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Studies of expression and mechanism of free-radical associated products in neuromuscular disorders.

Research Project

Project/Area Number 11670608
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionUniversity of Tsukuba

Principal Investigator

OHKOSHI Norio  University of Tsukuba, Institute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (80203751)

Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsmitochondrial encephalomyopathies / diabetic neuropathy / myositis / free-radical / apoptosis / nNOS / dystrophin / muscle regeneration / 糖尿病 / 末梢神経 / 虚血再環流 / ジストロブレビン / 骨格筋再生 / 多発筋炎 / カスパーゼ / 神経型NOS (nNOS) / テネイシン / Bax / Apaf-1 / 神経型NOS(nNOS) / α1シントロフィン
Research Abstract

The aim of this study is to clarify the expression and mechanism of free-radical associated products in neuromuscular disorders.
Hyperglycemia exacerbates the effect of ischemia-reperfusion on peripheral nerve in rat. After a 2-hour ischemia and 24-hour reperfusion of sciatic nerves of rats, the concentrations of lipid peroxide and loose myelin in the nerves were significantly increased in the diabetic rats, but not in the nondiabetic rats. Loose myelin may be increased as a result of the effects of oxygen free radicals produced by ischemia-reperfusion, which are exacerbated by hyperglycemia.
On ragged -red fibers in mitochondria! Encephalomyopathies, Mn-SOD, ec-NOS, nitrotyrosine were strongly stained by immunohistochemistry. And then, Fas, Fas-ligand, caspase 3, caspase 9, Bax, Apaf-1 and bcl-2 were also immunostained on ragged-red fibers. Therefore, The free-radical injury may induce apoptosis in the ragged-red fibers of mitochondrial encephalomyopathies.
In inclusion body myositis and rimmed-vacuole type distal myopathy, Fas was highly expressed in fibers with vacuole. The pathomechanism of the diseases may be involved of apoptosis associated with Fas. In polymyositis, however, Fas was not expressed. On the other hand, in dermatomyositis tenacin was stained in the network pattern in the interstitial areas. Tenacin also showed perifascicular atrophy. Tenacin is a very useful marker for diagnosis of dermatomyositis.
The expression of dystrophin, α-sarcoglycan, β-dystropglycan, α1-syntrophin, and nNOS were evaluated in regeneration skeletal mucles of rats after cardiotoxin-induced myonecrosis. The regeneration advances from the basement menbrane side to the subsarcolemmal side and from the proteins associated with structure of the basement membrane to the proteins associated with signal transmitting. The expression of nNOS is related to the muscle fiber type differentiation, and the role of nNOS is related to the function of the type 2B fibers of the muscle.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Hoshino S, Ohkoshi N, et al.: "Immunohistochemical staining of dystrophin on formalin fixed paraffing-embedded section in Duchenne muscular dystrophy, Becker muscular dystrophy, and manifesting carrier of Duchenne muscular dystrophy"Neuromuscular Disorders. 10. 425-429 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Harada K., Ohkoshi N. et al.: "Hyperglycemia exacerbates the effect of ischemia-reperfusion on peripheral nerve in rat"International Journal of Neuroscience. 105. 53-62 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S., Ohkoshi N. et al.: "The expressions of dystrophin and al-syntrophin during skeletal muscle regeneration"J Muscle Res Cell Mot. 22. 185-191 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshida M., Ohkoshi N. et al.: "Effect of riluzole on the acquisition and expression of amygdala kindling"Epilepsy Res.. 46. 101-109 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S., Ohkoshi N. et al.: "The expressions of dystrophin and a-sarcoglycan, and b-dystroglycan during skeletal muscle regeneration : immunohistochemical and western blot studies"Acta Histochemica. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S., Ohkoshi N. et al.: "The expressions of a-dystrobrevin and dystrophin during skeletal muscle regeneration"J Muscle Res Cell Mot. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S., Ohkoshi N. et al.: "The expressions of neuronal nitric oxide synthase and dystrophin during rat regenerating muscles"J Muscle Res Cell Mot. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S, Ohkoshi N, Watanabe M, Shoji S.: "Immunohistochemical staining of dystrophin on formalin fixed paraffin-embedded section in Duchenne muscular dystrophy, Decker muscular dystrophy, and manifesting carrier of Duchenne muscular dystrophy"Neuromuscular Disorders. 10(6). 425-429 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Harada K, Ohkoshi N, Shoji S, Yamamoto N, Nagata H.: "Hyperglycemia exacerbates the effect of ischemia-reperfusion on peripheral nerve in rat:"International Journal of Neuroscience. 105(1). 53-62 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S, Ohkoshi N, Ishii A, Shoji S, et al.: "The expressions of dystrophin and α1-syntrophin during skeletal muscle regeneration"J Muscle Res Cell Mot. 22(2). 185-191 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshida M, Noguchi E, Tsuru N, Ohkoshi N.: "Effect of riluzole on the acquisition and expression of amygdala kindling"Epilepsy Res.. 46(2). 101-109 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S, Ohkoshi N, Ishii A, Shoji S.: "The expressions of dystrophin and α-sarcoglycan, and β-dystroglycan during skeletal muscle regeneration: immunohistochemical and western blot studies"Acta Histochemica. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S, Ohkoshi N, Ishii A, Shoji S.: "The expressions of α-dystrobrevin and dystrophin during skeletal muscle regeneration"J Muscle Res Cell Mot. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hoshino S, Ohkoshi N, Ishii A, Shoji S.: "The expressions of neuronal nitric oxide synthase and dystrophin during rat regenerating muscles"J Muscle Res Cell Mot. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohkoshi N., Kohno Y., Hayashi A., Wada T., Shoji S.: "Acute vocal cord paralysis in hereditary neuropathy with liability to pressure palsies"Neurology. 56(10). 1415 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hoshino S., Ohkoshi N., Ishii A., Kameya S., Takeda S., Shoji S.: "The expressions of dystrophin and al-syntrophin during skeletal muscle regeneration"J Muscle Res Cell Mot. 22(2). 185-191 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohkoshi N., Harada K., Nagata H., Yato M., Shoji S.: "Ataxic Form of Chronic Inflammatory Demyelinating Polyradiculoneuro clinical features and pathological study of the sural nerves"European Neurology. 45(4). 241-248 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida M., Noguchi E., Tsuru N., Ohkoshi N.: "Effect of riluzole on the acquisition and expression of amygdala kindling"Epilepsy Res. 46(2). 101-109 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Harada S., Fuji C., Hayashi A., Ohkoshi N.: "An association between idiopathic Parkinson's disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2"Biochem Biophys Res Commun. 288. 887-892 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hoshino S., Ohkoshi N., Ishii A., Kameya S., Shoji S.: "The expressions of dystrophin and α-sarcoglycan, and β-dystroglycan during skeletal muscle regeneration: immunohistochemical and western blot studies"Acta Histochemica. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hoshino S, et al.: "Immunohistochemical staining of dystrophin on formalin fixed paraffing-embedded section in Duchenne muscular dystrophy, Becker muscular dystrophy, and manifesting carrier of Duchenne muscular dystrophy."Neuromuscular Disorders. 10(6). 425-429 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Butler MH, et al.: "Autoimmu-nity to gephyrin in stiff-man syndrome."Neuron. 26(2). 307-312 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yato M, et al.: "Ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)."European Journal of Neurology. 7(2). 227-230 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Harada K, et al.: "Hyperglycemia exacerbates the effect of ischemia reperfusion on peripheral nerve in rat."Intern J Neuroscience. 105(1). 53-62 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Harada K, et al.: "Sensory ataxic dominant neuropathy associated with polyarteritis nodosa."Internal Medicine. 39(10). 847-851 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hoshino S.et al.: "Immunostaining of dystrophin using catalyzed signal amplification."Muscle Nerve. 22(9). 1298-1299 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hoshino S,et al.: "Immunohistochemical staining of dystrophin on formalin fixed paraffing-embedded section in Duchenne muscular dystrophy, Becker muscular dystrophy,and menifesting carrier of Duchenne muscular dystrophy."Neuromuscular Disorders. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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