神経変性疾患の病態解明に関する研究

1998 Fiscal Year Annual Research Report

• Project/Area Number: 09470152
• Research Institution: Gunma University
• Principal Investigator: 岡本 幸市 群馬大学, 医学部, 教授 (00124652)
• Co-Investigator(Kenkyū-buntansha): 田中 真 群馬大学, 医学部, 講師 (40143226)
• Keywords: 筋萎縮性側索硬化症 / 脊髄小脳変性症 / アルツハイマー病 / ゴルジ装置

Research Abstract

筋萎縮性側索硬化症(ALS),脊髄小脳変性症(SCA),アルツハイマー病などの神経変性疾患について多面的な研究を行い,以下の成果を得ることができた.(1)16ALS剖検脳のBetz細胞でもGolgi装置のfragmentationがみられること(ALSで13.3%,非ALSで0.6%)を初めて明らかにした.その出現頻度は脊髄前角細胞での出現頻度に比して軽度であった.(2)ALSに特徴的な封入体であるBunina小体は抗Golgi装置関連抗体で免疫組織学的に陰性であることを報告した.(3)30例のALS剖検脳を検討し,痴呆を伴うALSの側頭葉病変の特徴を明らかにした.(4)英国のInstitute of Pschiatryの保存されていた72例のALS剖検例を検討した結果,英国においても痴呆を伴うALSが稀ならずみられることを明らかにした.(5)髄液中のタウとアミロイドβ蛋自の測定がアルツハイマー病の診断マーカーとして使用可能なことを多施設共同研究で明らかにした.(6)群馬県におけるSCA2のCAG延長と臨床徴候を解析した.(7)SCA6のCAG延長と臨床徴候との関連を明らかにした.(8)コドン291の欠失を示す副腎白質ジストロフィーの1家系の詳細を報告した.(9)高CK血症,高γ-グロブリン血症を伴うFriedreich病類似疾患の1家系を報告した.(10)活性化されたミクログリアはフェリチンの存在下で鉄依存性の脂質過酸化反応を起こすことを明らかにした.

Research Products

• [Publications] Okamoto K: "Temporal lobe pathology in patients with amyotrophic lateral sclerosis." Neuropathol. 18. 222-227 (1998)
• [Publications] Kanai M,Matsubara E,Isoe K,Urakami K,Nakashima K,Arai H,Sasaki H,Abe K,Iwatsubo T,Kosaka K,Watanabe M,Tomidokoro Y,Shizuka M,Mizushima K,Nakamura T,Igeta Y,Ikeda Y,Amari M,Kawarabayashi T,Ishiguro K,Harigaya Y,Wakabayashi K,Okamoto K,Hirai S,Shoji M: "Longitudinal study of cerebrospinal fluid levels of tau,Aβ1-40 and Aβ1-42(43)in Alzheimer's disease" A study in Japan.Ann Neurol. 44. 17-26 (1998)
• [Publications] Shoji M,Matsubara E,Kanai M,Watanabe M,Nakamura T,Tomidokoro Y,Shizuka M,Wakabayashi K,Igeta Y,Ikeda Y,Mizushima K,Amari M,Ishiguro K,Kawarabayashi T,Harigaya Y,Okamoto K,Hirai S: "Combination assay of CSF tau,β1-40 and Aβ1-42(43)as a biological marker of Alzheimer's disease." J Neurol Sci. 158. 134-140 (1998)
• [Publications] Shoji M,Kawarabayashi T,Sato M,Sasaki A,Matsubara E,Igeta Y,Kanai M,Tomidokoro Y,Shizuka M,Ishiguro K,Harigaya Y,Okamoto K,Hirai S: "Accumulation of Amyloid β protein transgenic mice." Neurobiol Aging. 19. S59-63 (1998)
• [Publications] Tanaka M,Hirai S,Kondo S,Sun X,Nakagawa T,Tanaka S,Hayashi K,Okamoto K: "Cerebral hyperfusion and hypometabolosm with altered striatal signal intesity in Chorea-acanthocytosis:A conbined PET and MRI study." Mov Disord. 13. 100-107 (1998)
• [Publications] Tanaka M,Yoshida T,Okamoto K,Hirai S: "Antioxidant properties of nicergoline;inhibition of brain autooxidation and superoxide production of neutrophils." Neurosci Lett. 248. 68-72 (1998)
• [Publications] Yoshida T,Tanaka M,Sotomatsu A,Okamoto K,Hirai S: "Serum of Behcet's disease enhances superoxide production of normal neutrophils." Free Rad Res. 28. 39-44 (1998)
• [Publications] Yoshida T,Tanaka M,Sotomatsu A,Hirai S,Okamoto K: "Activated microglia cause iron-dependent lipid peroxidation in the presence of ferritin." NeuroReport. 9. 1929-1933 (1998)
• [Publications] Kano S,Watanabe M,Kanai M,Koike R,Onodera O,Tsuji S,Okamoto K,Shoji M: "A Japanese family with adrenoleukodystrophy with a codon 291 deletion:a clinical,biochemical,pathological,and genetic report." J Neurol Sci. 158. 187-192 (1998)
• [Publications] Watanabe M,Sugai Y,Concannon P,Koenig M,Schmitt M,Sato M,Shizuka M,Mizushima K,Ikeda Y,Tomidokoro Y,Okamoto K,Shoji M: "Familial spinocerebellar ataxia with cerebellar atrophy,peripheral neuropathy,and the elevated level of serum creatine kinase,γ-globulin and alpha fetoprotein." Ann Neurol. 44. 265-269 (1998)
• [Publications] Ikeda Y,Tanaka M,Mizushima K,Okamoto K: "A case of eosinophilic polymyositis complicated by myasthenia gravis." Muscle Nerve. 21. 1356-1358 (1998)
• [Publications] Sun X,Tanaka M,Kondo S,Okamoto K,Hirai S: "Clinical significance of reduced cerebral metabolism in multiple sclerosois." Ann Nucl Med. 12. 89-94 (1998)
• [Publications] Mizuishima K,Watanabe M,Abe K,Aoki M,Itoyama Y,Shizuka M,Okamoto K,Shoji M: "Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan:CAG trinucleotide expansion and clinical characteristics." J Neurol Sci. 156. 180-185 (1998)
• [Publications] Shizuka M,Watanabe M,Igeta Y,Mizushima K,Kanai M,Tsuda T,Abe K,Okamoto K,Shoji M: "Spinocerebellar ataxia type 6:CAG trinucleotide expansion,clinical characteristics and sperm analysis." Eur J Neurol. 5. 381-387 (1998)
• [Publications] Shizuka M,Watanabe M,Ikeda Y,Mizushima K,Okamoto K,Shoji M: "Molecular analysis of a de novo mutation for spinocerebellar ataxia type 6 and(CAG)n repeat units in normal eldere controls." J Neurol Sci. 161. 85-87 (1998)
• [Publications] Stieber A,Chen Y,Wei S,Mourelatos Z,Gonatas J,Okamoto K,Gonatas NK: "The fragmented neuronal Golgi apparatus in amyotrophic lateral sclerosis incudes the trans-Golgi-network:functional implications." Acta Neuropathol. 95. 245-253 (1998)
• [Publications] Nagai M,Abe K,Okamoto K,Itoyama Y: "Identification of alternative splicing forms of GLT-1 mRNA in the spinal cord of amyotrophic lateral sclerosis patients." Neurosci Lett. 244. 165-168 (1998)
• [Publications] Mizushima K,Watanabe M,Kondo I,Okamoto K,Shizuka M,Abe K,Aoki M,Shoji M: "Analysis of spinocerebellar ataxia type 2 gene and haplotype analysis:(CGG)1-2 polymorphism and contribution to founder effects." J Medical Genetics. 36. 112-114 (1999)
• [Publications] Fujita Y,Okamoto K,Sakurai A,Amari M,Nakazato Y,Gonatas NK: "Fragmentation of the Golgi apparatus of Betz cells in patients with amyotrophic lateral sclerosis." J Neuro Sci. (In press).
• [Publications] Matsubara E,Ghiso J,Frangione B,Amari M,Tomidokoro Y,Ikeda Y,Harigaya Y,Okamoto K,Shoji M: "Lipoprotein-free amyloidogenic peptides in plasma are elevated in the patients with sporadic Alzheimer's disease and Down's syndrome." Ann Neurol. (in press).
• [Publications] Tomidokoro Y,Ishiguro K,Igeta Y,Matsubara E,Kanai M,Shizuka M,Kawarabayashi T,Harigaya Y,Kawatsu S,Ii K,Ikeda M,St.George-Hyslop PH,Hirai S,Okamoto K,Shoji M: "Carboxylterminal fragments of presenilin-1 are closely related to cytoskeletal abnormality in Alzheimer's brains." Biochem Biophys Res Commun. (in press).
• [Publications] 岡本幸市: "痴呆-私の診療-Treatable dementiaを中心に." 治療. 80. 1702-1706 (1998)
• [Publications] 岡本幸市,藤田行雄,森田真人: "Bunina小体,Golgi装置の異常." Clin Neurosci. 16. 907-909 (1998)
• [Publications] 岡本幸市: "痴呆を伴う筋萎縮性側索硬化症の海馬病変." 脳神経. 50. 915-922 (1998)
• [Publications] 岡本幸市: "Cortical neuronal ubiquitinated inclusion." Brain Medical. 10. 257-262 (1998)
• [Publications] 針谷康夫,岡本幸市: "眼瞼下垂とHorner症候群." Clin Neurosci. 16. 258-259 (1998)
• [Publications] 田中 真,宗宮 真,近藤 進,岡本幸市: "各種痴呆性疾患と前頭葉" 5.血管性痴呆.老年期痴呆. 12. 181-188 (1998)
• [Publications] 田中 真,吉田敏彦,岡本幸市,平井俊策: "フリーラジカル・NO^・と大脳基底核障害." Clin Neurosci. 16. 517-520 (1998)
• [Publications] 田中 真,市場 卓,近藤進,岡本幸市: "運動ニューロン疾患の脳循環代謝." Clin Neurosci. 16. 920-923 (1998)
• [Publications] 渡辺光法,菅井芳郎,岡本幸市: "高CK血症,高γ-グロブリン血症を伴うFriedreich病類似疾患." 神経内科. 48. 222- (1998)
• [Publications] 静 雅美,渡辺光法,岡本幸市: "McLeod症候群." Clin Neurosci. 16. 109 (1998)
• [Publications] 田中 真,岡本幸市: "糖尿病に伴う脳梗塞および脳血管性痴呆の薬物療法." 日本医事新報. 3875. 153-154 (1998)
• [Publications] 岸由美子,田中 真,市場 卓,井桁之総,岡本幸市: "慢性トルエン中毒にみられたhyperkinesie volutionelleとMRI所見." 神経内科. 49(supp). 28-29 (1998)
• [Publications] 増田俊和,水野裕司,金子広司,藤田秀樹,岡本幸市: "重症心身障害児(者)にみられた脳回転状皮膚." 神経内科. 49(supp). 46-47 (1998)
• [Publications] 東海林幹夫,甘利雅邦,岡本幸市: "Cockayne症候群:老人様顔貌と進行性脳萎縮." 神経内科. 49(supp). 148-149 (1998)
• [Publications] 内山 靖,酒井保治郎,岡本幸市: "神経難病に対する理学療法." 理学ジャーナル. 32. 449-466 (1998)
• [Publications] 岡本幸市,櫻井篤志,藤田行雄,Safa AL-Sarraj,P.N.Leigh: "痴呆を伴う運動ニューロン疾患の大脳病変." 厚生省特定疾患調査研究班(班長田代邦雄)1998年度報告書. (印刷中).
• [Publications] 岡本幸市: "頭痛・めまい.高齢者マニュアル.エキスパートナース28(福地義之助編)" 照林社, 1997 (77-78)
• [Publications] 岡本幸市: "進行性核上性麻痺.今日の治療指針,1998版" 日野原重明ら編,医学書院(東京), 1998 (241-242)
• [Publications] 岡本幸市: "椎骨動脈系の多発性脳梗塞で治療に難渋した1例.脳梗塞後遺症の薬物療法指針" 平井俊策編,ブアンメデイカル(東京), 1998 (162-163)
• [Publications] 岡本幸市: "Wallenberg症候群に伴う不定愁訴の1例.脳梗塞後遺症の薬物療法指針" 平井俊策編,ブアンメデイカル(東京), 1998 (164-165)
• [Publications] 岡本幸市: "アルツハイマー病/ピック病.臨床看護辞典,第二版" 高久史麿ら編,メヂカルフレンド, 1998 (41-44)