with the function blocking NMC-4 Fab" Nature Structural Biology. 5・3. 189-194 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Suzuki,A.Yoshioka et al: "The Role of Plotelet vWF in the Pinding of FVIII to Activated Platelet" Thrombosis Research. 90. 207-214 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中河いよう、高橋幸博 他: "アトピー性皮膚炎における可溶性トロンボモジュリン" 日本小児科学会雑誌. 102・9. 964-969 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高橋幸博,吉岡 章: "アンチトロンビン,トロンビン-アンチトロンビン複合体" 小児内科. 30(増刊). 105-107 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高橋幸博: "新生児の血栓症" 日本産婦人科新生児血液学会誌. 8・2. 1-2 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Nanami,Y.Takahashi et al: "Plasma levels of FVIIa are very low in neonates and intants" Thrombosis Haemostasis. 79. 689-690 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Sugimoto,A.Yoshioka et al: "Activated proteinC concentrate : A new tool for the treatment of acute thromboembolism in patients with congemital protein C deficiency" Thrombosis Haemostasis. 77・6. 1223-1224 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 杉本 充彦,他: "ずり応力下での血小板血栓形成ずり応力惹起血小板粘着-凝集装置を用いた研究の現況および将来展望" 血小板血栓形成の分子機構(ライフサイエンス出版). 9-14 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中一郎,吉岡 章: "症候からみた小児の診断学-紫斑,出血傾向-" 小児科診療. 60(増刊). 397-402 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中一郎,吉岡 章: "小児の臨床検査・最近の進歩,-血液凝固検査-" 小児科臨床. 50・4. 675-682 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中一郎,吉岡 章: "血液・造血器疾患の薬物治療 血友病" 医学と薬学. 40・3. 448-453 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 池田裕貴子、高橋幸博他: "洞不全症候群の経過中に腎梗塞と脳梗塞を発症した先天性プロテインS欠損症の1例" 奈良医学雑誌. 48・1. 45-52 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中 宏之、吉岡 章: "遺伝子治療の現況-血友病-" 周産期医学. 27・1. 89-94 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中 宏之: "第1X因子遺伝子プロモーター解析" 臨床病理(特集). 104(特). 107-116 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高宮 脩: "血栓傾向の検査" 小児科臨床. 50・4. 699-706 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Kodaira,O.Takamiya et al: "Resistance to activated protein C,and Arg 506 Gln factor V mutation are uncommon in eastern Asian population" Acta Haematologica. 98. 22-25 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] O.Takamiya,S.Kinoshita: "A simple method for detection of human FIX inhibited using EUSA" Scandinavian J.of Clinical Laboratory Investigation. 57. 683-688 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高宮脩、高橋幸博: "血液症候群III. Hageman trait" 日本臨床(領域別症候群シリーズ No.22). 28-30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 石田 文宏、高宮 脩: "血液症候群III、後天性血栓化傾向" 日本臨床(領域別症候群シリーズ No.22). 588-591 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] O.Takamiya: "Cleracterization of Monoclonal Auti-human Fair Antibody(B101/B1)that Recognized three-Dimentional Structure near Arg to Position 79 in the first EGF like Domai" Thrombosis and Haemostasis. 79. 104-109 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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