Study on the treatment of highly pathogenic avian influenza H5N1 infections by means of the analysis of pathogenesis of the illness

• Project/Area Number: 23659523
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Okayama University
• Principal Investigator: MORISHIMA Tsuneo 岡山大学, 大学院・医歯薬学総合研究科, 教授 (90157892)
• Co-Investigator(Kenkyū-buntansha): TSUKAHARA Hirokazu 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (90207340) ; YAMASHITA Nobuko 岡山大学, 大学院・医歯薬学総合研究科, 助教 (40379798)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: インフルエンザ / 脳症 / 多臓器不全 / 肺炎 / H5N1 / 新型インフルエンザ / サイトカイン / ケモカイン / チオレドキシン / 酸化ストレス

Research Abstract

The pathogenesis of highly pathogenic avian influenza H5N1 in humans has been closelsimilar to those of severe pneumonia and influenza-associated encephalopathy witcytokine storm. Using microarray assay we have analyzed gene expression in the acute phasof 2009pdm infection. Interestingly, gene expression profiles were different betweepneumonia patients and patients with CNS manifestations. Particularly, gene expressiorelated to ROD has been highly activated. Using mouse model, we have shown that thioredoxin-1(TRX) could suppress the oxidativstress and inflammatory changes resulting better outcome in pneumonia with influenzvirus infections. Taking together, anti-oxidant stress agents such as TRX could play an important rolin the severe pneumonia/ARD with H5N1 infections.

Research Products

• [Journal Article] Analysis of bronchoalveolar lavage fluid in a mouse model of bronchial asthma and H1N1 2009 infection (2013)
  • Author(s): Okada S, Hasegawa S, Hasegawa H, Ainai A, Atsuta R, Ikemoto K, Sasaki K, Toda S, Shirabe K, Takahara M, Harada S, Morishima T, Ichiyama T.
  • Journal Title: Cytokine Volume: 63(2) Issue: 2 Pages: 194-200
  • DOI: 10.1016/j.cyto.2013.04.035
• [Journal Article] Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated by gene expression profiling. (2013)
  • Author(s): Yamashita N, Tsukahara H, Tsuge M, Nagaoka Y, Yashiro M, Saito Y, Fujii Y, Takashi O, Morishima T.
  • Journal Title: Pediatr Int Volume: 55 Issue: 5 Pages: 572-577
  • DOI: 10.1111/ped.12139
  • Peer Reviewed
• [Journal Article] Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy (2013)
  • Author(s): Tsukahara H, Fujii Y, Matsubara K, Yamada M, Nagaoka Y, Saito Y, Yashiro M, Tsuge M, Goto S, Kitamura T, Hata A, Ichiyama T, Morishima T
  • Journal Title: Pediatr Int. Volume: 55 Issue: 4 Pages: 461-464
  • DOI: 10.1111/ped.12094
  • Peer Reviewed
• [Journal Article] Thioredoxin-1 and oxidative stress status in pregnant women at early third trimester of pregnancy: relation to maternal and neonatal characteristics (2013)
  • Author(s): Nakatsukasa Y, Tsukahara H, Tabuchi K, Tabuchi M, Magami T, Yamada M, Fujii Y, Yashiro M, Tsuge M, Morishima T.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 52 Issue: 1 Pages: 27-31
  • DOI: 10.3164/jcbn.12-71
  • NAID: 130004879319
  • ISSN: 0912-0009, 1880-5086
• [Journal Article] Redox-active protein thioredoxin-1 administration ameliorates influenza A virus (H1N1)-induced acute lung injury in mice. (2013)
  • Author(s): Yashiro M, Tsukahara H, Matsukawa A, Yamada M, Fujii Y, Nagaoka Y, Tsuge M, Yamashita N, Ito T, Yamada M, Masutani H, Yodoi J, Morishima T.
  • Journal Title: Crit Care Med. Volume: 41(1) Issue: 1 Pages: 171-81
  • DOI: 10.1097/ccm.0b013e3182676352
  • NAID: 120005300241
• [Journal Article] Unexpected cardiopulmonary arrest associated with influenza: our experience during the 2009 pandemic in Japan. (2013)
  • Author(s): Okumura A, Nakagawa S, Kawashima H, Muguruma T, Saito O, Fujimoto J, Toida C, Kuga S, Imamura T, Shimizu T, Kondo N, Morishima T
  • Journal Title: Influenza Other Respi Viruses Volume: 7 Issue: 5 Pages: 759-760
  • DOI: 10.1111/irv.12032
  • Peer Reviewed
• [Journal Article] Severe form of encephalopathy associated with 2009 pandemic influenza A (H1N1) in Japan. (2013)
  • Author(s): Okumura A, Nakagawa S, Kawashima H, Morichi S, Muguruma T, Saito O, Fujimoto JI, Toida C, Kuga S, Imamura T, Shimizu T, Kondo N, Morishima T.
  • Journal Title: J Clin Virol Volume: 56 Issue: 1 Pages: 25-30
  • DOI: 10.1016/j.jcv.2012.10.007
  • Peer Reviewed
• [Journal Article] National survey of pandemic influenza A (H1N1) 2009-associated encephalopathy in Japanese children. (2012)
  • Author(s): Kawashima H, Morichi S, Okumura A, Nakagawa S, Morishima T; collaborating study group on influenza-associated encephalopathy in Japan.
  • Journal Title: J Med Virol Volume: 84 Issue: 8 Pages: 1151-1156
  • DOI: 10.1002/jmv.23317
  • Peer Reviewed
• [Journal Article] Deaths associated with pandemic (H1N1) 2009 among children, Japan、2009-2010． (2011)
  • Author(s): Okumura A, Nakagawa S, Kawashima H, Muguruma T, Saito O, Fujimoto J, Toida C, Kuga S, Imamura T, Shimizu T, Kondo N, Morishima T
  • Journal Title: Emerg Infect Dis Volume: 17 Pages: 1993-2000
  • Peer Reviewed
• [Presentation] インフルエンザ感染におけるThioredoxin binding protein 2(TBP-2)の役割 (2012)
  • Author(s): 八代 将登
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡国際会議場
• [Presentation] インフルエンザ感染における局所サイトカイン・ケモカインの動態 (2012)
  • Author(s): 藤井 洋輔
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島国際会議場