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ROLE OF KALLIKREIN-KININ SYSTEM IN MAINTENANCE OF PREGNANCY

Research Project

Project/Area Number 15591780
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTokai University

Principal Investigator

SUGI Toshitaka  Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (70196707)

Co-Investigator(Kenkyū-buntansha) INOMO Akifumi  Tokai University, School of Medicine, Assistant Researcher, 医学部, 助手 (70338713)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsantiphospholipid antibodies / kininogen / recurrent pregnancy losses / factor XII / kallikrein-kinin system / platelet aggregation / 血小板凝集能 / カリクレイン / ブラジキニン / 血栓症 / プラジキニン
Research Abstract

Coagulation factor XII, prekallikrein and high molecular weight kininogen are known as proteins of kallikrein-kinin system. Recently, surprisingly high prevalence of factor XII deficiency among patients with RPL have been reported. We have now tested plasma samples from RPL patients for the presence of autoantibodies to factor XII. One hundred ninety one patients with RPL were screened for factor XII activity. We found 34 (17.8%) patients with factor XII deficiency (activity <60%). Thirteen (38.2%) of these 34 patients were positive for antiphospholipid antibodies. We hypothesized that factor XII deficiency may be partly due to presence of antibodies to factor XII and tested plasma samples from patients with factor XII deficiency for the presence of antibodies to factor XII by immunoblot and ELISA. We found that 53.5% of factor XII deficient patients with RPL were positive for IgG anti-factor XII antibodies (p<0.001, OR36.8). Anti-factor XII antibodies recognized the amino-terminal heavy chain region of factor XII. Literatures have reported that human factor XII binding to the glycoprotein Ib-IX-V complex via the amino-terminal heavy chain region inhibits thorombin-induced platelet aggregation. We hypothesize that autoantibodies to factor XII may be associated with RPL.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (47 results)

All 2006 2005 2004 2003 Other

All Journal Article (37 results) Book (4 results) Publications (6 results)

  • [Journal Article] Factor XII, kininogen and plasma prekallikrein in abnormal pregnancies.2005

    • Author(s)
      Sugi T, Makino T
    • Journal Title

      Current Drug Targets 6

      Pages: 551-557

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Preconception peripheral natural killer cell activity as a predictor of pregnancy outcome in patients with unexplained infertility.2005

    • Author(s)
      Matsubayashi H et al.
    • Journal Title

      An J Reprod Immunol 53

      Pages: 126-131

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] わが教室における不育症対策2005

    • Author(s)
      杉 俊隆, 牧野恒久
    • Journal Title

      産婦人科治療 91

      Pages: 199-204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 出生前診断における倫理上の問題点。不育症を中心として2005

    • Author(s)
      杉 俊隆
    • Journal Title

      産科と婦人科 72

      Pages: 1708-1714

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗リン脂質抗体の種類と検出法2005

    • Author(s)
      杉 俊隆, 牧野恒久
    • Journal Title

      産婦人科の実際 54

      Pages: 553-559

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 後天性血栓症素因の診断と対策2005

    • Author(s)
      杉 俊隆
    • Journal Title

      産婦人科の実際 54

      Pages: 903-910

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Factor XII, kininogen and plasma prekallikrein in abnormal pregnancies.2005

    • Author(s)
      Sugi T, Makino T.
    • Journal Title

      Current Drug Targets 6

      Pages: 551-557

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Preconception peripheral natural killer cell activity as a predictor of pregnancy outcome in patients with unexplained infertility.2005

    • Author(s)
      Matsubayashi H, Shida M, Kondo A, Suzuki T, Sugi T, Izumi S-I, Hosaka T, Makino T.
    • Journal Title

      Am J Reprod Immunol 53

      Pages: 126-131

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Preconception peripheral natural killer cell activity as a predictor of pregnancy outcome in patients with unexplained infertility.2005

    • Author(s)
      Matsubayashi H et al.
    • Journal Title

      Am J Reprod Immunol 53

      Pages: 126-131

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 出生前診断における倫理上の問題点 2)不育症を中心として2005

    • Author(s)
      杉 俊隆
    • Journal Title

      産科と婦人科 72

      Pages: 1708-1714

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 目で見る不妊、不育の免疫異常-抗リン脂質抗体-2004

    • Author(s)
      牧野恒久 ら
    • Journal Title

      Hormone Frontier in Gynecology 11

      Pages: 208-211

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗リン脂質抗体症候群と不育症2004

    • Author(s)
      杉 俊隆
    • Journal Title

      産婦人科の世界 56

      Pages: 1231-12337

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Platelet inhibition by single low-dose aspirin, using the newly developed aggregometry with the laser light scattering method.2004

    • Author(s)
      Haque SF et al.
    • Journal Title

      Tokai J Exp Clin Med 29

      Pages: 7-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid to late fetal loss.2004

    • Author(s)
      Sugi T et al.
    • Journal Title

      J Obstet Gynaecol Res 30

      Pages: 326-332

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] 研修医のための必修知識。自己抗体検査(抗リン脂質抗体、ループスアンチコアグラント)2004

    • Author(s)
      牧野恒久, 杉 俊隆
    • Journal Title

      日産婦誌 56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗リン脂質抗体症候群2004

    • Author(s)
      杉 俊隆
    • Journal Title

      産科と婦人科 71

      Pages: 1320-1325

    • NAID

      110007731034

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] 不育症とカリクレインーキニン系2004

    • Author(s)
      杉 俊隆
    • Journal Title

      臨床婦人科産科 58

      Pages: 1148-1151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗リン脂質抗体2004

    • Author(s)
      杉 俊隆
    • Journal Title

      周産期医学 34

      Pages: 609-611

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] 抗リン脂質抗体と不育症2004

    • Author(s)
      杉 俊隆, 牧野恒久
    • Journal Title

      産婦人科の実際 53

      Pages: 1003-1010

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗リン脂質抗体2004

    • Author(s)
      杉 俊隆
    • Journal Title

      産科と婦人科 71 Suppl

      Pages: 154-157

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid to late fetal loss.2004

    • Author(s)
      Sugi T, Matsubayashi H, Inomo M, Dan L, Makino T.
    • Journal Title

      J Obstet Gynaecol Res 30

      Pages: 326-332

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Platelet inhibition by single low-dose aspirin, using the newly developed aggregometry with the laser light scattering method.2004

    • Author(s)
      Haque SF, Izumi S-I, Hotta A, Matsubayashi H, Awaji H, Murano T, Yoshitake T, Yoshikata K, Sugi T, Nakazawa H, Ly C, Makino T.
    • Journal Title

      Tokai J Exp Clin Med 29

      Pages: 7-12

    • NAID

      110004700368

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 不育症とカリクレイン-キニン系2004

    • Author(s)
      杉 俊隆
    • Journal Title

      臨床婦人科産科 58

      Pages: 1148-1151

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 自己抗体を介したカリクレインーキニン系の破綻と流産2003

    • Author(s)
      杉 俊隆
    • Journal Title

      自己抗体と自己免疫2003

      Pages: 27-33

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ThrombophiliaとIUGR2003

    • Author(s)
      杉 俊隆, 牧野恒久
    • Journal Title

      周産期医学 33

      Pages: 1387-1390

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-annexin A5 antibodies in reproductive failure in relation to antiphospholipid antibodies and phosphatidylserine.2003

    • Author(s)
      Arai T et al.
    • Journal Title

      Am J Reprod Immunol 50

      Pages: 202-208

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗リン脂質抗体症候群2003

    • Author(s)
      杉 俊隆
    • Journal Title

      臨床婦人科産科 57

      Pages: 1043-1045

    • NAID

      110007731034

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 不育症、抗リン脂質抗体症候群-ヘパリン、アスピリン療法は有効か-2003

    • Author(s)
      杉 俊隆, 牧野恒久
    • Journal Title

      産婦人科の実際 52

      Pages: 1769-1774

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antiphospholipid antibodies (APA) and recurrent pregnancy loss : treating a unique APA positive population.2003

    • Author(s)
      Sugi T
    • Journal Title

      Human Reproduction 18

      Pages: 1553-1554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 今月の臨床。ここが聞いたい-産婦人科外来における対処と処方-2003

    • Author(s)
      杉 俊隆, 牧野恒久
    • Journal Title

      臨床婦人科産科 57

      Pages: 545-547

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗リン脂質抗体症候群2003

    • Author(s)
      杉 俊隆
    • Journal Title

      産婦人科の実際 52

      Pages: 731-739

    • NAID

      110007731034

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 自己抗体を介したカリクレインーキニン系の破綻と不育症2003

    • Author(s)
      杉 俊隆
    • Journal Title

      医学のあゆみ 204

      Pages: 1031-35

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Kininogen domain 3 contains regions recognized by antiphosphatidylethanolamine antibodies.2003

    • Author(s)
      Katsunuma J et al.
    • Journal Title

      J Thromb Haemost 1

      Pages: 132-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Kininogen domain 3 contains regions recognized by antiphosphatidylethanolamine antibodies.2003

    • Author(s)
      Katsunuma J, Sugi T, Inomo A, Matsubayashi H, Izumi S, Makino T.
    • Journal Title

      J Thromb Haemost 1

      Pages: 132-138

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antiphospholipid antibodies (APA) and recurrent pregnancy loss : treating a unique APA positive population.2003

    • Author(s)
      Sugi T, McIntyre JA.
    • Journal Title

      Human Reproduction 18

      Pages: 1553-1554

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-annexin A5 antibodies in reproductive failure in relation to antiphospholipid antibodies and phosphatidylserine.2003

    • Author(s)
      Arai T, Matsubayashi H, Sugi T, Kondo A, Shida M, Suzuki T, Izumi S-I, McIntyre JA, Makino T.
    • Journal Title

      Am J Reprod Immunol 50

      Pages: 202-208

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Factor XII, kininogen and plasma prekallikrein in abnormal pregnancies.

    • Author(s)
      Sugi T et al.
    • Journal Title

      Current Drug Targets (in press)

    • Related Report
      2004 Annual Research Report
  • [Book] 血栓症ナビゲーター2006

    • Author(s)
      杉 俊隆
    • Total Pages
      317
    • Publisher
      メディカルビュー社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 血栓症ナビゲーター2006

    • Author(s)
      杉 俊隆
    • Total Pages
      317
    • Publisher
      メディカルレビュー社
    • Related Report
      2005 Annual Research Report
  • [Book] 生殖医療のコツと落とし穴2004

    • Author(s)
      杉 俊隆
    • Total Pages
      256
    • Publisher
      中山書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Book] 今日の治療指針 2003年度版2003

    • Author(s)
      杉 俊隆
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] 杉 俊隆: "自己抗体を介したカリクレイン-キニン系の破綻と不育症"医学のあゆみ. 204. 1031-1035 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 杉 俊隆, 牧野恒久: "抗リン脂質抗体症候群"産婦人科の実際. 52. 731-739 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 杉 俊隆, 牧野恒久: "抗リン脂質抗体"臨床婦人科産科. 57. 1043-1045 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugi T, McIntyre JA: "Antiphospholipid antibodies(APA)and recurrent pregnancy loss : treating a unique APA positive population."Human Reproduction. 18. 1553-1554 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 杉 俊隆, 牧野恒久: "不育症、抗リン脂質抗体症候群。-ヘパリン、アスピリン療法は有効か-"産婦人科の実際. 52. 1769-1774 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arai T, Matsubayashi H, Sugi T, et al.: "Anti-annexin A5 antibodies in reproductive failure in relation to antiphospholipid and phosphatidylserine."Am J Reprod Immunol. 50. 202-208 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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