A nove gene therapy for Pseudomonas aeruginosa pneumonia.

• Project/Area Number: 12671495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Yokohama City University
• Principal Investigator: KURAHASHI Kiyoyasu Yokohama City University School of Medicine, Assistant professor, 医学部, 講師 (50234539)
• Co-Investigator(Kenkyū-buntansha): HATTORI Satoshi Yokohama City University School of Medicine, Trainer, 医学部, 助手 (40275037)
• Project Period (FY): 2000 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: cytokine / pneumonia / sepsis / Pseudomonas aeruginosa / exoenzymes / gene therapy / immune responses / macrophage

Research Abstract

1、Preliminary experiments
The airway instillation of isogenic mutant of Pseudomonas aeruginosa strain PA103 that is defective for production of ExoU and ExoT (PA103DUT) was shown not to cause lung injury, which was seen in the lung would be effective in preventing lung injury.
2、An animal model for Pseudomonal pneumonia
We evaluated the host response to Pseudomonas aeruginosa pneumonia and concomitant sepsis in a rat model. A manuscript is accepted for publication
3、Construction of adenovirus vectors
We have made adenovirus vector expressing the recombinant rat IL-10 gene. We also constructed adenovirus vector expressing the recombinant rat keratinocyte growth factor (KGF) gene. KGF is expected to prevent lung injury in acute lung injury for KGF is a potent growth factor for alveolar type II cells. We have confirmed the expression and production of KGF with the infection of this vector in vitro and in vivo. We are going to test the effect of the vector in an acute lung injury model.

Research Products

• [Publications] K.Kurahashi, S.Ota, A.Fujita, et al.: "Beneficial effect of protective ventilation on Pseudomonas aeruginosa pneumonia."Am J Respir Critical Care Med.. 165. A788 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 倉橋 清泰: "急性肺感染症モデルを用いた肺傷害の治療法"ICUとCCU. 27. 277-284 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kiyoyasu Kurahashi, Shuhei Ota, Kyota Nakamura, et al.: "The effect of lung-protective ventilation on severe Pseudomonas aeruginosa pneumonia and sepsis in rats."Am J Physiol Lung Cell Mol Physiol.. (In press). (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Kurahashi, S.Ota, A.Fujita, Y.Baba, M.Satoh, K.Nakamura, K.Uchida, Y.Nagashima, Y.Yamada.: "Beneficial effect of protective ventilation on Pseudomonas aeruginosa pneumonia."Am J Respir Critical Care Med.. 165. A788 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] K.Kurahashi.: "Novel therapeutic strategy for ALI/ARDS : a consideration using animal models of acute pulmonary infection."ICU and CCU.. 27(4). 277-284 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kiyoyasu Kurahashi, Shuhei Ota, Kyota Nakamura, Yoji Nagashima, Takuya Yazawa, Minako Satoh, Asako Fujita, Ritsuko Kamiya, Eri Fujita, Yasuko Baba, Kanji Uchida, Naoto Morimura, Tomio Andoh, Yoshitsugu Yamada.: "The effect of lung-protective ventilation on severe Pseudomonas aeruginosa pneumonia and sepsis in rats."Am J Physiol Lung Cell Mol Physiol. (in press ; to view the article, visit Articles in PresS of Am J Physiol Lung Cell Mol Physiol : (http://ajplung.physiology.org/cgi/content/abstract/00435.2003v1)).
  • Description: 「研究成果報告書概要(欧文)」より