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Single-domian antibody against the virulence associated with the type III secretion system of gram-negative bacteria

Research Project

Project/Area Number 26670791
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Emergency medicine
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Sawa Teiji  京都府立医科大学, 医学(系)研究科(研究院), 教授 (10206013)

Co-Investigator(Kenkyū-buntansha) 天谷 文昌  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60347466)
中嶋 康文  関西医科大学, 医学部, 教授 (70326239)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords緑膿菌 / 細菌性肺炎 / 抗体医療 / 酸型分泌システム / PcrV / 単鎖抗体 / 遺伝子組換え / 感染症 / 肺炎 / Ⅲ型分泌システム / 単一ドメイン抗体 / 多剤耐性菌 / 抗体療法 / 三型分泌システム / V抗原 / 抗体医薬品 / 3型分泌システム / 重症肺炎
Outline of Final Research Achievements

Pseudomonas aeruginosa, a gram-negative pathogen, causes life-threatening infections. The Pseudomonal type III secretion system functions as a molecular syringe to deliver type III secretory toxins directly into the cytosol of eukaryotic cells, and also acts to inhibit innate immune mechanisms, thereby preventing bacterial clearance. Antibodies against PcrV, the cap structure in the translocational needle of the type III secretory apparatus of P. aeruginosa, block TTS toxin translocation. We investigated the therapeutic use of a recombinant anti-PcrV single-chain antibody. We synthesized a recombinant single-chain antibody, in which the heavy (VH) and light chain (VL) variable regions of the anti-PcrV monoclonal IgG are joined by a flexible peptide linker. The functions of this synthetic antibody were tested, and future potentialityl for clinical use was evaluated. Promising preliminary data about inhalational antidy therapy against bacterial pneumonia was obtained in this study.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (57 results)

All 2018 2017 2016 2015 2014

All Journal Article (25 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 8 results,  Acknowledgement Compliant: 4 results) Presentation (26 results) (of which Int'l Joint Research: 3 results,  Invited: 14 results) Book (6 results)

  • [Journal Article] An outbreak of fluoroquinolone-resistant Pseudomonas aeruginosa ST357 harboring the exoU gene.2018

    • Author(s)
      Kainuma A, Momiyama K, Kimura T, Akiyama K, Inoue K, Naito Y, Kinoshita M, Shimizu M, Kato H, Shime N, Fujita N, Sawa T.
    • Journal Title

      J Infect Chemother.

      Volume: in press Issue: 8 Pages: 615-622

    • DOI

      10.1016/j.jiac.2018.03.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia.2017

    • Author(s)
      Hamaoka S, Niato Y, Katoh H, Shimizu M, Kinoshita M, Kainuma A, Akiyama K, Sawa T.
    • Journal Title

      Microbial Immunol

      Volume: 61 Issue: 2 Pages: 64-74

    • DOI

      10.1111/1348-0421.12467

    • NAID

      40021166122

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 緑膿菌感染症に対する能動、受動免疫療法2017

    • Author(s)
      佐和貞治
    • Journal Title

      第51回緑膿菌研究会公演記録

      Volume: 51 Pages: 20-23

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 臨床分緑膿菌株のMLST法により遺伝子解析2017

    • Author(s)
      甲斐沼篤, 秋山浩一, 内藤慶史, 木下真央, 濱岡早枝子, 加藤秀哉, 佐和貞治
    • Journal Title

      第51回緑膿菌研究会公演記録

      Volume: 51 Pages: 92-95

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 各種グラム陰性細菌V抗原抗体価の疫学調査2017

    • Author(s)
      木下真央, 甲斐沼篤, 内藤慶史,秋山浩一, 濱岡早枝子, 清水優, 加藤秀哉, 佐和貞治
    • Journal Title

      第51回緑膿菌研究会公演記録

      Volume: 51 Pages: 96-97

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Pseudomonas aeruginosa type III secretory toxin ExoU and its predicted homologs.2016

    • Author(s)
      Sawa T, Hamaoka S, Kinoshita M, Kainuma A, Niato Y, Akiyama K, Kato H.
    • Journal Title

      Toxins.

      Volume: 8 Issue: 11 Pages: 307-307

    • DOI

      10.3390/toxins8110307

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] The prophylactic effects of human IgG derived from sera containing high anti-PcrV titers against pneumonia-causing Pseudomonas aeruginosa.2016

    • Author(s)
      Kinoshita M, Kato H, Yasumoto H, Shimizu M, Hamaoka S, Naito Y, Akiyama K, Moriyama K, Sawa T.
    • Journal Title

      Hum Vaccin Immunother

      Volume: 12 Pages: 1-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cellular Stress Responses and Monitored Cellular Activities.2016

    • Author(s)
      Sawa T, Naito Y, Kato H, Amaya F.
    • Journal Title

      Shock

      Volume: 46 Issue: 2 Pages: 113-121

    • DOI

      10.1097/shk.0000000000000603

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epidemiological analysis of serum anti-Pseudomonas aeruginosa PcrV titers in adults.2016

    • Author(s)
      Yasumoto H, Katoh H, Kinoshita M, Shimizu M, Hamaoka S, Akiyama K, Naito Y, Sawa T
    • Journal Title

      Microbiology and Immunology

      Volume: 60 Issue: 2 Pages: 114-120

    • DOI

      10.1111/1348-0421.12353

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Protective effects of intravenous immunoglobulin and antimicrobial agents on acute pneumonia in leukopenic mice.2016

    • Author(s)
      Shimizu M, Katoh H, Hamaoka S, Kinoshita M, Akiyama K, Naito Y, Sawa T.
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 22 Issue: 4 Pages: 240-247

    • DOI

      10.1016/j.jiac.2016.01.006

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 感染症治療薬の新しい試み 難治性感染症に期待される抗菌免疫療法2016

    • Author(s)
      佐和貞治, 加藤秀哉, 清水優
    • Journal Title

      化学療法の領域

      Volume: 32 Pages: 96-106

    • Related Report
      2015 Research-status Report
  • [Journal Article] IV Immunoglobulin for Acute Lung Injury and Bacteremia in Pseudomonas aeruginosa Pneumonia.2015

    • Author(s)
      Katoh H, Yasumoto H, Shimizu M, Hamaoka S, Kinoshita M, Akiyama K, Sawa T.
    • Journal Title

      Critical Care Medicine

      Volume: 44 Issue: 1 Pages: 12-24

    • DOI

      10.1097/ccm.0000000000001271

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 緑膿菌の主要肺傷害因子 ―パタチン様ホスホリパーゼA2-Ⅲ型分泌毒素ExoU―.2015

    • Author(s)
      佐和貞治, 加藤秀哉, 安本寛章, 清水優, 濱岡早枝子, 木下真央, 秋山浩一.
    • Journal Title

      京都府立医科大学雑誌

      Volume: 124 Pages: 475-487

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 細菌感染と急性肺傷害2015

    • Author(s)
      佐和貞治.
    • Journal Title

      日本薬理学雑誌

      Volume: 145 Pages: 112-116

    • NAID

      130004827733

    • Related Report
      2015 Research-status Report
  • [Journal Article] 手術室における感染予防. 感染予防のための麻酔管理-整形外科医と麻酔科医の間での知識の共有.2015

    • Author(s)
      佐和貞治
    • Journal Title

      日本骨・関節感染症学会雑誌

      Volume: 28 Pages: 17-21

    • NAID

      40020387823

    • Related Report
      2015 Research-status Report
  • [Journal Article] 細菌の分泌装置-緑膿菌を中心に-.2015

    • Author(s)
      佐和貞治, 加藤秀哉
    • Journal Title

      Surgery Frontier

      Volume: 22 Pages: 56-61

    • Related Report
      2015 Research-status Report
  • [Journal Article] 緑膿菌性急性肺傷害に対する分子標的治療.2015

    • Author(s)
      佐和貞治.
    • Journal Title

      麻酔

      Volume: 64(増刊) Pages: 5078-5084

    • Related Report
      2015 Research-status Report
  • [Journal Article] 薬剤耐性緑膿菌臨床分離株の病原毒性評価.2015

    • Author(s)
      清水優, 秋山浩一, 濱岡早枝子, 木下真央, 安本寛章, 加藤秀哉, 木村武史, 藤田直久, 佐和貞治
    • Journal Title

      第49回緑膿菌感染症研究会講演記録

      Volume: 4 Pages: 84-87

    • Related Report
      2015 Research-status Report
  • [Journal Article] 薬剤耐性緑膿菌分離株のⅢ型分泌毒素遺伝子型解析2015

    • Author(s)
      秋山浩一, 清水優, 濱岡早枝子, 木下真央, 安本寛章, 加藤秀哉, 木村武史, 藤田直久, 佐和貞治.
    • Journal Title

      第49回緑膿菌感染症研究会講演会記録

      Volume: 49 Pages: 79-83

    • Related Report
      2015 Research-status Report
  • [Journal Article] 細菌の分泌装置ー緑膿菌を中心にー.2015

    • Author(s)
      佐和貞治、加藤秀哉.
    • Journal Title

      Surgery Frontier

      Volume: 22 Pages: 56-61

    • Related Report
      2014 Research-status Report
    • Open Access
  • [Journal Article] 細菌感染と急性肺傷害.2015

    • Author(s)
      佐和貞治.
    • Journal Title

      日薬理誌 Folia Pharmacol Jpn

      Volume: 145 Pages: 112-116

    • NAID

      130004827733

    • Related Report
      2014 Research-status Report
    • Open Access
  • [Journal Article] Anti-PcrV antibody strategies against virulent Pseudomonas aeruginosa.2014

    • Author(s)
      Sawa T, Ito E, Nguyen VH, Haight M.
    • Journal Title

      Hum Vaccin Immunother.

      Volume: 10 Issue: 10 Pages: 2843-2852

    • DOI

      10.4161/21645515.2014.971641

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] V-antigen homologs in pathogenic gram-negative bacteria. Microbiol Immunol.2014

    • Author(s)
      Sawa T, Katoh H, Yasumoto H.
    • Journal Title

      Microbiol Immunol

      Volume: 58 Issue: 5 Pages: 267-285

    • DOI

      10.1111/1348-0421.12147

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between Pseudomonas aeruginosa type III secretion, antibiotic resistance, and clinical outcome: a review.2014

    • Author(s)
      Sawa T, Shimizu M, Moriyama K, Wiener-Kronish JP.
    • Journal Title

      Crit Care

      Volume: 18 Issue: 6 Pages: 668-668

    • DOI

      10.1186/s13054-014-0668-9

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 緑膿菌感染症に対する抗体療法の作用機序と治療薬としての展望.2014

    • Author(s)
      佐和貞治
    • Journal Title

      感染症 The Infection

      Volume: 259 Pages: 155-60

    • Related Report
      2014 Research-status Report
    • Open Access
  • [Presentation] The single sequence type pandemic of clinical isolate Pseudomonas aeruginosa in a university hospital, Japan.2017

    • Author(s)
      Kainuma A, Akiyama K, Naito Y, Momiyama K, Inoue K, Kinoshita M, Kato,H, Sawa T.
    • Organizer
      16th International Conference on Pseudomonas, Liverpool, UK, Sep 5-9, 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Intranasal PcrV vaccination protects against acute pulmonary Pseudomonas aeruginosa infection2017

    • Author(s)
      Naito Y, Hamaoka S, Kainuma A,Kato H, Ishii JK, Sawa T.
    • Organizer
      ASM Microbe 2017, June 1, 2017, New Orleans, Louisiana, USA
    • Related Report
      2017 Annual Research Report
  • [Presentation] The Association Between Anti-Pcrv Titers And Protective E ects Against P. Aeruginosa In Pcrv Vaccinated Mice.2017

    • Author(s)
      Hamaoka S, Naito Y, Kato H, Kainuma A, Sawa T.
    • Organizer
      International Anesthesia Research Society Annual Meeting and International Symposium 2017, at the Grand Hyatt Washington in Washington, DC
    • Related Report
      2017 Annual Research Report
  • [Presentation] Epidemic propagation of Pseudomonas aeruginosa ST357 clones harboring exoU gene.2017

    • Author(s)
      Kainuma A, Momiyama K, Akiyama K, Naito Y, KInoshita M, Kato H, Sawa T.
    • Organizer
      Association of University Anesthesiologists, 64th Annual Meeting, May 4, 2017, at the Grand Hyatt Washington in Washington, DC
    • Related Report
      2017 Annual Research Report
  • [Presentation] 緑膿菌感染症に対する能動、受動免疫療法.2017

    • Author(s)
      佐和貞治
    • Organizer
      第53回緑膿菌感染症研究会
    • Place of Presentation
      大分
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 感染症スペシャリストが説きあかす難治性病原体の秘密.緑膿菌性細胞上皮傷害の分子病態メカニズム.2017

    • Author(s)
      佐和貞治.
    • Organizer
      角膜カンファレンス2017
    • Place of Presentation
      福岡
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] シンポジウム 病原因子と病態の接点を求めて.緑膿菌ワクチンの開発.2016

    • Author(s)
      佐和貞治.
    • Organizer
      第50回緑膿菌感染症研究会.
    • Place of Presentation
      東京
    • Year and Date
      2016-02-06
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Mitochondrial Stress and Outcomes in Septic Patients2016

    • Author(s)
      Sawa T
    • Organizer
      Annual Meeting and International Science Symposium 2016
    • Place of Presentation
      San Francisco, CA, USA
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 緑膿菌肺炎に対するγグロブリンの効果.2016

    • Author(s)
      佐和貞治
    • Organizer
      第38回呼吸療法医学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 膿菌性肺炎とガンマグロブリン製剤の新規効用のメカニズム.2016

    • Author(s)
      佐和貞治
    • Organizer
      第31回日本Shock学会総会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 緑膿菌V抗原に対する血清抗体価の疫学と緑膿菌性肺傷害に対する保護作用の検討.2016

    • Author(s)
      佐和貞治
    • Organizer
      第20回日本ワクチン学会学術集会.
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Presentation] 緑膿菌の病原毒性メカニズム解明と新規予防・治療法の開発2015

    • Author(s)
      佐和貞治.
    • Organizer
      COI研究会
    • Place of Presentation
      大阪
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 急性肺傷害のなぞ 研究から臨床へ.2015

    • Author(s)
      佐和貞治
    • Organizer
      巨椋池集中治療アカデミー宇治徳洲会病院
    • Place of Presentation
      宇治
    • Year and Date
      2015-08-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 急性肺傷害:炎症性メディエータと細胞性ストレス応答2015

    • Author(s)
      佐和貞治
    • Organizer
      第37回日本呼吸療法学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-07-18
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 生体侵襲と細胞性ストレス応答2015

    • Author(s)
      佐和貞治
    • Organizer
      第23回日本集中治療医学会東海北陸地方会
    • Place of Presentation
      福井
    • Year and Date
      2015-06-20
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 緑膿菌に対する抗体療法2015

    • Author(s)
      佐和貞治
    • Organizer
      第63回日本化学療法学会総会
    • Place of Presentation
      東京
    • Year and Date
      2015-06-06
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 緑膿菌に対する分子標的治療2015

    • Author(s)
      佐和貞治
    • Organizer
      第62回日本麻酔科学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Genotyping the Type III Secretory ExoU and Phenotyping Cytotoxicity in Carbapenem-Resistant Clinical Isolates of Pseudomonas Aeruginosa2015

    • Author(s)
      Akiyama K, Kato H, Shimizu M, Hamaoka S, Kinoshita M, Yasumoto H, Sawa T.
    • Organizer
      American Thoracic Society Conference 2015
    • Place of Presentation
      Denver
    • Year and Date
      2015-05-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Therapeutic Effect of Commercially Available Gamma-Globulin Solutions in Pseudomonas Aeruginosa-Induced Acute Lung Injury in the Murine Model2015

    • Author(s)
      Kato H, Shimizu M, Hamaoka S, Yasumoto H, Akiyama K, Kinoshita M, Sawa T.
    • Organizer
      American Thoracic Society Conference 2015
    • Place of Presentation
      Denver
    • Year and Date
      2015-05-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生体侵襲と細胞性ストレス応答.2015

    • Author(s)
      佐和貞治
    • Organizer
      岡山周術期セミナー.
    • Place of Presentation
      岡山
    • Year and Date
      2015-02-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 薬剤耐性緑膿菌臨床分離株の病原毒性評価2015

    • Author(s)
      清水優, 秋山浩一, 濱岡早枝子, 木下真央, 安本寛章, 加藤秀哉, 木村武史, 藤田直久, 佐和貞治
    • Organizer
      第49回緑膿菌感染症研究会
    • Place of Presentation
      東京
    • Year and Date
      2015-02-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 薬剤耐性緑膿菌分離株のⅢ型分泌毒素遺伝子型解析2015

    • Author(s)
      秋山浩一, 清水優, 濱岡早枝子, 木下真央, 安本寛章, 加藤秀哉, 木村武史, 藤田直久, 佐和貞治
    • Organizer
      第49回緑膿菌感染症研究会
    • Place of Presentation
      東京
    • Year and Date
      2015-02-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 多剤耐性緑膿菌に対するブレイクポイント・チェッカーボード法を用いた抗菌薬併用効果と治療効果の検討2015

    • Author(s)
      清水 優, 加藤秀哉, 木下真央, 濱岡早枝子, 安本寛章, 秋山浩一, 木村武史, 藤田直久, 橋本悟 ,佐和貞治
    • Organizer
      第41回日本集中治療医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-02-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 緑膿菌臨床分離株における PCR を用いた毒素表現型分析と DNA 分析2015

    • Author(s)
      秋山 浩一, 加藤秀哉, 安本寛章, 濱岡早枝子, 木下真央, 佐和貞治.
    • Organizer
      第41回日本集中治療医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-02-09
    • Related Report
      2014 Research-status Report
  • [Presentation] マウス緑膿菌性急性肺傷害モデルに対するガンマグロブリン製剤気管内投与の有用性の検討2015

    • Author(s)
      加藤 秀哉, 安本寛章, 清水優, 濱岡早枝子, 木下真央, 秋山浩一, 佐和貞治.
    • Organizer
      第41回日本集中治療医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-02-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 細菌感染とγグロブリン療法.2015

    • Author(s)
      佐和貞治.
    • Organizer
      敗血症forum, 2015.
    • Place of Presentation
      東京
    • Year and Date
      2015-02-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Book] Construction of a recombinant single-chain antibody fragment against bacterial type III secretion. Antibody Engineering,2018

    • Author(s)
      Sawa T, Kainuma A, Moriyama K, Naito Y.
    • Total Pages
      14
    • Publisher
      InTech
    • Related Report
      2017 Annual Research Report
  • [Book] Anti‐PcrV Immunization for Pseudomonas aeruginosa Pneumonia in Cystic Fibrosis, Progress in Understanding Cystic Fibrosis, Dr. Dinesh Sriramulu (Ed.)2017

    • Author(s)
      Naito Y, Moriyama K, Sawa T.
    • Total Pages
      24
    • Publisher
      InTech
    • ISBN
      9789535132912
    • Related Report
      2017 Annual Research Report
  • [Book] 麻酔科医のための周術期の薬物使用法.2015

    • Author(s)
      佐和貞治
    • Total Pages
      7
    • Publisher
      中山書店
    • Related Report
      2015 Research-status Report
  • [Book] まれな疾患の麻酔 A to Z.2015

    • Author(s)
      佐和貞治, 林和子.
    • Total Pages
      3
    • Publisher
      文光堂
    • Related Report
      2015 Research-status Report
  • [Book] 佐和貞治. TEXT麻酔・蘇生学  第6章外科的侵襲に対する生体反応. 改訂4版2014

    • Author(s)
      佐和貞治
    • Total Pages
      6
    • Publisher
      南山堂
    • Related Report
      2014 Research-status Report
  • [Book] 感染症. よくある術前合併症. 研修ノートシリーズ 麻酔科研修ノート 改訂第2版.2014

    • Author(s)
      佐和貞治.
    • Total Pages
      4
    • Publisher
      診断と治療社.
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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