Faculty Profiles - KUBOTA Ryuji

写真a

KUBOTA Ryuji

Organization

Research Field in ? Professor

Homepage

https://ccvd.kufm.kagoshima-u.ac.jp/~ni/

External link

Degree

博士（医学） ( 2000.6 鹿児島大学 )

Research Interests

HTLV-I
HTLV-I 関連脊髄症(HAM)
細胞傷害性Tリンパ球(CTL)
成人T細胞白血病(ATL)

Research Areas

Life Science / Immunology / Human T-cell leukemia virus type 1
Life Science / Neurology / HTLV-1-associated myelopathy

Education

Kagoshima University

Research History

Kagoshima University Research Field in Integrated Studies, Integrated Arts and Sciences Area ? Professor

2019.4
Kagoshima University Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Center for Chronic Viral Diseases Professor

2016.6 - 2019.3
Kagoshima University Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Health Research Course Infection and Immunity Associate Professor

2004.4 - 2016.5
NIH Neuroimmunology branch/NINDS Researcher

1994.4 - 1996.6

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Country：United States

Professional Memberships

日本HTLV-1学会（理事）

2014.6
日本神経感染症学会（評議員）

2005.4
日本神経免疫学会（評議員）

1993.1
日本内科学会

1992.8
日本神経学会（代議員）

1986.6

Studying abroad experiences

1996.4 - 1998.6 NIB/NINDS/NIH Visiting Researcher

Papers

Matsuura E, Nozuma S, Shigehisa A, Dozono M, Nakamura T, Tanaka M, Kubota R, Hashiguchi A, Takashima H . HTLV-1-associated myelopathy/tropical spastic paraplegia with sporadic late-onset nemaline myopathy: a case report. . BMC musculoskeletal disorders24 ( 1 ) 355 2023.5HTLV-1-associated myelopathy/tropical spastic paraplegia with sporadic late-onset nemaline myopathy: a case report.Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1186/s12891-023-06461-3

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Matsuura E, Nozuma S, Dozono M, Kodama D, Tanaka M, Kubota R, Takashima H . Iliopsoas Muscle Weakness as a Key Diagnostic Marker in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). . Pathogens (Basel, Switzerland)12 ( 4 ) 2023.4Iliopsoas Muscle Weakness as a Key Diagnostic Marker in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP).Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.3390/pathogens12040592

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Nozuma S, Matsuura E, Tanaka M, Kodama D, Matsuzaki T, Yoshimura A, Sakiyama Y, Nakahata S, Morishita K, Enose-Akahata Y, Jacoboson S, Kubota R, Takashima H . Identification and tracking of HTLV-1-infected T cell clones in virus-associated neurologic disease. . JCI insight8 ( 7 ) 2023.4Identification and tracking of HTLV-1-infected T cell clones in virus-associated neurologic disease.Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1172/jci.insight.167422

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Nagata R, Matsuura E, Nozuma S, Dozono M, Noguchi Y, Ando M, Hiramatsu Y, Kodama D, Tanaka M, Kubota R, Yamakuchi M, Higuchi Y, Sakiyama Y, Arata H, Higashi K, Hashiguchi T, Nakane S, Takashima H . Anti-ganglionic acetylcholine receptor antibodies in functional neurological symptom disorder/conversion disorder. . Frontiers in neurology14 1137958 2023Anti-ganglionic acetylcholine receptor antibodies in functional neurological symptom disorder/conversion disorder.Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.3389/fneur.2023.1137958

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Nozuma S, Matsuura E, Tashiro Y, Nagata R, Ando M, Hiramatsu Y, Higuchi Y, Sakiyama Y, Hashiguchi A, Michizono K, Higashi K, Matsuzaki T, Kodama D, Tanaka M, Yamano Y, Moritoyo T, Kubota R, Takashima H . Efficacy of l-Arginine treatment in patients with HTLV-1-associated neurological disease. . Annals of clinical and translational neurology10 ( 2 ) 237 - 245 2022.12Efficacy of l-Arginine treatment in patients with HTLV-1-associated neurological disease.Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1002/acn3.51715

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Tashiro Y, Matsuura E, Sagara Y, Nozuma S, Kodama D, Tanaka M, Koriyama C, Kubota R, Takashima H . High Prevalence of HTLV-1 Carriers Among the Elderly Population in Kagoshima, a Highly Endemic Area in Japan. . AIDS research and human retroviruses38 ( 5 ) 363 - 369 2022.5Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：AIDS Research and Human Retroviruses

Japan is one of the world's highly endemic areas for human T cell leukemia virus type 1 (HTLV-1), and it is known that the infection rate of HTLV-1 increases with age. The infection rate among the elderly has been estimated based on data from blood donors under the age of 65, and the actual number and rate of infection among the elderly are unknown. Data of 26,090 preoperative HTLV-1 screening tests conducted at Kagoshima University Hospital from 2001 to 2020, including 2726 HTLV-1-positive patients, were used for calculating the decadal infection rates for the year of birth. Estimated infection rates by birth year and demographic tables were used to estimate the current number of infected people in Kagoshima. The estimated total numbers of people infected with HTLV-1 in Kagoshima prefecture were 139,436 in 2005 and 80,975 in 2019. The infection rate increased with age for both men and women, reaching 17.3% for women born before the 1920s. Next, we tried to clarify whether the increase in infection rates with age was due to post-school age infections. The age of birth with the greatest increase in infection rate after 10 years was women born in the 1970s, and the increase in infection rate was only 0.98%, which is not a statistically significant increase. The number of infected people in Kagoshima was >80,000 in 2019. No data were available in this study to point to the involvement of horizontal transmission after school age in the high infection rate among the elderly. The high infection rate among the elderly is thought to have been high even when they were infants.

DOI： 10.1089/AID.2021.0164

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Kodama D, Tanaka M, Matsuzaki T, Nozuma S, Matsuura E, Takashima H, Izumo S, Kubota R . Anti-Human T-Cell Leukemia Virus Type 1 (HTLV-1) Antibody Assays in Cerebrospinal Fluid for the Diagnosis of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis. . Journal of Clinical Microbiology59 ( 5 ) 2021.4Reviewed International journal

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Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Clinical Microbiology

DOI： 10.1128/JCM.03230-20

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Satoshi Nozuma, Ryuji Kubota, Steven Jacobson . Human T-lymphotropic virus type 1 (HTLV-1) and cellular immune response in HTLV-1-associated myelopathy/tropical spastic paraparesis . Journal of NeuroVirology26 ( 5 ) 652 - 663 2020.10Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

<title>Abstract</title>Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the spinal cord and clinically characterized by progressive spastic paraparesis, urinary incontinence, and mild sensory disturbance. The interaction between the host immune response and HTLV-1-infected cells regulates the development of HAM/TSP. HTLV-1 preferentially infects CD4+ T cells and is maintained by proliferation of the infected T cells. HTLV-1-infected cells rarely express viral antigens in vivo; however, they easily express the antigens after short-term culture. Therefore, such virus-expressing cells may lead to activation and expansion of antigen-specific T cell responses. Infected T cells with HTLV-1 and HTLV-1-specific CD8+ cytotoxic T lymphocytes invade the central nervous system and produce various proinflammatory cytokines and chemokines, leading to neuronal damage and degeneration. Therefore, cellular immune responses to HTLV-1 have been considered to play important roles in disease development of HAM/TSP. Recent studies have clarified the viral strategy for persistence in the host through genetic and epigenetic changes by HTLV-1 and host immune responses including T cell function and differentiation. Newly developed animal models could provide the opportunity to uncover the precise pathogenesis and development of clinically effective treatment. Several molecular target drugs are undergoing clinical trials with promising efficacy. In this review, we summarize recent advances in the immunopathogenesis of HAM/TSP and discuss the perspectives of the research on this disease.

DOI： 10.1007/s13365-020-00881-w

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Other Link： https://link.springer.com/article/10.1007/s13365-020-00881-w/fulltext.html
Kazu Okuma, Madoka Kuramitsu, Toshihiro Niwa, Tomokuni Taniguchi, Yumiko Masaki, Gohzoh Ueda, Chieko Matsumoto, Rieko Sobata, Yasuko Sagara, Hitomi Nakamura, Masahiro Satake, Kiyonori Miura, Naoki Fuchi, Hideaki Masuzaki, Akihiko Okayama, Kazumi Umeki, Yoshihisa Yamano, Tomoo Sato, Masako Iwanaga, Kaoru Uchimaru, Makoto Nakashima, Atae Utsunomiya, Ryuji Kubota, Kenji Ishitsuka, Hiroo Hasegawa, Daisuke Sasaki, Ki-Ryang Koh, Mai Taki, Kisato Nosaka, Masao Ogata, Isao Naruse, Noriaki Kaneko, Sara Okajima, Kenta Tezuka, Emi Ikebe, Sahoko Matsuoka, Kazuo Itabashi, Shigeru Saito, Toshiki Watanabe, Isao Hamaguchi . Establishment of a novel diagnostic test algorithm for human T-cell leukemia virus type 1 infection with line immunoassay replacement of western blotting: a collaborative study for performance evaluation of diagnostic assays in Japan. . Retrovirology17 ( 1 ) 26 - 26 2020.8Reviewed International journal

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BACKGROUND: The reliable diagnosis of human T-cell leukemia virus type 1 (HTLV-1) infection is important, particularly as it can be vertically transmitted by breast feeding mothers to their infants. However, current diagnosis in Japan requires a confirmatory western blot (WB) test after screening/primary testing for HTLV-1 antibodies, but this test often gives indeterminate results. Thus, this collaborative study evaluated the reliability of diagnostic assays for HTLV-1 infection, including a WB-based one, along with line immunoassay (LIA) as an alternative to WB for confirmatory testing. RESULTS: Using peripheral blood samples from blood donors and pregnant women previously serologically screened and subjected to WB analysis, we analyzed the performances of 10 HTLV-1 antibody assay kits commercially available in Japan. No marked differences in the performances of eight of the screening kits were apparent. However, LIA determined most of the WB-indeterminate samples to be conclusively positive or negative (an 88.0% detection rate). When we also compared the sensitivity to HTLV-1 envelope gp21 with that of other antigens by LIA, the sensitivity to gp21 was the strongest. When we also compared the sensitivity to envelope gp46 by LIA with that of WB, LIA showed stronger sensitivity to gp46 than WB did. These findings indicate that LIA is an alternative confirmatory test to WB analysis without gp21. Therefore, we established a novel diagnostic test algorithm for HTLV-1 infection in Japan, including both the performance of a confirmatory test where LIA replaced WB on primary test-reactive samples and an additional decision based on a standardized nucleic acid detection step (polymerase chain reaction, PCR) on the confirmatory test-indeterminate samples. The final assessment of the clinical usefulness of this algorithm involved performing WB analysis, LIA, and/or PCR in parallel for confirmatory testing of known reactive samples serologically screened at clinical laboratories. Consequently, LIA followed by PCR (LIA/PCR), but neither WB/PCR nor PCR/LIA, was found to be the most reliable diagnostic algorithm. CONCLUSIONS: Because the above results show that our novel algorithm is clinically useful, we propose that it is recommended for solving the aforementioned WB-associated reliability issues and for providing a more rapid and precise diagnosis of HTLV-1 infection.

DOI： 10.1186/s12977-020-00534-0

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Daisuke Kodama, Masakazu Tanaka, Toshio Matsuzaki, Kimiko Izumo, Nobuaki Nakano, Eiji Matsuura, Mineki Saito, Masahiro Nagai, Masahisa Horiuchi, Atae Utsunomiya, Hiroshi Takashima, Ryuji Kubota, Shuji Izumo . Inhibition of ABL1 tyrosine kinase reduces HTLV-1 proviral loads in peripheral blood mononuclear cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. . PLoS neglected tropical diseases14 ( 7 ) e0008361 - 21 2020.7Reviewed International journal

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Human T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles of cellular genes in HTLV-1-infected CD4+ T cells await discovery. We performed microarray analysis of CD4+ T cells from HAM/TSP patients and found that the ABL1 is an important gene in HAM/TSP. ABL1 is a known survival factor for T- and B-lymphocytes and is part of the fused gene (BCR-ABL) known to be responsible for chronic myelogenous leukemia (CML). ABL1 tyrosine kinase inhibitors (TKIs), including imatinib, nilotinib, and dasatinib, are used clinically for treating CML. To evaluate whether ABL1 is indeed important for HAM/TSP, we investigated the effect of TKIs on HTLV-1-infected cells. We developed a propidium monoazide-HTLV-1 viability quantitative PCR assay, which distinguishes DNA from live cells and dead cells. Using this method, we were able to measure the HTLV-1 proviral load (PVL) in live cells alone when peripheral blood mononuclear cells (PBMCs) from HAM/TSP cases were treated with TKIs. Treating the PBMCs with nilotinib or dasatinib induced significant reductions in PVL (21.0% and 17.5%, respectively) in live cells. Furthermore, ABL1 siRNA transfection reduced cell viability in HTLV-1-infected cell lines, but not in uninfected cell lines. A retrospective survey based on our clinical records found a rare case of HAM/TSP who also suffered from CML. The patient showed an 84.2% PVL reduction after CML treatment with imatinib. We conclude that inhibiting the ABL1 tyrosine kinase specifically reduced the PVL in PBMCs from patients with HAM/TSP, suggesting that ABL1 is an important gene for the survival of HTLV-1-infected cells and that TKIs may be potential therapeutic agents for HAM/TSP.

DOI： 10.1371/journal.pntd.0008361

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Norihiro Takenouchi, Masakazu Tanaka, Teruaki Sato, Jinchun Yao, Jun ichi Fujisawa, Shuji Izumo, Ryuji Kubota, Eiji Matsuura . Expression of TSLC1 in patients with HAM/TSP . Journal of NeuroVirology26 ( 3 ) 404 - 414 2020.4Reviewed International journal

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Human T-lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic myelopathy characterized by slowly progressive spastic paraparesis and urinary dysfunction. A few biomarkers in the cerebrospinal fluid are known to be related to disease activity, but no biomarker has been reported in peripheral blood. This study aims to explore the expression level of the adhesion molecule during the expression level of the adhesion molecule among HAM/TSP disease activity. In lymphocyte function–associated antigen 1 and DNAX accessory molecule 1, no variation in expression levels specific to HTLV-1 infection was observed in CD4-positive T cells; however, TSLC1 expression was higher in HAM patients than in asymptomatic carriers and non-infected persons. TSLC1 tended to be higher in patients whose symptoms were worsening. On the contrary, the expression level of TSLC1 in CD8-positive T cells was lower in HAM patients than in asymptomatic carriers, and this tendency was stronger in patients whose symptoms had deteriorated. No significant correlation was found between TSLC1 and either of the transcription factors Tax or HBZ in any T cell group. Therefore, TSLC1 expression in CD4-positive T cells might be a useful biomarker of HAM/TSP disease activity.

DOI： 10.1007/s13365-020-00838-z

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Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh KR, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, Okayama A, Miura K, Satake M, Saito S, Itabashi K, Yamaguchi K, Kuroda M, Watanabe T, Okuma K, Hamaguchi I. . Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan . Microbiology and Immunology62 ( 10 ) 673 - 676 2018.10Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Microbiology and Immunology

DOI： 10.1111/1348-0421.12644

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Gao H, Ye X, Cai R, Xu Q, Liang L, Izumo S, Xing HQ, Kubota R . Multiple spotty lesions of the spinal cord in a Chinese patient with human T-lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis. . International Journal of Infectious Diseases8 1 - 3 2018.1Reviewed International coauthorship International journal

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Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Infectious Diseases

DOI： 10.1016/j.ijid.2017.12.022

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Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh KR, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, Okayama A, Miura K, Satake M, Saito S, Itabashi K, Yamaguchi K, Kuroda M, Watanabe T, Okuma K, Hamaguchi I . Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot analysis results. . Journal of Clinical Microbiology55 ( 9 ) 2838 - 2849 2017.7Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Clinical Microbiology

DOI： 10.1128/JCM.00659-17

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Kubota R. . Pathogenesis of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis . Clinical and Experimental Neuroimmunology8 ( 2 ) 117 - 128 2017.5Invited Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Clinical and Experimental Neuroimmunology

Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus that preferentially infects CD4+ lymphocytes in vivo. The virus causes a hematological malignancy known as adult T-cell leukemia, and an inflammatory disease in the central nervous system (CNS) called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 0.3% of HTLV-1-infected individuals develop HAM/TSP. HAM/TSP patients show spastic paraparesis and sphincter dysfunction, as well as sensory disturbance of the lower extremities, which corresponds to pathological lesions in the spinal cord. Although the majority of HAM/TSP patients progress slowly, this disease progresses rapidly in some patients. An increased HTLV-1 proviral load is more common in HAM/TSP patients than in asymptomatic HTLV-1 carriers, and is considered to be a strong risk factor for HAM/TSP development. A prominent cellular immune response in HAM/TSP patients is a significantly elevated number of HTLV-1 Tax-specific CD8+ cytotoxic T lymphocytes (CTL) in peripheral blood mononuclear cells compared with asymptomatic HTLV-1 carriers. Additionally, CD4+ and CD8+ lymphocytes accumulate in the perivascular areas of spinal cords in HAM/TSP patients. Viral DNA, mRNA and proteins are detected only in infiltrating CD4+ T cells, but not in neural cells. A high proportion of HTLV-1-specific CTL infiltrates the CNS. Furthermore, some neural cells surrounding the CTL, predominantly oligodendrocytes, undergo apoptosis. These findings suggest the pathogenesis that the HTLV-1-specific inflammation induced by the interaction of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ CTL causes bystander damage in the CNS. In the present review, a more exact pathogenesis of HAM/TSP is discussed based on virology, immunology and neuropathology.

DOI： 10.1111/cen3.12395

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Nozuma S, Matsuura E､Kodama D, Tashiro Y, Matsuzaki T, Kubota R, Izumo S, Takashima H. . Effects of host restriction factors and the HTLV-1 subtype on susceptibility to HTLV-1-associated myelopathy/tropical spastic paraparesis . Retrovirology14 ( 1 ) 26 2017.4Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Retrovirology

DOI： 10.1186/s12977-017-0350-9

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Xing HQ, Zhang Y, Izumo K, Arishima S, Kubota R, Ye X, Xu Q, Mori K, Izumo S. . Decrease of aquaporin-4 and excitatory amino acid transporter-2 indicate astrocyte dysfunction for pathogenesis of cortical degeneration in HIV-associated neurocognitive disorders . Neuropathology37 ( 1 ) 25 - 34 2017.2Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Neuropathology

DOI： 10.1111/neup.12321

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Wang J, Zhang Y, Xu Q, Zheng H, Yin Y, Ye X, Qiu J, Zhang Z, Liu Y, Hao Y, Wang W, Mori K, Izumo S, Kubota R, Shao Y. . Menin mediates Tat-induced neuronal apoptosis in brain frontal cortex of SIV-infected macaques and in Tat-treated cells . Oncotarget8 ( 11 ) 18082 - 18094 2017Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Oncotarget

DOI： 10.18632/oncotarget.14993

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Matsuura E, Nozuma S, Tashiro Y, Kubota R, Izumo S, Takashima H. . HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP): A comparative study to identify factors that influence disease progression . Journal of the Neurological Sciences371 112 - 116 2016.12Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of the Neurological Sciences

DOI： 10.1016/j.jns.2016.10.030

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Kuramitsu M, Okuma K, Yamochi T, Sato T, Sasaki D, Hasegawa H, Umeki K, Kubota R, Sobata R, Matsumoto C, Kaneko N, Naruse I, Yamagishi M, Nakashima M, Momose H, Araki K, Mizukami T, Mizusawa S, Okada Y, Ochiai M, Utsunomiya A, Koh KR, Ogata M, Nosaka K, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, Satake M, Okayama A, Mochizuki M, Izumo S, Saito S, Itabashi K, Kamihira S, Yamaguchi K, Watanabe T, Hamaguchi I. . Standardization of quantitative PCR for human T-Cell leukemia virus type 1 in Japan: A collaborative study . Journal of Clinical Microbiology53 ( 11 ) 3485 - 3491 2015.11Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Clinical Microbiology

DOI： 10.1128/JCM.01628-15

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Matsuura E, Yoshimura A, Nozuma S, Higuchi I, Kubota R, Takashima H. . Clinical presentation of axial myopathy in two siblings with HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP) . BMC Neurology15 ( 1 ) 18 2015.2Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Neurology

DOI： 10.1186/s12883-015-0275-7

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Matsuura E, Kubota R, Tanaka Y, Takashima H, Izumo S. . Visualization of HTLV-1-specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis . Journal of Neuropathology and Experimental Neurology74 ( 1 ) 2 - 14 2015.1Reviewed International journal

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neuropathology and Experimental Neurology

DOI： 10.1097/NEN.0000000000000141

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Nozuma S, Matsuura E, Matsuzaki T, Watanabe O, Kubota R, Izumo S, Takashima H. . Familial clusters of HTLV-1-associated myelopathy/tropical spastic paraparesis . PLoS ONE9 ( 5 ) e86144 2014.5Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：PLoS ONE

DOI： 10.1371/journal.pone.0086144

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Kawabata T, Higashimoto I, Takashima H, Izumo S, Kubota R. . Human T-lymphotropic virus type I (HTLV-I)-specific CD8+ cells accumulate in the lungs of patients infected with HTLV-I with pulmonary involvement . Journal of Medical Virology84 ( 7 ) 1120 - 1127 2012.7Reviewed International journal

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Medical Virology

DOI： 10.1002/jmv.23307

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久保田龍二 . HAMスペクトラム . 臨床神経学51 ( 11 ) 1044 - 1046 2011.12Invited

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Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Clinical Neurology

DOI： 10.5692/clinicalneurol.51.1044

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Kozako T, Yoshimitsu M, Akimoto M, White Y, Matsushita K, Soeda S, Shimeno H, Kubota R, Izumo S, Arima N. . Programmed death-1 (PD-1)/PD-1 ligand pathway-mediated immune responses against human T-lymphotropic virus type 1 (HTLV-1) in HTLV-1-associated myelopathy/tropical spastic paraparesis and carriers with autoimmune disorders . Human Immunology72 ( 11 ) 1001 - 1006 2011.11Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Human Immunology

DOI： 10.1016/j.humimm.2011.07.308

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Abdelbary NH, Abdullah HM, Matsuzaki T, Hayashi D, Tanaka Y, Takashima H, Izumo S, Kubota R. . Reduced Tim-3 expression on human T-lymphotropic virus type I (HTLV-I) tax-specific cytotoxic T lymphocytes in HTLV-I infection . Journal of Infectious Diseases203 ( 7 ) 948 - 959 2011.4Reviewed International journal

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Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Infectious Diseases

DOI： 10.1093/infdis/jiq153

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Kozako T, Akimoto M, Toji S, White Y, Suzuki S, Arima T, Suruga Y, Matsushita K, Shimeno H, Soeda S, Kubota R, Izumo S, Uozumi K, Arima N . Target epitopes of HTLV-1 recognized by class I MHC-restricted cytotoxic T lymphocytes in patients with myelopathy and spastic paraparesis and infected patients with autoimmune disorders . Journal of Medical Virology83 ( 3 ) 501 - 509 2011.3Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Medical Virology

DOI： 10.1002/jmv.21985

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Hazem M. Abdullah, Itsuro Higuchi, Ryuji Kubota, Eiji Matsuura, Akihiro Hashiguchi, Nashwa H. Abdelbary, Yukie Inamori, Hiroshi Takashima, Shuji Izumo . Histopathological differences between human T-lymphotropic virus type 1-positive and human T-lymphotropic virus type 1-negative polymyositis . Clinical and Experimental Neuroimmunology2 ( 1 ) 12 - 24 2011.1Reviewed International journal

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Objectives: Epidemiological studies show that human T-lymphotropic virus type 1 (HTLV-1) is closely associated with polymyositis (PM). However, the pathogenic roles of HTLV-1 in PM remain unknown. The present study aims to assess skeletal muscle morphology in the presence of HTLV-1 infection to compare the histopathological findings of HTLV-1-positive and HTLV-1-negative PM. Methods: Among the 68 patients with inflammatory myopathy diagnosed through muscle biopsy over the previous 10 years at Kagoshima University Hospital, we retrospectively selected 21 patients with PM not associated with any other disease
we evaluated HTLV-1 positivity through serology, confirmed it by nested polymerase chain reaction using DNA extracted from muscles, and then assessed the tissue viral load. Meticulous histopathological examination was carried out using routine histochemical and immunohistochemical staining, and specimens from selected cases were examined by electron microscopy. Results: The clinical and histopathological findings of muscle biopsy specimens of HTLV-1-positive (n = 11) and HTLV-1-negative PM cases (n = 10) were compared. Compared with HTLV-1-negative patients, HTLV-1-positive patients showed protracted clinical courses, prominent endomysial infiltrates, infrequent necrotic fibers and prominent regenerative activities. Furthermore, they showed frequent cytochrome c oxidase deficiency and ultrastructural abnormalities in mitochondria. Conclusions: These differences are significant, but not specific to HTLV-1-positive PM. Therefore, HTLV-1 might induce the clinical and histopathological modifications of PM observed in the present study. © 2011 Japanese Society for Neuroimmunology.

DOI： 10.1111/j.1759-1961.2011.00017.x

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Kamihira S, Yamano Y, Iwanaga M, Sasaki D, Satake M, Okayama A, Umeki K, Kubota R, Izumo S, Yamaguchi K, Watanabe T. . Intra- and inter-laboratory variability in human T-cell leukemia virus type-1 proviral load quantification using real-time polymerase chain reaction assays: A multi-center study . Cancer Science101 ( 11 ) 2361 - 2367 2010.11Reviewed International journal

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DOI： 10.1111/j.1349-7006.2010.01720.x

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Azakami K, Sato T, Araya N, Utsunomiya A, Kubota R, Suzuki K, Hasegawa D, Izumi T, Fujita H, Aratani S, Fujii R, Yagishita N, Kamijuku H, Kanekura T, Seino KI, Nishioka K, Nakajima T, Yamano Y. . Severe loss of invariant NKT cells exhibiting anti-HTLV-1 activity in patients with HTLV-1-associated disorders . Blood114 ( 15 ) 3208 - 3215 2009.11Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Blood

DOI： 10.1182/blood-2009-02-203042

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Xing HQ, Hayakawa H, Izumo K, Kubota R, Gelpi E, Budka H, Izumo S. . In vivo expression of proinflammatory cytokines in HIV encephalitis: An analysis of 11 autopsy cases: Original Article . Neuropathology29 ( 4 ) 433 - 442 2009.8Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Neuropathology

DOI： 10.1111/j.1440-1789.2008.00996.x

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Xing HQ, Hayakawa H, Gelpi E, Kubota R, Budka H, Izumo S. . Reduced expression of excitatory amino acid transporter 2 and diffuse microglial activation in the cerebral cortex in AIDS cases with or without HIV encephalitis . Journal of Neuropathology and Experimental Neurology68 ( 2 ) 199 - 209 2009.2Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neuropathology and Experimental Neurology

DOI： 10.1097/NEN.0b013e31819715df

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Hayashi D, Kubota R, Takenouchi N, Nakamura T, Umehara F, Arimura K, Izumo S, Osame M. . Accumulation of human T-lymphotropic virus type I (HTLV-I)-infected cells in the cerebrospinal fluid during the exacerbation of HTLV-I - Associated myelopathy . Journal of NeuroVirology14 ( 5 ) 459 - 463 2008.12Reviewed International journal

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of NeuroVirology

DOI： 10.1080/13550280802178538

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Hayashi D, Kubota R, Takenouchi N, Tanaka Y, Hirano R, Takashima H, Osame M, Izumo S, Arimura K. . Reduced Foxp3 expression with increased cytomegalovirus-specific CTL in HTLV-I-associated myelopathy . Journal of Neuroimmunology200 ( 1-2 ) 115 - 124 2008.8Reviewed International journal

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neuroimmunology

DOI： 10.1016/j.jneuroim.2008.06.005

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Xing HQ, Mori K, Sugimoto C, Ono F, Izumo K, Kubota R, Izumo S . Impaired astrocytes and diffuse activation of microglia in the cerebral cortex in simian immunodeficiency virus-infected macaque without simian immunodeficiency virus encephalitis. . Journal of Neuropathology and Experimental Neurology 67 ( 6 ) 600 - 611 2008.6Reviewed

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Matsuura E, Umehara F, Nose H, Higuchi I, Matsuoka E, Izumi K, Kubota R, Saito M, Izumo S, Arimura K, Osame M. . Inclusion body myositis associated with human T-lymphotropic virus-type I infection: Eleven patients from an endemic area in Japan . Journal of Neuropathology and Experimental Neurology67 ( 1 ) 41 - 49 2008.1Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neuropathology and Experimental Neurology

DOI： 10.1097/nen.0b013e31815f38b7

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Nose H, Kubota R, Seth NP, Goon PK, Tanaka Y, Izumo S, Usuku K, Ohara Y, Wucherpfennig KW, Bangham CRM, Osame M. Saito M. . Ex vivo analysis of human T lymphotropic virus type 1-specific CD4+ cells by use of a major histocompatibility complex class II tetramer composed of a neurological disease-susceptibility allele and its immunodominant peptide . Journal of Infectious Diseases196 ( 12 ) 1761 - 1772 2007.12Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Infectious Diseases

DOI： 10.1086/522966

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Obama K, Kubota R, Tara M, Furukawa Y. Osame M, Arimura K. . Killer cell immunoglobulin-like receptor/3DL2 expression in adult T-cell leukaemia . British Journal of Haematology138 ( 5 ) 666 - 667 2007.9Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：British Journal of Haematology

DOI： 10.1111/j.1365-2141.2007.06704.x

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Kubota R, Hanada K, Furukawa Y, Arimura K, Osame M, Gojobori T, Izumo S. . Genetic stability of human T lymphotropic virus type I despite antiviral pressures by CTLs . Journal of Immunology178 ( 9 ) 5966 - 5972 2007.5Reviewed International journal

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Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Immunology

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurological disease. Patients with HAM/TSP show high proviral load despite increased HTLV-I Tax-specific CTL. It is still unknown whether the CTL efficiently eliminate the virus in vivo and/or whether a naturally occurring variant virus becomes predominant by escaping from the CTL. To address these issues, we sequenced a large number of HTLV-I tax genes from HLA-A*02 HAM/TSP patients and estimated synonymous and nonsynonyxnous changes of the genes to detect positive selection pressure on the virus. We found the pressures in three of six CTL epitopes in HTLV-I Tax, where amino acid substitutions preferentially occurred. Although some of variant viruses were not recognized by the CTL, no variant viruses accumulated within 3-8 years, indicating genetic stability of HTLV-I tax gene. These results suggest that CTL eliminate the infected cells in vivo and naturally occurring variant viruses do not predominate. As Tax is a regulatory protein which controls viral replication, the amino acid substitutions in Tax may reduce viral fitness for replication. Viral fitness and host immune response may contribute to the viral evolution within the infected individuals. Furthermore, the genetic stability in the epitopes despite the antiviral pressures suggests that the three epitopes can be the candidate targets for HTLV-I vaccine development. Copyright © 2007 by The American Association of Immunologists, Inc.

DOI： 10.4049/jimmunol.178.9.5966

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出雲周二、久保田龍二、Hui Qin Xing . レトロウイルス感染と神経疾患 . 脳と神経58 ( 7 ) 595 - 604 2006.7レトロウイルス感染と神経疾患Invited

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Izumo S., Kubota R., Xing H.Q. . Retrovirus infection and neurological disorders . No to shinkei. Brain and nerve58 ( 7 ) 595 - 604 2006.7Reviewed

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Language：Japanese Publishing type：Research paper (scientific journal) Publisher：No to shinkei. Brain and nerve

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Nose H, Saito M, Usuku K, Sabouri AH, Matsuzaki T, Kubota R, Eiraku N, Furukawa Y, Izumo S, Arimura K, Osame M. . Clinical symptoms and the odds of human T-cell lymphotropic virus type 1- associated myelopathy/tropical spastic paraparesis (HAM/TSP) in healthy virus carriers: Application of best-fit logistic regression equation based on host genotype, age, and provirus load . Journal of NeuroVirology12 ( 3 ) 171 - 177 2006.6Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of NeuroVirology

DOI： 10.1080/13550280600827336

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Saito M, Nakagawa M, Kaseda S, Matsuzaki T, Jonosono M, Eiraku N, Kubota R, Takenouchi N, Nagai M, Furukawa Y, Usuku K, Izumo S, Osame M. . Decreased Human T Lymphotropic Virus Type I (HTLV-I) Provirus Load and Alteration in T Cell Phenotype after Interferon-α Therapy for HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis . Journal of Infectious Diseases189 ( 1 ) 29 - 40 2004.1Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Infectious Diseases

DOI： 10.1086/380101

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納光弘、宇宿功市郎、梅原藤雄、斉藤峰輝、古川良尚、久保田龍二、永井将弘、樋口逸郎、中川正法、有村公良、出雲周二 . HAMの病態と治療 . 日本内科学会雑誌92 ( 9 ) 1673 - 82 2003.9HAMの病態と治療

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Report on a pending question 5. Disease state and treatment of HAM. . Nihon Naika Gakkai Kaishi92 ( 9 ) 1673 - 1682 2003.9International journal

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Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Internal Medicine

DOI： 10.2169/naika.92.1673

CiNii Books

Other Link： https://jlc.jst.go.jp/DN/JALC/00232150146?from=CiNii
Kubota R, Furukawa Y, Izumo S, Usuku K, Osame M. . Degenerate specificity of HTLV-1-specific CD8+ T cells during viral replication in patients with HTLV-1-associated myelopathy (HAM/TSP) . Blood101 ( 8 ) 3074 - 3081 2003.4Reviewed International journal

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Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Blood

DOI： 10.1182/blood-2002-08-2477

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Furukawa Y, Kubota R, Eiraku N, Nakagawa M, Usuku K, Izumo S, Osame M. . Human T-cell lymphotropic virus type I (HTLV-I)-related clinical and laboratory findings for HTLV-I-infected blood donors . Journal of Acquired Immune Deficiency Syndromes32 ( 3 ) 328 - 334 2003.3Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Acquired Immune Deficiency Syndromes

DOI： 10.1097/00126334-200303010-00013

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Matsuyama W, Kubota R, Hashiguchi T, Momi H, Kawabata M, Nakagawa M, Arimura K, Osame M. . Purified protein derivative of tuberculin upregulates the expression of vascular endothelial growth factor in T lymphocytes in vitro . Immunology106 ( 1 ) 96 - 101 2002.5Reviewed International journal

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Publishing type：Research paper (scientific journal) Publisher：Immunology

DOI： 10.1046/j.1365-2567.2002.01395.x

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上原明子 , 岡本裕嗣 , 西垂水和隆 , 宇都正 , 久保田龍二 , 城之園学 , 榮樂信隆 , 有村公良 , 納光弘 . メチルプレドニゾロン超大量療法で中枢・末梢の伝導ブロックが改善したADEMの1例 . 臨床神経学42 ( 3 ) 237 - 9 2002.3メチルプレドニゾロン超大量療法で中枢・末梢の伝導ブロックが改善したADEMの1例Reviewed International journal

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Kubota R, Soldan SS, Martin R, Jacobson S. . Selected cytotoxic T lymphocytes with high specificity for HTLV-I in cerebrospinal fluid from a HAM/TSP patient. . Journal of NeuroVirology8 ( 1 ) 53 - 7 2002.2Reviewed International journal

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1080/135502802317247811

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Matsuyama W, Kubota R, Hamasaki T, Mizoguchi A, Iwami F, Wakimoto J, Kawabata M, Osame M. . Enhanced inhibition of lymphocyte activation by Mycobacterium avium complex in human T lymphotrophic virus type I carriers . Thorax56 ( 5 ) 394 - 397 2001.5Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Thorax

DOI： 10.1136/thorax.56.5.394

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Furukawa Y, Kubota R, Tara M, Izumo S, Osame M. . Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia . Blood97 ( 4 ) 987 - 993 2001.2Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Blood

DOI： 10.1182/blood.V97.4.987

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Nagai M, Kubota R, Greten TF, Schneck JP, Leist TP, Jacobson S . Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I provirus load. . Journal of Infectious Diseases183 ( 2 ) 197 - 205 2001.1Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1086/317932

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Kubota R, Nagai M, Kawanishi T, Osame S, Jacobson S . Increased HTLV type 1 tax-specific CD8+ cells in HTLV type 1-associated myelopathy/tropical spastic paraparesis: Correlation with HTLV type 1 proviral load . AIDS Research and Human Retroviruses16 ( 16 ) 1705 - 1709 2000.11Reviewed International journal

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：AIDS Research and Human Retroviruses

DOI： 10.1089/08892220050193182

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Kubota R, Soldan SS, Martin R, Jacobson S . An altered peptide ligand antagonizes antigen-specific T cells of patients with human T lymphotropic virus type I-associated neurological disease . Journal of Immunology164 ( 10 ) 5192 - 5198 2000.5Reviewed International journal

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Immunology

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurologic disease associated with HTLV-I infection, in which chronically activated, HTLV-I-specific CD8+ CTL have been suggested to be immunopathogenic. In HLA-A2 HAM/TSP patients, CD8+ HTLV-I-specific CTLs recognize an immunodominant peptide of the HTLV-I Tax protein, Tax11-19. We examined the functional outcome on activation of both cloned peripheral blood and cerebrospinal spinal fluid-derived CTL and bulk PBMC from HAM/TSP patients by altered peptide ligands (APL) derived from HTLV-I Tax11-19. In CTL clones generated from PBMC and CSF of HLA-A2 HAM/TSP patients, an APL substituted at position 5 significantly decreased CTL responses when compared with the native peptide. Moreover, these ligands were also shown to inhibit CTL responses to the native peptide in bulk PBMC of HLA-A2 HAM/TSP patients. These data suggest that a modification of an antigenic peptide at the central position can manipulate the T cell responses in bulk PBMC from different individuals with an inflammatory disease. Additionally, these results have implications for the potential use of APL-based immunotherapy in this T cell- mediated CNS disease.

DOI： 10.4049/jimmunol.164.10.5192

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Miley WJ, Suryanarayana K, Manns A, Kubota R, Jacobson S, Lifson JD, Waters D . Real-time polymerase chain reaction assay for HTLV type I DNA viral load cell-associated . AIDS Research and Human Retroviruses16 ( 7 ) 665 - 675 2000.5Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：AIDS Research and Human Retroviruses

DOI： 10.1089/088922200308891

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Kubota R, Kawanishi T, Matsubara H, Manns A, Jacobson S . HTLV-I specific IFN-γ+ CD8+ lymphocytes correlate with the proviral load in peripheral blood of infected individuals . Journal of Neuroimmunology102 ( 2 ) 208 - 215 2000.1Reviewed International journal

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neuroimmunology

DOI： 10.1016/S0165-5728(99)00175-7

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Abe M, Umehara F, Kubota R, Moritoyo T, Izumo S, Osame M . Activation of macrophages/microglia with the calcium-binding proteins MRP14 and MRP8 is related to the lesional activities in the spinal cord of HTLV-I associated myelopathy . Journal of Neurology246 ( 5 ) 358 - 364 1999.6Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neurology

DOI： 10.1007/s004150050363

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Lehky TJ, Levin MC, Kubota R, Bamford RN, Flerlage AN, Soldan SS, Leist TP, Xavier A, White JD, Brown M, Fleisher TA, Top LE, Light S, McFarland HF, Waldman TA, Jacobson S . Reduction in HTLV-I proviral load and spontaneous lymphoproliferation in HTLV-I-associated myelopathy/tropical spastic paraparesis patients treated with humanized anti-Tac . Annals of Neurology44 ( 6 ) 942 - 947 1998.12Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Neurology

Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease that results from an interaction of retroviral infection and immune activation. In this study, five doses (1 mg/kg) of humanized anti-Tac antibody were administered to 9 HAM/TSP patients at weeks 0, 2, 6, 10, and 14. Preliminary immunological studies on HAM/TSP patients treated with humanized anti-Tac indicate that there is a selective down-regulation of activated T cells and a decrease in the HTLV-I viral load in peripheral blood lymphocytes, most likely through the selective removal of HTLV-I-infected, activated CD4+ lymphocytes.

DOI： 10.1002/ana.410440613

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Shields MJ, Kubota R, Hodgson W, Jacobson S, Biddison WE, Ribaudo RK . The effect of human β2-microglobulin on major histocompatibility complex I peptide loading and the engineering of a high affinity variant: Implications for peptide-based vaccines . Journal of Biological Chemistry273 ( 43 ) 28010 - 28018 1998.10Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biological Chemistry

DOI： 10.1074/jbc.273.43.28010

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Kubota R, Kawanishi T, Matsubara H, Manns A, Jacobson S . Demonstration of human T lymphotropic virus type I (HTLV-I) tax-specific CD8+ lymphocytes directly in peripheral blood of HTLV-I-associated myelopathy/tropical spastic paraparesis patients by intracellular cytokine detection. . Journal of immunology (Baltimore, Md. : 1950)161 ( 1 ) 482 - 8 1998.7Reviewed International journal

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PubMed
Greten TF, Slansky JE, Kubota R, Soldan SS, Jaffee EM, Leist TP, Pardoll DM, Jacobson S, Schneck JP . Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19-specific CD8+ T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients . Proceedings of the National Academy of Sciences of the United States of America95 ( 13 ) 7568 - 7573 1998.6Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Proceedings of the National Academy of Sciences of the United States of America

DOI： 10.1073/pnas.95.13.7568

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Biddison WE, Kubota R, Kawanishi T, Taub DD, Cruikshank WW, Center DM, Connor EW, Utz U, Jacobson S . Human T cell leukemia virus type I (HTLV-I)-specific CD8+ CTL clones from patients with HTLV-I-associated neurologic disease secrete proinflammatory cytokines, chemokines, and matrix metalloproteinase. . Journal of immunology (Baltimore, Md. : 1950)159 ( 4 ) 2018 - 25 1997.8Reviewed International journal

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Saiga A, Orita S, Ninoura-Tada N, Maeda M, Aono Y, Asakawa M, Nakahara K, Kubota R, Osame M, Igarashi H. . cis-Acting inhibitory elements within the pol-env region of human T- cell leukemia virus type 1 possibly involved in viral persistence . Journal of Virology71 ( 6 ) 4485 - 4494 1997.6Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Virology

DOI： 10.1128/jvi.71.6.4485-4494.1997

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Izumo S, Umehara F, Kashio N, Kubota R, Sato E, Osame M . Neuropathology of HTLV-1-associated myelopathy (HAM/TSP). . Leukemia11 Suppl 3 82 - 4 1997.4Neuropathology of HTLV-1-associated myelopathy (HAM/TSP).Reviewed International journal

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Umehara F, Kore-eda Y, Arime T, Kubota R, Arimura K, Osame M . Chronic sensory ataxic neuropathy and ophthalmoplegia with oculomotor nerve hypertrophy associated with IgM antibodies against gangliosides containing disialosyl groups . Journal of Neurology Neurosurgery and Psychiatry62 ( 6 ) 673 - 674 1997Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neurology Neurosurgery and Psychiatry

DOI： 10.1136/jnnp.62.6.673

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Kubota R., Jacobson S. . Immunopathogenesis of HAM/TSP: Involvement of HTLV-I specific CD8+ lymphocytes . Journal of NeuroVirology3 ( SUPPL. 1 ) 1997Reviewed International coauthorship International journal

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of NeuroVirology

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Saito M, Furukawa Y, Kubota R, Usuku K, Sonoda S, Izumo S, Osame M, Yoshida M. . Mutation rates in LTR of HTLV-1 in HAM/TSP patients and the carriers are similarly high to Tax/Rex-coding sequence . Journal of NeuroVirology2 ( 5 ) 330 - 335 1996.10Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of NeuroVirology

DOI： 10.3109/13550289609146897

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Saito M, Furukawa Y, Kubota R, Usuku K, Sonoda S, Izumo S, Osame M, Yoshida M . Frequent mutation in pX region of HTLV-1 is observed in HAM/TSP patients, but is not specifically associated with the central nervous system lesions. . Journal of NeuroVirology 1 ( 3-4 ) 286 - 294 1995.9Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of neurovirology

Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia (ATL) and of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Recently it has been reported that defective HTLV-1 provirus was detected frequently in the central nervous system (CNS) lesions of HAM/TSP patients. Here we investigated sequence variations of the pX region of HTLV-1 in the CNS and peripheral blood lymphocytes (PBL) of the same patient. The results analyzing 9-13 clones isolated from each specimen indicated that the pX region is highly variable within a patient with HAM/TSP, and the mutations were found at almost random positions within the sequences analyzed. The frequency and pattern of those mutations did not appear to differ significantly between the CNS and PBL of the same patient, although they differed among patients. Similarly, frequent mutations were observed in an asymptomatic carrier of HTLV-1, although the variability was moderate, suggesting that the high variability of the pX sequence is not a specific event in HAM/TSP. However, one asymptomatic carrier showed much less frequent variations very similarly to an ATL patient; both of them harbored clonally expanded infected cells. Thus the apparent low variability was explained by clonal selection of a single species of the provirus by the clonal proliferation of infected cells. These results clearly indicate that mutations including defectives are not specifically associated with the CNS lesions in HAM/TSP patients, but suggest that the random mutations simply reflect the rate of viral replication in individuals and the variants were not inherited frequently.

DOI： 10.3109/13550289509114025

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Furukawa Y, Osame M, Kubota R, Tara M, Yoshida M . Human T-cell leukemia virus type-1 (HTLV-1) Tax is expressed at the same level in infected cells of HTLV-1-associated myelopathy or tropical spastic paraparesis patients as in asymptomatic carriers but at a lower level in adult T-cell leukemia cells. . Blood85 ( 7 ) 1865 - 70 1995.4Reviewed International journal

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Maroushek SR, Osame M, Izumo S, Kubota R, Sato E, Bartholomew C, Haase AT . Sequence analysis of human T cell lymphotropic virus type I (HTLV-I) Env genes amplified from central nervous system tissues of patients with HTLV-I-associated myelopathy or leukemia . Microbial Pathogenesis19 ( 5 ) 317 - 333 1995Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Microbial Pathogenesis

DOI： 10.1016/S0882-4010(96)80004-0

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Umehara F, Nakamura A, Izumo S, Kubota R, Ijichi S, Kashio N, Hashimoto K, Usuku K, Sato E, Osame M. . Apoptosis of T lymphocytes in the spinal cord lesions in HTLV-I-associated myelopathy: A possible mechanism to control viral infection in the central nervous system . Journal of Neuropathology and Experimental Neurology53 ( 6 ) 617 - 624 1994.11Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neuropathology and Experimental Neurology

DOI： 10.1097/00005072-199411000-00009

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Kubota R, Umehara F, Izumo S, Ijichi S, Matsumuro K, Yashiki S, Fujiyoshi T, Sonoda S, Osame M . HTLV-I proviral DNA amount correlates with infiltrating CD4+ lymphocytes in the spinal cord from patients with HTLV-I-associated myelopathy . Journal of Neuroimmunology53 ( 1 ) 23 - 29 1994.8Reviewed International journal

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neuroimmunology

DOI： 10.1016/0165-5728(94)90060-4

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Yamagata H, Miki T, Sakoda S, Yamanaka N, Davies J, Shelbourne P, Nakagawa M, Takenaga S, Kubota R, Ogihara T, Johnson K. . Detection of a premutation in Japanese myotonic dystrophy . Human Molecular Genetics3 ( 5 ) 819 - 820 1994.5Reviewed

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Publisher：Human Molecular Genetics

DOI： 10.1093/hmg/3.5.819

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Orita S, Kobayashi H, Saiga A, Kubota R, Osame M, Igarashi H. . A Spontaneous Point Mutation in the Human T-Cell Leukemia Virus Type 1 pX Gene Leads to Expression of a Novel Doubly Spliced pX-mRNA That Encodes a 25-kD, Amino-Terminal Deleted rex Protein . DNA and Cell Biology13 ( 4 ) 353 - 364 1994.4Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：DNA and Cell Biology

DOI： 10.1089/dna.1994.13.353

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Ijichi S, Yuasa Y, Kubota R, Yoshiie K, Niina K, Oda H, Osame M. . Lack of anti-coxiella burnetii seropositivity in patients with HTLV-I-associated myelopathy . Neurology44 ( 3 ) 1994.3Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Neurology

DOI： 10.1212/wnl.44.3_part_1.571

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Ijichi S, Izumo S, Eiraku N, Machigashira K, Kubota R, Nagai M, Ikegami I, Kashio N, Umehara F, Maruyama I, Osame M. . An autoaggressive process against bystander tissues in HTLV-I-infected individuals: A possible pathomechanism of HAM TSP . Medical Hypotheses41 ( 6 ) 542 - 547 1993.12Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Medical Hypotheses

DOI： 10.1016/0306-9877(93)90111-3

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Kuriyama M, Fujiyama J, Kubota R, Nakagawa M, Osame M . Osteoporosis and increased bone fracture in cerebrotendinous xanthomatosis . Metabolism42 ( 11 ) 1497 - 1498 1993.11Osteoporosis and increased bone fracture in cerebrotendinous xanthomatosisReviewed

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Hashimoto K, Lalkaka JA, Fujisawa J, Singhal BS, Machigashira K, Kubota R, Suehara M, Osame M, Yoshida M. . Limited Sequence Divergence of HTLV-I of Indian HAM/TSP Patients from a Prototype Japanese Isolate . AIDS Research and Human Retroviruses9 ( 6 ) 495 - 498 1993.6Reviewed International coauthorship International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：AIDS Research and Human Retroviruses

DOI： 10.1089/aid.1993.9.495

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Ijichi S, Hall WW, Kubota R, Osame M. . Lack of Evidence for HTLV-II Infection in Patients with HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in an Endemic Area . AIDS Research and Human Retroviruses9 ( 5 ) 379 - 380 1993.5Reviewed International coauthorship

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Language：English Publishing type：Research paper (scientific journal) Publisher：AIDS Research and Human Retroviruses

DOI： 10.1089/aid.1993.9.379

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Kubota R, Fujiyoshi T, Izumo S, Yashiki S, Maruyama I, Osame M, Sonoda S. . Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy . Journal of Neuroimmunology42 ( 2 ) 147 - 154 1993.2Reviewed International journal

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Neuroimmunology

DOI： 10.1016/0165-5728(93)90004-I

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Singhal BS, Lalkaka JA, Sonoda S, Hashimoto K, Nomoto M, Kubota R, Osame M . Human T-lymphotropic virus type I infections in Western India . AIDS7 ( 1 ) 138 - 139 1993Reviewed International coauthorship International journal

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DOI： 10.1097/00002030-199301000-00029

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PubMed
久保田龍二、中川正法、中村昭範、納光弘. . HAMに対するlymphocytapheresisの治療効果 . 臨床神経学32 ( 9 ) 984 - 988 1992.12Reviewed

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Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Clinical Neurology

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Furukawa Y, Fujisawa J, Osame M, Toita M, Sonoda S, Kubota R, Ijichi S, Yoshida M . Frequent clonal proliferation of human T-cell leukemia virus type 1 (HTLV-1)-infected T cells in HTLV-1-associated myelopathy (HAM-TSP). . Blood80 ( 4 ) 1012 - 6 1992.8Reviewed International journal

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PubMed
Hokezu Y, Kuriyama M, Kubota R, Nakagawa M, Hujiyama J, Osame M. . Cerebrotendinous xanthomatosis: cranial CT and MRI studies in eight patients . Neuroradiology34 ( 4 ) 308 - 312 1992.7Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Neuroradiology

DOI： 10.1007/BF00588188

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久保田龍二、中川正法、中村昭範、栗山勝、納光弘 . Cerebrotendinous xanthomatosisの1症例：頭部MRI異常および骨粗鬆症について . 臨床神経学32 ( 5 ) 488 - 93 1992.5Cerebrotendinous xanthomatosisの1症例：頭部MRI異常および骨粗鬆症についてReviewed

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PubMed
Kubota R., Nakagawa M., Nakamura A., Kuriyama M., Osame M. . Cerebrotendinous xanthomatosis - A case with brain MRI abnormality and osteoporosis . Clinical Neurology32 ( 5 ) 488 - 493 1992Reviewed

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中川正法、久保田龍二、中村昭範、藤山二郎、末原雅人 . 著名な呼吸不全を呈したrigid spine症候群の一例 . 臨床神経学31 ( 9 ) 997 - 1001 1991.12Reviewed

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Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Clinical Neurology

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M. Nakagawa, R. Kubota, S. Takenaga, A. Nakamura, M. Osame . Nationwide survey of necrotizing myelopathy associated with malignancy, in Japan . Clinical Neurology31 ( 5 ) 512 - 5 1991.5Nationwide survey of necrotizing myelopathy associated with malignancy, in JapanReviewed

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Nakagawa M, Nakamura A, Kubota R, Kakazu T, Kuba M, Nakasone K, Iwamasa T. . Necrotizing Myelopathy Associated with Malignancy Caused by Herpes Simplex Virus Type 2: Clinical Report of Two Cases and Literature Review. . Japanese Journal of Medicine30 ( 2 ) 182 - 188 1991Reviewed International journal

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Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Medicine

DOI： 10.2169/internalmedicine1962.30.182

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Nakagawa M, Nakahara K, Yoshidome H, Suehara M, Higuchi I, Fujiyama J, Nakamura A, Kubota R, Takenaga S, Arahata K, Asano J, Osame M . Epidemiology of progressive muscular dystrophy in okinawa, Japan: Classification with molecular biological techniques . Neuroepidemiology10 ( 4 ) 185 - 191 1991Reviewed International journal

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We studied the prevalence of various types of progressive muscular dystrophy (PMD) in Okinawa, Japan on December 31, 1989 and the incidence of Duchenne muscular dystrophy (DMD) in 5-year periods from 1957 to 1985. We classified patients with PMD clinically, electrophysiologically, molecular biologically and immunohistochemically with antidystrophin antibody, especially for sporadic cases of DMD, Becker muscular dystrophy (BMD) and limb-girdle muscular dystrophy (LG). The prevalence for all PMD in Okinawa was 7.13 X 10-5 for DMD, 1.82 X 10-5 for BMD in the male population, 1.55 X 10-5for LG, 1.14 X 10-5 for congenital muscular dystrophy, 2.03 X 10-5 for facioscapulohumeral muscular dystrophy (FSH), and 9.13 X 10-5 for myotonic dystrophy (MD) in the total population. The incidence of DMD in the period 1957-1985 was 15.41 X 10-5 live-born males (LBM) and 3.21 X 10-5 LBM for BMD. The incidence has apparently declined in Okinawa since 1975. The prevalence of BMD, FSH and MD was rather high in Okinawa compared with previous reports. Molecular biological techniques for classifying patients were indispensable for the epidemiological study of PMD. © 1991 S. Karger AG, Basel.

DOI： 10.1159/000110268

Scopus

PubMed
Nakagawa M., Kubota R., Takenaga S., Nakamura A., Osame M. . Nationwide survey of necrotizing myelopathy associated with malignancy, in Japan . Clinical Neurology31 ( 5 ) 512 - 515 1991Reviewed International journal

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Ijichi S, Eiraku N, Osame M, Izumo S, Kubota R, Maruyama I, Matsumoto M, Niimura T, Sonoda S. . Activated T lymphocytes in cerebrospinal fluid of patients with HTLV-I-associated myelopathy (HAM/TSP) . Journal of Neuroimmunology25 ( 2-3 ) 251 - 254 1989.12Reviewed International journal

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DOI： 10.1016/0165-5728(89)90143-4

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Ijichi S, Eiraku N, Osame M, Izumo S, Kubota R, Maruyama I, Matsumoto M, Sonoda S. . In vitro modulation of lymphocyte proliferation by prednisolone and interferon-α in patients with HTLV-I-associated myelopathy (HAM) . Journal of Neuroimmunology23 ( 2 ) 175 - 178 1989.7Reviewed International journal

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DOI： 10.1016/0165-5728(89)90037-4

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Iwamasa T, Utsumi Y, Sakuda H, Yoshitake H, Kakazu T, Kubota R, Nakagawa M . Two cases of necrotizing myelopathy associated with malignancy caused by herpes simplex virus type 2 . Acta Neuropathologica78 ( 3 ) 252 - 257 1989.5Reviewed International journal

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Two cases of necrotizing myelopathy were autopsied; one was complicated with lung carcinoma and the other with chronic type adult T cell leukemia (ATL leukemia). To our knowledge, they were the first cases of their type in Japan. In both cases, necrosis of the spinal cord was observed in the gray and white matter along most of its extent. Marked changes were found in the lumbar segment. The patients were not treated with intravenous cancer chemotherapy or irradiation. Immunohistochemical and electron microscopic examination revealed an extremely strong infection of herpes simplex virus (HSV) type 2. However, HSV type 1 and cytomegalovirus antigens were not detected. © 1989 Springer-Verlag.

DOI： 10.1007/BF00687754

Scopus

PubMed
Kitajima I, Amitani H, Fukunaga H, Iwata S, Kubota R, Izumo S, Osame M. . Two cases of male hypogonadal osteoporosis . Journal of Bone and Mineral Metabolism7 ( 1 ) 42 - 48 1989.3Reviewed International journal

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DOI： 10.1007/BF02377583

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Books

HTLV-1関連脊髄症

久保田龍二（ Role： Sole author）

今日の疾患辞典、プレシジョン 2020

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Language：Japanese Book type：Dictionary, encyclopedia
HTLV-1関連脊髄症

久保田龍二（ Role： Contributor）

Current Decision Support、エイド出版 2020

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Language：Japanese Book type：Dictionary, encyclopedia
HTLV-1関連脊髄症（HAM）診療ガイドライン2019

山野嘉久、内丸薫、久保田龍二　他（ Role： Joint author）

南江堂 2019

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Language：Japanese Book type：Scholarly book
ヒトTリンパ球向性ウイルス脊髄症(HAM)

久保田龍二（ Role： Sole author）

神経疾患最新の治療 2015-2017、南江堂 2015.1

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HTLV-1関連脊髄症(HAM)

久保田龍二、出雲周二（ Role： Joint author）

免疫性神経疾患ハンドブック 2013.1

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Language：Japanese Book type：Scholarly book
HTLV-1

久保田龍二（ Role： Sole author）

神経症候群I、日本臨床社 2013.1

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Language：Japanese Book type：Scholarly book
HAM

久保田龍二、納光弘（ Role： Joint author）

今日の診断基準,南江堂 2007.1

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Language：Japanese Book type：Scholarly book
HTLV-I

久保田龍二、納光弘（ Role： Joint author）

今日の診断基準,南江堂 2007.1

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Language：Japanese Book type：Scholarly book
HAM

久保田龍二,出雲周二（ Role： Joint author）

内科疾患診療マニュアル,中外医学社 2005

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Language：Japanese Book type：Scholarly book
Chapter 22 Retrovirus: HTLV-I associated diseases and immune dysfunction. In Effects of Microbes on the Immune System. International journal

Kubota R, Osame M, Jacobson S.（ Role： Joint author）

Lippincott Williams & Wilkins 2000

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Responsible for pages：349-371 Language：English Book type：Textbook, survey, introduction
Hypothetical pathogenesis of HAM/TSP: Occurrence of proliferative response of lymphocytes in the central nervous system. In HTLV-I and the Nervous System

Ijichi S, Eiraku N, Osame M, Izumo S, Kubota R, Maruyama I, Sonoda S（ Role： Joint author）

Alan R. Liss, Inc 1989

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Responsible for pages：337-342 Language：English Book type：Textbook, survey, introduction
Skin manifestations in HTLV-I-associated myelopathy (HAM): Xerosis and erythema. In HTLV-I and the Nervous System

Hashiguchi T, Osame M, Arimura K, Fujiyama J, Furukawa Y, Kubota R, Koreeda Y, Maruyama I, Matsumoto M, Tashiro M, Sato E（ Role： Joint author）

Alan R. Liss, Inc 1989

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Responsible for pages：443-448 Language：English Book type：Textbook, survey, introduction

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MISC

HAMにおけるPARP活性化を介した神経細胞死の検討

田中正和, 有島志保, 三輪正直, 野妻智嗣, 松浦英治, 高嶋博, 出雲周二, 久保田龍二

Neuroinfection (Web) 27 ( 2 ) 2022

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J-GLOBAL
抗HTLV-1抗体髄液検査はCLIA法が適している

兒玉大介, 田中正和, 松崎敏男, 松崎敏男, 野妻智嗣, 松浦英治, 高嶋博, 出雲周二, 久保田龍二

Neuroinfection (Web) 27 ( 2 ) 2022

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J-GLOBAL
HAM診断に適した髄液中抗HTLV-1抗体検査法

兒玉大介, 田中正和, 松崎敏男, 松崎敏男, 野妻智嗣, 松浦英治, 高嶋博, 出雲周二, 久保田龍二

日本神経学会学術大会プログラム・抄録集 63rd 2022

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髄液中抗HTLV-1抗体検査とHAM診断

児玉大介, 田中正和, 松崎敏男, 松崎敏男, 野妻智嗣, 松浦英治, 高嶋博, 出雲周二, 久保田龍二

日本HTLV-1学会学術集会 7th 2021

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Human T-lymphotropic virus type 1 (HTLV-1) and cellular immune response in HTLV-1-associated myelopathy/tropical spastic paraparesis Reviewed International coauthorship International journal

Satoshi Nozuma, Ryuji Kubota, Steven Jacobson

Journal of NeuroVirology 26 ( 5 ) 652 - 663 2020.10

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Language：English Publishing type：Article, review, commentary, editorial, etc. (scientific journal) Publisher：Springer Science and Business Media LLC

<title>Abstract</title>Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the spinal cord and clinically characterized by progressive spastic paraparesis, urinary incontinence, and mild sensory disturbance. The interaction between the host immune response and HTLV-1-infected cells regulates the development of HAM/TSP. HTLV-1 preferentially infects CD4+ T cells and is maintained by proliferation of the infected T cells. HTLV-1-infected cells rarely express viral antigens in vivo; however, they easily express the antigens after short-term culture. Therefore, such virus-expressing cells may lead to activation and expansion of antigen-specific T cell responses. Infected T cells with HTLV-1 and HTLV-1-specific CD8+ cytotoxic T lymphocytes invade the central nervous system and produce various proinflammatory cytokines and chemokines, leading to neuronal damage and degeneration. Therefore, cellular immune responses to HTLV-1 have been considered to play important roles in disease development of HAM/TSP. Recent studies have clarified the viral strategy for persistence in the host through genetic and epigenetic changes by HTLV-1 and host immune responses including T cell function and differentiation. Newly developed animal models could provide the opportunity to uncover the precise pathogenesis and development of clinically effective treatment. Several molecular target drugs are undergoing clinical trials with promising efficacy. In this review, we summarize recent advances in the immunopathogenesis of HAM/TSP and discuss the perspectives of the research on this disease.

DOI： 10.1007/s13365-020-00881-w

PubMed

Other Link： https://link.springer.com/article/10.1007/s13365-020-00881-w/fulltext.html
HAM患者に対するL-アルギニン内服治療の試み

松浦英治, 田代雄一, 野妻智嗣, 安藤匡宏, 平松有, 崎山佑介, 荒田仁, 田中正和, 久保田龍二, 高嶋博

Neuroimmunology 25 ( 1 ) 2020

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HTLV-1関連脊髄症の初発症状と疾患進行速度に関する検討

眞弓芳子, 古園麻衣, 松元陸, 田代雄一, 山野嘉久, 児玉大介, 田中正和, 久保田龍二, 野妻智嗣, 松浦英治, 高嶋博

日本神経学会学術大会プログラム・抄録集 61st 2020

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HTLV-1関連脊髄症における疾患特異的TCRレパトアの同定

野妻智嗣, 松浦英治, 田中正和, 久保田龍二, 高嶋博

Neuroimmunology 25 ( 1 ) 2020

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HPVワクチン関連疾患の臨床経過とワクチン接種後血液サイトカイン・自己抗体の検討

松浦英治, 荒田仁, 東桂子, 田中正和, 安藤匡宏, 平松有, 野妻智嗣, 田代雄一, 崎山佑介, 久保田龍二, 高嶋博

Neuroimmunology 25 ( 1 ) 2020

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HTLV-1関連脊髄症の初発症状は疾患進行の予測因子である。

松元陸, 眞弓芳子, 古園麻衣, 田代雄一, 松浦英治, 荒田仁, 山野嘉久, 田中正和, 久保田龍二, 高嶋博

Neuroinfection 24 ( 2 ) 2019

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HAM患者HTLV-1感染細胞のマイクロアレイ解析による治療標的分子の探索

久保田龍二, 田中正和, 春口志門, 児玉大介, 松浦英治, 高嶋博

日本HTLV-1学会学術集会 6th 2019

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【HTLV-1関連脊髄症-病態解明と治療の最新情報】HAMの臨床像と発症病理

久保田龍二

医学のあゆみ 267 ( 10 ) 737 - 740 2018.12

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Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal) Publisher：医歯薬出版(株)

HTLV-1関連脊髄症(HAM)は、HTLV-1感染者の約0.3%に発症する慢性進行性脊髄炎であり、痙性対麻痺、排尿排便障害、両下肢感覚障害を主徴とする。通常緩徐進行性で年単位の変化であるが、数ヵ月で発症進行する例や、ほとんど進行しない例もある。HAMは、痙性対麻痺症状に加え、血清中および髄液中の抗HTLV-1抗体陽性を証明し、ほかの神経疾患を除外して診断する。HTLV-1はおもにCD4+リンパ球に感染するが、HAMでは末梢血リンパ球中HTLV-1ウイルス量が高い。脊髄では下部胸髄を中心とした血管周囲のリンパ球浸潤が特徴的であり、側索・後索の脱髄が認められる。脊髄ではHTLV-1は浸潤CD4+ T細胞に存在し、神経系細胞への感染は認められていない。HTLV-1特異的CD8+細胞傷害性T細胞も高頻度に浸潤しており、これらの感染細胞と免疫細胞がHTLV-1特異的炎症を起こし、周囲の神経系細胞に傷害を起こしていると考えられる。(著者抄録)
HTLV-1関連細胞株と成人T細胞白血病ないしリンパ腫(ATL)に於けるサバイビンの抗原回復免疫組織化学

蓮井和久, 佐藤榮一, 宇都宮與, 木脇祐俊, 満田稔, 斉藤稔, 原博満, 久保田龍二, 出雲周二

日本組織細胞化学会総会・学術集会講演プログラム・予稿集 59回 62 - 62 2018.9

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Language：Japanese Publishing type：Research paper, summary (national, other academic conference) Publisher：日本組織細胞化学会
成人T細胞白血病(ATL)の末梢血組織標本のSurvivinの抗原回復免疫組織化学による解析

蓮井和久, 宇都宮與, 佐藤榮一, 原博満, 木脇祐俊, 満田稔, 斉藤稔, 久保田龍二, 出雲周二

日本病理学会会誌 107 ( 1 ) 307 - 307 2018.4

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Language：Japanese Publishing type：Research paper, summary (national, other academic conference) Publisher：(一社)日本病理学会
HAMに対するアミノ酸内服治療の効果

松浦英治, 田代雄一, 荒田仁, 橋口昭大, 中村友紀, 野妻智嗣, 松崎敏男, 田中正和, 久保田龍二, 久保田龍二, 高嶋博

Neuroimmunology 23 ( 1 ) 2018

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J-GLOBAL
HTLV‐1定量PCRの標準化のための参照品の作製

倉光球, 大隈和, 内丸薫, 山野嘉久, 長谷川寛雄, 野坂生郷, 岡山昭彦, 久保田龍二, 佐竹正博, 金子紀章, 渡邉俊樹, 浜口功

日本HTLV‐1学会学術集会 5th 56 2018

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J-GLOBAL
HTLV-1関連脊髄症(HAM)患者の臨床経過における排尿障害の意義について

古園麻衣, 眞弓芳子, 樋口雄二郎, 野妻智嗣, 田代雄一, 中村友紀, 橋口昭大, 松浦英治, 兒玉大介, 田中正和, 久保田龍二, 高嶋博

日本神経学会学術大会プログラム・抄録集 59th 2018

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HAM患者由来HTLV-1感染細胞のウイルス活性化によるToll様受容体の発現低下

久保田龍二, 児玉大介, 田中正和, 松浦英治, 高嶋博

日本HTLV-1学会学術集会 5th 2018

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J-GLOBAL
HAM患者に対するL-アルギニン内服治療の試み

田代雄一, 松浦英治, 橋口昭大, 中村友紀, 野妻智嗣, 松崎敏男, 兒玉大介, 田中正和, 久保田龍二, 高嶋博

日本神経学会学術大会プログラム・抄録集 59th 2018

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アルギニン塩酸塩を用いたHAM患者治療の試み

松浦英治, 田代雄一, 荒田仁, 崎山祐介, 中村友紀, 野妻智嗣, 松崎敏男, 兒玉大介, 橋口昭大, 岡本裕嗣, 田中正和, 久保田龍二, 高嶋博

Neuroinfection 23 ( 2 ) 2018

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J-GLOBAL
神経疾患治療ノート　HTLV-1関連脊髄症(HAM)

松浦英治, 久保田龍二

Clinical Neuroscience 35 ( 12 ) 1474 - 1475 2017.12

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成人T細胞白血病(ATL)細胞のリンパ節での動態のSurvivinの抗原回復免疫組織化学による解析

蓮井和久, 佐藤榮一, 原博満, 木脇祐俊, 満田稔, 斉藤稔, 久保田龍二, 出雲周二

日本病理学会会誌 106 ( 1 ) 355 - 355 2017.3

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HTLV-1 complete genome analysis identified a risk subtype for HTLV-1-associated myelopathy/tropical spastic paraparesis and subtype-specific amino acid changes International journal

S. Nozuma, E. Matsuura, T. Matsuzaki, O. Watanabe, D. Kodama, R. Kubota, S. Izumo, H. Takashima

JOURNAL OF THE NEUROLOGICAL SCIENCES 357 E114 - E114 2015.10

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DOI： 10.1016/j.jns.2015.08.365

Web of Science
Analysis of the association between the sex and disease courses of 132 consequent patients with HTLV-1-associated myelopathy/Tropic spastic paraparesis (HAM/TSP) International journal

Eiji Matsuura, Satoshi Nozuma, Ryuji Kubota, Shuji Izumo, Hiroshi Takashima

RETROVIROLOGY 12 2015.8

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Web of Science
HTLV-1 infected CD4+T cells of HAM/TSP patients are susceptible to tunicamycin-induced endoplasmic reticulum stress International journal

Daisuke Kodama, Ryuji Kubota, Toshio Matsuzaki, Hiroshi Takashima, Shuji Izumo

RETROVIROLOGY 12 2015.8

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Web of Science
HTLV‐1核酸検査の標準化および検出感度の検討:多施設共同研究

倉光球, 大隈和, 矢持忠徳, 山野嘉久, 長谷川寛雄, 上平憲, 岡山昭彦, 久保田龍二, 出雲周二, 成瀬功, 相良康子, 佐竹正博, 渡邉俊樹, 山口一成, 浜口功

日本HTLV‐1学会学術集会 2nd 28 2015

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J-GLOBAL
エクソーム解析によるHAM疾患感受性遺伝子の探索

野妻智嗣, 松浦英治, 久保田龍二, 児玉大介, 松崎敏男, 渡邊修, 三井純, 石浦浩之, 高橋祐二, 山野嘉久, 森下真一, 辻省次, 出雲周二, 高嶋博

日本神経学会学術大会プログラム・抄録集 54 ( Suppl. ) S153 - S153 2014.12

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J-GLOBAL
次世代シークエンサーを用いたHAM疾患感受性遺伝子の探索

野妻智嗣, 松浦英治, 久保田龍二, 児玉大介, 松崎敏男, 渡邊修, 三井純, 石浦浩之, 高橋祐二, 山野嘉久, 森下真一, 辻省次, 出雲周二, 高嶋博

Neuroinfection 19 ( 2 ) 204 - 204 2014.8

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J-GLOBAL
HAMスペクトラム

久保田龍二

神経内科 77 ( 3 ) 283 - 288 2012.9

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HTLV-Iと筋炎

松浦英治、久保田龍二、樋口逸郎

Clinical Neuroscience 30 ( 3 ) 322 - 323 2012.3

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HAMスペクトラム

久保田龍二

臨床神経学 51 1044 - 1046 2011.11

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Neural Bystander Damage by Infiltrating Virus-Infected T Cells and the Cytotoxic T Lymphocytes in HTLV-I-Associated Neurological Disease International journal

Eiji Matsuura, Ryuji Kubota, Yuetsu Tanaka, Hiroshi Takashima, Shuji Izumo

NEUROLOGY 76 ( 9 ) A433 - A433 2011.3

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Web of Science
A role of astrocyte dysfunction in pathogenesis of AIDS encephalopathy International coauthorship International journal

S. Izumo, H. Xing, H. Hayakawa, K. Mori, S. Arishima, R. Kubota, E. Gelpi, H. Budka

BRAIN PATHOLOGY 20 80 - 80 2010.9

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Web of Science
Neural bystander damage by infiltrating virus-infected T cells and the cytotoxic T lymphocytes in HTLV-I-associated neurological disease International journal

R. Kubota, E. Matsuura, S. Izumo

BRAIN PATHOLOGY 20 79 - 79 2010.9

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Web of Science
HTLV-1 associated polymyositis: a trial to unfold the story International journal

H. M. Abdullah, Higuchi, I, R. Kubota, E. Matsuura, A. Hashiguchi, N. H. Abdelbary, Y. Inamori, S. Izumo

BRAIN PATHOLOGY 20 93 - 94 2010.9

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Web of Science
Invariant NKT Cells have Anti-Human T-Lymphotropic Virus Type-1 (HTLV-1) Activity and the Frequency is Significantly Decreased in Patients with HTLV-1 Associated Disorders International journal

Y. Yamano, A. Utsunomiya, K. Takahashi, K. Azakami, K. Seino, K. Nishioka, N. Araya, R. Kubota, T. Sato, T. Nakajima

AIDS RESEARCH AND HUMAN RETROVIRUSES 25 ( 11 ) 1202 - 1202 2009.11

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Web of Science
Target Epitopes of Human T Lymphotropic Virus 1 Recognized by Class I MHC-Restricted Cytotoxic T Lymphocytes in HAM/TSP Patients and Infected Patients with Autoimmune Disorders International journal

Tomohiro Kozako, Masaki Akimoto, Yohann White, Shingo Toji, Kakushi Matsushita, Ryuji Kubota, Shuji Izumo, Shinsuke Suzuki, Kimiharu Uozumi, Hiroshi Shimeno, Shinji Soeda, Naomichi Arima

BLOOD 114 ( 22 ) 1043 - 1043 2009.11

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Web of Science
Bystander damage of the central nervous system by HTLV-I-specific CTL with target cell infiltration in HAM/TSP International journal

Eiji Matsuura, Ryuji Kubota, Mineki Saito, Masato Suehara, Toshio Matsuzaki, Kimiyoshi Arimura, Mitsuhiro Osame, Shuji Izumo

AIDS RESEARCH AND HUMAN RETROVIRUSES 23 ( 4 ) 596 - 596 2007.4

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Web of Science
Role of glial cells in central nervous system injury of human retroviral infection International journal

HuiQin Xing, Ryuji Kubota, Hitoshi Hayakawa, Shuji Izumo

AIDS RESEARCH AND HUMAN RETROVIRUSES 23 ( 4 ) 648 - 648 2007.4

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Web of Science
Increased CMV-specific CTL associated with decreased expression of Foxp3 in HAM/TSP International journal

Daisuke Hayashi, Ryuji Kubota, Hirohisa Nose, Kimiyoshi Arimura, Shuji Izumo, Mitsuhiro Osame

AIDS RESEARCH AND HUMAN RETROVIRUSES 23 ( 4 ) 615 - 615 2007.4

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Web of Science
In vivo selection of human T cell lymphotropic virus type-1-specific CD4(+) cells by disease susceptive class II allele and immunodominant peptide complex in HTLV-1-associated neurological disease International coauthorship International journal

Hirohisa Nose, Koichiro Usuku, Ryuji Kubota, Shuji Izumo, Kimiyoshi Arimura, Charles Bangham, Mitsuhiro Osame, Mineki Saito

AIDS RESEARCH AND HUMAN RETROVIRUSES 23 ( 4 ) 634 - 634 2007.4

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Web of Science
HLA-A*2402 determines a risk of HAM/TSP independently from the HTLV-I proviral load International journal

Norihiro Takenouchi, Ryuji Kubota, Toshio Matsuzaki, Yoshitaka Furukawa, Shuji Izumo, Kimiyoshi Arimura, Mitsuhiro Osame

AIDS RESEARCH AND HUMAN RETROVIRUSES 23 ( 4 ) 644 - 644 2007.4

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Web of Science
High expression of CD28 costimulatory molecule and low expression of CTLA4 inhibitory molecule on CD4(+) CD25(+) T cells in HTLV-I-associated myelopathy (HAM/TSP) International journal

Yoshihisa Yamano, Ryuji Kubota, Kimiyoshi Arimura, Shuji Izumo, Shoichi Ozaki, Kusuki Nishioka, Mitsuhiro Osame, Toshihiro Nakajima

AIDS RESEARCH AND HUMAN RETROVIRUSES 23 ( 4 ) 611 - 611 2007.4

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Web of Science
Genetic stability of HTLV-I despite antiviral pressures by cytotoxic T lymphocytes

Ryuji Kubota, Yoshitaka Furukawa, Kimiyoshi Arimura, Mitsuhiro Osame, Shuji Izumo

AIDS RESEARCH AND HUMAN RETROVIRUSES 23 ( 4 ) 612 - 613 2007.4

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HTLV-I-specific CTL with high TCR degeneracy efficiently recognize naturally occurring mutant viruses in patients with HAM TSP International journal

R. Kubota, K. Arimura, M. Osame, S. Izumo

JOURNAL OF NEUROIMMUNOLOGY 178 256 - 256 2006.9

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Web of Science
Visualization of HTLV-I Tax-specific cytotoxic T lymphocytes in the central nervous system of HTLV-I-associated myelopathy International journal

E. Matsuura, R. Kubota, M. Saito, M. Suehara, T. Matsuzaki, K. Arimura, M. Osame, S. Izumo

JOURNAL OF NEUROIMMUNOLOGY 178 257 - 257 2006.9

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Web of Science
Increased CTL responses to CMV in HAM/TSP patients: A relation of FOXP3(+) regulatory T cells

D. Hayashi, R. Kubota, H. Nose, K. Arimura, S. Izumo, M. Osame

JOURNAL OF NEUROIMMUNOLOGY 178 256 - 257 2006.9

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Web of Science
In vivo selection of T-cell receptor junctional region sequences by HLA-DRB1*0101 human T-cell lymphotropic virus type 1 (HTLV-1) envelope gp21 peptide complexes in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) International journal

H. Nose, M. Saito, A. H. Sabouri, K. Usuku, R. Kubota, S. Izumo, K. Arimura, M. Osame

JOURNAL OF NEUROIMMUNOLOGY 178 72 - 72 2006.9

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レトロウイルス感染と神経疾患

出雲周二、久保田龍二、Hui Qin Xing

脳と神経 58 595 - 604 2006.1

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ウイルスおよび細菌感染症の多発性硬化症への関わり

久保田龍二,出雲周二

神経研究の進歩,医学書院 50 ( 4 ) 503 - 515 2006

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Comparison of clinical symptoms and the odds for predicting Htlv-1 associated myelopathy/tropical spastic paraparesis (Ham/Tsp) in healthy virus carriers: Application of best-fit logistic regression equation based on the genotype, age, and provirus load. International journal

H Nose, M Saito, K Usuku, T Matsuzaki, S Izumo, R Kubota, Y Furukawa, K Arimura, M Osame

AIDS RESEARCH AND HUMAN RETROVIRUSES 21 ( 5 ) 464 - 464 2005.5

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Web of Science
Degeneracy of HTLV-I-specific Ctl inversely correlates with proviral load in patients with Ham/Tsp International journal

R Kubota, M Osame, S Izumo

AIDS RESEARCH AND HUMAN RETROVIRUSES 21 ( 5 ) 451 - 452 2005.5

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Web of Science
多発性硬化症の診断基準

久保田龍二,納光弘

Clinical Neuroscience,中外医学社 22 ( 7 ) 804 - 805 2004.1

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Mutations in HTLV-I Tax 11-19 epitope and mutant virus-specific T cells in patients with HAM/TSP. International journal

R Kubota, Y Furukawa, S Izumo, M Osame

AIDS RESEARCH AND HUMAN RETROVIRUSES 19 S42 - S42 2003

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Web of Science
Diversity of HTLV-I-specific CTL and proviral load in patients with HAM International coauthorship International journal

R Kubota, Y Furukawa, S Izumo, K Usuku, S Jacobson, M Osame

AIDS RESEARCH AND HUMAN RETROVIRUSES 17 S61 - S61 2001

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Web of Science
Pathogenesis of HTLV-1-associated inflammatory disorders International journal

S Izumo, N Takenouchi, T Moritoyo, R Kubota, M Osame

AIDS RESEARCH AND HUMAN RETROVIRUSES 17 S18 - S18 2001

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Existence of escape mutant in HTLV-1 Tax during the development of adult T-cell leukemia International journal

Y Furukawa, R Kubota, M Tara, S Izumo, M Osame

AIDS RESEARCH AND HUMAN RETROVIRUSES 17 S61 - S61 2001

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Web of Science
Differentiated HTLV-I Tax-specific CD8+cells correlate with the proviral load in HAM/TSP patients International coauthorship International journal

R Kubota, M Nagai, M Osame, S Jacobson

LEUKEMIA 14 ( 3 ) 546 - 546 2000.3

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Web of Science
Immunopathogenesis of HAM/TSP: Involvement of HTLV-I specific CD8+ lymphocytes Invited International coauthorship International journal

Kubota R, Jacobson S

3 ( SUPPL. 1 ) 1997

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Scopus
HIGHLY FREQUENT AND RANDOM MUTATIONS OF HTLV-1 PROVIRAL GENOME WITHIN INDIVIDUALS OF HAM/TSP PATIENTS AND ASYMPTOMATIC CARRIERS International journal

M SAITOL, Y FURUKAWA, R KUBOTA, K USUKU, S SONODA, S IZUMO, M OSAME, M YOSHIDA

AIDS RESEARCH AND HUMAN RETROVIRUSES 11 S141 - S141 1995

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Presentations

Kubota R, Tanaka M, Kodama D, Matsuura E, Takashima H Microarray analysis reveals down-regulation of Toll-like receptor genes in activated HTLV-1-infected cells from patients with HTLV-1-associated neurological disease. International conference

52th Annual Meeting of the Society for Leukocyte Biology,

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Event date： 2019.11

Language：English Presentation type：Poster presentation
Kubota R HAM: the inflammatory neurological disease caused by HTLV-1. Invited International conference

4th Precision Medicine Conference in Fujian

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Event date： 2019.9

Language：English Presentation type：Oral presentation (general)
Kubota R Molecular epidemiology of HTLV-1 in China, Taiwan, and Japan. Invited

CAMS/IBT seminar, Chengdu, China

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Event date： 2019.9

Language：English
Kodama D, Tanaka M, Matsuzaki T, Takashima H, Izumo S, Kubota R Inhibition of ABL1 decreases proviral load in HTLV-1 infected CD4+ T cells of HAM/TSP. International conference

19th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2019.4

Language：English Presentation type：Poster presentation
Kubota R, Tanaka M, Kodama D, Matsuura E, Takashima H Microarray analysis reveals down-regulation of Toll-like receptor genes in activated HTLV-1-infected cells from HAM/TSP patients. International conference

19th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2019.4

Language：English Presentation type：Oral presentation (general)
Tanaka M, Kodama D, Matsuura E, Takashima H, Izumo S, Kubota R. Effect of neuraminidase inhibitors on HTLV-1 infection and lymphocyte chemotaxis in HAM/TSP. International conference

19th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2019.4

Language：English Presentation type：Poster presentation
Kubota R HAM: the intractable neurological disease caused by HTLV-1. Invited International conference

3rd Precision Medicine Conference in Fujian

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Event date： 2018.12

Language：English Presentation type：Oral presentation (general)
久保田龍二 HTLV-1で起こる神経難病：HAM

日本学術会議九州・沖縄地区会議学術講演会

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Event date： 2018.9

Language：Japanese
久保田龍二、児玉大介、田中正和、松浦英治、高嶋　博 HAM患者由来HTLV-1感染細胞のウイルス活性化によるToll様受容体の発現低下

第5回日本HTLV-1学会学術集会

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Event date： 2018.8

Language：Japanese Presentation type：Oral presentation (general)
Kubota R: What is HTLV-1? Seminar in Taipei Blood Center, TBSF, Tapiei, Taiwan Invited

Seminar in Taipei Blood Center, TBSF, Tapiei, Taiwan

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Event date： 2018.5

Language：English
久保田龍二、児玉大介、田中正和、高嶋　博 HTLV-1 reduces the expression of Toll-like receptor genes in HAM/TSP patients.

第59回日本神経学会学術大会

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Event date： 2018.5

Language：English Presentation type：Poster presentation
Kubota R HTLV-1-specific inflammation in the spinal cord of HAM. Invited International conference

Recent Advances in HTLV-1 Research

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Event date： 2018.4

Language：English Presentation type：Oral presentation (general)
Kubota R, Kodama D, Takashima H Differential Expression of Nucleosome-Related Genes in Activated HTLV-1-Infected Cells of HAM/TSP Patients. International conference

XXIII World Congress of Neurology

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Event date： 2017.9

Language：English Presentation type：Poster presentation
Kodama D, Matsuzaki T, Takashima H, Kubota R, IzumoS Comparison of anti-HTLV-1 antibody screening tests of CLIA, CLEIA, and PA by ROC analysis using titers and logistic regression models for diagnosis of HAM/TSP. International conference

XXIII World Congress of Neurology

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Event date： 2017.9

Language：English Presentation type：Poster presentation
Kubota R HAM/TSP: clinical features and pathogenesis. Invited International conference

2nd Precision Medicine Conference in Fujian

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Event date： 2017.6

Language：English Presentation type：Oral presentation (invited, special)
Kubota R, Kodama D, Takashima H Gene Expression Profile of Activated HTLV-1-Infected Cells from HAM/TSP Patients. International conference

18th International Conference on Human Retrovirology: HTLV & Related Viruses,

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Event date： 2017.3

Language：English Presentation type：Poster presentation
久保田龍二、高嶋　博 HAM患者HTLV-1感染細胞のウイルス活性化時の遺伝子変動

第3回日本HTLV-1学会学術集会

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Event date： 2016.8

Language：Japanese Presentation type：Poster presentation
Kubota R HAM/TSP: clinical features and pathogenesis Invited International conference

Precision Medicine Conference in Fujian

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Event date： 2016.7

Language：English Presentation type：Oral presentation (general)
久保田龍二、高嶋　博、出雲周二 Gene expression profile of activated HTLV-1-infected cells from HAM patients

第57回日本神経学会学術大会

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Event date： 2016.5

Language：English Presentation type：Poster presentation
Kubota R HAM/TSP: clinical features and pathogenesis. Invited International conference

4th Cross-Strait Neurology Forum. Xiamen

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Event date： 2015.12

Language：English Presentation type：Oral presentation (general)
久保田龍二、高嶋　博、出雲周二 HAM患者末梢血中HTLV-1感染細胞特異的細胞表面分子の探索

第27回日本神経免疫学会学術集会

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Event date： 2015.9

Language：Japanese Presentation type：Oral presentation (general)
久保田龍二、高嶋　博、出雲周二マイクロアレイ解析によるHAM末梢血HTLV-1感染細胞特異的細胞表面分子の探索

第56回日本神経学会学術大会

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Event date： 2015.5

Language：Japanese Presentation type：Poster presentation
松浦英治、野妻智嗣、松﨑敏男、渡邊修、久保田龍二、出雲周二、高嶋博過去10年間に当科に入院した連続HAM患者の筋力低下パターン

第19回日本神経感染症学会学術集会

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Event date： 2014.9

Language：Japanese

Venue：金沢

国内学会
児玉大介、久保田龍二、松﨑敏男、高嶋博、出雲周二 HAM患者CD4+T細胞表面のN-アセチルラクトサミン－ガレクチン-3格子は細胞外ウイルス会合体かもしれない

第19回日本神経感染症学会学術集会

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Event date： 2014.9

Language：Japanese

Venue：金沢

国内学会
野妻智嗣、松浦英治、久保田龍二、児玉大介、松﨑敏男、渡邊修、三井純、石浦浩之、高橋祐二、山野嘉久、森下真一、辻省次、出雲周二、高嶋博次世代シークエンサーを用いたHAM疾患感受性遺伝子の探索

第19回日本神経感染症学会学術集会

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Event date： 2014.9

Language：Japanese

Venue：金沢

国内学会
久保田龍二、松﨑敏男、高嶋博、出雲周二 HTLV-1 HBZ特異的CTLのエピトープ同定とHAMにおける検出

第19回日本神経感染症学会学術集会

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Event date： 2014.9

Language：Japanese

Venue：金沢

国内学会
久保田龍二、齊藤峰輝、高嶋博、出雲周二 HAMにおけるHTLV-1抗原遺伝子変異とCTL認識

第1回日本HTLV-1学会学術集会

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Event date： 2014.8

Language：Japanese

Venue：東京

国内学会
野妻智嗣、松浦英治、松﨑敏男、渡邊修、久保田龍二、出雲周二、高嶋博エクソーム解析によるHAM疾患感受性遺伝子の探索

第55回日本神経学会総会

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Event date： 2014.5

Language：Japanese

Venue：福岡

国内学会
久保田龍二、松﨑敏男、高嶋博、出雲周二 HAMにおけるHTLV-1 HBZ特異的CTLの検出

第55回日本神経学会総会

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Event date： 2014.5

Language：Japanese

Venue：福岡

国内学会
児玉大介、出雲公子、久保田龍二、松﨑敏男、高嶋博、出雲周二 HAM/TSPのCD4+T細胞における特異的糖鎖の探索

第18回日本神経感染症学会総会

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Event date： 2013.10

Language：Japanese

Venue：宮崎

国内学会
久保田龍二、高嶋博、出雲周二 HTLV-1 HBZ特異的CTLエピトープの探索

第6回HTLV-I研究会

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Event date： 2013.8

Language：Japanese

Venue：東京

研究会
野妻智嗣、松浦英治、松﨑敏男、渡邊修、久保田龍二、出雲周二、高嶋博家族性HAMの臨床的解析

第6回HTLV-I研究会

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Event date： 2013.8

Language：Japanese

Venue：東京

研究会
松崎敏男、久保田龍二、斉藤峰輝、高嶋博、出雲周二神経内科における13年間のHTLV-1キャリア外来の実態

第6回HTLV-I研究会

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Event date： 2013.8

Language：Japanese

Venue：東京

研究会
児玉大介、出雲公子、久保田龍二、松﨑敏男、高嶋博、出雲周二 HAM/TSPのCD4+T細胞における糖鎖の特徴

第6回HTLV-I研究会

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Event date： 2013.8

Language：Japanese

Venue：東京

研究会
Matsuzaki T, Kubota R, Takashima H, Izumo S Early diagnosis of HTLV-1-associated myelopathy (HAM/TSP) in HTLV-1 carrier clinic. International conference

16th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2013.6

Language：English

Venue：Canada

国際学会
Matsuura E, Nozuma S, Matsuzaki T, Watanabe O, Kubota R, Izumo S, Takashima H Inflammation with HTLV-1-specific CTLs occurs in the spinal cord of HTLV-1 carriers and the brain of the patients with HAM/TSP. International conference

16th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2013.6

Language：English

Venue：Canada

国際学会
Nozuma S, Matsuura E, Matsuzaki T , Watanabe O, Kubota R, Izumo S, Takashima H Clinical features of familial HTLV-I-associated myelopathy/tropical spastic paraparesis. International conference

16th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2013.6

Language：English

Venue：Canada

国際学会
Kodama D, Izumo K, Kubota R, Matsuzaki T, Takashima H, Izumo S Characterization of glycans of CD4+T cells in HAM/TSP. International conference

16th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2013.6

Language：English

Venue：Canada

国際学会
Kubota R, Takashima H, Izumo S Impaired T cell receptor signaling in HTLV-1-infected CD4+ cells from HAM/TSP patients. International conference

16th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2013.6

Language：English

Venue：Canada

国際学会
久保田龍二、高嶋博、出雲周二 HAM患者HTLV-1感染CD4+T細胞における免疫能低下

第54回日本神経学会学術大会

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Event date： 2013.5

Language：Japanese

Venue：東京

国内学会
児玉大介、久保田龍二、出雲周二オミクス解析手法を用いたHAM病態の検討と治療標的候補遺伝子の探索

第17回日本神経感染症学会総会

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Event date： 2012.10

Language：Japanese

Venue：京都

国内学会
松浦英治、久保田龍二、出雲周二、高嶋博 HAM/TSP患者脊髄・大脳およびHTLV-1キャリア脊髄におけるHLTV-1ウイルス特異的細胞障害性T細胞の検出

第17回日本神経感染症学会総会

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Event date： 2012.10

Language：Japanese

Venue：京都

国内学会
久保田龍二、高嶋博、出雲周二 HAM患者HTLV-1感染細胞における免疫反応低下

第17回日本神経感染症学会総会

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Event date： 2012.10

Language：Japanese

Venue：京都

国内学会
久保田龍二、有島志保、松崎敏男、高嶋博、出雲周二 HTLV-I特異的CTL機能はHAMとキャリアで異なるのか？

第24回日本神経免疫学会

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Event date： 2012.9

Language：Japanese

Venue：長野

国内学会
久保田龍二、竹之内徳博、松崎敏男、高嶋博、出雲周二 HLA-A*24拘束性HTLV-I特異的CTLはHAM発症リスクを下げるか？

第21回日本組織適合性学会大会

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Event date： 2012.9

Language：Japanese

Venue：東京

国内学会
松浦英治、久保田龍二、高嶋博 HTLV-1特異的細胞障害性T細胞が関与する病態に関する検討（HAM患者の大脳・HTLV-1 carrierの脊髄の検討）

第24回日本神経免疫学会

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Event date： 2012.9

Language：Japanese

Venue：長野

国内学会
久保田龍二、有島志保、松崎敏男、高嶋博、出雲周二 HAMとキャリアにおけるHTLV-I特異的CTL機能の比較

第5回HTLV-I研究会

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Event date： 2012.8

Language：Japanese

Venue：東京

研究会
松浦英治、久保田龍二、高嶋博 HAMおよびHTLV-1キャリアの中枢神経におけるHTLV-1特異的細胞障害性T細胞の分布

第5回HTLV-I研究会

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Event date： 2012.8

Language：Japanese

Venue：東京

研究会
松崎敏男、久保田龍二、斎藤峰輝、吉村玲、高嶋博、出雲周二 HAMからみたATLの臨床

第5回HTLV-I研究会

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Event date： 2012.8

Language：Japanese

Venue：東京

研究会
久保田龍二、有島志保、松崎敏男、高嶋博、出雲周二 HAMとキャリアにおけるHTLV-I特異的CTL機能の比較検討

第53回日本神経学会総会

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Event date： 2012.5

Language：Japanese

Venue：東京

国内学会
松浦英治、久保田龍二、高嶋博 HTLV-1キャリアーの脊髄にHTLV-1特異的細胞障害性T細胞は浸潤している

第53回日本神経学会総会

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Event date： 2012.5

Language：Japanese

Venue：東京

国内学会
松崎敏男、久保田龍二、斎藤峰輝、高嶋博、出雲周二早期HAMの診断基準提唱と臨床

第53回日本神経学会総会

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Event date： 2012.5

Language：Japanese

Venue：東京

国内学会
Matsuura E, Watanabe O, Takashima H, Kubota R, Izumo S HTLV-1-specific cytotoxic T cell migration in the cerebrum of the patients with HAM/TSP. International conference

13th Asian Oceanian Congress of Neurology

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Event date： 2012.1

Language：English

Venue：Austria

国際学会
久保田龍二、Abdelbary NH、松崎敏男、林大輔、高嶋博、出雲周二 HAMにおけるT細胞疲労関連分子Tim-3発現の低下

第16回日本神経感染症学会

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Event date： 2011.11

Language：Japanese

Venue：東京

国内学会
久保田龍二 HTLV-I撲滅に向けての最新情報と今後の展望 Invited

第44回中国四国医学検査学会

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Event date： 2011.11

Language：Japanese
児玉大介、久保田龍二、出雲周二 HTLV-1関連脊髄症（HAM/TSP）のパスウェイ解析

第4回HTLV-I研究会

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Event date： 2011.9

Language：Japanese

Venue：東京

研究会
久保田龍二、竹之内徳博、松崎敏男、高嶋博、出雲周二 HLA-A24拘束性CTLはウイルス量を減少させるがHAM発症リスクを上げる

第4回HTLV-I研究会

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Event date： 2011.9

Language：Japanese

Venue：東京

研究会
久保田龍二、竹之内徳博、松崎敏男、高嶋博、出雲周二 HLA-A*24拘束性HTLV-I特異的CTLはHAM発症リスクを下げるか？

第23回日本神経免疫学会

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Event date： 2011.9

Language：Japanese

Venue：東京

国内学会
Kubota R Neural bystander damage in HTLV-I-associated myelopathy: an in situ tetramer staining study of HTLV-I-specific CD8+ T cells.

Departmental Seminar in Neuroimmunology, Max Planck Institute of Neurobiology

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Event date： 2011.6

Language：Japanese

Venue：Germany

その他
Kodama D, Kubota R, Izumo S Pathway analysis of HAM/TSP. International conference

25th Symposium of the International Association for Comparative Reseach on Leukemia and Related Diseases

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Event date： 2011.6

Language：English

Venue：Tokyo

国際学会
Matsuura E, Kubota R, Tanaka Y, Takashima H, Izumo S Neural bystander damage by infiltrating virus-infected T cells and the cytotoxic lymphocytes in HTLV-I-associated neurological disease. International conference

15th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2011.6

Language：English

Venue：Belgium

国際学会
Kodama D, Kubota R, Izumo S Gene expression and glycan profiling of CD4+ T cells in HAM/TSP. International conference

15th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2011.6

Language：English

Venue：Belgium

国際学会
Abdullah HM, Higuchi I, Kubota R, Matsuura E, Hashiguchi A, Abdelbary NH, Inamori Y, Takashima H, Izumo S Histopathologic differences between human T-lymphotropic virus type 1 (HTLV-1)-positive and HTLV-1-negative polymyositis. International conference

15th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2011.6

Language：English

Venue：Belgium

国際学会
Matsuzaki T, Kodama T, Kubota R, Izumo S Recent epidemiologic trends of HAM/TSP in Japan. International conference

15th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2011.6

Language：English

Venue：Belgium

国際学会
Kubota R. Takenouchi N, Matsuzaki T, Takashima H, Izumo S HLA-A24-restricted HTLV-I-specific CTL response reduces the HTLV-I proviral load but the HLA increases the risk of HAM/TSP. International conference

15th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2011.6

Language：English

Venue：Belgium

国際学会
Abdelbary NH, Abdullah HM, Matsuzaki T, Hayashi D, Tanaka Y, Takashima H, Izumo S, Kubota R Reduced Tim-3 expression on HTLV-I Tax-specific cytotoxic T lymphocytes in HTLV-I infection. International conference

15th International Conference on Human Retrovirology: HTLV & Related Viruses

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Event date： 2011.6

Language：English

Venue：Belgium

国際学会
松崎敏男、久保田龍二、出雲周二 HAM患者の全国疫学調査

第52回日本神経学会総会

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Event date： 2011.5

Language：Japanese

Venue：名古屋

国内学会
児玉大介、久保田龍二、出雲周二 HTLV-I関連脊髄症(HAM)における糖鎖グライコミクス解析

第52回日本神経学会総会

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Event date： 2011.5

Language：Japanese

Venue：名古屋

国内学会
久保田龍二、Abdelbary NH、松崎敏男、林大輔、高嶋博、出雲周二 HAMのHTLV-I特異的CTLにおけるT細胞疲労関連分子の検討

第52回日本神経学会総会第52回日本神経学会総会

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Event date： 2011.5

Language：Japanese

Venue：名古屋

国内学会
久保田龍二 HAMスペクトラム

第52回日本神経学会総会

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Event date： 2011.5

Language：Japanese

Venue：名古屋

国内学会
久保田龍二 HTLV-I関連脊髄症における感染リンパ球とCTLの浸潤によるneural bystander damage

新潟大学脳研セミナー

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Event date： 2010.11

Language：Japanese

Venue：新潟

その他
Izumo S, Xing H, Hayakawa H, Mori K, Arishima S, Kubota R, Gelpi E, Budka H A role of astrocyte dysfunction in pathogenesis of AIDS encephalopathy. International conference

17th International Congress of Neuropathology

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Event date： 2010.9

Language：English

Venue：Austria

国際学会
Abdullah HM, Higuchi I, Kubota R, Matsuura E, Hashiguchi A, Abdelbary NH, Inamori Y, Izumo S HTLV-I associated polymyositis: a trial to unfold the story. International conference

17th International Congress of Neuropathology

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Event date： 2010.9

Language：English

Venue：Austria

国際学会
Kubota R, Matsuura E, Izumo S Neural bystander damage by infiltrating virus-infected T cells and the cytotoxic lymphocytes in HTLV-I-associated neurological disease. International conference

17th International Congress of Neuropathology

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Event date： 2010.9

Language：English

Venue：Austria

国際学会
久保田龍二、松浦英治、田中勇悦、高嶋博、出雲周二 HTLV-I感染リンパ球とCTLの浸潤によるneural bystander damage

第3回HTLV-I研究会

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Event date： 2010.8

Language：Japanese

Venue：東京

研究会
小迫知弘、吉満誠、秋元正樹、久保田龍二、出雲周二、添田泰司、占野廣司、松下格司、魚住公治、有馬直道 HTLV-I感染者におけるHTLV-I特異的CTLの発現の多様性

第3回HTLV-I研究会

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Event date： 2010.8

Language：Japanese

Venue：東京

研究会
松崎敏男、久保田龍二、出雲周二 HAM患者の全国疫学調査

第3回HTLV-I研究会

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Event date： 2010.8

Language：Japanese

Venue：東京

研究会
児玉大介、久保田龍二、出雲周二 HAMのCD4+T細胞における遺伝子発現解析と糖鎖解析による感染細胞の特徴

第3回HTLV-I研究会

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Event date： 2010.8

Language：Japanese

Venue：東京

研究会
川端隆史、東元一晃、高嶋博、出雲周二、久保田龍二 HTLV-I関連肺疾患における肺胞洗浄液・肺生検組織でのHTLV-I特異的CTLの集積

第3回HTLV-I研究会

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Event date： 2010.8

Language：Japanese

Venue：東京

研究会
Abdelbary N 、Abdullah H 、松崎敏男、林大輔、田中勇悦、高嶋博、出雲周二、久保田龍二 Reduced Tim-3 expression on HTLV-I Tax-specific CTL in HTLV-I infection.

第3回HTLV-I研究会

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Event date： 2010.8

Language：Japanese

Venue：東京

研究会
児玉大介、久保田龍二、有村公良、出雲周二 HTLV-I関連脊髄症(HAM/TSP)患者末梢血CD4＋T細胞のトランスクリプトームの検討

第51回日本神経学会総会

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Event date： 2010.5

Language：Japanese

Venue：東京

国内学会
久保田龍二、松浦英治、出雲周二 HAM脊髄におけるHTLV-I特異的CTLの集積 International conference

第51回日本神経学会総会

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Event date： 2010.5

Language：English

Venue：東京

国際学会
久保田龍二、林大輔、出雲周二 HAM患者末梢血HTLV-I感染細胞におけるケモカインおよびFoxP3の発現

第22回日本神経免疫学会

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Event date： 2010.3

Language：Japanese

Venue：東京

国内学会
Abdelbary N、久保田龍二、臼杵扶佐子、山下暁朗、Abdulah H、出雲周二 HTLV-I roles in hUPF1 expression and phosphorylation.

第22回日本神経免疫学会

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Event date： 2010.3

Language：Japanese

Venue：東京

国内学会
Abdulah H, Higuchi I, Kubota R, Matsuura E, Hashiguchi A, Adbelbary N, Izumo S HTLV-I associated polymyositis: a traial to unfold the story.

第2回HTLV-I研究会

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Event date： 2009.8

Language：Japanese

Venue：東京

研究会
Abdelbary N, Kubota R, Usuki F, Abdulah H, Izumo S Possible effect of HTLV-I on hUPF1 expression and phosphorylation.

第2回HTLV-I研究会

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Event date： 2009.8

Language：Japanese

Venue：東京

研究会
児玉大介、久保田龍二、出雲周二 HTLV-I関連脊髄症(HAM/TSP)におけるRNAマイクロアレイ解析による検討

第2回HTLV-I研究会

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Event date： 2009.8

Language：Japanese

Venue：東京

研究会
佐藤知雄、阿座上和子、新谷奈津美、高橋克典、宇都宮與、久保田龍二、山野嘉久 HTLV-I関連疾患におけるinvariant NKT細胞の量的・機能的異常

第2回HTLV-I研究会

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Event date： 2009.8

Language：Japanese

Venue：東京

研究会
吉満誠、小迫知弘、鈴木伸介、松下格司、魚住公治、久保田龍二、出雲周二、有馬直道 HTLV-I感染者における免疫抑制性受容体の発現

第2回HTLV-I研究会

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Event date： 2009.8

Language：Japanese

Venue：東京

研究会
松崎敏男、久保田龍二、有村公良、出雲周二 HTLV-Iキャリア外来の現状とHAM患者の動向について

第50回日本神経学会総会

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Event date： 2009.5

Language：Japanese

Venue：宮城

国内学会
久保田龍二、松浦英治、有村公良、出雲周二抗原認識特異度の低いHTLV-I特異的CTLはウイルス淘汰圧が高い

第50回日本神経学会総会

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Event date： 2009.5

Language：Japanese

Venue：宮城

国内学会
児玉大介、久保田龍二、出雲周二 HTLV-I関連脊髄症（HAM/TSP）患者末梢血単核球を用いた合胞体形成の検討

第50回日本神経学会総会

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Event date： 2009.5

Language：Japanese

Venue：宮城

国内学会
久保田龍二、松浦英治、有村公良、出雲周二 HAM脊髄におけるHTLV-I特異的CTLとアポトーシス細胞の同定

第21回日本神経免疫学会

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Event date： 2009.4

Language：Japanese

Venue：大阪

国内学会
White Y, Yoshimitsu M, Kozako T, Akimoto M, Toji S, Matsushita K, Kubota R, Izumo S, Uozumi K, Shimeno S, Soeda S, Arima N Increased frequency of HTLV-I Tax specific CD8+ regulatory T-cells in HTLV-I infected individuals. International conference

51th American Society of Hematorogy Annual Meeting

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Event date： 2009.1

Language：English

Venue：USA

国際学会
Kubota R Impact of degenerate TCR recognition of HTLV-I-specific CTL on the viral load in patients with HAM/TSP.

Summer Seminar in Neuroimmunology Branch, NIH

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Event date： 2008.8

Language：Japanese

Venue：USA

その他
久保田龍二、竹之内徳博、松崎敏男、古川良尚、有村公良、出雲周二 HLA-A24はHTLV-Iウイルス量減少に関与するがHAM発症のリスクを上げる

第1回HTLV-I研究会

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Event date： 2008.8

Language：Japanese

Venue：東京

研究会
久保田龍二、竹之内徳博、出雲周二 HTLV-I関連脊髄症のウイルス制御におけるCTLの役割

第12回神経ウイルス学会

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Event date： 2008.7

Language：Japanese

Venue：鹿児島

研究会
久保田龍二 HTLV-I関連脊髄症におけるCTLの動態

第29回日本炎症・再生医学会

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Event date： 2008.7

Language：Japanese

Venue：東京

国内学会
久保田龍二、竹之内徳博、松崎敏男、古川良尚、有村公良、出雲周二 HLA-A24はHAMでは頻度が高いがウイルス量は低い

第49回日本神経学会総会

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Event date： 2008.5

Language：Japanese

Venue：神奈川

国内学会
久保田龍二、松浦英治、出雲周二 HAMにおけるHTLV-I特異的CTL

第12回日本神経感染症学会

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Event date： 2007.10

Language：Japanese

Venue：福岡

国内学会
Yamano Y, Kubota R, Arimura K, Ozaki S, Izumo S, Nishioka K, Osame M, Nakajima T High expression of CD28 costimulatory molecule and low expression of CTLA4 inhibitory molecule on CD4+CD25+ T cells in HTLV-I associated myelopathy (HAM/TSP). International conference

13th International Conference on Human Retrovirology: HTLV

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Event date： 2007.5

Language：English

Venue：Japan

国際学会
Hayashi D, Kubota R, Nose H, Arimura K, Izumo S, Osame M Increased CMV-specific CTL associated with decreased expression of Foxp3 in HAM/TSP. International conference

13th International Conference on Human Retrovirology: HTLV

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Event date： 2007.5

Language：English

Venue：Japan

国際学会
Kubota R, Furukawa Y, Arimura K, Osame M, Izumo S Genetic stability of HTLV-I despite antiviral pressures by cytotoxic T lymphocytes. International conference

13th International Conference on Human Retrovirology: HTLV

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Event date： 2007.5

Language：English

Venue：Japan

国際学会
Takenouchi N, Kubota R, Matsuzaki T, Furukawa Y, Izumo S, Arimura K, Osame M HLA-A*2402 determines a risk of HAM/TSP independently from the HTLV-I proviral load. International conference

13th International Conference on Human Retrovirology: HTLV

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Event date： 2007.5

Language：English

Venue：Japan

国際学会
Matsuura E, Kubota R, Saito M, Suehara T, Matsuzaki K, Arimura K, Osame M, Izumo S Bystander damage of the central nervous system by HTLV-I specific CTL with target cell infiltration in HAM/TSP. International conference

13th International Conference on Human Retrovirology: HTLV

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Event date： 2007.5

Language：English

Venue：Japan

国際学会
久保田龍二、有村公良、納光弘、出雲周二 HAM患者HTLV-I感染細胞でのTCR/CD3発現とTCRシグナルの低下

第48回日本神経学会総会

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Event date： 2007.5

Language：Japanese

Venue：名古屋

国内学会
Xing HQ, Kubota R, Hayakawa H, Izumo S Role of glial cells in central nervous system injury of human retroviral infection. International conference

13th International Conference on Human Retrovirology: HTLV

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Event date： 2007.5

Language：English

Venue：Japan

国際学会
Nose H, Usuku K, Kubota R, Izumo S, Arimura K, Bangham C, Osame M, Saito M In vivo selection of human T cell lymphotropic virus type-1-specific CD4+ cells by disease susceptive class II allele and immunodominant peptide complex in HTLV-I-associated neurological disease. International conference

13th International Conference on Human Retrovirology: HTLV

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Event date： 2007.5

Language：English

Venue：Japan

国際学会
久保田龍二、有村公良、納光弘、出雲周二 HAM患者患者末梢血CD4+細胞におけるTCR/CD3発現とTCRシグナルの低下

第19回日本神経免疫学会

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Event date： 2007.4

Language：Japanese

Venue：石川

国内学会
林大輔、久保田龍二、竹之内徳博、中村友紀、梅原藤雄、有村公良、出雲周二、納光弘 CSF HTLV-Iプロウイルス量の増加を伴った急性進行性HTLV-I-associated myelopathy (HAM)の1例

第19回日本神経免疫学会

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Event date： 2007.4

Language：Japanese

Venue：石川

国内学会
竹之内徳博、Jacobson Steven、久保田龍二、有村公良、出雲周二、納光弘 HTLV-I Receptorの新たな候補

第19回日本神経免疫学会

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Event date： 2007.4

Language：Japanese

Venue：石川

国内学会
松浦英治、久保田龍二、齊藤峰輝、松崎敏男、末原雅人、有村公良、出雲周二、納光弘 HTLV-I特異的CTLの浸潤によるHAM脊髄のbystander damage

第19回日本神経免疫学会

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Event date： 2007.4

Language：Japanese

Venue：石川

国内学会
梅原藤雄、松浦英治、能勢裕久、樋口逸郎、泉浩太郎、松岡英二、齊藤峰輝、久保田龍二、出雲周二、納光弘 HTLV-I感染に伴うInclusion Body Myositisが存在する

第19回日本神経免疫学会

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Event date： 2007.4

Language：Japanese

Venue：石川

国内学会
Izumo S, Xing HQ, Kubota R, Hayakawa H, Gelpi E, Budka H Microglial activation correlated with decreased expression of EAAT-2 in the cerebral cortex of HIV-1 infected patients: a neuroprotective role of microglia in AIDS encephalopathy. International conference

8th International Conference of Neuroimmunology

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Event date： 2006.10

Language：English

Venue：Japan

国際学会
Nose H, Saito M, Sabouri AH, Usuku K, Kubota R, Izumo S, Arimura K, Osame M In vivo selection of T-cell receptor junctional region sequences by HLA-DRB1*0101 human T-cell lymphotropic virus type 1 (HTLV-1) envelope gp21 peptide complexes in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). International conference

8th International Conference of Neuroimmunology

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Event date： 2006.10

Language：English

Venue：Japan

国際学会、一般
Matsuura E, Kubota R, Saito M, Suehara M, Matsuzaki T, Arimura K, Osame M, Izumo S Visualization of HTLV-I Tax-specific cytotoxic T lymphocytes in the central nervous system of HTLV-I-associated myelopathy International conference

8th International Conference of Neuroimmunology

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Event date： 2006.10

Language：English

Venue：Japan

国際学会、一般
Hayashi D, Kubota R, Nose H, Arimura K, Izumo S, Osame M Increased CTL responses to CMV in HAM/TSP: a relation of FOXP3+ regulatory T cells. International conference

8th International Conference of Neuroimmunology

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Event date： 2006.10

Language：English

Venue：Japan

国際学会、一般
Kubota R, Arimura K, Osame M, Izumo S HTLV-I-specific CTL with high TCR degeneracy efficiently recognize naturally occurring mutant viruses in patients with HAM/TSP. International conference

8th International Conference of Neuroimmunology

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Event date： 2006.10

Language：English

Venue：Japan

国際学会、一般
松浦英治、久保田龍二、斉藤峰輝、末原雅人、松崎敏男、有村公良、納光弘、出雲周二 HAM脊髄におけるHTLV-1特異的CTLの検出

第47回日本神経学会総会

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Event date： 2006.5

Language：Japanese

Venue：東京

国内学会
久保田龍二、林大輔、有村公良、納光弘、出雲周二 HAM患者末梢血中HTLV-I感染リンパ球の解析

第47回日本神経学会総会

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Event date： 2006.5

Language：Japanese

Venue：東京

国内学会
林大輔、久保田龍二、能勢裕久、有村公良、出雲周二、納光弘 HAMにおける慢性ウイルス感染に対するCTL反応

第47回日本神経学会総会

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Event date： 2006.5

Language：Japanese

Venue：東京

国内学会
久保田龍二、納光弘、出雲周二 HAMにおけるHTLV-IウイルスとCTLの相互作用

第10回日本神経感染症学会

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Event date： 2005.10

Language：Japanese

Venue：東京

国内学会
Kubota R, Osame M, Izumo S Degeneracy of HTLV-I-specific CTL inversely correlates with proviral load in patients with HAM/TSP. International conference

12th International Conference on Human Retrovirology: HTLV.

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Event date： 2005.6

Language：English

Venue：Jamaica

国際学会、招待
Nose H, Saito M, Usuku K, Matsuzaki T, Izumo S, Kubota R, Furukawa Y, Arimura K, Osame M Comparison of clinical symptoms and the odds for predicting HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) in healthy virus carriers: application of best-fit logistic regression equation based on the genotype, age, and provirus load. International conference

12th International Conference on Human Retrovirology: HTLV

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Event date： 2005.6

Language：English

Venue：Jamaica

国際学会、一般
久保田龍二、斎藤峰輝、納光弘、出雲周二 HAMにおけるCTLの多様性とHTLV-Iウイルス量およびウイルス変異の検討

第46回日本神経学会総会

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Event date： 2005.5

Language：Japanese

Venue：鹿児島

国内学会
久保田龍二、古川良尚、出雲周二、納光弘 HAMにおけるCTLによる正の選択圧とウイルスの安定性

第45回日本神経学会総会

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Event date： 2004.5

Language：Japanese

Venue：東京

国内学会
Kubota R, Izumo S, Osame M Immunopathogenesis of HAM/TSP. International conference

Therapeutics in HTLV-I Associated Neurologic Disease Workshop.

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Event date： 2004.3

Language：English

Venue：Jamaica

国際学会、招待
Kubota R, Saito M, Ijichi S, Nakagawa M, Izumo S, Osame M Interferon-alpha treatment for HAM/TSP. International conference

Therapeutics in HTLV-I Associated Neurologic Disease Workshop.

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Event date： 2004.3

Language：English

Venue：Jamaica

国際学会、招待
Kubota R, Furukawa Y, Izumo S, Osame M Mutations in HTLV-I Tax 11-19 epitope and mutant virus-specific T cells in patients with HAM/TSP.

11th International Conference on Human Retrovirology: HTLV

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Event date： 2003
Kubota R, Nagai M, Osame M, Jacobson S Differentiated HTLV-I Tax-specific cells correlate with the proviral load in HAM/TSP patients. Invited International conference

HTLV-I Molecular Biology and Pathogenesis.

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Event date： 2000

Language：English
Izumo S, Takenouchi N, Moritoyo T, Kubota R, Osame M Pathogenesis of HTLV-I-associated inflammatory disorders.

10th International Conference on Human Retrovirology: HTLV

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Event date： 2000
Furukawa Y, Kubota R, Tara M, Izumo S, Osame M Existence of escape mutant in HTLV-I tax during the development of adult T cell leukemia.

10th International Conference on Human Retrovirology: HTLV

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Event date： 2000
Kubota R, Furukawa Y, Izumo S, Usuku K, Jacobson S, Osame M Diversity of HTLV-I-specific CTL and proviral load in patients with HAM.

10th International Conference on Human Retrovirology: HTLV

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Event date： 2000
Nagai M, Kubota R, Greten TF, Schneck JP, Jacobson S Increased differentiated and activated HTLV-I Tax 11-19-specific CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I proviral load.

3rd International Symposium on Neurovirology

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Event date： 2000
Kubota R, Soldan SS, Martin R, Jacobson S An altered peptide ligand antagonizes antigen-specific CD8+ CTL in peripheral blood of HAM/TSP patients.

9th International Conference on Human Retrovirology: HTLV

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Event date： 1999
Nagai M, Kubota R, Schneck JP, Jacobson S Phenotypic analysis of HTLV-I Tax 11-19 specific CD8+ cells.

9th International Conference on Human Retrovirology: HTLV

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Event date： 1999
Umehara F, Izumo S, Moritoyo T, Abe M, Kubota R, Osame M Immunopathology of HTLV-I-associated myelopathy.

9th International Conference on Human Retrovirology: HTLV

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Event date： 1999
Kubota R, Kawanishi T, Mastubara H, Jacobson S Demonstration of HTLV-I Tax specific CD8+ cells directly in peripheral blood of HAM/TSP patients by intracellular cytokine detection. Invited International conference

3rd World Congress on Inflammation.

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Event date： 1997

Language：English
Levin MC, Lehky T, Bamford R, Kubota R, Xavier A, Soldan S, McFarland, Waldmann T, Jacobson S Decreased HTLV-I viral load in HAM/TSP patients following treatment with humanized anti-Tac.

8th International Conference on Human Retrovirology: HTLV

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Event date： 1997
Kubota R, Kawanishi T, Levin MC, Jacobson S Quantitative PCR for HTLV-I proviral DNA.

8th International Conference on Human Retrovirology: HTLV

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Event date： 1997
Kubota R, Kawanishi T, Mastubara H, Jacobson S Demonstration of HTLV-I Tax specific CD8+ cells directly in peripheral blood of HAM/TSP patients by intracellular cytokine detection.

8th International Conference on Human Retrovirology: HTLV

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Event date： 1997
Saito M, Furukawa Y, Kubota R, Usuku K, Sonoda S, Izumo S, Osame M, Yoshida M Highly frequent and random mutations of HTLV-I proviral genome within individuals of HAM/TSP patients and asymptomatic carriers.

1995 Annual meeting sponsored by the Laboratory of Tumor Cell Biology.

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Event date： 1995
Kubota R, Fujiyoshi T, Izumo S, Yashiki S, Maruyama I, Osame M, Sonoda S Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy.

3rd International Conference on Human Retrovirology: HTLV

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Event date： 1992
Hokezu Y, Izumo S, Maruyama I, Kubota R, Moritoyo T, Osame M Therapeutic trials in the patients with HAM in our department.

4th Annual Retrovirology Conference

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Event date： 1991
Hashimoto K, Machigashira K, Kubota R, Suehara M, Osame M, Lalkaka J, Singhal BS, Fujisawa J, Yoshida M Sequence analysis of HTLV-I from HAM/TSP in India.

8th Asian and Oceanian Congress of Neurology

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Event date： 1991
Kubota R, Nakagawa M, Nakamura A, Osame M Lymphocytapheresis on HAM. International conference

WHO Scientific Group on HTLV-I Infections and Associated Diseases.

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Event date： 1988
松浦英治, 田代雄一, 相良康子, 久保田龍二, 高嶋博鹿児島県のHTLV-1感染率について　高いHTLV-1感染率を示す鹿児島県の高齢者

日本老年医学会雑誌 2019.5 (一社)日本老年医学会

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松元陸, 眞弓芳子, 古園麻衣, 田代雄一, 松浦英治, 荒田仁, 山野嘉久, 田中正和, 久保田龍二, 高嶋博 HTLV-1関連脊髄症の初発症状は疾患進行の予測因子である

NEUROINFECTION 2019.9 日本神経感染症学会

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野妻智嗣, 松浦英治, 田中正和, 久保田龍二, 高嶋博 HTLV-1関連脊髄症における疾患特異的TCRレパトアの同定

神経免疫学 2020.10 日本神経免疫学会

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古園麻衣, 眞弓芳子, 樋口雄二郎, 野妻智嗣, 田代雄一, 中村友紀, 橋口昭大, 松浦英治, 兒玉大介, 田中正和, 久保田龍二, 高嶋博 HTLV-1関連脊髄症(HAM)患者の臨床経過における排尿障害の意義について

臨床神経学 2018.12 (一社)日本神経学会

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蓮井和久, 宇都宮與, 原博満, 木脇祐俊, 満田稔, 斉藤稔, 久保田龍二, 出雲周二 HTLV-1関連細胞株と成人T細胞白血病ないしリンパ腫に於けるサバイビンの抗原回復免疫組織化学

日本病理学会会誌 2019.4 (一社)日本病理学会

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蓮井和久, 佐藤榮一, 宇都宮與, 木脇祐俊, 満田稔, 斉藤稔, 原博満, 久保田龍二, 出雲周二 HTLV-1関連細胞株と成人T細胞白血病ないしリンパ腫(ATL)に於けるサバイビンの抗原回復免疫組織化学

日本組織細胞化学会総会・学術集会講演プログラム・予稿集 2018.9 日本組織細胞化学会

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Kubota Ryuji, Tanaka Masakazu, Matsuura Eiji, Takashima Hiroshi HTLV-1感染細胞のマイクロアレイ解析によるHAMに対する治療標的分子の検索

臨床神経学 2020.11 (一社)日本神経学会

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Kodama Daisuke, Tanaka Masakazu, Matsuzaki Toshio, Nozuma Satoshi, Matsuura Eiji, Takashima Hiroshi, Izumo Shuji, Kubota Ryuji HTLV-1型感染者における抗HERV-K10抗体への高い反応性

臨床神経学 2020.11 (一社)日本神経学会

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Kubota Ryuji, Kodama Daisuke, Tanaka Masakazu, Takashima Hiroshi HTLV-1はHAM/TSP患者におけるToll様受容体遺伝子の発現を抑制する

臨床神経学 2018.12 (一社)日本神経学会

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松浦英治, 荒田仁, 東桂子, 田中正和, 安藤匡宏, 平松有, 野妻智嗣, 田代雄一, 崎山佑介, 久保田龍二, 高嶋博 HPVワクチン関連疾患の臨床経過とワクチン接種後血液サイトカイン・自己抗体の検討

神経免疫学 2020.10 日本神経免疫学会

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田代雄一, 橋口昭大, 中村友紀, 野妻智嗣, 松崎敏男, 兒玉大介, 松浦英治, 久保田龍二, 高嶋博 HAM患者に対するアミノ酸内服治療の試み

NEUROINFECTION 2017.9 日本神経感染症学会

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児玉大介, 松崎敏男, 高嶋博, 久保田龍二, 出雲周二 HAM患者CD4+T細胞サバイバル遺伝子ABL1の阻害による感染細胞の劇的アポトーシス誘導

神経免疫学 2017.10 日本神経免疫学会

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松浦英治, 田代雄一, 荒田仁, 橋口昭大, 中村友紀, 野妻智嗣, 松崎敏男, 田中正和, 久保田龍二, 高嶋博 HAMに対するアミノ酸内服治療の効果

神経免疫学 2018.9 日本神経免疫学会

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Kodama Daisuke, Matsuzaki Toshio, Tanaka Masakazu, Matsuura Eiji, Takashima Hiroshi, Kubota Ryuji, Izumo Shuji HAM/TSPにおける生存遺伝子ABL1の阻害はHTLV-1感染CD4+T細胞を劇的に減少させる

臨床神経学 2018.12 (一社)日本神経学会

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田中正和, 兒玉大介, 松浦英治, 高嶋博, 久保田龍二 HAM/TSPにおけるneuraminidase阻害剤がHTLV-1感染症とリンパ球走化性に与える効果

臨床神経学 2018.12 (一社)日本神経学会

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Nozuma Satoshi, Matsuura Eiji, Matsuzaki Toshio, Kubota Ryuji, Jacobson Steven, Takashima Hiroshi ウイルス性神経疾患における免疫病原性CSFのTCRレパトア特性(Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease) International coauthorship

臨床神経学 2021.9 (一社)日本神経学会

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野妻智嗣, 松浦英治, 田中正和, 松崎敏男, 久保田龍二, 高嶋博 HTLV-1感染細胞を標的としたTCRレパトア解析によるHAMの診断および病勢指標となるバイオマーカーの探索

神経免疫学 2021.10 (一社)日本神経免疫学会

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野妻智嗣, 松浦英治, 田中正和, 児玉大介, 松崎敏男, 久保田龍二, 高嶋博感染細胞を標的としたTCRレパトア解析によるHAMでのバイオマーカー探索

臨床神経学 2022.10 (一社)日本神経学会

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松浦英治, 野妻智嗣, 東桂子, 田中正和, 久保田龍二, 高嶋博 HPVワクチン後脳症患者に見られるサイトカインの上昇について

臨床神経学 2022.10 (一社)日本神経学会

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兒玉大介, 田中正和, 松崎敏男, 野妻智嗣, 松浦英治, 高嶋博, 出雲周二, 久保田龍二 HAM診断に適した髄液中抗HTLV-1抗体検査法

臨床神経学 2022.10 (一社)日本神経学会

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野妻智嗣, 松浦英治, 堂園美香, 田中正和, 児玉大介, 松崎敏男, 久保田龍二, 高嶋博その他　TCRレパトア解析によるHAMでの病原性クローンの同定・追跡

神経免疫学 2022.10 (一社)日本神経免疫学会

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蓮井和久, 佐藤榮一, 原博満, 木脇祐俊, 満田稔, 斉藤稔, 久保田龍二, 出雲周二成人T細胞白血病(ATL)細胞のリンパ節での動態のSurvivinの抗原回復免疫組織化学による解析

日本病理学会会誌 2017.3 (一社)日本病理学会

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蓮井和久, 宇都宮與, 佐藤榮一, 原博満, 木脇祐俊, 満田稔, 斉藤稔, 久保田龍二, 出雲周二成人T細胞白血病(ATL)の末梢血組織標本のSurvivinの抗原回復免疫組織化学による解析

日本病理学会会誌 2018.4 (一社)日本病理学会

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松浦英治, 田代雄一, 荒田仁, 崎山祐介, 中村友紀, 野妻智嗣, 松崎敏男, 兒玉大介, 橋口昭大, 岡本裕嗣, 田中正和, 久保田龍二, 高嶋博アルギニン塩酸塩を用いたHAM患者治療の試み

NEUROINFECTION 2018.10 日本神経感染症学会

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田代雄一, 松浦英治, 橋口昭大, 中村友紀, 野妻智嗣, 松崎敏男, 兒玉大介, 田中正和, 久保田龍二, 高嶋博 HAM患者に対するL-アルギニン内服治療の試み

臨床神経学 2018.12 (一社)日本神経学会

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松浦英治, 田代雄一, 野妻智嗣, 安藤匡宏, 平松有, 崎山佑介, 荒田仁, 田中正和, 久保田龍二, 高嶋博 HAM患者に対するL-アルギニン内服治療の試み

神経免疫学 2020.10 日本神経免疫学会

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Research Projects

HTLV-1関連脊髄症（HAM）の自然免疫解析による病態解明と新規治療研究

2022.4

科研費、基盤(B)

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Authorship：Principal investigator Grant type：Competitive
HAMならびに類縁疾患の患者レジストリによる診療連携体制および相談機能の強化と診療ガイドラインの改訂

2022.4

厚労科研

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Authorship：Coinvestigator(s) Grant type：Competitive
HTLV-1の総合的な感染対策に資する研究

2020.4

AMED

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Authorship：Coinvestigator(s) Grant type：Competitive
HTLV-1感染細胞を標的としたHAMの新規治療法開発

2019.4 - 2021.3

科研費、基盤(C)

久保田龍二

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Authorship：Principal investigator Grant type：Competitive
HAMガイドライン活用促進と医療水準均てん化に関する研究

2019.4 - 2021.3

厚労科研

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Authorship：Coinvestigator(s)
中国福健省ならびに台湾と西南日本におけるHTLV-1関連疾患の比較研究

2017.4 - 2019.3

科研費、基盤(B)

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Authorship：Principal investigator Grant type：Competitive
HTLV-1の疫学研究及び総合対策に資する研究

2017.4 - 2019.3

AMED AMED

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Authorship：Coinvestigator(s) Grant type：Competitive
HAMならびにHTLV-1陽性難治性疾患に関する国際的な総意形成を踏まえた診療ガイドラインの作成

2016.4 - 2018.3

厚労科研

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Authorship：Coinvestigator(s) Grant type：Competitive
HTLV-1疫学研究及び検査法の標準化に関する研究

2014.4 - 2016.3

厚労科研

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Authorship：Coinvestigator(s)
HAM動物モデルの作製と新規治療法開発

2012.4 - 2014.3

科研費、基盤(C)

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Authorship：Principal investigator Grant type：Competitive
中枢神経組織におけるウイルス特異的細胞傷害性Ｔリンパ球の検出

2005.4 - 2006.3

科研費、萌芽

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Authorship：Coinvestigator(s) Grant type：Competitive
テトラマーを用いた細胞傷害性Tリンパ球の刺激法の開発

2004.4 - 2005.3

科研費、萌芽

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Authorship：Principal investigator Grant type：Competitive
HTLV-I関連脊髄症における細胞傷害性Tリンパ球動態とウイルス変異に関する研究

2002.4 - 2003.3

科研費、基盤(C)

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Authorship：Principal investigator Grant type：Competitive

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Other research activities

HTLV-1関連脊髄症（HAM）診療ガイドライン2019

2017.4

-

2019.3
HAM診療マニュアル第２版

2015.4

-

2016.3

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HAM診療マニュアル第2版策定委員会委員長として策定委員会を組織し、マニュアルを作成した。
HAM診療マニュアル

2013

-

2015

Social Activities

鹿児島県HTLV-1対策協議会委員

Role(s)： Advisor

2019