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MOLECULAR PATHOLOGICAL ANALYSIS OF NERVOUS DISEASES CAUSED BY CHRONIC VIRAL INFECTION

Research Project

Project/Area Number 08457193
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKAGOSHIMA UNIVERSITY

Principal Investigator

IZUMO Shuji  KAGOSHIMA UNIVERSITY Faculty of Medicine, Professor, 医学部, 教授 (30143811)

Co-Investigator(Kenkyū-buntansha) ISASHIKI Yasushi  KAGOSHIMA UNIVERSITY Faculty of Medicine, Associate Professor, 医学部, 助教授 (70168160)
EIZURU Yoshito  KAGOSHIMA UNIVERSITY Faculty of Medicine, Professor, 医学部, 教授 (00041351)
OSAME Mitsuhiro  KAGOSHIMA UNIVERSITY Faculty of Medicine, Professor, 医学部, 教授 (10041435)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsHTLV-I / HAM / in situ PCR / proviral load / persistent infection / immunohistochemistry / molecular pathology / HTLV-I / ウイルス
Research Abstract

In order to clarify pathogenesis of the nervous diseases caused by chronic viral infection, we firstly investigated localization of HTLV-I infected cells in the spinal cord lesion of HAM/TSP using double staining of in situ PCR for HTLV-I provirus and immunohistochemistry of cell surface markers. HTLV-I proviral DNA was localized at infiltrated UCHL-1+ T-cells especially in the perivascular areas. Numbers of HTLV-I+ cells were positively correlated with the disease activity and negatively with duration of illness. In addition, proviral loads of peripheral blood mononuclear cells in 202 HAM/TSP patients and 206 HTLV-I carriers were measured by quantitative PCR using TaqMan PCR method. The proviral load of HAM/TSP patients was much higher than that of healthy carrier and correlated with the disease progression rate, anti-HTLV-I Ab titers, and the values of. neopterin in CSF.A high proviral load and frequent Tax protein expression were also demonstrated in PBMC and CSF cells of HAM/TSP pa … More tients using in situ PCR and highly sensitive immunohistochemistry technique. Taken together, these findings suggested that HTLV-I proviral load and expression of its antigens are important in pathogenic mechanism of HAM/TSP and a therapeutic method to reduce viral load and its expression may be suitable for the treatment of HAM/TSP.
We also investigated a mode of persistent infection in HTLV-I carriers. Among 500 blood samples collected from a longitudinal series of patients, all HTLV-I sero-positive samples were positive for PCR detection of HTLV-I provirus and all of HTLV-I sero-negative blood samples were negative for HTLV-I provirus. This suggested that sero-negative HTLV-I carrier is rare and infection from a sero-negative blood donner may not be frequent in HTLV-I infection. Totally 100 tonsils were collected from a series of patients who received tonsillectomy and examined localization of HTLV-I infected cells. All tonsils from HTLV-I sero-positive patients showed increased area of marginal zone and HTLV-I provirus was detected only from such areas. These findings suggested a possibility that the tonsil might be a site of persistent infection and a reservoir of infected cells in HTLV-I infected individuals. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Izumo-S, et al.: "Neuropathology of HTLV-I-associated myelopathy(HAM / TSP)." Leukemia.11. 82-84 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Osame-M, et al.: "Recent studies on the epidemiology,clinical features and pathogenic mechanisms of HTLV-I associated myelopathy(HAM / TSP)and other diseases associated to HTLV" J.Neuro Virology.3. 50-51 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa-M, et al.: "Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis." J.Neurovirol.2. 345-355 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nagai-M, et al.: "Characterization of a unique T-cell clone established from a patient with HAM/TSP which recognized HTLV-I-infected T-cell antigens as well as spinal cord tissue antigens." J.Neuroimmunol.65. 65-97 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moritoyo-F, et al.: "Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+ T lymphocytes." Ann Neurol.40. 84-90 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Umehara-F, et al.: "Expression of adhesion molecules and monocyte chemoattractant protein 1(MCP-in the spinal cord lesions in HTLV-I-associated myelopathy." Acta Neuropathol.91. 343-350 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kitze-B, et al.: "Diversity of intrathecal antibody synthesis against HTLV I and its relation to HTLV I associated myelopathy." J.Neurol.243. 393-400 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 出雲 周二, 他.: "細胞レベルでのin situPCR-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. 656-657 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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, 278 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Izumo-S,Umehara-F,Osame-M.: "Neuropathology of human T lymphotropic virus type I-associated myelopathy." Neuropathology. 17. 49-51 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Izumo-S,Umehara-F,Kashio-N,Kubota-R,Osame-M.: "Neuropathology of HTLV-I-associated myelopathy (HAM/TSP)." Leukemia. 11. 82-84 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Osame-M,Nakagawa-M,Umehara-F,Ijichi-S,Moritoyo-T,Higuchi-I,Usuku-K,Arimura-K,Izumo-S.: "Recent studies on the epidemiology, clinical features and pathogenic mechanisms of HTLV-I associated myelopathy (HAM/TSP) and other diseases associated to HTLV." J.Neuro Virology. 3. s50-51 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Achiron-A,Higuchi-I,Takenouchi-N,Matsuoka-E,Hashimoto-K,Izumo-S,Shohat-B,Osame-M.: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamano-Y,Kizte-B,Yashiki-S,Usuku-K,Fujiyoshi-T,Kaminagayoshi-T,Unoki-K,Izumo-S,Osame-M,Sonoda-S.: "Preferential recognition of synthetic peptides from HTLV-I gp21 envelope protein by HLA-DRB1 alleles associated with HAM/TSP (HTLV-I-associated myelopathy/tropical spastic paraparesis)." J Neuroimmunol. 76. 50-60 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Harada-K,Eizuru-Y,Isashiki-Y,Ihara-S,Minamishima-Y.: "Genetic analysis of a clinical isolate of human cytomegalovirus exhibiting resistance against both ganciclovir and cidofovir." Arch.Virol.142(2). 215-225 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Izumo-S,Goto-I,Itoyama-Y,Okajima-T,Watanabe-S,Kuroda-Y,Araki-S,Mori-M,Nagataki-S,Matsukura-S,Akamine-T,Nakagawa-M,Yamamoto-I,Osame-M.: "Interferon-alpha is effective in HTLV-I-associated myelopathy : A multicenter, randomized, double-blind, controlled trial." Neurology. 46. 1016-1021 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakagawa-M,Nakahara-K,Maruyama-Y,Kawabata-M,Higuchi-I,Kubota-H,Izumo-S,Arimura-K,Osame-M.: "Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis." J.Neurovirol. 2. 345-355 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nagai-M,Yashiki-S,Fujiyoshi-T,Fujiyama-C,Kitze-B., Izumo-S., Osame, M., Sonoda, S.: "Characterization of a unique T-cell clone established from a patient with HAM/TSP which recognized HTLV-I-infected T-cell antigens as well as spinal cord tissue antigens." J.Neuroimmunol. 65. 65-97 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moritoya-T,Reinhart-TA,Moritoyo-H,Sato-E,Izumo-S,Osame-M,Haase-AT.: "Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+T lymphocytes." Ann Neurol. 40. 84-90 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Umehara-F,Izumo-S,Takeya-M,Takahashi-K,Sato-E,Osame-M.: "Expression of adhesion molecules and monocyte chemoattractant protein 1(MCP-1) in the spinal cord lesions in HTLV-I-associated myelopathy." Acta Neuropathol. 91. 343-350 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kitzu-B,Usuku-K,Izumo-S,Nakamura-M,Shiraki-H,Ijichi-S,Yashiki-S,Fujiyoshi-T,Sonoda-S,Osame-M.: "Diversity of intrathecal antibody synthesis against HTLV I and its relation to HTLV I associated myelopathy." J Neurol. 243. 393-400 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Higuchi-I,Hashimoto-K,Matsuoka-E,Rosales-R,Nakagawa-M,Arimura-K,Izumo-S,Osame-M.: "The main HTLV-I harboring cells in the muscles of viral carrier with polymyositis are not macrophages but CD4+ lymphocytes." Acta Neuropathol. 92. 358-361 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Saito-M,Furukawa-Y,Kubota-R,Usuku-K,Izumo-S,Osame-M.: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Izumo-S ; Kashio-N ; Hashimoto-K ; Osame-M.: "In situ PCR detection of HTLV-1 provirus in spinal cord lesions with HAM/TSP." Tanpakushitsu-Kakusan-Koso. 44. 656-659 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Izumo-S,Umehara-F,Osame-M.HAM/TSP.Eds ; Iijima-S,et al.: Gastrointestinal tract, urinary organs, soft tissues, bone and joint, eye, and nervous system. In Current Encyclopedia of Pathology, suppl.3.Nakayama-Shoten Co., 215-221 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Izumo-S,et al.: "Neuropathology of human T lymphotropic virus type I-associated myelopathy." Neuropathology.17. 49-51 (1997)

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

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakagawa-M,et al.: "Therapeutic trials in 200 patiens with HTLV-I-assocciated myelopathy/tropical spastic paraparesis." J.Neurovirol.2. 345-355 (1996)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [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" 蛋白・核酸・酵素. 44. 656-659 (1996)

    • Related Report
      1996 Annual Research Report
  • [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)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ijichi S.et al.: "HAM/TSP : Recent Perspectives in Japan." J.AIDS and HR.13. 26-32 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakagawa M. et al.: "Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis." J. Neurovirol.2. 345-355 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagai M.et al.: "Characterization of a unique T-cell clone established from a patient with HAM/TSP which recognized HTLV-I-infected T-cell antigens as well as spinal cord tissue antigens." J.Neuroimmunol.65. 97-105 (1996)

    • Related Report
      1996 Annual Research Report
  • [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)

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

    • Related Report
      1996 Annual Research Report
  • [Publications] Kitze B.et al.: "Diversity of intrathecal antibody synthesis against HTLV I and its relation to HTLV I associated myelopathy." J Neurol.243. 393-400 (1996)

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

    • Related Report
      1996 Annual Research Report
  • [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)

    • Related Report
      1996 Annual Research Report
  • [Publications] Osame M.et al.: "HTLV-I-associated myelopathy (HAM/TSP),in Human T-cell lymphotropic virus type I." John Wiley & Sons Ltd., 21 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 出雲周二他: "HAM/TSP.現代病理学大系 補遺3" 中山書店, 7 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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