生体侵襲・生体反応相互作用から生じる臓器不全の病態解明とその予防・治療体系の確立

• 研究課題/領域番号: 21249086
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 救急医学
• 研究機関: 北海道大学
• 研究代表者: 丸藤 哲 北海道大学, 大学院・医学研究科, 教授 (30125306)
• 研究分担者: ジェスミン サブリナ (JESMIN SUBRINA / JESMIN Subrina) 国立国際医療センター研究所, 遺伝子診断治療開発研究部, 室長 (60374261) ; 澤村 淳 北海道大学, 大学院・医学研究科, 准教授 (00241448) ; 水谷 太郎 筑波大学, 医学医療系, 教授 (80181890)
• 連携研究者: 和田 剛志 北海道大学, 医学部附属病院, 助教 (30455646)
• 研究期間 (年度): 2009 – 2012
• 研究課題ステータス: 完了 (2012年度)
• 配分額: 47,580千円 (直接経費: 36,600千円、間接経費: 10,980千円); 2012年度: 9,100千円 (直接経費: 7,000千円、間接経費: 2,100千円); 2011年度: 9,100千円 (直接経費: 7,000千円、間接経費: 2,100千円); 2010年度: 9,100千円 (直接経費: 7,000千円、間接経費: 2,100千円); 2009年度: 20,280千円 (直接経費: 15,600千円、間接経費: 4,680千円)
• キーワード: 敗血症 / 臓器不全 / 神経内分泌反応 / 凝固線溶系 / VEGF / 生体侵襲 / 生体反応 / アセチルコリン受容体 / DIC / 外傷

研究概要

生体侵襲と生体反応に基づく臓器不全発症機序の研究をさらに発展させ、神経内分泌反応・凝固線溶反応・免疫炎症反応三者の連関の病態生理を明確にすることにより臓器不全発症機序を体系的かつ網羅的に解明し臓器不全の新たな予防および治療方法の確立を目指した。具体的には神経内分泌反応の賦活あるいは抑制が抗炎症反応と凝固線溶反応制御を通じて臓器不全発症を予防して生体侵襲に対して生体恒常性を維持することにより症例の予後を改善することの証明を試みた。

研究成果

• [雑誌論文] Time-dependent alterations of VEGF and its signaling molecules in acute lung injury in a rat model of sepsis (2012)
  • 著者名/発表者名: Jesmin S, Zaedi S, Islam AM, SultanaSN, Iwashima Y, Wada T, Yamaguchi N, HiroeM, Gando S
  • 雑誌名: Inflammation 巻: 35 号: 2 ページ: 484-500
  • DOI: 10.1007/s10753-011-9337-1
  • 査読あり
• [雑誌論文] Angiogenic factors and their soluble receptors predict organ dysfunction and mortality in post-cardiac arrest syndrome (PCAS) (2012)
  • 著者名/発表者名: Wada T, Jesmin S, Gando S, Yanagida Y, Mizugaki A, Sultana SN, Zaedi S, Yokota H
  • 雑誌名: Critical Care 巻: 16 号: 5
  • DOI: 10.1186/cc11648
  • 査読あり
• [雑誌論文] Using angiogenic factors and their soluble receptors to predict organ dysfunction in patients with disseminated intravascular coagulation associated with severe trauma (2012)
  • 著者名/発表者名: Wada T, Jesmin S, Gando S, SultanaSN, Zaedi S, Yokota H
  • 雑誌名: Critical Care 巻: 16 号: 2
  • DOI: 10.1186/cc11309
  • 査読あり
• [雑誌論文] Disseminated intravascular coagulation (DIC) at an early phase of trauma continuously proceeds to DIC at a late phase of trauma (2012)
  • 著者名/発表者名: Murakami H, Gando S, Mineji H, Sawamura A, Sugano M, Uegaki S, Jesmin S
  • 雑誌名: Thrombosis and Hemostasis 巻: 18(4) 号: 4 ページ: 364-369
  • DOI: 10.1177/1076029611426138
  • 査読あり
• [雑誌論文] Imbalance between macrophage migration inhibitory factor and cortisol induces multiple organ dysfunction in patients with trauma (2012)
  • 著者名/発表者名: Hayakawa M、 Katabami Kenichi, Wada T, Minami Y, Sugano M, Shimojima H, Kubota N, Uegaki S, Sawamura A, Gando S
  • 雑誌名: Inflammation 巻: 34 号: 3 ページ: 193-197
  • DOI: 10.1007/s10753-010-9223-2
  • 査読あり
• [雑誌論文] The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised contorilled trial (2011)
  • 著者名/発表者名: Robert I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T
  • 雑誌名: Lancet 巻: 377 号: 9771 ページ: 1096-1101
  • DOI: 10.1016/s0140-6736(11)60278-x
  • 査読あり
• [雑誌論文] Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase (2011)
  • 著者名/発表者名: Hayakawa M, 他7名
  • 雑誌名: Surgery 巻: 149 号: 2 ページ: 221-230
  • DOI: 10.1016/j.surg.2010.06.010
  • 査読あり
• [雑誌論文] Microvascular thrombosis and multiple organ dysfunction (2010)
  • 著者名/発表者名: Gando S
  • 雑誌名: Critical Care Med 巻: 38 (Suppl.) ページ: S35-S42
  • DOI: 10.1097/ccm.0b013e3181c9e31d
  • 査読あり
• [雑誌論文] Sivelestat improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagulation (2010)
  • 著者名/発表者名: Hayakawa M, Katabami K, Wada T, SuganoM, Sawamura A, Gando S
  • 雑誌名: SHOCK 巻: 33 号: 1 ページ: 14-18
  • DOI: 10.1097/shk.0b013e3181aa95c4
  • 査読あり
• [雑誌論文] Japanese Society of Thrombosis Hemostasis/DIC subcommittee. Frequency and hemostatic abnormality in pre-DIC patients (2010)
  • 著者名/発表者名: Okamoto K, Hatada T, Uchiyama T, Kawasugi K, Mayumi T, Gando S, Kushimoto S, Seki Y, Madoiwa S, Asakura H, Koga S, Iba T, Maruyama I
  • 雑誌名: Thrombosis Research 巻: 126 号: 1 ページ: 74-78
  • DOI: 10.1016/j.thromres.2010.03.017
  • 査読あり
• [雑誌論文] Microvascular thrombosis and multiple organ dysfunction. (2010)
  • 著者名/発表者名: Gando S.
  • 雑誌名: Crit Care Med 巻: 38(Suppl.)
  • 査読あり
• [雑誌論文] Sivelestat improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagul ation. (2010)
  • 著者名/発表者名: Hayakawa M.
  • 雑誌名: SHOCK 巻: 33 ページ: 14-18
  • 査読あり
• [雑誌論文] Frequency and hemostatic abnormality in pre-DIC patients. (2010)
  • 著者名/発表者名: Okamoto K.
  • 雑誌名: Thromb Res 巻: 126 ページ: 74-78
  • 査読あり
• [学会発表] Angiogenic factors and their soluble receptors for predicting organ dysfunction in disseminated intravascular coagulation associated with sepsis (2012)
  • 著者名/発表者名: Wada T, Jesmin S, Yanagida Y, Terashima T, Gando S.
  • 学会等名: 15^<th> WFSA World Conguress of Anaesthesiologists
  • 発表場所: Buenos Aires ConventionCenter(Argenia)
• [学会発表] Angiogenic factors and their solube receptors to predict organ dysfunction in patients with DIC associated with severe trauma (2012)
  • 著者名/発表者名: Wada T, Jesmin S, Gando S, SultanaSN, Zaedi S, Yokota H
  • 学会等名: The 32^<nd> International Symposium on Intensive Care and Emergency Medicine
  • 発表場所: Brussel Meeting Center (Belgium)
• [学会発表] Thrombin-activated fibrinolysis inhibitor and organ dysfunction in DIC associated with sepsis (2011)
  • 著者名/発表者名: Gando S
  • 学会等名: Sepsis 2011
  • 発表場所: Beijing International Convention Center (China)
  • 年月日: 2011-10-27
• [学会発表] Low TAFI activity promotes organ dysfunction and poor progress in DIC associated with sepsis (2011)
  • 著者名/発表者名: Gabdo S
  • 学会等名: Chest 2011
  • 発表場所: Hawaii Convention Center (USA)
  • 年月日: 2011-10-24
• [学会発表] Time dependent alterations of VEGF and its signal in molecules in acute lung injury in a rat model of sepsis (2011)
  • 著者名/発表者名: Wada T, Jesmin S,Zaedi S, GandoS
  • 学会等名: 24^<rd> European Society of Intensive CareMedicine Annual Congress
  • 発表場所: The InternationalCongress Center Berlin (Germany)
  • 年月日: 2011-10-15
• [学会発表] Time-dependent expression of endotheline-1 in lungs and the effects of TNF-α blocking peptide on entodhelin-1 levels in lungs in endotoxemic rat model (2011)
  • 著者名/発表者名: Shinji U
  • 学会等名: 24rd European Society of Intensive Care Medicine Annual Congress
  • 発表場所: Exhibition Centre Berlin (Germany)
  • 年月日: 2011-10-03
• [学会発表] Time-dependent alterations of VEGF and its signal in molecules in acute lung injury in a raat model of sepsis (2011)
  • 著者名/発表者名: Wada T
  • 学会等名: 24rd European Society of Intensive Care Medicine Annual Congress
  • 発表場所: Exhibition Centre Berlin (Germany)
  • 年月日: 2011-10-02
• [学会発表] Low TAFI activity promotes organ dysfunction and poor progress in DIC associated with sepsis (2011)
  • 著者名/発表者名: Gando S, Sawamura A, Hayakawa M, Sugano M, Uegaki S, Kubota N, Jesmin S
  • 学会等名: Chest2011O
  • 発表場所: Hawaii Convention Center (USA)
• [学会発表] Thrombin-activated fibrinolysis inhibitor and organ dysfunction in DIC associated with sepsis (2011)
  • 著者名/発表者名: Hayakawa M, Sawamura A, Sugano M, Uegaki S, Kubota N, Gando S, Jesmin S
  • 学会等名: Chest 2011
  • 発表場所: Hawaii ConventionCenter (USA)
• [学会発表] Time-dependent expression of endotheline-1 in lungs and the effects of TNF-α blocking peptide on entodhelin-1 levels in lungs in endotoxemic rat model (2011)
  • 著者名/発表者名: Jesmin S, Wada T, Zaedi S, Suhana SN, Yamagushi Y, Iwashima A, Gando S
  • 学会等名: 24^<th> European Society of IntensiveCare Medicine Annual Congress
  • 発表場所: The InternationalCongress Center Berlin (Germany)
• [学会発表] Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase. (2010)
  • 著者名/発表者名: Sawamura A.
  • 学会等名: CHEST
  • 発表場所: Vancouver Convention Center, Vancouver, Canada
  • 年月日: 2010-11-02
• [学会発表] Disseminated intravascular coagulation at an early phase of trauma continuously proceeds to DIC at a late phase of trauma (2010)
  • 著者名/発表者名: Murakami H, Gando S, Hayakawa M, Sawamura A, Sugano M, Kubota N, Uegaki S, Jesmin S
  • 学会等名: 6th Congress of Asia Pacific Society onThrombos is and Haemostatasis
  • 発表場所: Bali InternationalConvention Center (Indonesia)
  • 年月日: 2010-10-13
• [学会発表] Disseminated intravascular coagulation at an early phase of trauma continuously proceeds to DIC at a late phase of trauma. (2010)
  • 著者名/発表者名: Murakami H.
  • 学会等名: 6th Congress of Asia Pacific Society on Thrombos is and Haemostatasis.
  • 発表場所: Grand Hyatte Hotel, Bali, Indonesia
  • 年月日: 2010-10-13
• [学会発表] Disseminated intravascular coagulation at an early phase of trauma continuously proceeds to DIC at a late phase of trauma. (2010)
  • 著者名/発表者名: Murakami H.
  • 学会等名: 6th Congress of Asia Pacific Society on Thrombosis and Haemostatasis.
  • 発表場所: Grand Hyatte Hotel, Bali, Indonesia
  • 年月日: 2010-10-13
• [学会発表] Coagulopathy of trauma-disseminated intravascular coagulation with hemorrhagic phenotype- (2010)
  • 著者名/発表者名: Gando S.
  • 学会等名: The Second International Symposium on Critical Care Bleeding.
  • 発表場所: Moltoke Palace, Copenhagen, Denmark 招待講演
  • 年月日: 2010-09-07
• [学会発表] Coagulopathy of trauma -disseminated intravascular coagulation with hemorrhagic phenotype- (2010)
  • 著者名/発表者名: Gando S.
  • 学会等名: The Second International Symposium on Critical Care Bleeding.
  • 発表場所: Moltoke Palace, Copenhagen, Denmark(招待講演)
  • 年月日: 2010-09-07
• [学会発表] Coagulpathy of critical bleeding-disseminated intravascular coagulation- (2010)
  • 著者名/発表者名: Gando S.
  • 学会等名: The Second International Symposium on Critical Care Bleeding.
  • 発表場所: Moltoke Palace, Copenhagen, Denmark 招待講演
  • 年月日: 2010-09-06
• [学会発表] Coagulpathy of critical bleeding -disseminated intravascular coagulation- (2010)
  • 著者名/発表者名: Gando S.
  • 学会等名: The Second International Symposium on Critical Care Bleeding.
  • 発表場所: Moltoke Palace, Copenhagen, Denmark(招待講演)
  • 年月日: 2010-09-06
• [学会発表] 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 trauma. (2010)
  • 著者名/発表者名: Gando S.
  • 学会等名: 21st International Thrombosis Congress.
  • 発表場所: Mariotte Hotel, Milan, Italy
  • 年月日: 2010-07-09
• [学会発表] Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase (2010)
  • 著者名/発表者名: Sawamura A, Gando S, Kubota N, Uegaki S, Shimojima H, Sugano M, Ikeo M
  • 学会等名: Chest 2010
  • 発表場所: VancouverConvention Center (Canada)
• [学会発表] Coagulpathy of critical bleeding - disseminated intravascular coagulation (2010)
  • 著者名/発表者名: Gando S
  • 学会等名: The second International Symposium on Critical Care Bleeding
  • 発表場所: Moltoke Palace, Copenhagen (Denmark)
• [学会発表] Coagulopathy of trauma - disseminated intravascular coagulation with hemorrhagic phenotype (2010)
  • 著者名/発表者名: Gando S
  • 学会等名: The second International Symposium onCritical Care Bleeding
  • 発表場所: Moltoke Palace, Copenhagen (Denmark)
• [学会発表] 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 trauma (2010)
  • 著者名/発表者名: Gando S, Sawamura A, Hayakawa M, Kubota N, Uegaki S, Sugano M
  • 学会等名: 21st International Thrombosis Congress
  • 発表場所: Milan Marriott Hotel (Italy)