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Proteomic analysis for the cell-death related prteins makes it possible to address the pathophysiology of sepis

Research Project

Project/Area Number 25462831
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionJuntendo University

Principal Investigator

Iba Toshiaki  順天堂大学, 医学部, 教授 (40193635)

Co-Investigator(Kenkyū-buntansha) HAYASHI Nobuhiro  東京工業大学, 生命理工学研究科, 准教授 (80267955)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsproteome / sepsis / cell-death / DAMPs / histone / nucleosome / protein C / pentraxin 3 / 敗血症 / バイオマーカー / プロテオーム解析 / ヒストン / 血管内皮細胞 / pentraxin-3 / 細胞死 / 重症度診断 / インターロイキン6 / プロカルシトニン / SAPS II / 血中マーカー
Outline of Final Research Achievements

It is known that various types of cell-death is induced in sepsis. Damage-associated molecular patterns from the dead cell is know to activate further inflammation. In the first study, we measured circulating levels of DAMPs in the sepsis patient. The result shows that the levels of histones, nucleosome and HMGB-1 increases significantly in non-survivors. Thus, we think these DAMPs are useful as bio-markers for severity of sepsis. In the second study, we examined the toxicity of DAMPs to the vascular endothelial cells. The results showed that histone H3 and H4 showed the strong toxicity. In the third study, we examined the protective effects of physiological serum proteins. As a result, significant protective effects of either albumin, activated protein C or pentraxin 3 to the histone H3 were revealed.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (26 results)

All 2016 2015 2014 2013

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (3 results)

  • [Journal Article] Potential diagnostic markers for disseminated intravascular coagulation of sepsis2016

    • Author(s)
      Toshiaki Iba, Takashi Ito, Ikuro Maruyama, Bernd Jilma, Thorsten Brenner, Marcella C.A. Muller, Nicole P. Juffermans, Jecko Thachil
    • Journal Title

      Blood Reviews

      Volume: 30 Issue: 2 Pages: 149-155

    • DOI

      10.1016/j.blre.2015.10.002

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DAMP and DIC: The role of extracellular DNA and DNA-binding proteins in the pathogenesis of DIC2016

    • Author(s)
      Patricia C. Liaw, Takashi Ito, Toshiaki Iba, Jecko Thachil, Sacha Zeerleder
    • Journal Title

      Blood Reviews

      Volume: 印刷中 Issue: 4 Pages: 257-261

    • DOI

      10.1016/j.blre.2015.12.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Physiological Levels of Pentraxin 3 and Albumin Attenuate Vascular Endothelial Cell Damage Induced by Histone H3 In Vitro.2016

    • Author(s)
      Iba T, Hamakubo T, Nagaoka I, Sato K, Thachil J
    • Journal Title

      Microcirculation

      Volume: 23 Issue: 3 Pages: 240-247

    • DOI

      10.1111/micc.12269

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The usefulness of antithrombin activity monitoring during antithrombin supplementation in patients with sepsis-associated disseminated intravascular coagulation.2015

    • Author(s)
      Iba T, Saitoh D, Gando S, Thachil J.
    • Journal Title

      Thrombosis Research

      Volume: 135 Issue: 5 Pages: 897-901

    • DOI

      10.1016/j.thromres.2015.03.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The effect of plasma-derived activated protein C on leukocyte cell-death and vascular endothelial damage.2015

    • Author(s)
      Iba T, Nagakari K.
    • Journal Title

      Thrombosis Research

      Volume: 135 Issue: 5 Pages: 963-969

    • DOI

      10.1016/j.thromres.2015.03.012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kinetics of Circulating Damage-Associated Molecular Patterns in Sepsis.2015

    • Author(s)
      Miki T, Iba T
    • Journal Title

      Journal of Immunology Research

      Volume: 2015 Pages: 424575-424575

    • DOI

      10.1155/2015/424575

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparins attenuated histone-mediated cytotoxicity in vitro and improved the survival in a rat model of histone-induced organ dysfunction.2015

    • Author(s)
      Iba T, Hashiguchi N, Nagaoka I, Tabe Y, Kadota K, Sato K
    • Journal Title

      Intensive Care Medicine Experimental

      Volume: 3 Issue: 1 Pages: 36-36

    • DOI

      10.1186/s40635-015-0072-z

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of antithrombin and recombinant thrombomodulin attenuates leukocyte-endothelial interaction and suppresses the increase of intrinsic damage-associated molecular patterns in endotoxemic rats.2014

    • Author(s)
      Iba T, Miki T, Hashiguchi N, Yamada A, Nagaoka I.
    • Journal Title

      J Surg Res

      Volume: 187 Issue: 2 Pages: 581-586

    • DOI

      10.1016/j.jss.2013.10.058

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combination of antithrombin and recombinant thrombomodulin modulates neutrophil cell-death and decreases circulating DAMPs levels in endotoxemic rats.2014

    • Author(s)
      Iba T, Miki T, Hashiguchi N, Tabe Y, Nagaoka I.
    • Journal Title

      Thromb Res

      Volume: E pub Issue: 1 Pages: 169-173

    • DOI

      10.1016/j.thromres.2014.04.015

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Is the neutrophil a ‘prima donna’ in the procoagulant process during sepsis?2014

    • Author(s)
      Iba T, Miki T, Hashiguchi N, Tabe Y, Nagaoka I.
    • Journal Title

      Critical Care

      Volume: 8 Issue: 4 Pages: 230-237

    • DOI

      10.1186/cc13983

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation - The View from Japan.2014

    • Author(s)
      Iba T, Gando S, Thachil J.
    • Journal Title

      J Thromb Haemost

      Volume: E pub Issue: 7 Pages: 1010-1019

    • DOI

      10.1111/jth.12596

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of hemoperfusion using polymyxin B-immobilized fibers on acute lung injury in a rat sepsis model.2014

    • Author(s)
      Iba T, Nagaoka I, Yamada A, Nagayama M, Miki T.
    • Journal Title

      Int J Med Sci

      Volume: 11 Issue: 3 Pages: 255-261

    • DOI

      10.7150/ijms.6276

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neutrophil extracellular traps (NETs), damage-associated molecular patterns (DAMPs) and cell-death during sepsis.2014

    • Author(s)
      Iba T, Murai M, Nagaoka I, Tabe Y
    • Journal Title

      Acute Medicine & Surgery

      Volume: 1 Pages: 2-9

    • NAID

      130004542349

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neutrophil cell-death in response to infection and its relation to coagulation.2013

    • Author(s)
      Iba T, Hashiguchi N, Nagaoka I, Tabe Y, Murai M.
    • Journal Title

      J Intensive Care

      Volume: 1 Issue: 1

    • DOI

      10.1186/2052-0492-1-13

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Circulating Damage-associated Molecular Patterns play major roles in the development of coagulation disorder in infectious diseases2016

    • Author(s)
      Iba T
    • Organizer
      第80回日本循環器病学会
    • Place of Presentation
      仙台国際会議場
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] DIC研究における最近の動向2016

    • Author(s)
      射場敏明
    • Organizer
      第43回日本集中治療医学会学術集会
    • Place of Presentation
      神戸国際展示場
    • Year and Date
      2016-02-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 感染症における自然免疫と凝固反応2015

    • Author(s)
      射場敏明
    • Organizer
      第16回日本検査血液学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-07-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Where to use thrombomodulin and antithrombin in DIC?2015

    • Author(s)
      Iba T
    • Organizer
      XXV Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Tronto
    • Year and Date
      2015-06-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 重症感染症におけるNETsの役割と凝固異常2015

    • Author(s)
      射場敏明
    • Organizer
      第36回日本血栓止血学会
    • Place of Presentation
      京都
    • Year and Date
      2015-05-29 – 2015-05-31
    • Related Report
      2014 Research-status Report
  • [Presentation] 敗血症DICの病態と自然免疫2015

    • Author(s)
      射場敏明
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      甲府
    • Year and Date
      2015-05-22 – 2015-05-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 重症敗血症とDIC2015

    • Author(s)
      射場敏明
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府総合市民会館
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 血清プロテオミクス法による 敗血症重症度マーカーの検索2014

    • Author(s)
      氏本慧、三木隆弘、Thanai Paxton、米澤貴之、鄭雄一、射場敏明、長岡功、林宣宏
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation - The View from Japan.2014

    • Author(s)
      Iba-T
    • Organizer
      International Journal of Thrombosis and Haemostasis
    • Place of Presentation
      Milwaukee
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 敗血症救命医療の最前線2014

    • Author(s)
      射場敏明
    • Total Pages
      7
    • Publisher
      医薬ジャーナル
    • Related Report
      2013 Research-status Report
  • [Book] 救急・集中治療最新ガイドライン2014-’152014

    • Author(s)
      射場敏明
    • Total Pages
      3
    • Publisher
      総合医学社
    • Related Report
      2013 Research-status Report
  • [Book] 救急・集中治療レビュー2014-’152014

    • Author(s)
      射場敏明、三木隆弘
    • Total Pages
      5
    • Publisher
      総合医学社
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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