• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pathophysiological study on influenza-associated encephalopathy by measuring small molecule

Research Project

Project/Area Number 16591056
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTokyo Medical University

Principal Investigator

KAWASHIMA Hisashi  Tokyo Medical University, Medicine, Lecturer, 医学部, 講師 (70224772)

Co-Investigator(Kenkyū-buntansha) TAKEKUMA Kouji  Tokyo Medical University, Medicine, Assistant Professor, 医学部, 助教授 (80246173)
KASHIWAGI Yasuyo  Tokyo Medical University, Medicine, Lecturer, 医学部, 講師 (00287129)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsinfluenza-associated encephalopahty / astrocyte / NOx / IL-6 / glia cell / nitrotyrosine / apoptosis / 亜鉛 / グルタミン酸
Research Abstract

The number of patients with a new type of influenza-associated encephalopathy and influenza-associated sudden death in children is increasing in Japan on a nationwide scale. The actual pathophysiology is not known, because the virus could not be detected in the central nervous system (CNS) of affected patients. We found that NOx levels and D-ROM in serum and cerebrospinal fluid (CSF) obtained from patients with influenza-associated encephalopathy were high and also reported that extraordinary increases of excitatory amino acid levels in CSF were found in those patients. The NWS virus infected mice body weights were significantly reduced at day 6 p.i. and the virus was obviously detected in the brain on day 1 p.i. The amount of iNOS mRNA in the infected mouse brain was greater than control mouse in each brain region, particularly olfactory bulb and hippocampus on day 1p.i. As for olfactory bulb, the hippocampus iNOS mRNA expression was markedly detected on day 3, and 6 p.i. as well. There was a marked increase of metabolites of nitric oxide in the olfactory bulb and hippocampus. As for immunohistichemistry, positive staining of iNOS was detected mostly in the hippocampus of infected mouse brain. Moreover, both anti-iNOS and GFAP stains were positive mostly around the capillary blood vessels of the hippocampus from an initial stage. These results indicate that NWS virus can invade the brain through the olfactory pathways and then enhance the astrocytes and iNOS which activate the NO production and the expansion of capillary blood vessels. Thus these activations may cause the severe influenza-associated encephalopathy.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (29 results)

All 2006 2005 2004

All Journal Article (27 results) Book (2 results)

  • [Journal Article] Primary biomarkers in cerebral spinal fluid obtained from patients with influenza-associated encephalopathy analyzed by metabolomix2006

    • Author(s)
      Kawashima H et al.
    • Journal Title

      International Journal of Neuroscience 116(8)

      Pages: 927-936

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Diagnostic and predictive value of CSF d-ROM level in influenza virus associated encephalopathy2006

    • Author(s)
      Yamanaka G, Kawashima H et al.
    • Journal Title

      Journal of the Neurological Science 243(1-2)

      Pages: 71-75

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Therapy of childhood generalized morphea2006

    • Author(s)
      Kawashima H et al.
    • Journal Title

      Pediatrics International 48(3)

      Pages: 342-5

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hydranecephalywith cholestasis and giant hepatitis2006

    • Author(s)
      Kawashima H et al.
    • Journal Title

      Journal of Clinical Gastroenterology 40(10)

      Pages: 956-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Discordant endocrinopathy in a sibling with Shwachman-daimond syndrome2006

    • Author(s)
      Kawashima H et al.
    • Journal Title

      Journal of Tropical Pediatrics 52(6)

      Pages: 445-7

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Diagnostic and predictive value of CSF d-ROM level in influenza virus associated encephalopathy2006

    • Author(s)
      Yamanaka G, Kawashima H et al.
    • Journal Title

      Journal of Neurological Science 243(1-2)

      Pages: 71-5

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Serum nitrite/nitrate and enterovirus-related type-1 diabetes mellitus in children2006

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

      Thw Journal of Tokyo Medical University 64(3)

      Pages: 272-6

    • NAID

      10017480789

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nitrite/nitrate (NO_x) and zinc concentration in influenza-associated encephalopathy in children with different sequela2005

    • Author(s)
      Kawashima H et al.
    • Journal Title

      Neurochemical Research 30(3)

      Pages: 311-314

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Efficacy of plasma exchange and methylprednisolone pulse therapy on influenza-associated encephalopahty2005

    • Author(s)
      Kawashima H et al.
    • Journal Title

      Journal of Infection 51(2)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Clinical application of rapid assay of interleukin-6 in influenza-associated encephalopathy2005

    • Author(s)
      Nakamura M, Kawashima H et al.
    • Journal Title

      Disease Markers 21(4)

      Pages: 1-4

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] インフルエンザ脳症の現状2005

    • Author(s)
      河島尚志
    • Journal Title

      東京医大雑誌 63

      Pages: 97-103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nitrite/nitrate (NOx) and zinc concentration in influenza-associated encephalopathy in children with different sequela2005

    • Author(s)
      Kawashima H et al.
    • Journal Title

      Neurochemical Research 30(3)

      Pages: 311-314

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Efficacy of plasma exchange and methylprednisolone pulse therapy on influenza-associated encephalopathy2005

    • Author(s)
      Kawashima H et al.
    • Journal Title

      Journal of Infection 51(2)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] al Clinical application of rapid assay of interleukin-6 in influenza-associated encephalopathy2005

    • Author(s)
      Nakamura M, Kawashima H et.
    • Journal Title

      Disease Markers 21(4)

      Pages: 1-4

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Update of influenza-associated encephalopathy (Japanese)2005

    • Author(s)
      Kawashima H.
    • Journal Title

      Journal of Tokyo Medical University 97-103

      Pages: 63-63

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nitrite/nitrate (NOx) and zinc concentration in influenza …2005

    • Author(s)
      Kawashima H, Amaha M et al.
    • Journal Title

      Neurochemical Research 30(3)

      Pages: 311-314

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Efficacy of plasma exchange and methylprednisolone pulse …2005

    • Author(s)
      Kawashima H, Togashi T et al.
    • Journal Title

      Journal of Infection 51(2)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Diagnosis and evaluation of febrile infants under 4 months …2005

    • Author(s)
      Kawashima H, Kobayashi K.
    • Journal Title

      Journal of Infection Nov 21(Epub ahead of print)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A case of Reye syndrome with rotavirus infection accompanied …2005

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

      Journal of Infection Oct 12(Epub ahead of print)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinical application of rapid diagnosis of rapid assay of …2005

    • Author(s)
      Nakamura M, Yamanaka G et al.
    • Journal Title

      Disease Markers 21(4)

      Pages: 199-202

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Beta-catenin interacts with the FUS proto-oncogene product and…2005

    • Author(s)
      Sato S, Idogawa M, et al.
    • Journal Title

      Gastroenterology 129(4)

      Pages: 1225-1236

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Serum and cerebrospinal fluid nitrite/nitrate levels in patients with rotavirus gastroenteritis induced convulsion2004

    • Author(s)
      Kawashima H, Inage Y et al.
    • Journal Title

      Life Science 74(11)

      Pages: 1397-1405

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enterovirus-related type 1 diabetes mellitus and antibodies to glutamic acid decarboxylase in Japan2004

    • Author(s)
      Kawashima H, Ihara T et al.
    • Journal Title

      Journal of Infection 49(2)

      Pages: 147-151

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Extraordinary changes in excitatory amino acid levels in cerebrospinal fluid of influenza-associated encephalopathy of children2004

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

      Neurochemical Research 29(8)

      Pages: 1537-1540

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enteroviral hepatitis2004

    • Author(s)
      Kawashima H, Shimizu R et al.
    • Journal Title

      Pediatric International 46(2)

      Pages: 130-134

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sudden infant death syndrome due to parainfluenza virus 2 associated with hemophagocytic syndrome2004

    • Author(s)
      Kashiwagi Y, Kawashima H et al.
    • Journal Title

      Journal of Infection 49(4)

      Pages: 329-332

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Virological and immunological characteristics of a 19-year-old Japanese female with fatal outcome with Epstein-Barr virus-associated hemophagocytic syndrome2004

    • Author(s)
      Sato S, Kawashima H et al.
    • Journal Title

      Journal of Clinical Virology 31(3)

      Pages: 235-238

    • Related Report
      2004 Annual Research Report
  • [Book] 今日の小児治療指針 第14版 (大関武彦他 編集)2006

    • Author(s)
      河島尚志
    • Total Pages
      840
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 今日の小児治療指針 第14版(大関武彦他 編集)2006

    • Author(s)
      河島尚志
    • Total Pages
      840
    • Publisher
      医学書院
    • Related Report
      2006 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi