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The presence of mutant HTLV-I in the central nervous system

Research Project

Project/Area Number 06670656
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

KOBAYASHI Takuro  Kyushu Univ. Medicine Professor, 医学部, 教授 (40158902)

Co-Investigator(Kenkyū-buntansha) OHYAGI Yasumasa  Kyushu Univ. Medicine Resident, 医学部, 医員
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsliposphingolipid / leukodystrophy / detoxication / galactosylceramidase / Krabbe disease / beta-glucosidase / β-glucosidase
Research Abstract

For these ten years we have studied the pathogenetic mechanism of globoid cell leukodystrophy, a genetic demyelinating disorder deficient in galctosylceramidase I activity, and reported that galactosylsphingosine, a lyso compound of galactosylceramide, accumulates in the tissue of the patients and suggested that the cytotoxicity of the acumulated lysocompound leads to the cell death and subsequent demyelination. We have also the accumulation of lysocompounds in other lipid storage diseases such as GM1 gangliosidosis and metachromatic leukodystrophy. For one of the treatment of these lipid storage diseases we hypothesized if we could detoxicate the accumulated lysosphingolipids, and we obtained some data on this project as follows :
1. In 1994, we examined the synthetic pathway of the lysosphingolipid, When conduritol B epoxide (CBE), a competitive inhibitor of beta-glucosidase, was included in the medium of cultured fibroblasts, the accumulation of glucosylsphingosine, a lysocompound of … More glocosylceramide, was observed. The accumulated glucosylsphingosine was dependent on the dose of added CBE.Next, we added in the medium both CBE and PDMP, an inhibitor of glucosylceramide synthesis, and found the deceased accumulation of glucosylsphingosine. From these data we concluded that the synthesis of glucosylsphingosine is catalyzed not only by the glucosylation of sphingosine but also by the deacylation of glucosylceramide.
2. In 1995, we examined the degradative pathway of the lysospingolipid. For this purpose, we characterized molecular properties of galactosylceramidase I, a degrading enzyme of galactosylsphingosine and found mutations in adult patients with globod cell leukodystrophy. We obtained cDNA fragments of the gene after amplification by PCR from the patients and sequenced the total nucleotides in the amino acid coding region. In the 4 patients, we found new point mutations which replace evolutionally-conserved amino acids to others. We are now atempting to confirm that the mutations found in the patients are causative for the deficiency of the enzyme activity by expression of the mutated cDNA in eucaryotic cells. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Yamaguti Y, et al.: "The synthetic pathway for glucosylsphingosine in cultured fibroblasts" J. Biochem.116. 704-710 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi T, et al.: "Adrenoleukodystrophy gene encodes an 80 kDa membrane protein" Biochem. Biophys. Res. Commun.201. 1027-1034 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinnoh N. et al.: "Adrenoleukodystrophy:The restoration of peroxisomal β-oxidation by transfection of normal cDNA" Biochem. biophys. Res. Commun.210. 830-836 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ymada T, and Kobayashi, T.: "The mutation in amyloid precursor protein inhibits both α-and β-secretion" Neurosci. Lett.191. 103-106 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasutake T. et al.: "Molecular analysis of x-linked adrenoleukodystrophy patients" J. Neurol. Sci.131. 58-64 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 小林卓郎: "遺伝性白質変性症の診断基準、病型分類、重症度" 内科. 75. 1349-1351 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 小林卓郎: "遺伝性白質変性症の病態" 福岡医学雑誌. 86. 330-333 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamaguti Y.et al.: "The synthetic pathway for glucosylsphingosine in cultured fibroblasts." J.Biochem.116. 704-710 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobatashi T.et al.: "Adrenoleukodystrophy gene encodes an 80 kDa membrane protein." Biochem. Biophys. Res. Commun.201. 1027-1034 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinnoh N.et al.: "Adrenoleukodystrophy : The restoration of peroxisomal beta-oxidation by transfection of noormal cDNA." Biochem. Biophys. Res. Commun.210. 830-836 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamada T.et al.: "The mutation in amyloid precursor protein inhibits both alpha-and beta-secretion." Neurosci.Lett.191. 103-106 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasutake T.et al.: "Moleular analysis of x-linked adrenoleukodystrophy patients." J Neurol Sci. 131.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 1995: "58-64"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinnoh N. et al.: "Adrenoleukodystrophy: The restoration of peroxisomal β-oxidation by transfection of normal cDNA" Biochem. biophys. Res. Commun.210. 830-836 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamada T, and Kobayashi, T.: "The mutation in amyloid precursor protein inhibits both α- and β-secretion" Neurosci. Lett.191. 103-106 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yasutake T. et al.: "Molecular analysis of x-linked adrenoleukodystrophy patients" J. Neurol. Sci.131. 58-64 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小林卓郎: "遺伝性白質変性症の診断基準、病型分類、重症度" 内科. 75. 1349-1351 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小林卓郎: "遺伝性白質変性症の病態" 福岡医学雑誌. 86. 330-333 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamaguti Y,Sasagasako N: "The synthetic pathway for glucosylsphingosine in cultured fibroblasts" Journal of Biochemistry. 116. 704-710 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kobayashi T,Yamada T: "Adrenoleukodystrophy gene encodes and 80KDa membrane protein" Biochem.biophys.Res.Commun.201. 1027-1034 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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