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Genetic predisposition of cerebrovascular diseases and their prophylactic strategy

Research Project

Project/Area Number 16615004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 臨床疫学
Research InstitutionShimane University

Principal Investigator

MASUDA Junichi  Shimane University, Faculty of Medicine, Professor, 医学部, 教授 (70173747)

Co-Investigator(Kenkyū-buntansha) KOBAYASI Syotai  Shimane University, Faculty of Medicine, Director of Hospital, 医学部, 病院長 (00118811)
NABIKA Toru  Shimane University, Faculty of Medicine, Professor, 医学部, 教授 (50180534)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordscerebrovascular diseases / arteriosclerosis / PVH / lacunes / oxidative stress / isoprostane / NO synthase / methylated arginines / ADMA / HPLC / 多検体測定 / 一酸化窒素
Research Abstract

First part of the research focused on the role of oxidate stress and nitric oxide (NO), since they are thought to play important roles in the pathogenesis of cerebral arteriosclerosis, a major cause of white matter lesions in the brain. Therefore, we examined whether NO metabolites (NOx) and 8-iso-prostaglandin F(2α) (IsoP) levels in vivo correlated with the severity of periventricular hyperintensity (PVH) to evaluate potential roles of oxidative stress and NO in white matter lesions. Participants (687 males and 528 females) of a health-screening examination were recruited into the study. The plasma NOx and urinary IsoP levels were measured, respectively. PVH was diagnosed on the basis of MRIs. In nonparametric univariate trend analyses, plasma NOx as well as aging, presence of hypertension and of lacunes, mean blood pressure, and high-density lipoprotein cholesterol showed highly significant monotone correlation with PVH severity (P</=0.01). By the multivariate ordinal regression anal … More ysis, the plasma NOx (P=0.002) and urinary IsoP (P=0.01) levels were found to be independent factors influencing the severity of PVH together with aging (P<0.001), presence of hypertension (P<0.001) and lacunes (P<0.001), and mean blood pressure (P=0.001). From these results, we concluded that oxidative stress and NO have a close correlation with PVH severity.
In the second part, we have established an automated column-switching HPLC system with post-column fluorescence derivatization for the analysis of methylated arginines including asymmetric dimethylarginine (ADMA), an inhibitor for NO synthase. An on-line extraction on an ion-exchange column followed by a separation on a reversed phase column was applied in the system, which did not require any pre-treatment of plasma samples. Excellent separation of methylated arginines, linearity of calibration curve, recovery and reproducibility was obtained with the system. The results showed that this method was useful for the clinical evaluation of methylated arginines in human plasma. Less

Report

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

    (17 results)

All 2005 2004

All Journal Article (15 results) Book (2 results)

  • [Journal Article] Lysophosphatidylcholine posttranscriptionally inhibitsinterferon-γ-induced IP-10,Mig and I-Tac expression in endothelial cells.2005

    • Author(s)
      Sheikh A M
    • Journal Title

      Cardiovascular Research 65

      Pages: 263-271

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lysophosphatidylcholine induces tPA gene expression through CRE-dependent mechanism.2005

    • Author(s)
      Sheikh A M
    • Journal Title

      Biochemical and Biophysical Research Communications 329

      Pages: 71-77

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 脳血管障害の危険因子2005

    • Author(s)
      益田順一
    • Journal Title

      臨床病理 53

      Pages: 422-429

    • NAID

      10016685136

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Lysophosphatidylcholine posttranscriptionally inhibits interferon-γ-induced IP-10, Mig and I-Tac expression in endothelial cells.2005

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

      Cardiovascular Research 65

      Pages: 263-271

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lysophosphatidylcholine induces tPA gene expression through CRE-dependent mechanism.2005

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

      Biochemical and Biophysical Research Communications 329

      Pages: 71-77

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lysophosphatidylcholine induces tPA gene expression through CRE-dependent mechanism2005

    • Author(s)
      Sheikh A M
    • Journal Title

      Biochemical and Biophysical Research Communications 329

      Pages: 71-77

    • Related Report
      2005 Annual Research Report
  • [Journal Article] New genetic model rat for congenital cataracts due to a connexin 46(Gja3)mutation.2005

    • Author(s)
      Yoshida M
    • Journal Title

      Pathology International 55

      Pages: 732-737

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neuronal cell death induced by cystatin C in vivo and in cultured human CNS neurons is inhibited with catheps in B.2005

    • Author(s)
      Nagai A
    • Journal Title

      Brain Reseach 1066

      Pages: 120-128

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Correlation of NO metabolites and 8-iso-prostaglandin F2a with periventricular hyperintensity severity.2004

    • Author(s)
      Shibata H
    • Journal Title

      Arterioscierosis,Thrombosis,and Vascular Biology 24

      Pages: 1659-1663

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 尿中8-iso-prostaglandin F2_a(IsoP).広範囲 血液・尿科学検査 免疫学的検査 第6版2004

    • Author(s)
      柴田 宏
    • Journal Title

      日本臨床 62

      Pages: 544-546

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 頚動脈硬化の病理2004

    • Author(s)
      益田順一
    • Journal Title

      脳卒中 26

      Pages: 614-616

    • NAID

      10017000495

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation of NO metabolites and 8-iso-prostaglandin F2a with periventricular hyperintensity severity.2004

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

      Arteriosclerosis, Thrombosis, and Vascular Biology 24

      Pages: 1659-1663

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Moyamoya Disease2004

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

      Stroke (Mohr JP, Choi DW, Grotta JC, Weir B, Wolf PA (eds)) Pathophysiology, Diagnosis, and Management(4th ed.Philadelphia : Churchill Livingstone)

      Pages: 603-618

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation of NO metabolites and 8-iso-prostaglandin F_2α with periventricular hyperintensity severity2004

    • Author(s)
      Shibata H
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology 24

      Pages: 1659-1663

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 広範囲 血液・尿化学検査 免疫学的検査 -その数値をどう読むか-[第6版]2004

    • Author(s)
      柴田 宏
    • Journal Title

      日本臨床62,Suppl 11 62

      Pages: 544-546

    • Related Report
      2004 Annual Research Report
  • [Book] Stroke.Pathophysiology,Diagnosis,and Management.4th ed.2004

    • Author(s)
      Mohr JP
    • Publisher
      Churchill Livingstone
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Stroke. Pathophysiology, Diagnosis, and Management 4th ed.2004

    • Author(s)
      Mohr JP
    • Publisher
      Churchill Livingstone
    • Related Report
      2004 Annual Research Report

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

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