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Research on the pathogenesis, clinical features, diagnostic methods and treatment of acute encephalitis/encephalopathy.

Research Project

Project/Area Number 17209037
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionOkayama University

Principal Investigator

MORISHIMA Tsuneo  Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Professor (90157892)

Co-Investigator(Kenkyū-buntansha) OKABE Nobuhiko  Okayama University, Infectious Disease, Surveillance Center, National Institute of Infectious Diseases, Director (10057028)
NUNOI Hiroyuki  University of Miyazaki, Faculty of Medicine, Professor (50218260)
MIZUGUCHI Masashi  the University of Tokyo, Graduate School of Medicine, Professor (20209753)
KIMURA Hiroshi  Nagoya University, Graduate School of Medicine, Assistant Professor (30303621)
ICHIYAMA Takashi  Yamaguchi University, Graduate School of Medicine, Lecture (20263767)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥47,840,000 (Direct Cost: ¥36,800,000、Indirect Cost: ¥11,040,000)
Fiscal Year 2007: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2006: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2005: ¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Keywordsacute encephalitis / acute encephalopathy / influenza / HHV-6 / rotavirus / pathogenesis / インフルエンザウイルス / マイコプラズマ / 炎症性サイトカイン / 血管内皮細胞 / アデノウイルス / サイトカイン / HHV6 / SSPE / SNPs
Research Abstract

The annual incidence of acute encephalitis/encephalopathy among children younger than 15 years old is approximately 1,000 cases and 25% of them are influenza-associated encephalopathy, followed by encephalopathy/encephalitis caused by HHV-6 or 7 (12%), mumps and rotavirus CNS encephalitis/encephalopathy (4-5%). Although the pathogenesis of influenza-associated encephalopathy is still unclear, several reports have suggested that the pathogenesis involves cytokines such as soluble tumor necrosis factor (sTNF) receptor-1, interleukin-1β (IL-1β), IL-6, TNF-a, IL-8, and IL-10. It has been suggested that neurons and hepatocytes are induced to undergo apoptosis in influenza-associated encephalopathy as a consequence of hypercytokinemia. In contrast, the pathogenesis of other viral encephalitis/encephalopathy is still unclear. In rotavirus encephalopathy, the virus replication could not be found in the brain, while severe brain and lung edema was found associated with hyper cytokinemia. Therefore, not only in influenza but in other virus infections, brain damage may occur due to hyper cytokinemia without virus replication. These findings might be important for the management of the illness. In addition, we could develop multiplex PCR system for the early diagnosis of HSV encephalitis, HHV-6 encephalopathy and EBV CNS infections.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (49 results)

All 2007 2006 2005 Other

All Journal Article (44 results) (of which Peer Reviewed: 11 results) Presentation (3 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Simultaneous quantification of Epstein-Barr virus, Citomegalovirus, and human Herpesvirus 6 DNA in transplant recipients by multiplex real-time PCR assay.2007

    • Author(s)
      Wada K, et al.
    • Journal Title

      J Clin Microbiol 45

      Pages: 1426-1432

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Genetic diversity of coxsackievirus A16 associated with hand, foot, mouth disease epidemics in Japan from 1983 to 2003.2007

    • Author(s)
      Hosoya M., et. al.
    • Journal Title

      Journal of Clinical Microbiology 45

      Pages: 112-120

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cysteinyl leukotrienes enhance TNF-α-induced matrix metallo proteinase-9 in human monocytes/macrophages.2007

    • Author(s)
      Ichiyama T, et. al.
    • Journal Title

      Clin Exp Allergy 37

      Pages: 608-614

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 冬に多くみられる急性脳炎・脳症2007

    • Author(s)
      森島恒雄
    • Journal Title

      小児科 48・4

      Pages: 399-403

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic diversity of coxsackievirus A16 associated with hand, foot, and mouth disease epidemics in Japan from 1983 to 2003.2007

    • Author(s)
      Hosoya M, Kawasaki Y, et al.
    • Journal Title

      J Clin Microbiol 45・1

      Pages: 112-120

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Analysis of Gene Expression Profiles by Oligonucleotide Microarray in Children with Influenza.2006

    • Author(s)
      Kawada J, et al.
    • Journal Title

      J Gen Virol 87

      Pages: 1677-1683

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prognostic predictive values of serum cytochrome c, cytokines and other laboratory measurements in acute encephalopathy with multiple organ failure.2006

    • Author(s)
      Hosoya M, et al.
    • Journal Title

      Arch Dis Child 91

      Pages: 469-472

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Serum levels of matrix metalloproteinase-9 and its tissue inhibitor (TIMP-1) in acute disseminated encephalomyelitis.2006

    • Author(s)
      Ichiyama T, et al.
    • Journal Title

      J Neuroimmunol 172

      Pages: 182-186

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The mildest form of acute necrotizing encephalopathy associated with in fluenza A.2006

    • Author(s)
      Okumura A, et al.
    • Journal Title

      Neuropediatrics 37 37

      Pages: 261-263

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Serum levels of matrix metalloproteinase-9 and its tissue inhibitor(TIMP-1) in acute disseminated encephalomyelitis.2006

    • Author(s)
      Ichiyama T, et al.
    • Journal Title

      J Neuroimmunol 172

      Pages: 182-186

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The mildest form of acute necrotizing encephalopathy associated with influenza A.2006

    • Author(s)
      Okumura A, et al.
    • Journal Title

      Neuropediatrics 37

      Pages: 261-263

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A missense mutation of the toll-like receptor 3 gene in a patient with influenza-associated encephalopathy.2006

    • Author(s)
      Hidaka F, Matsuo S, et al.
    • Journal Title

      Clinical Immunology 119

      Pages: 188-194

    • Related Report
      2006 Annual Research Report
  • [Journal Article] インフルエンザ流行時期に心膜心筋炎に横紋筋融解症を合併した10歳女児例2006

    • Author(s)
      久保尚美, 大塚珠美, 小泉博彦, 等
    • Journal Title

      小児科 47・9

      Pages: 1413-11417

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prognostic predictive values of serum cytochromec,cytokines and other laboratory measurements in acute cncephalopathy with multiple organ failure.2006

    • Author(s)
      hosoya M, Kawasaki Y, Katayose M, et al.
    • Journal Title

      Arch. Dis. Child. 91・6

      Pages: 469-472

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic diversity of enterovirus 71 associated with hand, foot and mouth disease epidemics in Japan from 1983 to 20032006

    • Author(s)
      Hosoya M, Kawasaki Y, Sato M, Honzumi K, et al.
    • Journal Title

      Pediatr. Infect. Dis.J 25・8

      Pages: 691-694

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Measles encephalitis : direct viral invasion or autoimmune-mediated inflammation?2006

    • Author(s)
      Hosoya M
    • Journal Title

      Intern. Med. 45・14

      Pages: 841-842

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 亜急性硬化性全脳炎に対するリバリン療法2006

    • Author(s)
      細矢光亮
    • Journal Title

      小児科 47

      Pages: 1093-1101

    • Related Report
      2006 Annual Research Report
  • [Journal Article] CSF cytokine and chemokine profiles in acute disseminated encephalomyelitis.2006

    • Author(s)
      Ishizu T, Munohara M, Ichiyama T, et al.
    • Journal Title

      J Neuroimmunol. 175

      Pages: 52-58

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Acute enchepalopathy with refractory status epilepicus : bilateral mesial temporal and claustral lesions, related to DNA oxidative damage.2006

    • Author(s)
      Shiihara T, Kato M, Ichiyama T, et al.
    • Journal Title

      J. Neurol. Sci. 250

      Pages: 159-161

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Serum levels of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases 1 in sub acute sclerosing pan encephalitis.2006

    • Author(s)
      Ichiyama T, Siba P, Suarkia D, et al.
    • Journal Title

      J. Neurol. Sci. 252

      Pages: 45-48

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Evaluation of Apoptosis in Epstein-Barr Virus-Associated Haemophagocytic Lymphohistiocytosis.2006

    • Author(s)
      Kawada J, Kimura H, Shibuya Y, et al.
    • Journal Title

      J Med Virol 17・78

      Pages: 400-407

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Quantitative analysis of herpesvirus load in the lymph nodes of patients with histiocytic necrotizing lymphadenitis using a real-time PCR.2006

    • Author(s)
      Maeda N, Yamashita Y, Kimura H
    • Journal Title

      Diagnostic Molecular pathology 15

      Pages: 49-55

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Analysis of Gene Expression Profiles by Oligonucleotide Microarray in Children with Influenza.2006

    • Author(s)
      kawada J, Kimura H, Kamachi Y
    • Journal Title

      J Gen Virol 87

      Pages: 1677-1683

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Rapid detection of Epstein-Barr virus DNA by loop-mediated isothermal amplification method.2006

    • Author(s)
      Iwata S, Shibata Y, Kawada J
    • Journal Title

      J Clin Virol 37

      Pages: 128-133

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pathogenesis of Chronic Active Epstein-Barr Virus Infection : Is This an Infectious Disease, Lymphoproliferative Disorder, or Immunodeficiency?2006

    • Author(s)
      kimura H
    • Journal Title

      Rev Med Virol 16

      Pages: 251-261

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 無菌性髄膜炎症候群2006

    • Author(s)
      木村 宏
    • Journal Title

      今日の小児治療指針(第14版)大関武彦, 古川漸, 横田俊一郎編

      Pages: 257-257

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 単純ヘルペスウイルス2006

    • Author(s)
      木村 宏, 森島恒雄
    • Journal Title

      小児感染症マニュアル2007 日本小児感染症学会編

      Pages: 279-284

    • NAID

      10013630951

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Transient encephalopathy with reversible white matter lesions in children.2006

    • Author(s)
      Okumura A, Noda E, Ikuta T
    • Journal Title

      Neuropediatrics 37

      Pages: 159-162

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The mildest form of acute necrotizing encephalopathy associated with influenza A.2006

    • Author(s)
      Okumura A, Kidokoro H, Mizuguchi M, et al.
    • Journal Title

      Neuropediatrics 37

      Pages: 261-263

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Posterior reversible encephalopathy syndrome in a child with bronchial asthma.2006

    • Author(s)
      Kurahashi H, Okumura A, Koide T, et al.
    • Journal Title

      Brain Dev 28

      Pages: 544-546

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The value of diffusion-weighted imaging in children with acute central nervous system symptoms.2006

    • Author(s)
      Suzuki M, Hayakawa F, Okumura A, et al.
    • Journal Title

      J Pediatr Neurol 4

      Pages: 33-39

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Rapid detection of herpes simplex virus DNA in cerebrospinal fluid : comparison between loop-mediated isothermal amplification and real-time PCR.2005

    • Author(s)
      Kimura H, et al.
    • Journal Title

      Med Microbiol Immunol 194

      Pages: 181-185

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Analysis of cyokine levels in cerebrospinal fluid in mumps meningitis : comparison with echovirhu type 30 meningitis.2005

    • Author(s)
      Ichiyama T, et al.
    • Journal Title

      Cytokine 30

      Pages: 243-247

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Analysis of serum soluble CD40 ligand in patients with influenza virus-associated encephalopathy2005

    • Author(s)
      Ichiyama T, et al.
    • Journal Title

      J Neurol Sci 239

      Pages: 53-57

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Analysis of cytokine levels in cerebrospinal fluid in mumps meningitis:comparison with echovirus type 30 meningitis.2005

    • Author(s)
      Ichiyama T, et al.
    • Journal Title

      Cytokine 30

      Pages: 243-247

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis.2005

    • Author(s)
      Kamei S, Sekizawa T, et al.
    • Journal Title

      J.Neurol.Neurosurg.Psychiatry. 76(11)

      Pages: 1544-1549

    • Related Report
      2005 Annual Research Report
  • [Journal Article] HHV-6 and seizures.2005

    • Author(s)
      Yamashita N, Morishima T.
    • Journal Title

      Herpes. 12(2)

      Pages: 46-49

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of serum soluble CD40 ligand in patients with influenza virus-associated encephalopathy.2005

    • Author(s)
      Ichiyama T, Morishima T, et al.
    • Journal Title

      J.Neurol.Sci. 239(1)

      Pages: 53-57

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Rapid detection of herpes simplex virus DNA in cerebrospinal fluid : comparison between loop-mediated isothermal amplification and real-time PCR.2005

    • Author(s)
      Kimura H, Ihira M, Enomoto Y, et al.
    • Journal Title

      Med Microbiol Immunol (Berl) 194(4)

      Pages: 181-185

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Delirious behavior in children with influenza : its clinical features and EEG findings.2005

    • Author(s)
      Okumura A, Nakano T, et al.
    • Journal Title

      Brain.Dey. 27(4)

      Pages: 271-274

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Apoptosis under hypercytokinemia is a possible pathogenesis in influenza-associated encephalopathy.2005

    • Author(s)
      Nunoi H, Mercado MR, et al.
    • Journal Title

      Pediatr.Int. 47(2)

      Pages: 175-179

    • NAID

      10016473876

    • Related Report
      2005 Annual Research Report
  • [Journal Article] One-Step Multiplex Real-time PCR Assay to Analyse the Latency Patterns of Epstein Barr Virus Infection.

    • Author(s)
      Kubota N, Wada K, Ito Y, Shimoyama Y, Nakamura S, Nishiyama Y, Kimura H.
    • Journal Title

      Journao of Virological Method (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum levels of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases 1 in influenza-associated encephalopathy.

    • Author(s)
      Ichiyama T, Morishima T, Kajimoto M, et al.
    • Journal Title

      Pediatr. Infect. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Elevated CSF IL-6 in a patient with respiratory syncytial virus cncephalopathy.

    • Author(s)
      Otake Y, Yamagata T, Morimoto Y, et al.
    • Journal Title

      Brain. Dev. (in press)

    • Related Report
      2006 Annual Research Report
  • [Presentation] Influenza associated encephalopathy in Japan2007

    • Author(s)
      Wada T
    • Organizer
      Option for Control Influenza 6th
    • Place of Presentation
      トロント カナダ
    • Related Report
      2007 Annual Research Report
  • [Presentation] Intravenous immunoglobulin inhibits nuclear factor-kappa B actuvation and affects Fcγ recepotr expression in monocytes/macrophages. The 8th International Kawasaki Disease Symposium.2005

    • Author(s)
      Ichiyama T, et al.
    • Organizer
      The 8th International Kawasaki Disease Symposium
    • Place of Presentation
      サンディエゴ
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Intravenous immunoglobulin inhibits nuclear factor-kappa B activation and affects Fc γ receptor expression in monocytes/ macrophages. The 8th International Kawasaki Disease Symposium.2005

    • Author(s)
      Ichiyama T, et al.
    • Organizer
      The 8th International Kawasaki Disease Symposium
    • Place of Presentation
      San Diego.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 医学書院東京2006

    • Author(s)
      奥村彰久
    • Total Pages
      872
    • Publisher
      急性脳症、Reye症候群. 今日の小児治療指針第14版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] ウイルス検出用オリゴヌクレオチドセット、EBV、CMV及びHHV-6の分析方法及び検出キット2006

    • Inventor(s)
      木村宏
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Number
      2006-157532
    • Filing Date
      2006-06-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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