1997 Fiscal Year Final Research Report Summary
MOLECULAR PATHOLOGICAL ANALYSIS OF NERVOUS DISEASES CAUSED BY CHRONIC VIRAL INFECTION
| Project/Area Number |
08457193
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | KAGOSHIMA UNIVERSITY |
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Principal Investigator |
IZUMO Shuji KAGOSHIMA UNIVERSITY Faculty of Medicine, Professor, 医学部, 教授 (30143811)
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| 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)
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| Project Period (FY) |
1996 – 1997
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| Keywords | HTLV-I / HAM / in situ PCR / proviral load / persistent infection / immunohistochemistry / molecular pathology |
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| 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
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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
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[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
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[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
