| Project/Area Number |
06670676
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | OSAKA MEDICAL COLLEGE |
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Principal Investigator |
KIMURA Fumiharu OSAKA MECLICAL COLLEGE ASSISTANT, 医学部, 助手 (90204990)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Simon OSAKA MEDICAL COLLEGE RESEARCH FELLOW, 医学部, 専攻手医
NAKAJIMA Hideto OSAKA MEDICAL COLLEGE RESEARCH FELLOW, 医学部, 専攻手医
ITO Takumi OSAKA MEDICAL COLLEGE RESEARCH FELLOW, 医学部, 専攻手医
YAMASAKI Hidetomo OSAKA MEDICAL COLLEGE RESEARCH FELLOW, 医学部, 専攻手医
FURUTAMA Daisuke OSAKA MEDICAL COLLEGE RESEARCH FELLOW, 医学部, 専攻手医
篠田 恵一 大阪医科大学, 医学部, 助手 (60187367)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | ALS / apoptosis / VSC 4.1 / PC 12 / Dihydropyridine / 1g G / VGCC / Campylobacter jejuni / Apoptosis / PC12 / IMR-32 / Calbindin D-28K / autoimmuhe |
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| Research Abstract |
1) Prior studies demonstrated that most patients with sporadic ALS possess immunoglobulins that bind to purified L-type voltage gated calcium channel (VGCC). Using Western transfer and Enzyme-Linked Immunosorbent Assay, alpha 1 subunit of VGCC is now identified as the major VGCC antigen to which ALS IgG binds. In addition, VGCC-binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both alpha 1 and beta subunits of VGCC.Aprimary role for ALS IgG in disease pathogenesis might also be suggested because selective antibody binding to exposed extracellular VGCC epitopes is found.
2) VGCC-enriched subsarcolemmal membrane fractions were prepared from biopsied quadriceps muscle of patients with ALS,without apparent neuromuscular disease, and tested for DHP binding with [3H] PN200-110. ALS muscle VGCCs possessed eightfold higher binding affinities for [3H] PN200-110 than did VGCCs from muscle fractions of othe
… More
r patients, independent of denervation-induced increases in DHP binding site number. Similarly elevated DHP binding affinities were observed in specimens from patients with autoimmune motor neuropathies, suggesting that ALS and immune mediated motoneuron disease share skeletal muscle L-type VGCC alterations.
3) There was no cytotoxic effect of ALS IgG (1mg/ml) on high K^+ stimulated neurite bearing cell expansion rate of PC 12 cell in which neurite growth of PC12 is dependent to Ltype Ca channel, confirmed by the inhibition of nifedipine.
4) We reported two Guillain-Barre syndrome (GBS) patients with culture-proven Campylobacter jejuni (Penner 19, Lior 7). Elevated anti-C.jejuni IgA antibody declined to the normal range within one month, elevation of anti-C.jejuni IgM antibody lasted for 3 month, and the titers of anti-C.jejuni IgG antibody was still elevated at one year after the neurologic onset. Serological criteria for antecedent C.jejuni infection in GBS patients should require 1) high titer of serum IgA and/or IgM antibody against C.jejuni followed by seroconversion of the, IgA and/or IgM 2) a 4-fold decline of IgG serum dilution against C.jejuni. Anti-C.jejuni antibodies in CSF reached to the maximum value at one month after their neurologic onset which may not be responsible for a main pathomechanism at development of GBS.The levels of anti-GM1 antibodies in seurm and CSF were paralleled with those of anti-C.jejuni antibodies. Less
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