1997 Fiscal Year Annual Research Report

ウイルスの潜伏持続感染による神経疾患の病態に関する分子病理学的解析.

Research Project

Project/Area Number	08457193
Research Institution	KAGOSHIMA UNIVERSITY
Principal Investigator	出雲周二鹿児島大学, 医学部, 教授 (30143811)
Co-Investigator(Kenkyū-buntansha)	伊佐敷靖鹿児島大学, 医学部, 助教授 (70168160) 栄鶴義人鹿児島大学, 医学部, 教授 (00041351) 納光弘鹿児島大学, 医学部, 教授 (10041435)
Keywords	HTLV-1 / HAM / in situ PCR / プロウイルス量 / 持続感染 / 免疫組織化学 / 分子病理
Research Abstract	本研究の目的はHAMなどの難治性ウイルス神経疾患の病態を分子病理学的に解析し、ウイルスの持続感染が成立する機序、持続感染から発症に至る経過、疾患の進展に関わる要因をウイルスと生体の相互作用の観点から明らかにすることである。出雲・納らはHAM患者206例、患者家族を含むHTLV-Iキャリアー202例の末梢血HTLV-Iプロウイルス量をTaqMan PCR法にて定量した。HAM患者ではウイルス量が多く、急速進行例は特に高値で、プロウイルス量と抗体価、髄液ネオプテリン値とに相関をみとめた。また、末梢血リンパ球、髄液細胞の塗沫標本のHTLV-I in situ PCR、高感度免疫染色によるTax蛋白の発現を検討し、陽性細胞はHAMの病脳期間の短い例で多く、髄液ネオプテリン値と相関していた。病巣でのHTLV-Iの局在はHAM剖検例の新鮮凍結標本を用いてin situ PCRと免疫染色の2重染色法で検討し、脊髄病巣のHTLCC-I感染細胞は血管周囲の浸潤T細胞であり、グリア細胞など神経組織固有の細胞ではないことを明らかにした。以上の結果よりHAMの病勢にウイルスの動態が深く関与しており、ウイルス量、ウイルス蛋白発現の抑制がHAMの治療戦略として有効であることを明らかにできた。一方、HTLV-Iの潜伏感染様式を探るために伊佐敷、出雲は500連続症例の血中プロウイルスと抗体の有無を検討した。抗体陽性者とプロウイルス陽性者は完全に一致し、抗体陰性のまま長期経過するキャリアーはほとんどいないことが明となった。また、扁桃摘出術の連続100例について扁桃組織での感染細胞の有無を検討し、抗体陽性者全例で傍皮質領域にプロウイルスが存在していた。母乳による母児間感染での感染成立・潜在部位として扁桃組織が重要であることを初めて示した。ヘルペスウイルス群による神経感染症についてもサイトメガロウイルス脳炎例でのガンシクロビン耐性の機序を栄鶴.伊佐敷らが明らかにした。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Izumo-S,et al.: "Neuropathology of human T lymphotropic virus type I-associated myelopathy." Neuropathology.17. 49-51 (1997)
[Publications] Izumo-S,et al.: "Neuropathology of HTLV-I-associated myelopathy (HAM/TSP)" Leukemia.11. 82-84 (1997)
[Publications] Osama-M,et al.: "Recent studies on the epidemiology,clinical features and pathogenic mechanisms of HTLV-1 associated myelopathy (HAM/TSP) and other diseases associated to HTLV" J.Neuro Virology.3. 50-51 (1997)
[Publications] Achiron-A,et al.: "Detection of HTLV type I provirus by in situ polymerase chain reaction in mouthwash mononuclear cells of HAM/TSp patients and HTLV type I carriers." Aids Research & HR.13. 1067-1070 (1997)
[Publications] Yamano-Y,et al.: "Preferential recognition of synthetic peptides from HTLV-I gp21 envelope protein by HLA-DRB1 alleles associated with HAM/TSP." J Neuroimmunology.76. 50-60 (1997)
[Publications] Harada-K,et al.: "Genetic analysis of a clinical isolate of human cytomegalovirus exhibiting resistance against both ganciclovir and cidofovir." Arch.Virol.142(2). 215-225 (1997)
[Publications] Izumo-S.,et al.: "Interferon-alpha is effective in HTLV-I-associated myelopathy : A multicenter,randomized,double-blind,controlled trial." Neurology. 46. 1016-1021 (1996)
[Publications] Nakagawa-M,et al.: "Therapeutic trials in 200 patiens with HTLV-I-assocciated myelopathy/tropical spastic paraparesis." J.Neurovirol.2. 345-355 (1996)
[Publications] Nagai-M,et al.: "Characterization of a unique T-cell clone established from a patien with HAM/TSP which resognized HTLV-I-infected T-cell antigens as well as spinal cord tissue antigens." J.Neuroimmunol.65. 65-97 (1996)
[Publications] Moritoyo-T,et al.: "Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+T lymphocytes." Ann Neurol.40. 84-90 (1996)
[Publications] Umehara-F,et al.: "Expression of adhesion molecules and monocute chemoattractant protein 1(MCP-in the spinal cord lesions in HTLV-I-associated myelopathy." Acta Neuropathol.91. 343-350 (1996)
[Publications] Kitze-B,et al.: "Diversity of intrathecal antibody synthesis against HTLVI and its relation to HTLVI associated myelopathy." J Neurol.243. 393-400 (1996)
[Publications] Higuchi-I,et al.: "The main HTLV-I harboring cells in the muscles of viral carrier with polymyositi are not macrophages but CD4+ lymphocytes." Acta Neuropathol.92. 358-361 (1996)
[Publications] Saito-M,et al.: "Mutation rates in LTR of HTLV-I in HAM/TSP patients and the carriers are similarly high to Tax/Rex-cording sequence." J Neurovirol.2. 330-335 (1996)
[Publications] 出雲周二,他.: "細胞レベルでのin situ PCR-HAM病巣におけるHTLV-1の局在.特集;in situ PCR最前線." 蛋白・核酸・酵素. 44. 656-659 (1996)
[Publications] 出雲周二,他.: "HAM/TSP,現代病理学大系補遺3.消化腺泌尿器軟部組織骨・関節眼病理神経系." 中山書店, 7 (1996)

1997 Fiscal Year Annual Research Report

ウイルスの潜伏持続感染による神経疾患の病態に関する分子病理学的解析.

Principal Investigator

出雲 周二 鹿児島大学, 医学部, 教授 (30143811)

Research Products

[Publications] Izumo-S,et al.: "Neuropathology of human T lymphotropic virus type I-associated myelopathy." Neuropathology.17. 49-51 (1997)

[Publications] Izumo-S,et al.: "Neuropathology of HTLV-I-associated myelopathy (HAM/TSP)" Leukemia.11. 82-84 (1997)

[Publications] Osama-M,et al.: "Recent studies on the epidemiology,clinical features and pathogenic mechanisms of HTLV-1 associated myelopathy (HAM/TSP) and other diseases associated to HTLV" J.Neuro Virology.3. 50-51 (1997)

[Publications] Achiron-A,et al.: "Detection of HTLV type I provirus by in situ polymerase chain reaction in mouthwash mononuclear cells of HAM/TSp patients and HTLV type I carriers." Aids Research & HR.13. 1067-1070 (1997)

[Publications] Yamano-Y,et al.: "Preferential recognition of synthetic peptides from HTLV-I gp21 envelope protein by HLA-DRB1 alleles associated with HAM/TSP." J Neuroimmunology.76. 50-60 (1997)

[Publications] Harada-K,et al.: "Genetic analysis of a clinical isolate of human cytomegalovirus exhibiting resistance against both ganciclovir and cidofovir." Arch.Virol.142(2). 215-225 (1997)

[Publications] Izumo-S.,et al.: "Interferon-alpha is effective in HTLV-I-associated myelopathy : A multicenter,randomized,double-blind,controlled trial." Neurology. 46. 1016-1021 (1996)

[Publications] Nakagawa-M,et al.: "Therapeutic trials in 200 patiens with HTLV-I-assocciated myelopathy/tropical spastic paraparesis." J.Neurovirol.2. 345-355 (1996)

[Publications] Nagai-M,et al.: "Characterization of a unique T-cell clone established from a patien with HAM/TSP which resognized HTLV-I-infected T-cell antigens as well as spinal cord tissue antigens." J.Neuroimmunol.65. 65-97 (1996)

[Publications] Moritoyo-T,et al.: "Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+T lymphocytes." Ann Neurol.40. 84-90 (1996)

[Publications] Umehara-F,et al.: "Expression of adhesion molecules and monocute chemoattractant protein 1(MCP-in the spinal cord lesions in HTLV-I-associated myelopathy." Acta Neuropathol.91. 343-350 (1996)

[Publications] Kitze-B,et al.: "Diversity of intrathecal antibody synthesis against HTLVI and its relation to HTLVI associated myelopathy." J Neurol.243. 393-400 (1996)

[Publications] Higuchi-I,et al.: "The main HTLV-I harboring cells in the muscles of viral carrier with polymyositi are not macrophages but CD4+ lymphocytes." Acta Neuropathol.92. 358-361 (1996)

[Publications] Saito-M,et al.: "Mutation rates in LTR of HTLV-I in HAM/TSP patients and the carriers are similarly high to Tax/Rex-cording sequence." J Neurovirol.2. 330-335 (1996)

[Publications] 出雲周二,他.: "細胞レベルでのin situ PCR-HAM病巣におけるHTLV-1の局在.特集;in situ PCR最前線." 蛋白・核酸・酵素. 44. 656-659 (1996)

[Publications] 出雲周二,他.: "HAM/TSP,現代病理学大系 補遺3.消化腺 泌尿器 軟部組織 骨・関節 眼病理 神経系." 中山書店, 7 (1996)

出雲周二鹿児島大学, 医学部, 教授 (30143811)

[Publications] 出雲周二,他.: "HAM/TSP,現代病理学大系補遺3.消化腺泌尿器軟部組織骨・関節眼病理神経系." 中山書店, 7 (1996)