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Application of gene therapy to alveolar and epithelial cells for treatmant of acute lung injury.

Research Project

Project/Area Number 13470317
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionYamagata University (2003)
Hirosaki University (2001-2002)

Principal Investigator

KOTONI Naoki  Yamagata University, Department of Anesthesiology, Professor and Chair, 医学部, 教授 (30205405)

Co-Investigator(Kenkyū-buntansha) SAKAI Michiko  Yamagata University, Department of Anesthesiology, Assistant Professor, 医学部, 助手 (20143092)
高橋 敏  弘前大学, 医学部・附属病院, 助手 (10236276)
橋本 浩  弘前大学, 医学部・附属病院, 助手 (00218421)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2002: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2001: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsalveolar macrophage / alveolar lymphocyte / cytokine / adhesion molecules / acute lung injury / flow cytometry / operative magnitude / inflammation / 遺伝子治療 / 抗菌能 / 表皮細胞 / 遺伝子診断 / エンドトキシンショック / 喫煙 / プロスタグランジン
Research Abstract

1.Effects of alveolar lymphocytes on mild hypercapnea
To evaluate the mild hypercapnea on alveolar cell functions, we studied anesthetic patients maintained mild hypercapnea or normocapnea.
To harvest alveolar cells were performed immediately after induction, 2, 4, and 6 hours after induction of anesthesia, and at the end of the surgery. Phagocytic and microbicidal activities were evaluated. Also, harvested cells were dissolved in guanidinium buffer. Total RNA was isolated and cDNA was synthesized with a reverse transcriptase. By specific primers of interleukin-1beta and 8, interferon-gamma, tumor necrosis factor-alpha, semi-quantitative analysis was performed by polymerase chain reaction.
We analyzed neutrophil and macrophage derived adhesion molecules including CD10a,b,c, CD18, 49d, and 54, and lymphocyte derived adhesion molecules (CD 4 and 8) by a flowcytometry.
Inter-group differences were not detected in any parameters of phagocytic and microbicidal functions. However, Expression of … More pro-inflammatory cytokines, activated lymphocytes and neutrophil and macrophage derived adhesion molecules were much greater in hypercapneic patients than in normocapneic patients.
Our results suggest that mild hypercapnea may protect pulmonary inflammatory reactions during anesthesia and surgery.
2.Operative magnitude seriously modulates alveolar cell functions.
We evaluated the effects of operative magnitude on alveolar macrophages functions.
We studied patients undergoing major, moderate and minor surgery. Study protocol was described previously. Expression of pro-inflammatory cytokines, activated lymphocytes, and adhesion molecules significantly increase as the operative magnitude increased. The decrease in phagocytic and microbicidal activities was much greater in patients undergoing major surgery.
These results suggest that increase in operative magnitude seriously aggravate pulmonary functions.
3.Perioperative hypothermia decreases all alveolar cell functions.
We evaluated the effects of operative magnitude on alveolar macrophages functions.
We studied perioperative hypothermic and normothermic patients. All alveolar cell functions decreased by hypothermia.
These results may imply increase in rate of postoperative pulmonary infections. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Kotani Naoki et al.: "Cerebrospinal fluid interleukin 8 concentrations and the subsequent development of postherpetic neuralgia."American Journal of Medicine. 116. 318-324 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani Naoki et al.: "Rebound perioperative hyperkalemia in six patients after cessation of ritodrine for premature labor."Anesthesia and Analgesia. 93. 709-711 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani Naoki et al.: "Insertion of intradermal needles into painful points provides analgesia for intractable abdominal scar pain."Regional Anesthesia and Pain Medicine. 26. 532-538 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani Naoki et al.: "Intraoperative prostaglandin E1 improves antimicrobial and inflammatory responses in alveolar immune cells."Critical Care Medicine. 29. 1943-1949 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani Naoki et al.: "Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympatho-adrenal responses."Anesthesiology. 95. 349-356 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani Naoki et al.: "Recovery of intraoperative microbicidal and inflammatory functions of alveolar immune cells after a tobacco smoke-free period."Anesthesiology. 94. 999-1006 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani N, Kudo R, Sakurai Y, Sawamura D, Sessler DI, Okada H, Nakayama H, Yamagata T, Yasujima M, Hashimoto H, Matsuki A.: "Cerebrospinal fluid interleukin 8 concentrations and the subsequent development of postherpetic neuralgia."American Journal of Medicine. 116(5). 318-324 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani N, Hashimoto H, Kushikata T, Muraoka M, Tonosaki M, Matsuki A.: "Rebound perioperative hyperkalemia in six patients after cessation of ritodrine for premature labor."Anesthesia and Analgesia. 93(3). 709-711 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani N, Kushikata T, Suzuki A, Hashimoto H, Muraoka M, Hashimoto H, Matsuki A.: "Insertion of intradermal needles into painful points provides analgesia for intractable abdominal scar pain."Regional Anesthesia and Pain Medicine. 26(6). 532-538 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani N, Hashimoto H, Kushikata T, Yoshida H, Muraoka M, Takahashi S, Matsuki A.: "Intraoperative prostaglandin E1 improves antimicrobial and inflammatory responses in alveolar immune cells."Critical Care Medicine. 29(10). 1943-1949 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani N, Hashimoto H, Sato Y, Sessler DI, Yoshioka H, Kitayama M, Yasuda T, Matsuki A: "Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympatho-adrenal responses."Anesthesiology. 95(2). 349-356 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani N, Kushikata T, Hashimoto H, Sessler DI, Muraoka M, Matsuki A.: "Recovery of intraoperative microbicidal and inflammatory functions of alveolar immune cells after a tobacco smoke-free period."Anesthesiology. 94(6). 999-1006 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kotani N, et al.: "Cerebrospinal fluid interleukin 8 concentrations and the subsequent development of postherpetic neuralgia."American Journal of Medicine. 116(5). 318-324 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kotani N.: "Insertion of intradermal needles into trigger points provides analgesia for intractable abdominal scar pain"Regional Anesthesia and Pain Medicine. 26(6). 532-538 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] kotani N.: "Intraoperative prostaglandin E1 improves antimicrobial and inflammatory responses in alveolar immune cells"Critical Care Medicine. 29(10). 1543-1549 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kotani N.: "Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting analgesic requirement, and sympatho-adrenal responses"Anesthesiology. 95(2). 349-356 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kotani N.: "Recovery of intraoperative microbicidal and inflammatory functions of alveolar immune cells after a tobacco smoke-free period"Anesthesiology. 94(6). 999-1006 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kotani N.: "Rebound perioperative hyperkalemia in six patients after cessation of ritodrine for premature labor"Anesthesia and Analgesia. 93(3). 709-711 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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