Updated on 2024/11/15

写真a

 
KUBOTA Ryuji
 
Organization
Research Field in ? Professor
Title
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   Professor

    2021.4

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

    2019.4 - 2021.3

  • 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

  • Masakazu Tanaka, Norihiro Takenouchi, Shiho Arishima, Toshio Matsuzaki, Satoshi Nozuma, Eiji Matsuura, Hiroshi Takashima, Ryuji Kubota .  HLA-A*24 Increases the Risk of HTLV-1-Associated Myelopathy despite Reducing HTLV-1 Proviral Load. .  International journal of molecular sciences25 ( 13 )   2024.6HLA-A*24 Increases the Risk of HTLV-1-Associated Myelopathy despite Reducing HTLV-1 Proviral Load.Reviewed International journal

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    Increased human T-cell leukemia virus type 1 (HTLV-1) proviral load (PVL) is a significant risk factor for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is controversy surrounding whether HTLV-1-specific cytotoxic T lymphocytes (CTLs) are beneficial or harmful to HAM/TSP patients. Recently, HTLV-1 Tax 301-309 has been identified as an immunodominant epitope restricted to HLA-A*2402. We investigated whether HLA-A*24 reduces HTLV-1 PVL and the risk of HAM/TSP using blood samples from 152 HAM/TSP patients and 155 asymptomatic HTLV-1 carriers. The allele frequency of HLA-A*24 was higher in HAM/TSP patients than in asymptomatic HTLV-1 carriers (72.4% vs. 58.7%, odds ratio 1.84), and HLA-A*24-positive patients showed a 42% reduction in HTLV-1 PVL compared to negative patients. Furthermore, the PVL negatively correlated with the frequency of Tax 301-309-specific CTLs. These findings are opposite to the effects of HLA-A*02, which reduces HTLV-1 PVL and the risk of HAM/TSP. Therefore, we compared the functions of CTLs specific to Tax 11-19 or Tax 301-309, which are immunodominant epitopes restricted to HLA-A*0201 or HLA-A*2402, respectively. The maximum responses of these CTLs were not different in the production of IFN-γ and MIP-1β or in the expression of CD107a-a marker for the degranulation of cytotoxic molecules. However, Tax 301-309-specific CTLs demonstrated 50-fold higher T-cell avidity than Tax 11-19-specific CTLs, suggesting better antigen recognition at low expression levels of the antigens. These findings suggest that HLA-A*24, which induces sensitive HTLV-1-specific CTLs, increases the risk of HAM/TSP despite reducing HTLV-1 PVL.

    DOI： 10.3390/ijms25136858

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  • Nozuma S, Yoshimura A, Pai SC, Chen HJ, Matsuura E, Tanaka M, Kodama D, Dozono M, Matsuzaki T, Takashima H, Yang YC, Kubota R .  Geographic characteristics of HTLV-1 molecular subgroups and genetic substitutions in East Asia: Insights from complete genome sequencing of HTLV-1 strains isolated in Taiwan and Japan. .  PLoS neglected tropical diseases18 ( 2 ) e0011928   2024.2Geographic characteristics of HTLV-1 molecular subgroups and genetic substitutions in East Asia: Insights from complete genome sequencing of HTLV-1 strains isolated in Taiwan and Japan.Reviewed International coauthorship International journal

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

    DOI： 10.1371/journal.pntd.0011928

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  • 久保田 龍二 .  HAMの臨床と病態 .  Ｓｋｉｎ　Ｃａｎｃｅｒ39 ( 2 ) 120 - 124   2024HAMの臨床と病態Invited

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本皮膚悪性腫瘍学会  

    DOI： 10.5227/skincancer.39.120

  • Madoka Kuramitsu, Haruka Momose, Yuichiro Uchida, Kenji Ishitsuka, Ryuji Kubota, Masahito Tokunaga, Atae Utsunomiya, Kunihiko Umekita, Yuuki Hashikura, Kisato Nosaka, Ki-Ryang Koh, Hitomi Nakamura, Yasuko Sagara, Rieko Sobata, Masahiro Satake, Koh Nagata, Yuri Hasegawa, Daisuke Sasaki, Hiroo Hasegawa, Tomoo Sato, Yoshihisa Yamano, Kou Hiraga, Kenta Tezuka, Emi Ikebe, Sahoko Matsuoka, Kazu Okuma, Toshiki Watanabe, Kiyonori Miura, Isao Hamaguchi .  Performance evaluation of Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test for different diagnostic situations. .  Microbiology spectrum11 ( 6 ) e0207823   2023.11Performance evaluation of Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test for different diagnostic situations.Reviewed International journal

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

    The World Health Organization estimated that 5-10 million people are infected with human T-cell leukemia virus type 1 (HTLV-1). This number is likely to be underestimated because reliable endemic data are available for only approximately 1.5 billion people worldwide. The point-of-care test is a powerful tool for the easy and quick detection of infections without the requirement for expensive instruments and laboratory equipment. Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test that was evaluated in this study, might significantly advance our understanding of the global epidemiology of HTLV-1 infection.

    DOI： 10.1128/spectrum.02078-23

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  • EIJI MATSUURA, 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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    <h4>Background</h4>Sporadic late onset nemaline myopathy (SLONM) is a muscle disorder characterized by the presence of nemaline rods in muscle fibers. SLONM has no known genetic cause but has been associated with monoclonal gammopathy of undetermined significance and with human immunodeficiency virus (HIV) infection. Human T-cell leukemia virus-1 (HTLV-1) is a known causative agent of adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraplegia (HAM/TSP), a chronic inflammatory neurological disease. HTLV-1 has been reported to be implicated in inflammatory myopathies, as well as in HIV infection.; however, there have been no reports of an association between HTLV-1 infection and SLONM to date.<h4>Case presentation</h4>A 70-year-old Japanese woman presented with gait disturbance, lumbar kyphosis, and respiratory dysfunction. The diagnosis of HAM/TSP with SLONM was made based on characteristic clinical symptoms of HAM/TSP, such as spasticity in the lower extremities, and cerebrospinal fluid test results; and of SLONM, such as generalized head drooping, respiratory failure, and muscle biopsy results. Steroid treatment was initiated and improvement in her stooped posture was observed after 3 days of treatment.<h4>Conclusion</h4>This is the first case report of SLONM combined with HTLV-1 infection. Further studies are needed to elucidate the relationship between retroviruses and muscle diseases.

    DOI： 10.1186/s12891-023-06461-3

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  • EIJI MATSUURA, Nozuma S, Dozono M, Daisuke Kodama, Masakazu Tanaka, 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 )   2023.4Reviewed International journal

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    Human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive neurological disease that arises from HTLV-1 infection. Pathologically, the condition is characterized by diffuse myelitis, which is most evident in the thoracic spinal cord. Clinical manifestations of the infectious disease, HAM/TSP, are empirically known to include weakness of the proximal muscles of the lower extremities and atrophy of the paraspinal muscles, which is characteristic of the distribution of disturbed muscles usually seen in muscular diseases, except that the upper extremities are almost normal. This unique clinical presentation is useful information for physicians and physical therapists involved in diagnosing and rehabilitating patients with HAM/TSP, as well as critical information for understanding the pathogenesis of HAM/TSP. However, the precise pattern of muscle involvement in this condition has yet to be reported. The purpose of this study was to identify the muscles affected by HAM/TSP in order to understand the pathogenesis of HAM/TSP as well as to aid in the diagnosis and rehabilitation of HAM/TSP. A retrospective review of medical records was conducted on 101 consecutively admitted patients with HAM/TSP at Kagoshima University Hospital. Among 101 patients with HAM/TSP, all but three had muscle weakness in the lower extremities. Specifically, the hamstrings and iliopsoas muscle were the most frequently affected in over 90% of the patients. Manual muscle testing (MMT) revealed that the iliopsoas was the weakest of the muscles assessed, a consistent feature from the early to advanced stages of the disease. Our findings demonstrate a unique distribution of muscle weakness in HAM/TSP, with the proximal muscles of the lower extremities, particularly the iliopsoas muscle, being the most frequently and severely affected.

    DOI： 10.3390/pathogens12040592

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

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

    Human T lymphotropic virus type 1-assoicated (HTLV-1-associated) myelopathy/tropical spastic paraparesis (HAM/TSP) is a neuroinflammatory disease caused by the persistent proliferation of HTLV-1-infected T cells. Here, we performed a T cell receptor (TCR) repertoire analysis focused on HTLV-1-infected cells to identify and track the infected T cell clones that are preserved in patients with HAM/TSP and migrate to the CNS. TCRβ repertoire analysis revealed higher clonal expansion in HTLV-1-infected cells compared with noninfected cells from patients with HAM/TSP and asymptomatic carriers (ACs). TCR clonality in HTLV-1-infected cells was similar in patients with HAM/TSP and ACs. Longitudinal analysis showed that the TCR repertoire signature in HTLV-1-infected cells remained stable, and highly expanded infected clones were preserved within each patient with HAM/TSP over years. Expanded HTLV-1-infected clones revealed different distributions between cerebrospinal fluid (CSF) and peripheral blood and were enriched in the CSF of patients with HAM/TSP. Cluster analysis showed similarity in TCRβ sequences in HTLV-1-infected cells, suggesting that they proliferate after common antigen stimulation. Our results indicate that exploring TCR repertoires of HTLV-1-infected cells can elucidate individual clonal dynamics and identify potential pathogenic clones expanded in the CNS.

    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   2023Reviewed International journal

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    <h4>Objective</h4>Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD).<h4>Methods</h4>Clinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Correlations between serum anti-gAChR antibodies and clinical symptoms and laboratory data were analyzed. Data analysis was conducted in 2021.<h4>Results</h4>Of the 59 patients with FNSD/CD, 52 (88.1%) exhibited autonomic disturbances and 16 (27.1%) were positive for serum anti-gAChR antibodies. Cardiovascular autonomic dysfunction, including orthostatic hypotension, was significantly more prevalent (75.0 vs. 34.9%, <i>P</i> = 0.008), whereas involuntary movements were significantly less prevalent (31.3 vs. 69.8%, <i>P</i> = 0.007), among anti-gAChR antibody-positive compared with -negative patients. Anti-gAChR antibody serostatus did not correlate significantly with the frequency of other autonomic, sensory, or motor symptoms analyzed.<h4>Conclusions</h4>An autoimmune mechanism mediated by anti-gAChR antibodies may be involved in disease etiology in a subgroup of FNSD/CD patients.

    DOI： 10.3389/fneur.2023.1137958

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  • Satoshi Nozuma, 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   2022.12Reviewed International journal

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

    <h4>Objective</h4>HTLV-1 infection causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the efficacy and safety of l-arginine in patients with HAM/TSP.<h4>Methods</h4>This open-label, single-arm, Phase 2 study enrolled patients diagnosed with HAM/TSP. Patients received l-arginine at a dose of 20 g orally for 1 week and were followed-up for 3 weeks. The primary endpoint was change in walking speed in the 10-m walk test (10MWT). The main secondary endpoints were change in Timed Up and Go Test (TUGT) time, improvement in inflammatory markers in cerebrospinal fluid (CSF), safety, and tolerability.<h4>Results</h4>The study enrolled 20 patients (13 [65%] female) with a mean age of 67.8 years (95% CI 62.3 to 73.3). Although the primary endpoint, the changes in 10MWT time between baseline (Day 0) and Day 7, did not reach statistical significance (mean percent change in time -3.5%, 95% CI -10.8% to 3.7%; P = 0.32), a significant improvement was detected between baseline and Day 14 (-9.4%, 95% CI -16.6% to -2.2%; P = 0.01). Significant improvements were also observed in selected secondary endpoints, including in TUGT time (-9.1%, 95% CI -15.5% to -2.7%; P < 0.01), and in neopterin concentration in CSF (-2.1 pmol/mL, 95% CI -3.8 to -0.5; P = 0.01). Adverse events were infrequent, mild, and resolved rapidly.<h4>Interpretation</h4>l-arginine therapy improved motor function and decreased CSF inflammatory markers. l-arginine thus represents a promising therapeutic option for patients with HAM/TSP.<h4>Trial registration number</h4>UMIN000023854.

    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)  

    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<sup>+</sup> 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<sup>+</sup> 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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    Language：English   Publishing type：Research paper (scientific journal)  

    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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    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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    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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    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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    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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    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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    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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    DOI： 10.1128/JCM.01628-15

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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 .  Standardization of Quantitative PCR for Human T-cell Leukemia Virus Type 1 in Japan: A Collaborative Study. .  Journal of Clinical Microbiology.53 ( 11 ) 3485 - 3491   2015.11Standardization of Quantitative PCR for Human T-cell Leukemia Virus Type 1 in Japan: A Collaborative Study.Reviewed International journal

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    DOI： 10.1128/JCM.01628-15.

  • 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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    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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    DOI： 10.1371/journal.pone.0086144

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  • 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HTLV-1特異的CTLはHAM発症リスクを下げるか? .  MHC: Major Histocompatibility Complex19 ( 2 ) 168 - 168   2012.8Reviewed International journal

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    Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本組織適合性学会  

  • 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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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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  • 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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    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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    DOI： 10.2169/naika.92.1673

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  • 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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    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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    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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    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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    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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    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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    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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    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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    PubMed

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

    DOI： 10.1097/00002030-199301000-00029

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

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

    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<sup>-5</sup> for DMD, 1.82 X 10<sup>-5</sup> for BMD in the male population, 1.55 X 10<sup>-5</sup>for LG, 1.14 X 10<sup>-5</sup> for congenital muscular dystrophy, 2.03 X 10<sup>-5</sup> for facioscapulohumeral muscular dystrophy (FSH), and 9.13 X 10<sup>-5</sup> for myotonic dystrophy (MD) in the total population. The incidence of DMD in the period 1957-1985 was 15.41 X 10<sup>-5</sup> live-born males (LBM) and 3.21 X 10<sup>-5</sup> 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

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

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

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

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

    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

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  • 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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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Bone and Mineral Metabolism  

    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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    Language：Japanese Book type：Scholarly book

  • 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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  • 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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  • 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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  • 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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  • HAM疾患活動性バイオマーカーとしてのCADM1の検討

    竹之内徳博, 竹之内徳博, 田中正和, 松浦英治, 久保田龍二, 中嶋伸介, 大高時文, 上野孝治, 大隈和

    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<sup>+</sup> 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<sup>+</sup> 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：(株)中外医学社  

  • 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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    Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE BV  

    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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  • 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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  • 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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  • 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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  • 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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  • 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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  • HLA-A24拘束性HTLV-I特異的CTLはHAM発症リスクを下げるか?

    久保田龍二, 竹之内徳博, 松崎敏男, 高嶋博, 出雲周二

    日本神経免疫学会学術集会抄録集   23rd   2011

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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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    Language：English   Publishing type：Research paper, summary (international conference)   Publisher：MARY ANN LIEBERT INC  

    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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    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

  • 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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    Authorship：Lead author   Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE BV  

    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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    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

  • 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

  • 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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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 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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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • Retrovirus infection and neurological disorders International coauthorship

    Shuji Izumo, Ryuji Kubota, Hui Qin Xing

    No to shinkei. Brain and nerve   58 ( 7 )   595 - 604   2006

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    Scopus

    PubMed

  • 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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  • 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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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 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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    Authorship：Lead author   Language：English   Publishing type：Research paper, summary (international conference)   Publisher：MARY ANN LIEBERT INC PUBL  

    Web of Science

  • A patient of ADEM with central and peripheral conduction block improved with ultra-high-dose methylprednisolone

    UEHARA Akiko, OKAMOTO Yuhji, NISHITARUMIZU Kazutaka, UTO Tadashi, KUBOTA Ryuhji, JOHNOSONO Manabu, EIRAKU Nobutaka, ARIMURA Kimiyoshi, OSAME Mitsuhiro

    42 ( 3 )   237 - 239   2002.3

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    Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)  

    CiNii Books

    Other Link： http://search.jamas.or.jp/link/ui/2003138628

  • 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

  • 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

  • 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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    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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    Authorship：Lead author   Language：English   Publishing type：Research paper, summary (international conference)   Publisher：STOCKTON PRESS  

    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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    Authorship：Lead author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：Journal of NeuroVirology  

    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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    Web of Science

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Presentations

  • Nozuma S, Matsuura E, Dozono M, Yoshida T, Tanaka M, Kodama D, Kubota R, Takashima H   Characterizing pathological HTLV-1-infected T cell clones in HAM/TSP.   International conference

    21th International Conference on Human Retrovirology: HTLV & Related Viruses  2024.6 

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    Event date： 2024.6

    Language：English   Presentation type：Poster presentation  

  • Kubota R, Tanaka M, Kodama D, Dozono M, Nozuma S, Takashima H   Comparison of phenotypes and functions in HTLV-1 Tax-specific cytotoxic T-lymphocytes between HAM patients and carriers.   International conference

    21th International Conference on Human Retrovirology: HTLV & Related Viruses,  2024.6 

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    Event date： 2024.6

    Language：English   Presentation type：Poster presentation  

    Venue：London  

  • Dozono M, Nozuma S, Matsuura E, Yoshida T, Tanaka M, Kodama D, Kubota R, Takashima H   Efficacy of l-arginine in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis   International conference

    21th International Conference on Human Retrovirology: HTLV & Related Viruses  2024.6 

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    Event date： 2024.6

    Language：English   Presentation type：Poster presentation  

    Venue：London  

  • Tanaka M, Arishima S, Kodama D, Nozuma S, Takashima H, Miwa M, Kubota R   Investigation of HAM pathogenesis due to PARP-mediated neuronal death   International conference

    21th International Conference on Human Retrovirology: HTLV & Related Viruses  2024.6 

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    Event date： 2024.6

    Language：English   Presentation type：Poster presentation  

    Venue：London  

  • Kodama D, Tanaka M, Matsuzaki T, Nozuma S, Matsuura E, Takashima H, Izumo S, Kubota R   Molecular-targeted agents for treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).   International conference

    21th International Conference on Human Retrovirology: HTLV & Related Viruses  2024.6 

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    Event date： 2024.6

    Language：English   Presentation type：Oral presentation (general)  

    Venue：London  

  • 久保田龍二   HAMの臨床と病態   Invited

    第40回日本皮膚悪性腫瘍学会  2024.5 

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    Event date： 2024.5

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Venue：宮崎   Country：Japan  

  • 久保田龍二   HAMの病態と治療   Invited

    第96会日本生化学会大会  2023.11 

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    Event date： 2023.11

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Venue：福岡   Country：Japan  

  • 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)  

  • 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, 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  

  • 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 

    　More details

    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 

    　More details

    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

  • 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

  • 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 

    　More details

    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

  • 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

  • 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

  • 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

  • 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

  • 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   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

  • 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

  • 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、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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 久保田 龍二   HTLV-1が引き起こす血液癌(ATL)と脊髄症(HAM)の現状と治療法開発　HAMの病態と治療   Invited

    日本生化学会大会プログラム・講演要旨集  2023.10  (公社)日本生化学会

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    Language：Japanese   Presentation type：Oral presentation (invited, special)  

  • 隅田 泰生, 立尾 清悟, 内田 友一朗, 久保田 龍二, 吉満 誠   HTLV-1が引き起こす血液癌(ATL)と脊髄症(HAM)の現状と治療法開発　抗糖鎖抗体/CAR-NKによるHTLV-1関連疾患の治療法開発  

    日本生化学会大会プログラム・講演要旨集  2023.10  (公社)日本生化学会

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    Language：Japanese   Presentation type：Oral presentation (invited, special)  

  • 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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    Language：Japanese   Presentation type：Poster presentation  

  • 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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    Language：Japanese   Presentation type：Oral presentation (general)  

  • 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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  • 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   抗HTLV-1抗体髄液検査はCLIA法が適している   International coauthorship

    NEUROINFECTION  2022.10  日本神経感染症学会

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    Language：Japanese   Presentation type：Poster presentation  

  • 土元 香菜子, 森 理紗, 田中 正和, 兒玉 大介, 野妻 智嗣, 松浦 英治, 高嶋 博, 久保田 龍二   HTLV-1関連疾患における末梢血と気管支肺胞洗浄液中の感染細胞数の比較と肺胞移行能の検討   International coauthorship

    NEUROINFECTION  2022.10  日本神経感染症学会

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    Language：Japanese   Presentation type：Poster presentation  

  • 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   HTLV-1感染細胞を標的としたHAMでのバイオマーカー探索   International coauthorship

    NEUROINFECTION  2022.10  日本神経感染症学会

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    Language：Japanese   Presentation type：Poster presentation  

  • 出雲 周二, Xing HuiQin, 久保田 龍二   HIV脳症のUp to Date　HIV脳症の神経病理学   International coauthorship

    NEUROINFECTION  2022.10  日本神経感染症学会

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    Language：Japanese   Presentation type：Poster presentation  

  • 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   HAMにおけるPARP活性化を介した神経細胞死の検討   International coauthorship

    NEUROINFECTION  2022.10  日本神経感染症学会

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  • 吉田 崇志, 松浦 英治, 野妻 智嗣, 堂園 美香, 児玉 大介, 田中 正和, 久保田 龍二, 高嶋 博   HTLV-1関連脊髄症/熱帯性痙性対麻痺(HAM/TSP)の診断マーカーとしての腸腰筋の筋力低下について   International coauthorship

    神経免疫学  2023.9  (一社)日本神経免疫学会

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    Language：Japanese   Presentation type：Poster presentation  

  • Kodama Daisuke, Tanaka Masakazu, Matsuzaki Toshio, Nozuma Satoshi, Matsuura Eiji, Takashima Hiroshi, Izumo Shuji, Kubota Ryuji   HTLV-1のcell-to-cell感染におけるLacNAcの関与とその阻害剤の発見(Involvement of LacNAc in HTLV-1 cell-to-cell contact infection and the discovery of its inhibitors)  

    臨床神経学  2023.9  (一社)日本神経学会

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    Language：English   Presentation type：Poster presentation  

  • 堂園 美香, 重久 彩乃, 吉田 崇志, 野妻 智嗣, 中村 友紀, 橋口 昭大, 松浦 英治, 久保田 龍二, 高嶋 博   ネマリンミオパチー合併を認めたHAM/TSPの一例  

    NEUROINFECTION  2023.10  日本神経感染症学会

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    Language：Japanese   Presentation type：Poster presentation  

  • 久保田 龍二   HTLV-1と関連疾患　HAMの臨床と病態   Invited

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集  2024.4  (一社)日本皮膚悪性腫瘍学会

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    Language：Japanese   Presentation type：Oral presentation (invited, special)  

  • 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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▼display all

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

    Grant number：22H03121  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    久保田 龍二, 田中 正和

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\17420000 （ Direct Cost: \13400000 、 Indirect Cost：\4020000 ）

  • 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

  • HTLV-1関連眼疾患の診断法確立のための臨床的研究

    Grant number：16K11268  2016.4 - 2023.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中尾 久美子, 久保田 龍二

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    今年度に採取できた眼内液と血液について、 TaqManリアルタイムPCRアッセイでHTLV-1 proviral loadを測定し、CLEIA法でsIL-2Rを測定した。
    前年度までに測定したHTLV-1 proviral loadがコピー数が少ないために正確に測定できていないことが判明したため、低コピー数検体の修正を行った。8.67 copy/100 cells の tax 遺伝子を含む DNA を順次希釈し、β-アクチン遺伝子とtax遺伝子のコピー数を測定して実測曲線と予測曲線をひき、このグラフから補正式を求め、β-アクチン遺伝子とtax遺伝子のコピー数を補正して、HTLV-1 proviral loadを (tax コピー数)/((β-アクチン コピー数)/2) x 100 (% copy/100 cells)によって算出した。眼内液と末梢血液の両方でHTLV-1 tax遺伝子とβ-アクチン遺伝子を測定できたHAU７例とHTLV-1キャリアに発症したサルコイドーシスによるぶどう膜炎１例の測定値を補正した結果、HAUでは眼内液のproviral loadは10.3ー29.3 (copy/100 cells)で、末梢血液のproviral loadに比べて3ー266倍と非常に高い症例もあったが、一方で0.7ー1.1倍と高くない症例もあった。またHTLV-1キャリアのサルコイドーシスでも眼内液のproviral loadが高く、眼内液のHTLV-1 proviral load 単独ではHAU診断の指標とはならないと考えられた。

  • 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

  • Development of HTLV-1 peptide vaccine for treatment and prevention of ATL

    Grant number：15K09481  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Arima Naomichi

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    To see if HTLV-1 related protein can be the candidate for cytotoxic T lymphocyte (CTL) -type vaccination target for prevention and treatment of adult T-cell leukemia/lymphoma (ATL), we chose HBZ, constitutively expressing HTLV-1 related protein in ATL, as CTL-type vaccination target. Although we detect HBZ-specific CTL in HAM/TSP patients, another HTLV-1 virus assosiated neurological disorder, we were not able to detect HBZ-specific CTL in ATL patients, who were postive for HTLV-1 Tax-CTL . We were not able to detect HBZ-specific CTL even in ATL patients after allogeneic hematopoietic stem cell transplantation. Thus, we concluded that HBZ protein has too weak immunogenecity to elicit vaccination effect for prevention and treatment of ATL.

  • 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) 

  • Comparable studies on HTLV-1 associated diseases between costal area of Fujian province, China, and south-western Japan. International coauthorship

    Grant number：25305017  2013.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Izumo Shuji

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\11050000 （ Direct Cost: \8500000 、 Indirect Cost：\2550000 ）

    HTLV-1 is distributed worldwide, and Fujian province is an only area where HTLV-1-positive blood donors were found in China. But information of HTLV-1 in China is limited, and there are few reports about patients with HTLV-1-associated diseases from China. This project is planned to encourage and support HTLV-1 study in Fujian province China, in order to find the patients, find HTLV-1-hot areas, and begin original HTLV-1 researches in China.
    We invited Chinese researchers to Japan for training of HTLV-1 study. We also visited regional center hospitals and blood centers in Fujian province and give lectures about HTLV-1 related diseases. As a result, HTLV-1 infection was found to be endemic in the coastal area of Fujian province, especially in northern region, where several ATL patients have been experienced. In addition, one HAM/TSP patient with typical clinical features was confirmed by international diagnostic criteria. HTLV-1 is endemic in the coastal area of Fujian province, China.

  • Molecular pathologic study on pathogenesis of HIV-associated neurocognitive disorders (HANDs) International coauthorship

    Grant number：25461285  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    IZUMO Syuji, KUBOTA RYUJI, FURUKAWA YOSHITAKA, MORI KAZYYASU

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\5070000 （ Direct Cost: \3900000 、 Indirect Cost：\1170000 ）

    To understand the pathogenesis of HIV-1 associated neurocognitive disorders (HANDs) we immunohistochemically analyzed brains from simian immunodeficiency virus (SIV)-macaque models and autopsy brains from HIV-1-infected individuals. A highly virulent SIV302-2-infected animals efficiently developed SIV encephalitis with multinuclear giant cells. Concerning the cortical degenerative changes, astrocyte-specific functional molecules, EAAT-2, AQP4, and connexin43 were proportionally reduced in the frontal cortex, and neuronal, as well as astrocytic, apoptosis was observed. A double immunohistochemistry demonstrated that reduction of AQP4 preceded EAAT-2 reduction, suggesting that a primary damage of astrocyte and blood-brain barrier disturbance induce excitatory neuronal cell death. Menin and TGF-beta were expressed in the apoptotic neurons suggesting their roles in pathogenesis of HANDs. These data confirm two independent pathogenic processes in HANDs.

  • 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

  • Neuropathogenesis of retrovirus infection : diverse in vivo and ex vivo analysis of HAM/TSP and AIDS encephalopathy. International coauthorship

    Grant number：19390243  2007 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    IZUMO Shuji, KUBOTA Ryuji, HURUKAWA Yoshitaka, OKAMOTO Mika, ARIMURA Kimiyoshi, UMEHARA Hujio, MORI Kazuyasu

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\18330000 （ Direct Cost: \14100000 、 Indirect Cost：\4230000 ）

    In order to clarify neuropathogenesis of retrovirus-induced neurological disorders we performed diverse in vivo and ex vivo analysis of HAM/TSP and AIDS encephalopathy. We demonstrated presence of infected mononuclear cells and accumulation of virus-specific cytotoxic T lymphocytes in the inflammatory lesions of HAM/TSP. Additional studies on AIDS encephalopathy, as well as HTLV-1-associated polymyositis, suggest that invasion of infected mononuclear cells in the site of the nervous system and immune responses against these infected cells is a common pathogenic process of retrovirus induced neurological disorders. We also demonstrated that degeneration of the cerebral cortex occurs in AIDS encephalopathy independently from the inflammatory process, and dysfunction of astrocytes may have a role in this degenerative process.

  • The development of a novel molecular targeting therapeutic intervention in HTLV-1-associated myelopathy(HAM)

    Grant number：19591015  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YAMANO Yoshihisa

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

  • 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

  • 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

    Grant number：17659267  2005 - 2006

    日本学術振興会  科学研究費助成事業  萌芽研究

    納 光弘, 出雲 周二, 久保田 龍二

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\3200000 （ Direct Cost: \3200000 ）

    HTLV-Iに感染したCD4陽性細胞とHTLV-Iに特異的なCD8陽性細胞障害性T細胞(CTL)の免疫反応がHAM発症に深く関与していると類推されてきたが、HAM患者の脊髄に実際にHTLV-I特異的CTLが浸潤しているのかは不明であった。昨年の我々の研究によりHAMの脊髄でHTLV-I特異的CTLの存在が明らかとなり、浸潤しているCD8陽性細胞のうち20%をこえる細胞がTax11-19特異的CTLであることも判明した。今年度の研究ではサンプルをふやして同じ結果を確認した。また、HTLV-I Tax蛋白に対する特異抗体を使って中枢神経系内においてHTLV-I感染細胞の同定を行い二重染色でこれらの細胞がCD4陽性細胞であることを確認した。加えてパーフォリン、グランザイムBおよびTNF-αなどCTLの細胞障害関連分子の同定をおこない、CTLが中枢において活動性を持つことを確認した。さらにCTLによりアポトーシスを起こしている細胞を検出し、二重染色によりこれらアポトーシス細胞が浸潤細胞の多い血管周囲の主に希突起膠細胞であることを確認した。
    HTLV-I感染CD4陽性細胞とHTLV-I特異的CD8陽性CTLが中枢神経系へ浸潤しこれらの細胞を中心とする炎症が起こり、その結果、希突起膠細胞などの中枢神経系細胞がbystander damageを被るというHAMの発症機序が明らかとなった。HTLV-I特異的CTLがHAM発症に深く関与しており、HAMの治療戦略上CTLのコントロールが重要であることが判明した。

  • 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

  • T細胞増殖関連Sonic Hedgehog分子とHAM患者ウイルス抑制機構の研究

    Grant number：15659210  2003 - 2004

    日本学術振興会  科学研究費助成事業  萌芽研究

    宇宿 功市郎, 古川 良尚, 久保田 龍二, 出雲 周二

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\3100000 （ Direct Cost: \3100000 ）

    ヒトリンパ球好性ウイルスI型(HTLV-I)感染者においては、宿主個体内においてウイルス発現に対する抑制機構が存在し、それによりウイルス複製と宿主免疫機構が一定の平衡状態にあることが知られている。その分子機構は長年にわたりHTLV-I研究分野における未解決の課題であったが、2001年以降に、この問題の解明に重要な手がかりを与える2つの新知見が相次いで報告された。一つは形態形成にかかわる細胞内シグナル伝達分子として報告されたSonic hedgehog分子(Shh)が、T細胞の分化および活性化CD4陽性リンパ球のクローナルな増殖に関与するという報告であり、二つ目は、Shhシグナル伝達系の最下流に位置する因子であり、かつHTLV-I感染細胞中で転写因子CREBを介してTaxと結合し、LTRからのウイルスの転写制御にかかわる転写因子であるGli2分子が、HTLV-Iウイルスの発現調整に極めて重要な役割を果たすという報告である。
    本研究ではこれら分子のHAM発症における意義を明らかにすることを目的としていた。対象と方法であるが、対象はHAM患者、無症候性キャリアー、正常コントロール末梢血中リンパ球であり、方法としてはそのリンパ球中の各分子の発現をRT-PCRとフローサイトメーターにより定量し、各種免疫学的パラメーター、臨床症状と比較することであった。今回の検討の結果であるが、ShhとGli2分子はHTLV-I感染者で発現増強していることが判明した。ShhとGli2分子の発現細胞の表面抗原や臨床症状との関連についての解析では、報告書の時点ではHAM発症を規定する明確なものには行き着かなかった。結論であるが、T細胞におけるShhやGli2の発現増強とHTLV-I感染との関連が示唆された。今後ともHAM発症を規定する因子の一つとして研究を継続させたい。

  • 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

  • Exploitation of new therapies for HTLV-I-assotiated myelopathy

    Grant number：14207031  2002 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    OSAME Mitsuhiro, ARIMURA Kimiyoshi, UMEHARA Fujio, KUBOTA Ryuji, IZUMO Shuji, USUKU Koichiro

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\37050000 （ Direct Cost: \28500000 、 Indirect Cost：\8550000 ）

    In this research project, we have deeply improved our understanding for the pathogenesis of HTLV-I-associated myelopathy(HAM) and developed a hopeful therapy for the disease. It is an initial event that HTLV-I-infected cells infiltrate into the central nervous system for the development of HAM, where matrix metalloproteinase(MMP)-2 and -9 play an important role. We found that a selective MMP inhibitor specific for MMP-2 and -9, N-Biphenyl sulfonyl-phenylalanine hydroxamic acid(BPHA), significantly inhibited migration activity of CD4+ T lymphocytes (which are a main reservoir of HTLV-I) from HAM patients. This suggests that the compound is a candidate for a new therapy for HAM patients. We had identified many genetic factors which increase susceptibility for the disease, and we newly identified two genetic factors, polymorphism of interleukin-10 promoter, and the length of tandem repeat in MMP-9 promoter. Using these host genetic factors, we made a formula to predict the risk of the development of HAM. When we utilized it for HTLV-I asymptomatic carriers, the carriers with high risk values showed faint abnormalities on the neurological examination, suggesting that the formula is very useful for prediction of the prognosis. In a genetic analysis of HTLV-I, the ratio of non-synonymous change to synonymous change (dN/dS ratio) of HTLV-I gene was lower in HAM patients than in HTLV-I carriers, implying that viral replication is more effectively inhibited in HAM patients than in the carriers. Moreover, HAM patients with HLA-A^*02 had lower dN/dS ratio than those without HLA-A^*02, suggesting that HL-A^*02 has an inhibitory effect on viral replication. Additionally, an analysis of dN/dS ratio, cytotoxic T lymphocytes(CTL) epitopes and frequency of mutant virus demonstrated that CTL had antiviral pressure in vivo, however, a mutant virus did not predominate. Further studies are needed to establish a more effective therapy for HAM patients.

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Other research activities

  • HTLV-1キャリア診療ガイドライン2024

    2024.4

  • HTLV-1感染の診断指針第3版

    2024.3

  • 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

  • 令和5年度鹿児島県中・高校生インターンシップ

    Role(s)： Lecturer

    2023.7

  • JICAナイジェリア研修生講義

    Role(s)： Lecturer

    2023.6

  • 宮崎県立都城泉ヶ丘高校理数科講演会

    Role(s)： Lecturer

    2019.6

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    Audience： High school students

    Type：Lecture

    なぜ僕はHTLV-1研究をするようになったのか？

  • 平成30年度霧島市医師会医療センター院内感染研修会

    Role(s)： Lecturer

    2018.5

  • Seminar in Taipei Blood Center, TBSF, Tapiei, Taiwan

    Role(s)： Lecturer

    2018.3

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    Audience： Researchesrs

    Type：Seminar, workshop

  • 平成29年度南薩医師会前期医学会

    Role(s)： Lecturer

    2017.7

  • 第30回鹿児島脊椎脊髄研究会

    Role(s)： Lecturer

    2016.12

  • Seminar in Neurology Department of Fujian Medical University, China

    Role(s)： Lecturer

    2015.12

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    Audience： Teachers,　Researchesrs

    Type：Seminar, workshop

  • HTLV-1 meeting in Xiamen University, China

    Role(s)： Lecturer

    Xiamen University  Xiamen University  2014.1

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    Type：Seminar, workshop

    HAM: clinical features and pathogenesis

  • 日本赤十字社九州ブロック血液センターセミナー

    Role(s)： Lecturer

    日本赤十字社九州ブロック血液センター  2013.12

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    HTLV-1, HAMの歴史と最新の知見

  • 市民公開講座、鹿児島市

    Role(s)： Lecturer

    厚生労働科学研究費補助金難治性疾患克服研究事業  かごしま県民交流センター  2012.11

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    HAMとはどのような病気なのか？

  • 第44回中国四国医学検査学会

    Role(s)： Lecturer

    アスティとくしま  2011.11

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    HTLV-I撲滅に向けての最新情報と今後の展望

  • シスメックスフォーラムイン鹿児島

    Role(s)： Lecturer

    シスメックス  鹿児島東急ホテル  2011.5

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    Type：Seminar, workshop

    HTLV-I撲滅に向けての最新情報と今後の展望

  • 鹿児島県立加治木高校龍門講座

    Role(s)： Lecturer

    鹿児島県立加治木高校  2010.12

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    Type：Lecture

    九州に多いウイルス：HTLV-I

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