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Establishment of cytokines-balance analysis and gene therapy in septic condition

Research Project

Project/Area Number 21592301
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionHokkaido University

Principal Investigator

SAWAMURA Atsushi  北海道大学, 大学院・医学研究科, 講師 (00241448)

Co-Investigator(Kenkyū-buntansha) GANDO Satoshi  北海道大学, 大学院・医学研究科, 教授 (30125306)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords敗血症病態 / TNF-α / IL-6 / TNF-αKO / Western Blotting / TNF-αKOマウス / 遺伝子治療
Research Abstract

Cytokine production in TNF-αdeficiency
In TNF-αKO, an appreciable decline was observed at 0ng/ml, 0.1ng/ml, and 1ng/ml compared to wild type mice.
Investigation into the neutralization of TNF-αand IL-6
TNF-αconcentration exhibited a decline to approximately half the value at mAb IL-6 compared to the control. A significant decline was observed with the addition of mAb TNF-αand rIL6+rTNF-α.(2) IL-6 concentration exhibited approximately 20% with the addition of mAb TNF-αcompared to the control. A further decline by half was exhibited with the addition of mAb IL-6. A significant decline was observed with the addition of rIL6+rTNF-α. 3. STAT3 activation due to Western Blotting was significantly positive regarding TNF-αKO compared to the Wild Type. STAT3 activation with the addition of rIL6 was negative regarding both Wild Type and TNF-αKO. SOCS3 activation was negative regarding both Wild Type and TNF-αKO. SOCS3 activation with the addition of rIL6 was negative regarding both Wild Type and TNF-αKO.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (47 results)

All 2012 2011 2010 2009 2007

All Journal Article (32 results) Presentation (15 results)

  • [Journal Article] 輸血関連急性肺傷害(TRALI)の診断と治療指針2012

    • Author(s)
      澤村淳
    • Journal Title

      救急・集中治療ガイドライン

      Pages: 194-195

    • Related Report
      2011 Final Research Report
  • [Journal Article] 敗血症が発症に関与したと考えられた生体肝移植術後posterior reversible encephalopathy syndrome(PRES)の3症例Posterior reversible encephalopathy syndrome presenting after a liver transplantation : a report of three Cases2011

    • Author(s)
      澤村淳、久保田信彦、上垣慎二、早川峰司、鈴木友巳、嶋村剛、丸藤哲
    • Journal Title

      日本救急医学会雑誌

      Volume: 22(7) Pages: 337-343

    • Related Report
      2011 Final Research Report
  • [Journal Article] 特集・ショックの病態と治療III症例から学ぶショック治療の実際ショックに合併したDIC管理の実際-DICの診断と治療・治療効果判定2011

    • Author(s)
      澤村淳、菅野正寛、久保田信彦、上垣慎二、早川峰司、丸藤哲
    • Journal Title

      救急医学

      Volume: 35 Pages: 482-490

    • Related Report
      2011 Final Research Report
  • [Journal Article] 特集血栓・塞栓I総論4.血栓・塞栓の治療2011

    • Author(s)
      澤村淳、菅野正寛、久保田信彦、上垣慎二、早川峰司、丸藤哲
    • Journal Title

      救急医学

      Volume: 35 Pages: 1768-1772

    • Related Report
      2011 Final Research Report
  • [Journal Article] 播種性血管内凝固症候群(DIC)2011

    • Author(s)
      丸藤哲、澤村淳、早川峰司、上垣慎二、久保田信彦、菅野正寛、平安山直美、向井信貴、三浪陽介
    • Journal Title

      救急・集中治療

      Volume: 23 Pages: 53-64

    • Related Report
      2011 Final Research Report
  • [Journal Article] I侵襲に対する生体反応感染性・非感染性生体2011

    • Author(s)
      丸藤哲、澤村淳、早川峰司、菅野正寛上垣慎二、久保田信彦、向井信貴、山本浩
    • Journal Title

      侵襲と生体反応救急医

      Volume: 35 Pages: 747-752

    • Related Report
      2011 Final Research Report
  • [Journal Article] 特集・変貌するDICの診断と治療炎症と凝固線溶反応-TAFIと補体活性化-2011

    • Author(s)
      丸藤哲、澤村淳、早川峰司、菅野正寛上垣慎二、久保田信彦
    • Journal Title

      Thrombosis Medicine

      Volume: 1 Pages: 21-26

    • Related Report
      2011 Final Research Report
  • [Journal Article] 特集:外傷(頭部・胸腹部・四肢・骨盤)と感染総説外傷と局所・全身反応2011

    • Author(s)
      丸藤哲、澤村淳、早川峰司、菅野正寛上垣慎二、久保田信彦、向井信貴、山本浩
    • Journal Title

      日本外科感染症学会雑誌

      Volume: 8 Pages: 297-305

    • Related Report
      2011 Final Research Report
  • [Journal Article] 特集:凝固炎症反応連関から見た敗血症の病態と治療TAFIを介した凝固炎症反応とOPTIMIST2011

    • Author(s)
      丸藤哲、澤村淳、早川峰司、久保田信彦、上垣慎二、菅野正寛、向井信貴、本間多恵子
    • Journal Title

      Thrombosis Medicine

      Volume: 1 Pages: 151-156

    • Related Report
      2011 Final Research Report
  • [Journal Article] Efficacy of Ciprofloxacin as an anti-inflammatory agent in patients with sepsis2011

    • Author(s)
      Sawamura A, Hayakawa M, Sugano M, Henzan N, Kubota N, Uegaki S, Gando S
    • Journal Title

      J Jpn Surg Infec

      Volume: 8 Pages: 679-685

    • NAID

      40019184887

    • Related Report
      2011 Final Research Report
  • [Journal Article] Disseminated intravascular coagulation at an early phase of trauma is associated with consumpution coagulopathy and excessive fibrinolysis both and neutrophil erastase2011

    • Author(s)
      Hayakawa M, Sawamura A, Gando S, Kubota N, Uegaki S, Shimojima H, Sugano M, Ieko M
    • Journal Title

      Surgery

      Volume: 23 Pages: 221-230

    • Related Report
      2011 Final Research Report
  • [Journal Article] Dramatic changes of the gut flora immediately after severe and sudden insults2011

    • Author(s)
      Hayakawa M, Asahara T, Henzan N, Murakami H, Yamamoto H, Mukai N, Minami Y, Sugano M, Kubota N, Uegaki S, Kamoshida H, Sawamura A, Nomoto K, Gando S
    • Journal Title

      Dig Dis Sci

      Volume: 56 Pages: 2361-2365

    • NAID

      120003370665

    • Related Report
      2011 Final Research Report
  • [Journal Article] Time-dependent expression of endothelin-1 in lungs and the effects of TNF-αblocking peptide on acute lung injury in an endotoxemic rat model2011

    • Author(s)
      Jesmin S, Yamaguchi N, Zaedi S, Nusrat Sultana S, Iwashima Y, Sawamura A, Gando S
    • Journal Title

      Biomed Res

      Volume: 32 Pages: 9-17

    • Related Report
      2011 Final Research Report
  • [Journal Article] Trauma, shock, and disseminated intravascular coagulation : lessons from the classical literature2011

    • Author(s)
      Gando S, Sawamura A, Hayakawa M
    • Journal Title

      Ann Surg

      Volume: 254 Pages: 10-19

    • Related Report
      2011 Final Research Report
  • [Journal Article] Low TAFI activity and insufficient activation of fibrinolysis by both plasmin and neutrophil elastase promote organ dysfunction in disseminated intravascular coagulation associated with sepsis2011

    • Author(s)
      Hayakawa M, Sawamura A, Gando S, Jesmin S, Naito S, Ieko M
    • Journal Title

      Thromb

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Journal Article] 心膜腔穿刺法、心膜切開法2010

    • Author(s)
      澤村淳
    • Journal Title

      医学書院

      Pages: 103-105

    • Related Report
      2011 Final Research Report
  • [Journal Article] 外傷急性期の血液凝固線溶系-現在の世界的論点を整理する2010

    • Author(s)
      丸藤哲、澤村淳、早川峰司、菅野正寛、久保田信彦、上垣慎二、平安山直美
    • Journal Title

      日本救急医学会雑誌

      Volume: 21 Pages: 765-778

    • NAID

      10030254693

    • Related Report
      2011 Final Research Report
  • [Journal Article] 急性期DIC診断基準の特徴と今後の展望2010

    • Author(s)
      丸藤哲、澤村淳、早川峰司
    • Journal Title

      日本血栓止血学会誌

      Volume: 21 Pages: 588-594

    • NAID

      10027675280

    • Related Report
      2011 Final Research Report
  • [Journal Article] 救急・集中治療領域における真菌分離頻度と薬剤感受性からみた真菌感染症対策2010

    • Author(s)
      澤村淳、菅野正寛、久保田信彦、上垣慎二、早川峰司、丸藤哲
    • Journal Title

      救急医学

      Volume: 34 Pages: 1719-1722

    • NAID

      40017383420

    • Related Report
      2011 Final Research Report
  • [Journal Article] 鈍的外傷患者におけるFDP(fibrin/fibrinogen degradation products)高値と大量出血の関連性2010

    • Author(s)
      早川峰司、和田剛志、菅野正寛、下嶋秀和、上垣慎二、澤村淳、丸藤哲
    • Journal Title

      日本救急医学会雑誌

      Volume: 21 Pages: 165-719

    • NAID

      130004542264

    • Related Report
      2011 Final Research Report
  • [Journal Article] Sivelestat(selective neutrophil elastase inhibitor) improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagulation patients2010

    • Author(s)
      Hayakawa M, Katabami K, Wada T, Sugano M, Hoshino H, Sawamura A
    • Journal Title

      Gando S SHOCK

      Volume: 33 Pages: 14-18

    • NAID

      120002693627

    • Related Report
      2011 Final Research Report
  • [Journal Article] Imbalance between macrophage migration inhibitory factor and cortical induces multiple organ dysfunction in patients with blunt trauma2010

    • Author(s)
      Hayakawa M, Katabami K, Wada T, Sugano M, Hoshino H, Sawamura A, Gando S
    • Volume
      34
    • Pages
      193-197
    • Related Report
      2011 Final Research Report
  • [Journal Article] 症例から学ぶ小児救急疾-外傷;鈍外傷による気管裂傷2009

    • Author(s)
      澤村淳
    • Journal Title

      小児外科

      Volume: 41 Pages: 551-554

    • Related Report
      2011 Final Research Report
  • [Journal Article] 救急集中治療領域における血小板・凝固線溶系モニタリングの実際2009

    • Author(s)
      丸藤哲、澤村淳、早川峰司、久保田信彦、平安山直美、菅野正寛、和田剛志、方波見謙一
    • Journal Title

      日本救急医学会雑誌

      Volume: 20 Pages: 1-15

    • Related Report
      2011 Final Research Report
  • [Journal Article] III代謝・体液系モニタリング凝固線溶系2009

    • Author(s)
      丸藤哲、澤村淳、早川峰司、久保田信彦、平安山直美、菅野正寛、和田剛志、方波見謙一
    • Journal Title

      救急医学

      Volume: 33 Pages: 311-315

    • Related Report
      2011 Final Research Report
  • [Journal Article] 敗血症治療における生理的抗凝固物質の役割.血液フロンティア2009

    • Author(s)
      丸藤哲、澤村淳、早川峰司
    • Journal Title

      特集・トロンボモデュリンとプロテインCの新展開

      Volume: 19 Pages: 751-759

    • Related Report
      2011 Final Research Report
  • [Journal Article] Expression of 4 protease-activated receptors is associated with increased levels of TNF-alpha, tissue factor, and fibrin in the frontal cortex of endotoxemic rat2009

    • Author(s)
      Jesmin S, Gando S, Zaedi S, Sawamura A
    • Journal Title

      Thromb Res

      Volume: 124 Pages: 498-501

    • Related Report
      2011 Final Research Report
  • [Journal Article] Effects of antithrombin in patients with disseminated intravascular coagulation diagnosed by newly developed diagnostic criteria for critical illness2009

    • Author(s)
      Sawamura A, Gando S, Hayakawa H, Hoshino H, Kubota N, Sugano M
    • Journal Title

      Clin Appl Thromb Hemost

      Volume: 15 Pages: 561-566

    • Related Report
      2011 Final Research Report
  • [Journal Article] Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality2009

    • Author(s)
      Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T, Katabami K
    • Journal Title

      Thromb Res

      Volume: 124 Pages: 608-613

    • Related Report
      2011 Final Research Report
  • [Journal Article] Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma2009

    • Author(s)
      Sawamura A, Hayakawa H, Gando S, Hoshino H, Kubota N, Henzan N, Sugano M
    • Journal Title

      Thromb Res

      Volume: 124 Pages: 706-710

    • Related Report
      2011 Final Research Report
  • [Journal Article] Protease-activated receptor2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates renal fibrin deposition in a rat model of acute renal failure2009

    • Author(s)
      Jesmin S, Gando S, Zaedi S, Prodhan SH, Sawamura A, Miyauchi T, Hiroe M, Yamaguchi N
    • Journal Title

      SHOCK

      Volume: 32 Pages: 626-632

    • Related Report
      2011 Final Research Report
  • [Journal Article] 敗血症における凝固異常・血管内皮傷害(特集救急医療領域における感染症)-(敗血症) Coagulation disturbance and endothelial cell injury in sepsis2007

    • Author(s)
      丸藤哲、澤村淳、早川峰司, 他
    • Journal Title

      救急医学

      Volume: 31(10) Pages: 1326-1334

    • Related Report
      2011 Final Research Report
  • [Presentation] Thrombin-activated fibrinolysis inhibitor and organ dysfunction in DIC associated with sepsis2011

    • Author(s)
      Hayakawa M, Sawamura A, Sugano M, Uegaki S, Kubota N, Gando S, Jesmin S
    • Organizer
      Sepsis 2011
    • Place of Presentation
      Bejing, People's Republic of China
    • Year and Date
      2011-10-27
    • Related Report
      2011 Final Research Report
  • [Presentation] Low TAFI activity promotes organ dysfunction and poor progress in DIC associated with sepsis2011

    • Author(s)
      Gando S, Sawamura A, Hayakawa M, Sugano M, Uegaki S, Kubota N, Jesmin S
    • Organizer
      Chest 2011
    • Place of Presentation
      Honolulu, U. S. A
    • Year and Date
      2011-10-25
    • Related Report
      2011 Final Research Report
  • [Presentation] coagulation at an early phase of trauma continuously proceeds to DIC at a late phase of trauma2011

    • Author(s)
      Gando S, Hayakawa M, Sawamura A, Kubota N, Uegaki S, Sugano M
    • Organizer
      International Critical Care Congress 2011
    • Place of Presentation
      New Delhi, India
    • Related Report
      2011 Final Research Report
  • [Presentation] Pharmacokinetics and pharmacodynamics of recombinant human soluble thrombomodulin in DIC patients with severe renal impairment2011

    • Author(s)
      Hayakawa M, Homma T, Yamamoto H, Mukai N, Sugano M, Uegaki S, Kubota N, Sawamura A, Gando S
    • Organizer
      24th European Society of Intensive Care Medicine Annual Congres
    • Place of Presentation
      Berlin, Federal Republic of Germany
    • Related Report
      2011 Final Research Report
  • [Presentation] Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive firrinolysis both by plasmin and neutrophil elastase2010

    • Author(s)
      Sawamura A, Gando S, Hayakawa M, Kubota N, Uegaki S, Sugano M
    • Organizer
      Chest 2010
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-11-02
    • Related Report
      2011 Final Research Report
  • [Presentation] Dramatic changes in the gut flora in critical illness immediately after severe insult2010

    • Author(s)
      Hayakawa H, Asahara T, Henzan N, Murakami H, Yamamoto H, Mukai N, Minami Y, Sugano M, Kubota N, Uegaki S, Kamoshida H, Sawamura A, Nomoto K, Gando S
    • Organizer
      23rd European Society of Intensive Care
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2010-10-13
    • Related Report
      2011 Final Research Report
  • [Presentation] The effects of recombinant human soluble thrombomodulin in the experimental endotoxemic mouse induced by lipopolysaccharide2010

    • Author(s)
      Sawamura A, Hayakawa H, Gando S, Kubota N, Uegaki S, Sugano M
    • Organizer
      23rd European Society of Intensive Care
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2010-10-11
    • Related Report
      2011 Final Research Report
  • [Presentation] 外傷急性期患者における急性期DIC診断基準の評価2010

    • Author(s)
      澤村淳、丸藤哲、早川峰司
    • Organizer
      第33回日本血栓止血学会学術集会
    • Place of Presentation
      鹿児島
    • Related Report
      2011 Final Research Report
  • [Presentation] DIC at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase, and continues to DIC at late phase of trauma2010

    • Author(s)
      Gando S, Hayakawa H, Sawamura A, Kubota N, Uegaki S, Sugano M
    • Organizer
      21st International Thrombosis Congress
    • Place of Presentation
      Milan, Italy
    • Related Report
      2011 Final Research Report
  • [Presentation] Disseminated intravascular coagulation at an early phase of trauma continuously proceeds to DIC at a phase of trauma2010

    • Author(s)
      Murakami H, Gando S, Hayakawa M, Sawamura A, Kubota N, Uegaki S, Sugano M, Mukai N
    • Organizer
      6th Congress of Asia Pacific society on Thrombosis and Hemostasis
    • Place of Presentation
      Bali, Republic of Indonesia
    • Related Report
      2011 Final Research Report
  • [Presentation] Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma2009

    • Author(s)
      Sawamura A, Hayakawa H, GandoS, Hoshino H, Kubota N, Henzan N, Sugano M
    • Organizer
      22th European Society of Intensive Care
    • Place of Presentation
      Vienna, Republic of Austria
    • Year and Date
      2009-10-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Fibrinogenolysis during the early stage of trauma predicts the occurrence of massive bleeding in patients with blunt trauma2009

    • Author(s)
      Hayakawa H, Wada T, Sugano M, Kubota N, Sawamura A, Gando S
    • Organizer
      22th European Society of Intensive Care
    • Place of Presentation
      Vienna, Republic of Austria
    • Year and Date
      2009-10-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Disseminated intravascular coagulation with a fibrinolytic phenotype modified through fibrinogenolysis at an early phase of trauma predicts mortality2009

    • Author(s)
      Gando S, Sawamura A, Hayakawa M, Kubota N, Sugano M, Wada T, Katabami K
    • Organizer
      22th Congress International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Boston, U. S. A
    • Year and Date
      2009-07-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 生体肝移植術後に出現したposterior reversible encephalopathy syndrome(PRES)の二症例2009

    • Author(s)
      澤村淳、方波見謙一、三浪陽介、和田剛志、菅野正寛、下嶋秀和、上垣慎二、久保田信彦、早川峰司、丸藤哲
    • Organizer
      第37回日本救急医学会総会・学術集会
    • Place of Presentation
      盛岡
    • Related Report
      2011 Final Research Report
  • [Presentation] Disseminated intravascular coagulation at an early phase of trauma2009

    • Author(s)
      Sawamura A, Gando S, Hayakawa M, Hoshino H, Kubota N, Henzan N, Sugano M, Wada T, Katabami K
    • Organizer
      15th International Meeting Danubian
    • Place of Presentation
      Beograd, Republic of Serbia
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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