1997 Fiscal Year Final Research Report Summary
Cytotoxic T cell mediated paraneoplastic neurological syndromes
| Project/Area Number |
08670699
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
TANAKA Keiko Niigata University Medical Hospital Assistant, 医学部・附属病院, 助手 (30217020)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJI Shoji Niigata University, Brain Research Institute, Proffessor, 脳研究所, 教授 (70150612)
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| Project Period (FY) |
1996 – 1997
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| Keywords | paraneoplastic / recombinant HuD protein / cytotoxic T cell / HLA class I / microinjection |
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| Research Abstract |
Paraneoplastic sensory neuronopathy (PSN) has been shown to harbor characteristic antineuronal autoantibody "anti-Hu" in their sera and cerebrospinal fluid. Creation of animal models exhibiting clinical or pathological features seen in PSN by means of passive transfer of anti-Hu positive IgG has not been achieved. Although, anti-Hu antibody was shown to induce neuronal cell lysis in vitro, this result has not been reproduced so far. Since prominent T cell infiltration are seen in the central nervous system and posterior spinal ganglion of the patients with anti-Hu syndrome, we studied cytotoxic T cell (CTL) activety in peripheral mononuclear cells from a pantient with PSN harboring anti-Hu antibody. The activated CD8+ T cells from the pantient's venous blood were shown to lyse her own fibroblasts which were incubated with interferon-alpha to induce HLA class I molecules on their surface and the recombinant HuD protein was injected into the cells by microinjector. This is the first report showning the existence of CTL in a patient with PSN.
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[Publications] Takano H,Onodera O,Takahashi H,Igarashi S,Yamada M,Oyake M,Ikeuchi T,Koide R,Tanaka H,Iwabuchi K,Tsuji S: "Somatic mosaicism of expanded-CAG repeats in brains of patients with dentaterubral-pallidoluysian atrophy : Cellular population-dependent dynamics of mitotic instability" Am J Hum Genet. 58. 1212-1222 (1996)
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[Publications] Igarashi S,Takiyama Y,Cancel G,Rogaeva EA,Sakaki H,Wakisaka A,Zhou Y-X,Takano H,Endo K,Sanpei K,Oyake M,Tanaka H,Stevanin G,Abbas N,Durr A,Rogaev EI,Sherrington R,Tsuda T,Ikeda M,Cassa E,Nishizawa M,Benomar A,Julien J,Weissenbach J,Wang GX,Agid Y,St.George-Hyslop PH,Brice A,Tsuji S: "Intergeneration instability of the CAG repeat of the gene for Machado-Joseph disease (MJDI) is affected by the genotype of the normal chromosome : implications for the molecular mechanisms of the instability of the CAG repeat" Hum Mol Genet. 5. 923-932 (1996)
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[Publications] Sanpei K,Takano H,Igarashi S,Sato T,Oyake M,Sasaki H,Wakisaka A,Tashiro K,Ishida Y,Ikeuchi T,Koide R,Saito M,Sato A,Tanaka T,Hanyu S,Takiyama Y,Nishizawa M,Shimizu N,Nomura Y,Segawa M,Iwabuchi K,Eguchi I,Tanaka H,Takahashi H,Tsuji S: "Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT" Nature Genet. 14. 277-284 (1996)
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[Publications] Oyake M,Onodera O,Shiroishi T,Takano H,Takahashi Y,Kominami R,Moriwaki K,Ikeuchi T,Igarashi S,Tanaka H,Tsuji S: "Molecular cloning of murine homologue dentaterubral-pallidoluysian atrophy (DRPLA) cDNA : Strong consevation of a polmorphic CAG repeat in the murine gene" Genomics. 40. 205-207 (1997)
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[Publications] Takano M,Aida T,Tsuneki I,takakuwa K,Hasegawa I,Tanaka H,Saito M,Tsujyi S,Sonoda T,Hatae M,Chen J-T,Takahashi K,Hasagawa K,Toyoda MN,Saito N,Yakshiji M,Araki T,Tanaka K: "Muutational analysis of BRCA1 gene in ovarian and breast-ovarian cancer families in Japan" Jpn J Cancer Res. 88. 407-413 (1997)
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[Publications] Ishikawa K,Tanaka H,Ohkosi N,fujita T,Yoshizawa K,Ikeuchi T,Watanabe M,Hayashi A,Takiyama Y,Nishizawa M,Nakano I,Masyubayashi K,Miwa M,Shoji S,Kanazawa I,Tsuji S,Mizusawa H: "Japanese Families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associate with mild CAG expansions in the spinocerrebellar ataxia type 6 gene in chromosome 19p13.1" Am J Hum Genet. 61. 336-346 (1997)
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[Publications] Ikeuchi K,Asaga T,Saito M,Tanaka H,Higuchi S,Tanaka K,Saida K,Uyama E,Mizusawa H,Fukuhara N,Nonaka I,Takamori, Tsuji S: "Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chormosome 9" Ann Neurol. 41. 432-437 (1997)
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[Publications] Ikeuchi T,Takano H,Koide R,Horokawa Y,Honma Y,Onishi Y,Igarashi S,Takano H,Nakao N,Sahashi K,Tsukagoshi H,Inoue K,Takahashui H,Tsuji S : Spinocerebellar ataxia type: "Spinocerebellar ataxia type 6 CAG repeat expansion in alpha 1A voltage-dependent calcium channel gene and clininal variations in Japanese population" Ann Neurol. 42. 879-884 (1997)
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[Publications] Igarashi S,Koide R,Shimohata T,Yamada M,Hayashi Y,Takano H,Date H,Oyake M,Sato T,Egawa S,Ikeuchi T,Tanaka H,Nakano T,Tanaka K,Hozumi I,Inuzuka T,Takahashi H,Tsuji S: "Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch" Nature Geneto. 18. 111-117 (1998)
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